Treatment of warts using anthralins and occlusion

A method of treating a patient having one or more warts includes the steps of: applying to the wart an amount of a composition consisting essentially of an anthralin active ingredient and a pharmaceutical carrier; covering the wart and skin areas peripheral to the wart with an adhesive tape, such that the adhesive tape adheres to peripheral skin areas, whereby the adhesive tape provides an occluding environment for the wart treated with the composition. The occluding environment is maintained for a desired period of time, and the adhesive tape is removed. For a number of times as desired, a fresh amount of anthralin-containing composition is applied, and a fresh piece of adhesive tape is applied to recreate the occluding environment.

FIELD OF THE INVENTION 
The present invention relates to the field of treating warts, also known as 
verruca vulgaris, and more specifically with the topical treatment of 
warts using treating agents known as anthralins. 
BACKGROUND OF THE INVENTION 
A wide variety of warts are found on human skin and are caused by the human 
papilloma virus (HPV). For example, the following types of warts are found 
on human skin and are caused by the human papilloma virus (HPV): common 
warts (verruca vulgaris), plantar warts, palmar warts, planar warts 
(verruca plana), mosaic warts, and venereal warts (condyloma accuminatum). 
These skin growths are unsightly, irritating, and potentially oncogenic 
(carcinogenic), and their removal is desired. 
Throughout the years a number of therapies have been developed for treating 
warts, and these therapies can be categorized in the following seven 
categories: (1) locally destructive chemicals; (2) surgically destructive 
methods; (3) blister-producing methods; (4) cellular inhibition; (5) 
altering the cutaneous environment; (6) immune stimulation; and (7) 
miscellaneous methods. See the article by Vance entitled "Verruca Vulgaris 
(Warts)", pages 743-745, in Conn's Current Therapy 1992, edited by Robert 
E. Rakel, M.D., W. B. Saunders Company, (1992). 
Treatment methods using locally destructive chemicals include using the 
following chemicals: salicylic acid (in films, plasters, pads, and tapes); 
lactic acid; trichloracetic acid (TCA); bichloroacetic acid (BCA); nitric 
acid; and glacial acetic acid. 
Surgically destructive methods include the following techniques: excision; 
electrocautery; electrodesiccation; curettage; blunt dissection; and laser 
vaporization or coagulation. 
Blister-producing methods include the following techniques: liquid nitrogen 
cryotherapy; carbon dioxide cryotherapy; and cantharidin. 
Cellular inhibition methods include use of the following agents: 
podophyllin and podophyllotoxin; 5-fluorouracil; bleomycin; colchicine; 
interferon local injections; and radiation. 
Methods for altering the cutaneous environment include the following agents 
or techniques: retinoids; formalin; glutaraldehyde; aluminum chloride; and 
heat therapy. 
Immune stimulation methods of treatment include the following: 
dinitrochlorobenzene (DNCB); interferon systemic injections; and 
vaccination, autologous or intralesional. 
Miscellaneous methods include: hypnosis; and tape occlusion. On page 745 of 
the Vance article, there is a statement that hypnosis and tape occlusion 
probably have a placebo effect providing an about 20% cure. 
Currently, there are a number of over-the-counter products on the market 
that are used for treating warts. One such product is Pedia Patch (TM) of 
Tsumura International, Inc., Shakopee, Minn. 55379. This product contains 
a quantity of salicylic acid in a sticky base. The salicylic acid/sticky 
base is retained and carried by a piece of adhesive tape. In use, the 
salicylic acid/sticky base is applied to the wart, and free ends of the 
adhesive tape are applied to peripheral skin areas to keep the treating 
agent in place on the skin. This product employs two of the 
above-mentioned seven wart treatment methods simultaneously, namely: (1) a 
locally destructive chemical (salicylic acid); and (7) tape occlusion. 
A second over-the-counter wart treatment product is Duo Plant (R) a plantar 
wart removal system of Schering Plough, Healthcare Products, Inc., 
Memphis, Tenn. 38151. This product is a gel that includes alcohol 57.6% 
w/w, ether 16.42% w/w, ethyl lactate, hydroxypropyl cellulose, and 
polybutene in flexible collodion. The gel is applied directly to the wart, 
and the solvents evaporate leaving a film with treating agent. 
A third over-the-counter wart treatment product is Dr. Scholls Clear Away 
Plantar Wart Remover System (TM) of Schering Plough Healthcare Products, 
Inc., Memphis, Tenn. This product includes adhesive-tape-containing discs 
which contain salicylic acid (40%) in a rubber-based vehicle. The 
salicylic acid/rubber base is retained and carried by the piece of 
adhesive tape. In use, the salicylic acid/rubber base is applied to the 
wart, and free ends of the adhesive tape are applied to adjacent skin 
areas to keep the treating agent in place on the skin. This product 
employs two of the above-mentioned seven wart treatment methods 
simultaneously, namely: (1) a locally destructive chemical (salicylic 
acid); and (7) tape occlusion. 
A fourth over-the-counter wart treatment product is Compound W (TM) of 
Whitehall Laboratories, Inc., New York, N.Y. 10017. The active ingredient 
in the product is salicylic acid (17% w/w). Inactive ingredients in the 
product include: acetone; collodion; alcohol (2.2% w/w); camphor; castor 
oil; ether (63.5%); menthol; and Polysorbate 80. In use, this product is 
applied as a liquid coating to a wart. When the solvents evaporate, the 
wart is covered by a flexible film which contains the active ingredient. 
Fifth and sixth over-the-counter wart treatment products are Transplantar 
(TM) and Transversol (TM), respectively, made by Bradley Pharmaceutical 
Co., 383 Route 46 West, Fairfield, N.J. 07004. Each of these products 
employs salicylic acid in a gum base. A piece of adhesive tape retains and 
carries the salicylic acid/gum base composition. In use, the salicylic 
acid/gum base composition is placed over the wart, and the adhesive tape 
is applied to adjacent skin to keep the device in position. This product 
employs two of the above-mentioned seven wart treatment methods 
simultaneously, namely: (1) a locally destructive chemical (salicylic 
acid); and (7) tape occlusion. 
Another wart treatment product is Occlusal-HP (TM), by Gen Derm 
Corporation, Lincolnshire, Ill. 60069. It is noted that Occlusal HP 
contains 17% salicylic acid in a polyacrylic vehicle containing ethyl 
acetate, isopropyl alcohol, butyl acetate, polyvinyl butyral, dibutyl 
phthalate, acrylates copolymer, and nitrocellulose. The pharmacologic 
activity of Occlusal-HP is generally attributed to the keratolytic action 
of salicylic acid which results in mechanical removal of epidermal cells 
infected with wart viruses. 
Another wart treatment product is a plaster called Sal-Acid Plaster (TM) by 
Pedinol Pharmacal, Inc., 30 Banfi Plaza, Farmingdale, N.Y. 11735. This 
product contains 40% salicylic acid. 
Yet another wart treatment product is disclosed in the 1990 edition of the 
Physicians Desk Reference (PDR), published by Medical Economics Data 
Production Company, Montvale, N.J. This wart treatment product is Viranol 
(TM) gel made by American Dermal Corp., Bedminster Industrial Park, P.O. 
Box 900, Plumsteadville, Pa. 18949. Viranol gel has 12% salicylic acid as 
its active ingredient. 
Aside from the treatments mentioned above which have attained the status of 
generally accepted methods and techniques in medical practice for treating 
warts, there are publications in the literature which disclose still other 
methods and techniques for treating warts. Of special relevance with 
respect to the present patent are publications which disclose anthralin or 
its analogs or derivatives in the treatment of warts. 
Anthralin is also known as dithranol, and its chemical name is 
1,8-dihydroxy-9(10H)-anthracenone. An alternate chemical name for 
anthralin is 1,8-dihydroxyanthrone. Still another accepted chemical name 
for anthralin is 1,8-dihydroxy,9-anthrone. Commercial preparations 
containing anthralin include Anthra-Derm, Antraderm, Batidrol, Cignolin, 
Cigthranol, Drithocreme, Psoradrate, and Psoriacide. The triacetate is 
known as 1,8,9-anthracenetriol triacetate and, alternatively, as 
1,8,9-triacetoxyanthracene, which is known commercially as Exolan. See The 
Merck Index, Tenth Edition, (1983) for the entry "Anthralin". 
In an article by Flindt-Hansen et al entitled "Wart Treatment With 
Anthralin", in Acta. Derm. Venereol. (Stockh.) 64: 177-180, 1984, there is 
a disclosure that 27 patients were treated with Anthraderm (2% anthralin 
and 0.5% salicylic acid in a wax preparation enclosed in a lipstick-like 
container). More specifically, the treatment involved application of the 
Anthraderm twice a day by the patients. Every 2 weeks gentle cutting and 
scraping of the warts were performed in a clinic. Undergoing this 
treatment of topical application of Anthraderm and periodic cutting and 
scraping, 15 (56%) of the 27 patients were cured; that is, no wart tissue 
was visible. There is a teaching that in psoriasis, the effect of 
anthralin is thought to consist in a reduction of the cell turn over 
caused by an inhibition of the cell metabolism. These pharmacological 
effects in the cell metabolism might be beneficial in the treatment of the 
benign tumour produced by replicating wart virus. There is no disclosure 
that any tape occlusion was used. 
In an article by Hjorth et al entitled "Anthralin Stick (Anthraderm) in the 
Treatment of Mosaic Warts", in Acta. Derm. Venereol. (Stockh.) 66: 
181-182, 1986, there is a disclosure that anthralin in a wax-based stick 
(2% anthralin stick) that was used for 2 months was effective against 
common warts. More specifically, there were 30 patients treated. After a 
mean of 7 months of treatment (range, 3 to 10 months), warts in 17 
patients were cleared, and warts in 7 patients persisted. The remaining 6 
patients dropped out. The treatment involved daily application of 2% 
anthralin stick supplemented by weekly paring (cutting or shaving) of the 
wart. By having 17 patients out of 30 patients cleared of warts, the 
percentage of patients cleared of warts is 57%. There is no disclosure 
that any tape occlusion was used. 
In an article by Mare et al entitled "Dithranol in the Treatment of 
Inflammatory Linear Verrucous Epidermal Nevus" in Acta Derm Venereol 
(Stockh), Vol. 69 (Short Reports), pages 77-80, (1989), there is a 
disclosure that dithranol (also known as anthralin) was used to treat a 
patient with the short contact anthralin therapy (SCAT) method to treat 
the psoriasis condition known as inflammatory linear verrucous epidermal 
nevus (ILVEN). Over an 8 week period, the concentration of the anthralin 
was increased in the following increments in the short contact anthralin 
therapy (SCAT) method: 0.5%, 1%, 2%, 3%, 4%, and 5%. There is no 
disclosure that the anthralin was used in treating common warts. There is 
no disclosure that any tape occlusion was used. 
By and large, anthralin is used primarily in the treatment of psoriasis. 
Psoriasis is a condition of the skin in which skin cells mature abnormally 
rapidly resulting in increased cellular turnover and rapid growth of the 
skin. There is no involvement of the human papilloma virus (HPV) in 
psoriasis. Aside from anthralin, other conventional treatments for 
psoriasis include topical corticosteroids, tar, UV-B radiation, psoralens 
and UV-A radiation, and bland emollients. 
More specifically with respect to the treatment of psoriasis, the following 
U.S. patents discloses compositions containing anthralin or its 
derivatives or analogs for treating psoriasis: U.S. Pat. Nos. 4,465,688; 
4,495,203; 4,504,494; 4,696,941; and 4,866,095. More specifically, in U.S. 
Pat. No. 4,465,688, from column 13, line 49 to column 14, line 2, a 
composition is disclosed which contains 
9,10-dihydro-1,8,9-trihydroxy-9,10-anthracene-alpha,beta-endo-N-ethyl 
succinimide (a compound related to anthralin) approximately 1.47% by 
weight; salicylic acid, approximately 0.68% by weight; and petroleum 
jelly, approximately 97.85% by weight. The composition is prepared in the 
form of a suspension that is applied once a day for three weeks. Excellent 
results are obtained on the psoriasis areas very similar to those obtained 
with anthralin but with no primary irritation and without staining of the 
skin. In this patent there is a nominal disclosure that warts can also be 
treated with the 
9,10-dihydro-1,8,9-trihydroxy-9,10-anthracene-alpha,beta-endo-N-ethyl 
succinimide, but no specific protocol for treating warts is disclosed. In 
this respect, there is no disclosure that any tape occlusion is used for 
treating warts with the 
9,10-dihydro-1,8,9-trihydroxy-9,10-anthracene-alpha,beta-endo-N-ethyl 
succinimide. U.S. Pat. No. 4,866,095 has disclosures similar to U.S. Pat. 
No. 4,465,688. 
U.S. Pat. No. 4,504,494 discloses that anthralin compositions are used in 
the treatments of psoriasis and warts. In this patent, Examples IV, VII, 
VIII, XIII, and XIV disclose compositions which contain anthralin and an 
aromatic ester vehicle. Some of the examples also contain a solid material 
such as silica. The patent gives special emphasis to the treatment of 
psoriasis. There is no specific disclosure on the treatment of warts with 
anthralin. Also, there is no disclosure that any tape occlusion is used. 
U.S. Pat. No. 4,495,203 has disclosures similar to U.S. Pat. No. 
4,504,494. 
U.S. Pat. No. 4,696,941 discloses compounds related to anthralin that are 
used in the treatment of psoriasis, acne, warts, and rheumatism. Treatment 
of psoriasis, acne, and warts is by topical treatment. Treatment of 
rheumatism is by injection. Examples 9-18 disclose topically administrable 
compositions. There is no specific example of treatment of warts. Also, 
there is no disclosure that any tape occlusion is used. 
Additional publications relating to the use of anthralin to treat psoriasis 
are discussed below. 
In an article by Gottlieb et al entitled "Anthralin Decreases Keratinocyte 
TGF-alpha Expression and EGF-Receptor Binding in Vitro", in The Journal of 
Investigative Dermatology, Vol. 98, No. 5, May 1992, pages 680-685, there 
is a disclosure that anthralin is an effective topical treatment for 
active psoriasis. It is suggested that pharmacologically relevant 
concentrations of anthralin have the ability to strongly inhibit 
keratinocyte proliferation in vitro, possibly by affecting early steps in 
mitogenic signalling pathways. Anthralin diminishes ligand binding to the 
epidermal growth factor (EGF) receptor via a reduction in binding 
affinity. There are teachings that anthralin treatment has been reported 
to inhibit granulocyte function, inhibit the lipoxygenase pathways, 
inhibit DNA replication and repair, inhibit mitochondrial respiration, and 
decrease calmodulin activity in vitro. In vivo, anthralin decreases 
plasminogen activator levels in plaques, inhibits mitochondrial ATP 
synthesis, and normalizes keratin expression. There is no disclosure of 
any treatment methods that employ anthralin that make use of an irritant 
response generated by anthralin. In this article, there is no disclosure 
of the use of anthralin in treating warts. Moreover, there is no 
disclosure that any occlusion device was used. 
In an article by Ashton et al entitled "Anthralin: Historical and Current 
Perspectives" in the Journal of the American Academy of Dermatology, 
Volume 9, Number 2, August 1983, pages 173-191, there is an extensive 
review of the uses of anthralin therapy. The only medical condition 
discussed in the entire article that is treated with anthralin is 
psoriasis. There is no mention whatsoever of the use of anthralin to treat 
warts. On pages 187-188, there are recommendations for the use of 
anthralin in treating psoriasis. Since anthralin has the immediate side 
effects of skin irritation and staining, its use should be closely 
monitored. In essence, the irritant effects of anthralin are to be avoided 
in the treatment of psoriasis. Anthralin is administered in the form of 
the commercially available Drithocreme (TM). 
In the Physicians' Desk Reference, 1993, under a listing for American 
Dermal Corporation, Plumsteadville, Pa. 18949, Drithocreme (TM) is 
disclosed to be comprised of anthralin (approximately 0.1%, 0.25%, 0.5%, 
or 1%) in a base of white petrolatum, sodium lauryl sulfate, cetostearyl 
alcohol, ascorbic acid, salicylic acid, chlorocresol, and purified water. 
In the Ashton et al article, In Table II on page 187, there are suggested 
guidelines for home use of anthralin cream (Drithocreme(TM)) or ointment 
(Anthra-Derm(TM)) in the treatment of psoriasis. The guidelines suggest 
that anthralin should start a 0.1% and increase to 0.25%, 0.5%, and 1%. 
The treatment should continue for 1 to 2 weeks with this step-wise 
increase in the strength of the anthralin. The stepwise increase in the 
concentration of the anthralin used is to avoid skin irritation; that is, 
to avoid an irritant response. Moreover, on page 188, there is a 
suggestion that "short contact therapy" may be a practical outpatient 
therapy for the future. 
It is noted that Drithocreme (TM) described in the Physicians' Desk 
Reference listing for American Dermal Corporation, Plumsteadville, Pa. 
18949 is currently a product of Dermik Laboratories, Inc., Collegeville, 
Pa. Drithocreme (TM) is available in four concentrations (approximately 
0.1%, 0.25%, 0.5%, and 1%[HP]) for the treatment of psoriasis. In 
literature published by Dermik Laboratories for using Drithocreme (TM), it 
is recommended that the 0.1% strength anthralin formulation of Drithocreme 
(TM) be used for at least one week to assess each patient's individual 
tolerance to anthralin. 
In an article by Lowe et al entitled "Anthralin for psoriasis: 
Short-contact anthralin therapy compared with topical steroid and 
conventional anthralin", in Journal of the American Academy of 
Dermatology, Vol. 10, No. 1, pages 69-72, January 1984, there is a 
disclosure that conventional overnight (approximately 8 hours) anthralin 
therapy for psoriasis uses anthralin in a range of 0.1%-0.5% anthralin. On 
page 70 there is a statement that no higher concentration than 0.5% was 
used in conventional anthralin therapy for psoriasis, as higher 
concentrations in petrolatum would be irritating if left on overnight. It 
is clear that in the treatment of psoriasis, the irritant effects of 
anthralin are to be avoided. On the other hand, higher anthralin 
concentrations, in the range of 0.5%-3%, are left on for 10 minutes and 
then washed off with soap and hot water. With this short contact anthralin 
therapy, the initial concentration of anthralin was 0.5%, and this was 
increased to 1% and 3% at 3-day intervals. A key objective of the short 
contact anthralin therapy is to avoid an irritant response to anthralin. 
A brochure published by Dermik Laboratories, Inc. entitled "Anthralin 
Therapy Simplified", that accompanies the Drithocreme (TM) product, 
includes text of a letter written by Nicholas J. Lowe, M.D., the same Dr. 
Lowe who coauthored the above-mentioned article. The Lowe letter discloses 
that Drithocreme (TM) can also be used for short contact anthralin therapy 
(SCAT) for treating psoriasis without causing skin irritation. The SCAT 
method of treating psoriasis is employed with a key intended purpose of 
avoiding an irritant/immunologic response to anthralin. The recommended 
dosage and contact time for Drithocreme (TM) is Drithocreme (TM) 
containing 1% anthralin for 10 minutes. However, under certain 
circumstances, short contact anthralin therapy can be employed up to 60 
minutes. There is no disclosure of the use of any concentration of 
Drithocreme (TM) for treating warts. In addition, there is no disclosure 
that Drithocreme (TM) any tape occlusion was used. 
In an article by De Groot et al entitled "Contact allergy to dithranol" in 
Contact Dermatitis, Vol. 7, pages 5-8, 1981, there is a disclosure that a 
patient having common warts on the hands was treated with collodion 
containing dithranol 3%, salicylic acid 25%, and acetone 10%. After two 
applications, the patient had stopped the treatment because she 
experienced itching and noticed small blisters on the her hands. 
Examination of the patient showed a systemic response; that is, there were 
papulovesicular eczematous lesions on both arms, legs, and abdomen. The 
hands showed an oozing vesicular dermatitis, the warts being swollen. The 
eczematous reaction subsided with topical steroid medication in a couple 
of days. After running a series of patch tests, it was determined that the 
patient was allergic to dithranol. Three weeks after two applications of 
the collodion containing the dithranol 3%, salicylic acid 25%, and acetone 
10%, all warts had completely cleared. The authors theorized that the 
curing of the warts in the patient was probable attributable to the 
contact allergic dermatitis induced by dithranol. This patient was a 
relatively rare person who had a contact dermatitis to dithranol. There is 
no suggestion in the article that most patients, not having a systemic 
allergic response to dithranol, are to be treated with dithranol to elicit 
an irritant response in the treatment of warts. In this article, there is 
also a disclosure that patients suffering from the condition known as 
alopecia areata were simultaneously treated with dithranol and 
2,4-dinitrochlorobenzene (DNCB) wherein the DNCB is a known 
immuno-stimulating agent. As a result, these patients had a contact 
allergy to dithranol. There is no disclosure that tape occlusion was 
employed in any of the treatment methods. 
In an article by Kanerva entitled "Electron microscopic observations of 
dyskeratosis, apoptosis, colloid bodies and fibrillar degeneration after 
skin irritation with dithranol", in J. Cutan. Pathol., Vol. 17, pages 
37-44, 1990, there is a disclosure that healthy skin on the backs of 
volunteers was treated with dithranol using the epicutaneous Finn chamber 
occlusion technique. The dithranol concentrations used were 0.2% dithranol 
in petrolatum and 0.1% dithranol in petrolatum. The results were the 
observations, under the electron microscope, of dyskeratosis, apoptosis, 
colloid bodies and fibrillar degeneration after skin irritation of the 
healthy skin with dithranol. There is a statement on page 37 that 
cell-mediated immunity is believed to play an important role in regression 
(not treatment) of plane warts. On page 43, there is a statement that 
immunocompetent lymphocytes are seen under the electron microscope to be 
apposed to Langerhans cells (LC) after dithranol irritation. In the 
article, dithranol is referred to as an anti-psoriatic drug, and there is 
no mention of the treatment of warts in this article. Also, there is no 
mention of the use of tape occlusion. 
As stated above, warts are caused by the human papilloma virus (HPV). There 
are findings reported in the literature that human papilloma virus may be 
implicated in certain forms of cancer See Franceschi et al, "Genital warts 
and cervical neoplasia: An epidemiological study", Br. J. Cancer, Vol. 48, 
pages 621-628, (1983) and Crum et al, "Human papillomavirus Type 16 and 
Early Cervical Neoplasia", The New England Journal of Medicine, Vol. 310, 
No. 14, pages 880-883, (Apr. 5, 1984). In view of the link between the 
human papilloma virus and cancer, the prompt and effective treatment and 
destruction of warts is strongly indicated. 
Upon reviewing the prior art cited above, certain conclusions can be made 
about the prior art as a whole. First, none of the prior art discloses the 
use of an anthralin with tape occlusion to treat warts. Second, the prior 
art treatments of warts which do involve tape occlusion include only solid 
materials such as solid salicylic acid. Third, tape occlusion for treating 
warts is not disclosed as being used with a liquid or pasty material. 
A fourth conclusion that can be made about the prior art is that of the 
seven techniques for treating warts discussed above (that is: (1) locally 
destructive chemicals; (2) surgically destructive methods; (3) 
blister-producing methods; (4) cellular inhibition; (5) altering the 
cutaneous environment; (6) immune stimulation; and (7) miscellaneous 
methods), tape occlusion (in technique No. 7) is used in conjunction only 
with technique No. 1 which involves the locally destructive chemical 
salicylic acid. Tape occlusion is not used in conjunction with technique 
Nos. 2-6. 
A fifth conclusion that can be made about the prior art is that tape 
occlusion by itself probably has a placebo effect providing an about a 20% 
cure. 
A sixth conclusion that can be made about the prior art is that the 
treatment of warts with anthralin without concomitant tape occlusion (as 
described by Flindt-Hansen et al and Hjorth et al) has resulted in a wart 
clearing rate no greater than 57%. 
A seventh conclusion that can be made about the prior art is that the mode 
of operation of anthralin in the treatment of warts is thought to consist 
of a reduction of the replication of the wart virus caused by an 
inhibition of the cell metabolism. 
An eighth conclusion that can be made about the prior art is that immune 
stimulation methods of wart treatment do not include anthralin as an 
immune stimulating agent. 
A ninth conclusion that can be made about the prior art is that there is no 
disclosure of any treatment methods employing tape occlusion that make use 
of an immune response generated by an active ingredient. As a corollary 
conclusion, there is no disclosure of any wart treatment methods employing 
tape occlusion that make use of an immune response generated by anthralin. 
A tenth conclusion that can be made about the prior art is that anthralin 
is employed in the treatment of psoriasis in a manner clearly designed to 
avoid an undesired immunologic/irritant response to anthralin. 
An eleventh conclusion that can be made about the prior art is that when 
salicylic acid is used with tape or film occlusion for treating warts, the 
range of salicylic acid is in a range of 17% to 40%. In this respect, it 
is recalled that in Compound W (TM) of Whitehall Laboratories, Inc., New 
York, N.Y. 10017, the active ingredient in the product is salicylic acid 
at 17% w/w. It is also recalled that in the article by De Groot et al 
entitled "Contact allergy to dithranol" discussed above, there is a 
disclosure that a patient having common warts on the hands was treated 
with collodion containing dithranol 3%, salicylic acid 25%, and acetone 
10%. It is further recalled that in Dr. Scholls Clear Away Plantar Wart 
Remover System of Schering Plough Healthcare Products, Inc., Memphis, 
Tenn., the product includes adhesive-tape-containing discs which contain 
salicylic acid (40%) in a rubber-based vehicle. 
A twelfth conclusion that can be made about the prior art is that when 
salicylic acid is used to stabilize (acidify) an anthralin, salicylic acid 
is present in an amount of less than 2.0% by weight. In this respect, it 
is recalled that in U.S. Pat. No. 4,465,688, from column 13, line 49 to 
column 14, line 2, a composition is disclosed which contains 
9,10-dihydro-1,8,9-trihydroxy-9,10-anthracene-alpha,beta-endo-N-ethyl 
succinimide (a compound related to anthralin) approximately 1.47% by 
weight; salicylic acid, approximately 0.68% by weight; and petroleum 
jelly, approximately 97.85% by weight. It is also recalled that an 
anthralin ointment employs a pharmaceutical carrier described in the 
British Pharmacopoeia as Lassar's paste. This carrier includes 240 g. of 
zinc oxide finely sifted, 20 g. of salicylic acid finely sifted, 240 g. of 
starch finely sifted, and 500 g. of white soft paraffin. Anthralin 
ointments containing the Lassar's paste can include anthralin in 
concentrations ranging from 0.5% to 5.0%. Thus, the percentage of 
salicylic acid in a Lassar's paste based ointment is less than 2.0% by 
weight. 
A thirteenth conclusion that can be made from the prior art is that a 
therapeutic amount of salicylic acid for treating warts by tape or film 
occlusion is equal to or greater than 17% salicylic acid by weight. 
A fourteenth conclusion that can be made about the prior art, which is a 
corollary of the thirteenth conclusion, is that the presence of salicylic 
acid in a composition for treating warts by tape or film occlusion in an 
amount less than 17% by weight of the composition is a less than 
therapeutic amount of salicylic acid for treating the warts. 
In forming a fifteenth conclusion, it is recalled that the lowest 
percentage of salicylic acid in a wart treating composition that is 
discussed hereinabove is 12% salicylic acid in Viranol gel. From the 
percentage of salicylic acid in Viranol and from the percentages of 
salicylic acid in other wart-treating products, it may be concluded that 
the lowest effective percentage of salicylic acid in a wart treating 
composition is 12% salicylic acid. It is noted, however, that Vironal gel 
is not used with tape occlusion. 
Considering a prudent 3% margin of error with respect to the 17% 
therapeutic amount of salicylic acid for tape occlusion for treating 
warts, it is further concluded, as a sixteenth conclusion, that an amount 
of less than 14% by weight of salicylic acid for tape occlusion for 
treating warts is less than a therapeutic amount of salicylic acid for 
tape occlusion. 
Furthermore, considering a prudent 3% margin of error with respect to the 
12% therapeutic amount of salicylic acid in Vironal gel for treating warts 
topically, it is further concluded, in a seventeenth conclusion, that an 
amount of less than 9% by weight of salicylic acid for treating warts 
topically (without tape occlusion) is less than a therapeutic amount of 
salicylic acid for topical treatment of warts. 
SUMMARY OF THE INVENTION 
Accordingly, it is an object of the invention to provide a method of 
treating warts that employs the use of an anthralin with tape occlusion. 
Another object of the invention is to provide a method of treating warts 
which employs tape occlusion using a liquid or pasty material. 
Still another object of the invention is to provide a method of treating 
warts which employs tape occlusion in conjunction with blister-producing 
methods, cellular inhibition, altering the cutaneous environment, or 
immune stimulation. 
Yet another object of the invention is to provide a method of treating 
warts which results in a wart clearing rate greater than two-thirds. 
Another object of the invention is to provide a method of treating warts 
employing tape occlusion that make use of an immune response generated by 
an active ingredient. 
Even another object of the invention is to provide a method of treating 
warts in which the mode of operation of anthralin includes anthralin as an 
immune stimulating agent. 
Still another object of the invention is to provide a method of treating 
warts employing tape occlusion that makes use of an immune response 
generated by anthralin. 
In accordance with the invention, a method is provided for treating a 
patient (a human being or animal) who has one or more warts. The method 
includes the steps of (a). applying to a wart an amount of a composition 
consisting essentially of an anthralin active ingredient in a 
concentration greater than 0.5% by weight and a pharmaceutical carrier, 
(b). covering the wart and skin area peripheral to the wart with a tape 
which provides an occluding environment for the wart, and (c). maintaining 
the tape in position over the wart and peripheral skin area for a 
predetermined period, the tape providing an occluding environment for the 
wart for the predetermined period of time. The predetermined period of 
time can be in a range spanning 1-18 hours. 
In accordance with the invention, the following additional steps can be 
employed: (d). removing the tape after the predetermined period of time; 
and repeating the steps (a) through (d) periodically until a desired level 
of wart removal has been obtained. It is noted that normal periodic 
hygiene, such as washing with soap and water during a bath, shower, or 
sink wash up, may take place after a sequence of above steps (a) through 
(d) and before a repetition of steps (a) through (d). 
It is noted that after the tape is removed from the wart, the wart may be 
pared or scraped or scored. The generic term for paring, scraping, and 
scoring is debriding. Thus, further in accordance with the invention, the 
method of treating warts of the invention can further include the step of 
debriding the wart prior to repeating steps (a) through (d) set forth 
above. 
The pharmaceutical carrier for the anthralin may include an oil base for 
dissolving and suspending the anthralin, an oil-soluble acidifying agent, 
an aqueous medium, and a water-soluble antioxidant, such that the 
pharmaceutical carrier and the anthralin are present in the form of an 
emulsion, e.g. an oil-in-water emulsion. 
In the pharmaceutical carrier, the oil base may be petrolatum; the 
oil-soluble acidifying agent may be salicylic acid (in an amount less than 
12% by weight); the aqueous medium may be purified water; and the 
water-soluble antioxidant may be ascorbic acid. The emulsion may be a 
cream. More specifically, the cream may be an oil-in-water emulsion. 
The pharmaceutical carrier may also include a surfactant for stabilizing 
the oil-in-water emulsion. The anthralin may be present in a concentration 
range spanning 0.50%-1.50% by weight, or more broadly in a concentration 
ranging from 0.50%-5.0% by weight, or even more broadly in a concentration 
ranging from 0.50%-10.0% by weight. 
More specifically, the anthralin may be present in a concentration range 
spanning 0.50% to 10.0% by weight, and the predetermined time for tape 
occlusion is at least 1 hour and may be in a range from 1-18 hours, such 
as overnight. 
The tape used for tape occlusion may be commonly employed adhesive tape 
such as Johnson and Johnson waterproof adhesive tape or a plastic film 
(with or without an adhesive layer). In the present patent, the terms tape 
occlusion and film occlusion are deemed to be equivalent. The plastic film 
can be applied as a solution of a film-forming material and a solvent. A 
swab, applicator tip, or spray method of application can be used. When the 
solvent evaporates, the film is formed providing the tape occlusion. For 
example, a solution of the film-former collodion dissolved in the solvent 
acetone can be used. When the acetone evaporates, a film of collodion will 
provide tape occlusion. In addition, if desired, a tape can be placed over 
the collodion film. 
If desired, the anthralin can be dissolved along with the film-former in 
the solvent. Then, when the solvent evaporates, the anthralin is present 
in the tape that provides the tape occlusion. 
Another form of administration of anthralin for treating warts in an 
environment of tape occlusion is the use of a foam-containing tape or 
film. Pores or interstitial spaces in the foam can be loaded with 
anthralin particles. The foam can have an adhesive layer for adhering the 
foam to skin. If the foam is porous, an outer non-porous layer can be 
provided on the back of the foam to enhance tape occlusion. A suitable 
foam tape that can be loaded with anthralin particles, or particles 
containing anthralin and a stabilizing amount of salicylic acid is 
Microfoam Surgical Tape(TM), made by the 3M Company, St. Paul, Minn. 
55144. Other suitable tapes have ridges and pores but do not contain a 
foam. With such a tape, particles containing anthralin can be loaded 
behind the ridges and pores. Then a non-porous tape can be provided as a 
backing layer. The combination of the porous tape, the particles 
containing anthralin, and the non-porous backing tape form a slow-release, 
anthralin-releasing wafer. The non-porous backing tape can have a portion 
extending beyond the anthralin-containing particles and the porous layer. 
This portion can include a quantity of adhesive for facilitating adhesion 
of the wafer to the skin of a user peripheral to warts being treated. A 
suitable porous tape for this form of anthralin administration with tape 
occlusion can be the tape known as Transpore(TM), by the 3M Company, St. 
Paul, Minn. 55144. 
A slow-release, anthralin-releasing wafer can also be made by using a 
porous foam, a quantity of anthralin-containing particles placed behind 
the porous foam, and a non-porous backing layer placed behind the 
anthralin-containing particles. The non-porous backing layer can have a 
portion extending beyond the anthralin-containing particles and the porous 
layer. This portion can include a quantity of adhesive for facilitating 
adhesion of the wafer to the skin of a user peripheral to warts being 
treated. 
Yet another carrier for the anthralin can be an aqueous solution that has 
the ability to gel in the presence of an cation. More specifically, 
anthralin can be mixed with a quantity of Gelrite (TM) which is a purified 
anionic heteropolysaccharide derived from gellan gum. An aqueous solution 
Gelrite (TM) in the presence of a cation has the ability to gel. Upon 
contact with the salts present on a patients skin, the Gelrite (TM) can 
gel. Gelrite (TM) is made by Merck & Co., Inc., Whitehouse Station, N.J. 
Further in accordance with the invention, a method is provided for treating 
a wart comprising the steps of: obtaining a composition containing 
anthralin in a carrier together with a non-therapeutic amount of salicylic 
acid; applying the composition directly on the wart; providing an 
occluding environment for the wart. The occluding environment can be 
provided by a quantity of an adhesive tape. 
Still further in accordancewith the invention, a kit can be provided which 
contains a composition containing anthralin, in either a tube or small 
bottle having an applicator tip, along with a waterproof adhesive tape or 
other suitable occlusion device. The tape can be a roll of tape or 
premeasured geometrical shapes and sizes for occlusion. 
Whenever an anthralin is employed, a stabilizing (acidifying) amount of 
salicylic acid can also be employed. As mentioned above, the amount of 
salicylic acid used is less than a therapeutic amount; that is a 
non-therapeutic amount of salicylic acid is employed. More specifically, a 
stabilizing (acidifying) amount of salicylic acid is less than 12% by 
weight of salicylic acid. Even more specifically, a stabilizing 
(acidifying) amount of salicylic acid is less than 5% by weight of 
salicylic acid. 
Aside from using the generic anthralin per se, other anthralins can be 
employed. That is, derivatives or analogs of generic anthralin can be 
employed. As mentioned hereinabove, derivatives or analogs of anthralin 
are disclosed in the following U.S. Pat. Nos. 4,465,688; 4,696,941; and 
4,866,095. In this respect, for their disclosure of anthralin derivatives 
or analogs, U.S. Pat. Nos. 4,465,688, 4,696,941, and 4,866,095 are 
incorporated herein by reference. For purposes of the present invention 
the term anthralin is deemed to include the derivatives or analogs of 
anthralin disclosed in U.S. Pat. Nos. 4,465,688, 4,696,941, and 4,866,095. 
Although a knowledge of the mechanism of operation of the anthralin in 
treating the warts is not necessary for instructing a person with ordinary 
skill in the art as to how to make and use the invention, a suggested 
explanation may be of value. However, it is understood that the inventors 
are not bound by any theoretical explanation as to why the compositions 
and the methods of the invention are efficacious in treating warts. 
It is thought that the use of anthralin with tape occlusion in treating 
warts, in accordance with the invention, elicits an immune response in the 
patient localized at the warts. The patient's immune response helps 
destroy the virus infected cells that are present in the warts and helps 
in preventing further virus and wart growth. 
It is understood that the method of the invention can be used to treat a 
wide variety of warts which are found on human skin and which are caused 
by the human papilloma virus (HPV). For example, the method of the 
invention can be used to treat the following types of warts: common warts 
(verruca vulgaris), plantar warts, palmar warts, planar warts (verruca 
plana), mosaic warts, and venereal warts (condyloma accuminatum).

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
Treatment of Eight Patients 
Eight patients having warts have been successfully treated with 1 percent 
anthralin cream (specifically 1.0 percent Drithocreme (TM), a product of 
Dermik Labs, Inc.) with occlusion conditions under adhesive tape, and the 
case histories are described as follows. 
Patient number one was a 28 year old female who was seen for treatment of 
mosaic wart virus infection of her right plantar (bottom surface) foot and 
right first toe. She had previously been treated with salicylic acid with 
adhesive occlusion overnight, cryosurgery (liquid nitrogen therapy), and 
carbon dioxide laser surgery without clearing of her warts. Since other 
conventional therapy had failed, the patient after consent, started 1.0 
percent anthralin cream (specifically-1.0 percent Drithocreme (TM), 
product of Dermik Labs, Inc.) under occlusion with adhesive tape each 
night and removal in the morning. This was repeated each night. The 
patient was seen one month later. The warts on her right first toe were 
cleared and approximately 10 percent of the warts were left on her right 
foot. The patient was instructed to use the topical 1.0 percent anthralin 
for 2 weeks longer. The patient returned 5 weeks later or 9 weeks from 
baseline and was clinically clear of her warts. There was no recurrence of 
the right plantar foot warts at this follow-up visit. 
Patient number two was an 11 year old female who first presented to an 
inventor at age 10 for a giant cluster of warts on her right medial 
plantar foot. She had been previously treated by her mother with 
over-the-counter salicylic acid, then by an inventor with both cantharidin 
and salicylic acid with adhesive tape occlusion each night and with 
cryosurgery without improvement. After parental consent the patient was 
treated with 1.0 percent anthralin cream with adhesive tape occlusion 
eight hours nightly with removal in the morning, for a period of 2 weeks. 
At the follow-up appointment 2 weeks later the warts were only 20 percent 
decreased from baseline exam. Upon further questioning to the mother she 
had not been using adhesive occlusion, she had applied gauze between the 
1.0 percent anthralin cream and the adhesive tape. The mother and patient 
were re-educated on the use of 1.0 percent anthralin cream with adhesive 
tape occlusion 8 hours each night. Three weeks later, or 5 weeks from 
baseline, the warts were clinically cleared. 
Patient number three was a 44 year old female who presented to an inventor 
at age 43 for treatment of a wart on her right second finger. She was 
treated with cryosurgery and then excisional surgery. The wart recurred, 
and the patient was treated approximately 1 year later, after consent, 
with 1.0 percent anthralin cream under adhesive tape occlusion and was 
seen 3 weeks later. The wart was 50 percent improved. This wart infection 
was a resistant cluster of warts. The patient was seen 4 weeks later after 
7 weeks of continuous use of the above therapy, and was found to be 75 
percent clear of the wart cluster. The patient continued 1.0 percent 
anthralin cream another 2 weeks and was seen again. The warts were 95 
percent gone. The patient continued this therapy another 4 weeks and was 
clinically clear of warts. This represented a time from baseline to 
clearing of 13 weeks. 
Patient number four was seen at age 36 by an inventor for the treatment of 
resistant left plantar foot warts and a left fourth toe wart. He was 
status post cryosurgical treatment, carbon dioxide laser surgery, and 
excisional surgery with recurrence of the warts. The inventor first 
attempted to treat the patient with dinitrochlorobenzene (DNCB) 
sensitization to induce a contact allergy and clear the warts from the 
immunologic reaction. However, 7 weeks later the patient was seen and had 
no clearing of the warts and no response to DNCB. Approximately 2 and one 
half weeks later via phone the patient indicated there was no change in 
his warts and no reaction to DNCB. 
Therefore the patient failed 9 and one half weeks of DNCB therapy. The 
patient after consent was started on 1.0 percent anthralin cream under 
adhesive tape occlusion nightly with removal in the morning. The patient 
was seen 2 weeks later and was noted to have at least 50 percent 
diminution in his left plantar foot and left fourth toe warts. 
Approximately 3 weeks later the patient returned and 75 percent of the 
left plantar foot wart cluster was gone, and the left fourth toe wart was 
completely clear. The patient was treated another 3 weeks on 1.0 percent 
anthralin cream under adhesive tape occlusion and was noted to have 
complete clearing of his left plantar foot wart and the left fourth toe 
wart was still clear. 
After approximately 8 weeks using 1.0 percent anthralin cream under 
adhesive occlusion his warts which were previously refractory to multiple 
treatment modalities were now clear. 
Patient number five was a 13 year old female who had a refractory wart on 
her left elbow. She had been previously treated with topical cantharidin, 
oral vitamin A, DNCB and then when these treatments failed she was started 
after parental consent on 1.0 percent anthralin cream with adhesive tape 
occlusion nightly, with removal in the morning. Three weeks later she was 
completely clear of the refractory wart on her left elbow. 
Patient number six was an 11 year old female who had a refractory wart on 
her left foot. She had been previously treated with cantharidin, and 
topical salicylic acid under adhesive occlusion. Since the above two 
regimens failed after parental consent she was started on 1.0 percent 
topical anthralin cream under adhesive tape occlusion. Two weeks later the 
resistant wart was clear. 
Patient number seven was a 19 year old female who had a resistant wart on 
her right foot. She had been previously treated with cryosurgery, topical 
salicylic acid under occlusion, and cantharidin without success. She was 
placed on topical 1.0 percent anthralin cream under adhesive tape 
occlusion nightly with removal in the morning, after consent was obtained. 
Approximately two and one half weeks later her wart was clear. 
Patient eight was a 60 year old male who had a refractory mosaic wart virus 
cluster on his left plantar foot. He was treated with topical salicylic 
acid with adhesive tape occlusion, cryosurgery, DNCB, then after all 
previous methods had failed, and after consent he was started on topical 
1.0 percent anthralin cream under adhesive occlusion eight hours each day. 
Approximately two weeks later 50 percent of the wart cluster was cleared, 
he was continued on this therapy. Four weeks later his warts on his left 
plantar foot were cleared. This was 6 weeks after starting topical 1.0 
percent anthralin under adhesive occlusion for 8 hours each day. 
Then 6 weeks later the patient complained of a new wart adjacent to his 
previous wart site. This wart was excised. Due to the proximity of the 
previous wart the inventor is inclined to call this wart a recurrence. 
For convenience, the results of treating the eight patients described above 
are presented in the following "Patient Treatment Table." 
______________________________________ 
Patient Treatment Table 
______________________________________ 
Treating agent: 
1.0 percent anthralin cream, specifically 
1.0 percent Drithocreme .TM., 
a product of Dermik Labs, Inc. 
Treatment conditions: 
under adhesive tape occlusion 
______________________________________ 
Time between 
Location 
Status After 
Baseline Exam 
Age of of End of and end of 
Patient 
Sex patient Wart(s) 
Treatment 
Treatment 
______________________________________ 
1 F 28 foot, toe 
clear 9 weeks 
2 F 11 foot clear 5 weeks 
3 F 44 finger clear 13 weeks 
4 M 36 foot, toe 
clear 8 weeks 
5 F 13 elbow clear 3 weeks 
6 F 11 foot clear 2 weeks 
7 F 19 foot clear 2.5 weeks 
8.sup.(1) 
M 60 foot clear.sup.(1) 
6 weeks 
______________________________________ 
Footnotes: 
.sup.(1) Six weeks after clearing of original wart, a new wart appeared 
adjacent to site of the original wart and may be deemed to be a 
recurrence. 
Other modes of administration of anthralin for treating warts are 
contemplated. For example, it is contemplated that the anthralin can be 
administered to the warts by intralesional injection. In other words, the 
use of a depot or deposition method of treating warts with anthralin is 
also contemplated. 
It is known in the prior art to treat common warts by intralesional 
injection of bleomycin. It is also known in the prior art to treat 
venereal warts by intralesional injection of podophyllotoxin or 
interferon. However, the use of intralesional injection of anthralin to 
treat warts is not contemplated. Moreover, the intralesional injection of 
anthralin accompanied by tape occlusion is not contemplated in the prior 
art. 
Turning back to a discussion of the method of the invention, more 
specifically, an injectable solution/suspension containing anthralin is 
first prepared. In doing so, a quantity of bacteriostatic saline (NaCl for 
injection) is obtained. This bacteriostatic saline is a drug diluent and 
contains approximately 0.9% by weight NaCl, benzyl alcohol as a 
preservative, and water for injection adjusted for desired pH 
(substantially neutral) with NaOH or HCl as necessary. Approximately 5 
grams of anthralin are dissolved and/or suspended in 100 ml of the 
bacteriostatic saline. 
After preparing the injectable anthralin, a wart is selected for treatment. 
Prior to treating with the injectable anthralin composition, the wart may 
be pretreated. One way of pretreating the wart is to pare it or scrape it 
to remove or separate surface material. Another way of pretreating the 
wart is to score the wart with a small gauge needle, e.g. No. 21 or No. 27 
gauge, in a cross-hatch pattern, like a tic-tac-toe grid. A generic term 
that includes paring, scraping, and scoring is debriding. 
Then the selected wart, whether or not pretreated, is injected with the 
injectable anthralin composition. A fine gauge needle such as a No. 27 or 
No. 30 needle can be used. The injection can be superficial. This is 
especially desirable for pretreated warts. Also, the injection can be 
relatively deep. This is especially desirable for warts that have not been 
pretreated. Also, if desired, both superficial injections and deep 
injections can be carried out on the same wart. 
It is contemplated that each injection treatment of a wart will administer 
from 0.05 to 0.2 cc of the injectable anthralin composition per wart. 
It is contemplated that patients having warts that are debrided and then 
treated with superficial injection can be treated at at least 24 hour 
intervals, e.g. 3 times per week in a doctor's office. After each 
treatment and between treatments, a tape is placed over the treated wart 
to permit tape occlusion in accordance with the invention. 
Alternatively, with superficial intralesional injection of an anthralin 
into a wart, tape occlusion need not be employed. 
It is contemplated that patients who are treated with deep injection of the 
injectable anthralin composition can be treated once a week; that is the 
predetermined period of time between deep injections is contemplated to be 
approximately 5-7 days. Tape occlusion is applied to the injection-treated 
warts between treatments. 
Alternatively, with deep intralesional injection of an anthralin into a 
wart, tape occlusion need not be employed. Stated more generally, it is 
contemplated that intralesional injection of anthralin into warts can be 
carried out without using tape occlusion between treatments. 
Injection treatments are continued until a desired level of wart resolution 
is attained. 
It is also contemplated that prior to topical application of an 
anthralin-containing composition to a wart, the wart can be pretreated by 
debriding the wart. The debriding of the wart facilitates penetration of 
the anthralin-containing composition into the wart. For example, a wart 
can be scored by a sharp needle, and an anthralin-containing composition 
can be added dropwise onto the scored wart. Then, the scored and 
anthralin-treated wart is covered by a tape for carrying out tape 
occlusion. 
EMBODIMENT IN THE DRAWING 
With reference to FIG. 1, a kit 10 is provided which includes a package 12 
(which may be a box) for housing a container which contains a quantity of 
an anthralin-containing composition for treating a wart 14 (shown in FIG. 
2). The kit 10 also includes means for providing an occluding environment 
for the wart 14 in accordance with the principles of the invention. 
More specifically, the kit 10 can include an anthralin-containing 
composition in a tube 16 and/or in a bottle 18 which may contain an 
applicator tip. The anthralin-containing composition can also be in a 
sprayable formulation and be sprayed by a spray dispenser. 
To provide an occluding environment for a wart, the kit 10 can also include 
a roll of adhesive tape 20 and/or a stack of adhesive patches 22. An 
instruction sheet 21 can also be provided in the kit 10. 
Generally, for a kit, one or more specific anthralin-containing 
compositions and one or more specific elements for providing an occluding 
environment are provided. 
In FIG. 2, a drop 24 of anthralin-containing composition is being dispensed 
from a tube 16 onto the wart 14. 
In FIG. 3, a patch 22 has been placed over the wart 14 and adjacent 
peripheral skin to provide an occluding environment for the 
anthralin-treated wart for a predetermined period of time. 
In FIG. 4, after the predetermined period of time, the patch 22 is being 
removed from the wart 14 and the adjacent skin areas. 
In FIGS. 5 and 6, another device 26 is provided for carrying out the 
principles of the invention. The device 26 includes an outermost flexible 
occlusion-providing layer 28 which contains an adhesive coating on its 
inner side, a flexible layer 30 containing a quantity of anthralin 
attached to the occlusion-providing layer 28, and a peel off strip 32 
attached to the occlusion-providing layer 28. The flexible 
anthralin-containing layer 30 can be a foam tape loaded with anthralin 
particles, or particles containing anthralin and a stabilizing amount of 
salicylic acid. A suitable foam tape for this purpose is Microfoam 
Surgical Tape(TM), made by the 3M Company, St. Paul, Minn. 55144. 
To use the device 26, the peel off strip 32 is removed, the flexible layer 
30 containing the anthralin is placed on top of the wart 14, and the 
exposed adhesive-containing portion 34 of the occlusion-providing layer 28 
is placed on areas of skin peripheral to the wart 14. The 
occlusion-providing layer 28 provides occlusion to the anthralin-treated 
wart 14 for a predetermined period of time until it is removed. 
Formulations Containing Anthralin 
A large number of compositions containing an anthralin can be used 
topically with tape occlusion to treat warts. The following formulations 
for compositions containing an anthralin and a pharmaceutical carrier may 
be used topically with tape occlusion in accordance with the principles of 
the invention. 
EXAMPLE 1 
In an article by M. Whitehead entitled "Pharmaceutical formulations of 
anthralin", in the British Journal of Dermatology, Vol. 105 (suppl 20), 
pages 28-32 (1981), there are disclosures of pharmaceutical formulations 
of anthralin. In the Whitehead article, there is a disclosure that 
anthralin is soluble in a pharmaceutical carrier of a 50% paraffin paste 
only to the extent of 0.1%. In an anthralin formulation in a 50% paraffin 
paste that exceeds 0.1% anthralin, the anthralin present above 0.1% is in 
a suspension. The Whitehead article also teaches that salicylic acid in 
the pharmaceutical carrier serves as an acidifying agent for anthralin 
compositions which decompose rapidly in alkaline conditions. The article 
also teaches that when the pharmaceutical carrier for anthralin is an 
emulsion of white soft paraffin and water, the oxygen in the water may 
degrade the anthralin. Ascorbic acid is added as an antioxidant. Thus, the 
emulsion, which is a cream, contains droplets of oil which contain 
acidulated anthralin, and the oil droplets are surrounded by an aqueous 
phase which contains the antioxidant ascorbic acid. Thus, the 
anthralin-containing oil droplets are surrounded by oxygen-free water. 
EXAMPLE 2 
As mentioned above, Drithocreme(TM) marketed by Dermik Labs is comprised of 
anthralin (0.1%, 0.25%, 0.5%, or 1%) in a pharmaceutical carrier comprised 
of a base of white petrolatum, sodium lauryl sulfate, cetostearyl alcohol, 
ascorbic acid, salicylic acid, chlorocresol, and purified water. In view 
of the teachings in the Whitehead article, the respective functions of the 
anthralin and the pharmaceutical carrier components of the Drithocreme 
(TM) listed above can be deduced as follows. Anthralin (0.1%, 0.25%, 0.5%, 
or 1%) is the active ingredient. In the pharmaceutical carrier, white 
petrolatum is a solvent for and suspending agent for anthralin; sodium 
lauryl sulfate and cetostearyl alcohol are surfactants; ascorbic acid is 
an antioxidant; salicylic acid is an oil-soluble acid; chlorocresol is an 
antibacterial; and purified water is a suspending medium that works with 
the white petrolatum and the surfactants to form the cream carrier. The 
surfactants help maintain the emulsion of the oil droplets in the aqueous 
medium. 
EXAMPLE 3 
Alternative formulations of an anthralin cream also include the anthralin 
active ingredient and the pharmaceutical carrier which includes an oil 
base for dissolving and suspending the anthralin, an oil-soluble 
acidifying agent, an aqueous medium, and a water-soluble antioxidant. In 
addition, alternative anthralin cream formulations may also include a 
surfactant for stabilizing the oil-in-water emulsion. 
EXAMPLE 4 
The Whitehead article also teaches other anthralin-containing formulations. 
For example, an anthralin ointment employs a pharmaceutical carrier 
described in the British Pharmacopoeia as Lassar's paste. This carrier 
includes 240 g. of zinc oxide finely sifted, 20 g. of salicylic acid 
finely sifted, 240 g. of starch finely sifted, and 500 g. of white soft 
paraffin. Anthralin ointments containing the Lassar's paste can include 
anthralin in concentrations ranging from 0.5% to 5.0%. It is noted that 
the percentage of salicylic acid in a Lassar's paste based ointment is 
approximately 2.0% by weight. 
EXAMPLE 5 
In chapter 7, by Ashton et al entitled "Anthralin Therapy of Psoriasis" in 
the book Practical Psoriasis Therapy, by Lowe, published by Yearbook 
Medical Publishers, Chicago, Ill., 1986, pages 59-71, a number of 
anthralin containing formulations are described for treating psoriasis. 
For example, on page 59, an ointment containing anthralin is provided by 
dissolving anthralin in chloroform and then adding the 
chloroform/anthralin solution to the pharmaceutical carrier petrolatum. 
After mixing, the chloroform is allowed to evaporate off, leaving the 
suspension of anthralin in petrolatum. 
EXAMPLE 6 
A composition containing anthralin for treating warts by tape occlusion is 
obtained as follows. 
Mix the following ingredients in the amounts specified. 
______________________________________ 
Ingredient Weight Percent 
______________________________________ 
Ethyl alcohol 41.5 
Laureth-4 0.5 
Isopropyl alcohol 
6.0 
anthralin 1.0 
Purified water balance 
______________________________________ 
Ascorbic acid can be used to adjust the pH to a desired level and to serve 
as an antioxidant. 
The composition in this example contains approximately 1% anthralin. Other 
suitable compositions can be made in accordance with this example which 
include anthralin in the following percentages: 0.5%, 1%, 3%, 4%, and 5%. 
EXAMPLE 7 
A composition containing anthralin for treating warts by tape occlusion is 
obtained as follows. 
Mix the following ingredients in the amounts specified. 
______________________________________ 
Ingredient Weight Percent 
______________________________________ 
Ethyl alcohol 72.2 
Propylene glycol 
26.8 
anthralin 1.0 
______________________________________ 
The composition in this example contains approximately 1% anthralin. 
Other topical dermatological compositions are presented below. 
EXAMPLE 8 
A formulation employing a water soluble gel as a carrier is obtained as 
follows. More details of the gel carrier are described in U.S. Pat. No. 
4,837,378, incorporated herein by reference. 
A 30 kilogram batch of a composition of the present invention containing 
anthralin (as 0.75% by weight) is prepared as follows. 180grams 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 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 grams of propylene glycol (3% by weight 
of the final weight of the composition), 24 grams of methyl paraben (0.08% 
by weight of the final weight of the composition), and 6.0 grams of propyl 
paraben (0.02% by weight of the final weight of the composition). The 
mixture is added to 300 grams of anthralin dispersed in 11.4 liters of 
distilled water maintained at 50 degrees Centigrade. Parts A and B are 
then mixed thoroughly and gelling of the composition results. A cold 
aqueous solution of NaOH is then used to adjust the final pH value to 
approximately 5.25. Ascorbic acid, 1 gram, is added as an anti-oxidant for 
the anthralin. 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 compositions can be made in accordance with 
this example which include anthralin in the following percentages: 0.5%, 
2%, 3%, 4%, 5%, and 10%. 
EXAMPLE 9 
Another composition containing anthralin for treating warts by tape 
occlusion is obtained by mixing the following ingredients in suitable 
amounts: allantoin, carbomer 934P, methylparaben, polyethylene glycol 400, 
propylene glycol, sodium hydroxide, ascorbic acid, purified water and 
anthralin. 
EXAMPLE 10 
A composition containing anthralin for treating warts by tape occlusion is 
obtained as follows. 
Mix the following ingredients in the amounts specified. 
______________________________________ 
Ingredient Weight Percent 
______________________________________ 
Ethyl alcohol 48.0 
Laureth-4 0.5 
Isopropyl alcohol 
4.0 
Propylene glycol 
10.0 
anthralin 1.0 
Purified water balance 
______________________________________ 
Ascorbic acid can be used to adjust the pH to a desired level and to serve 
as an anti-oxidant. 
The composition in this example contains approximately 1% anthralin. Other 
suitable compositions can be made in accordance with this example which 
include anthralin in the following percentages: 0.5%, 2%, 3%, 4%, 5%, and 
10%. 
EXAMPLE 11 
A lotion composition is obtained as follows. Mix the following ingredients 
in the amounts specified. 
______________________________________ 
Ingredient Weight Percent 
______________________________________ 
Ethoxylated cetyl-stearyl alcohol 
7 
Cetyl alcohol 0.75 
Isostearyl neopentanoate 
5 
Butylated hydroxyanisole 
0.10 
Polyoxyl 40 stearate 
0.25 
Water, deionized or distilled 
71.8 
Propylene glycol 4 
Acetone 10 
Dioctyl sodium sulphosuccinate 
0.1 
anthralin 1 
______________________________________ 
other suitable compositions can be made in accordance with this example 
which include anthralin in the following percentages: 0.5%, 2%, 3%, 4%, 
5%, and 10%. 
EXAMPLE 12 
A cream composition is obtained as follows. Mix the following ingredientsin 
the amounts specified. 
______________________________________ 
Ingredient Weight Percent 
______________________________________ 
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 
62.30 
Propylene glycol 4 
Acetone 11 
Dioctyl sodium sulphosuccinate 
0.1 
anthralin 1 
______________________________________ 
Other suitable compositions can be made in accordance with this example 
which include in the following percentages: 0.5%, 2%, 4%, 5%, and 10%. 
EXAMPLE 13 
A cream composition is obtained as follows. Mix the following ingredients 
in the amounts specified. 
______________________________________ 
Ingredient Weight Percent 
______________________________________ 
Ethoxylated cetyl-stearyl alcohol 
15 
Cetyl alcohol 1.25 
Decyl oleate 5 
Butylated hydroxyanisole 
0.10 
Polyoxyl 40 stearate 
0.25 
Water, deionized or distilled 
62.30 
Propylene glycol 4 
Acetone 11 
Dioctyl sodium sulphosuccinate 
0.1 
anthralin 1 
______________________________________ 
Other suitable compositions can be made in accordance with this example 
which include anthralin in the following percentages: 0.5%, 2%, 4%, 5%, 
and 10%. 
EXAMPLE 14 
A gel composition is obtained as follows. Mix the following ingredients in 
the amounts specified. 
______________________________________ 
Ingredient Weight Percent 
______________________________________ 
Water, deionized or distilled 
55.65 
Butylated hydroxyanisole 
0.10 
Dioctyl sodium sulphosuccinate 
1 
Colloidal Bentonite 3.5 
Carboxy vinyl polymer (acid form) 
1 
Ethyl alcohol 36 
Diisopropanolamine 0.75 
anthralin 1 
______________________________________ 
Other suitable compositions can be made in accordance with this example 
which include anthralin in the following percentages: 0.5%, 2%, 4%, 5%, 
and 10%. 
EXAMPLE 15 
A lotion is obtained by mixing the following ingredients in suitable 
amounts: anthralin (approximately 1% by weight); and a pharmaceutical 
carrier which includes isopropyl alcohol (approximately 80% by weight), 
purified water (approximately 9% by weight), and propylene glycol 
(approximately 10% by weight). 
EXAMPLE 16 
An oil-in-water emulsion containing anthralin in ointment form is obtained 
as follows. 
Part A is comprised of a 1.67% aqueous solution of anthralin. 
Part B is an ointment base comprised of: 
______________________________________ 
Ingredient Weight Percent 
______________________________________ 
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 1% anthralin. Other suitable compositions can be made in 
accordance with this example which include anthralin in the following 
percentages: 0.5%, 2%, 3%, 4%, 5%, and 10%. 
EXAMPLE 17 
A mineral-oil-based anthralin ointment is obtained as follows. 
Part A is comprised of a 3.33% aqueous solution/suspension of anthralin. 
Part B is an ointment base comprised of: 
______________________________________ 
Ingredient Parts 
______________________________________ 
glycerin 5 
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 1% 
anthralin. Other suitable compositions can be made in accordance with this 
example which include anthralin in the following percentages: 0.5%, 2%, 
3%, 4%, 5%, and 10%. 
From the volumes in this example, it is easy to convert to approximate 
weight percents. To make the conversion, certain inherent properties of 
water, isopropyl alcohol, glycerin, and mineral oil are employed. More 
specifically, to make the conversion to approximate weight percents, the 
known densities of water, isopropyl alcohol, glycerin, and mineral oil are 
employed. The known density of water is approximately 1 g/ml. The known 
density of isopropyl alcohol is approximately 0.78 g/ml. The known density 
of 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 predominately water. By taking 30 ml. of part A, 
approximately 1 gram of anthralin (30 g..times.3.33%) and approximately 28 
grams of water (30 g..times.93.34%) are obtained. 
By taking 70 ml. of part B, approximately 3.9 grams of isopropyl alcohol (5 
ml..times.0.78 g/ml.), approximately 6.25 grams of glycerin (5 
ml..times.1.25 g/ml.), and approximately 51 grams of mineral oil (60 
ml..times.0.85 g/ml.) are obtained. The weight of 70 ml. of part B is 
approximately 61.15 grams (3.9 g.+6.25 g.+51 g.). 
Therefore, the total weight of parts A and B combined is approximately 
91.15 grams (30 g.+61.15 g.). 
In the combination of parts A and B, the weight percents of the individual 
carrier components are as approximately as follows: water, 31%; isopropyl 
alcohol, 4.3%; glycerin, 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 percentages of the water and water-miscible alcohols is 
approximately 42.2% (31%+11.2%). 
EXAMPLE 18 
There is a well known and commercially available liquid-absorbed wipe known 
as Erycette (TM) which is a 2% erythromycin topical solution absorbed into 
a wipe material comprised of fibrous material. These wipes are packaged in 
individually sealed aluminum foil packets called Pledgets. As disclosed on 
the Pledget package, each milliliter of liquid absorbed on the cloth wipe 
contains 20 mgm erythromycin base in a vehicle consisting of alcohol (66%) 
and propylene glycol and may contain citric acid to adjust pH. Each 
pledget is filled to contain 0.8 ml. of solution. 
Now in accordance with the principles of the present invention, a 1% 
anthralin topical solution is prepared and is absorbed into a quantity of 
an absorbent wipe material comprised of fibrous material such as cloth, 
paper, or synthetic fibers. Alternatively, an open-cell foam absorbent 
material can be used. The wipes are packaged in individually sealed 
aluminum foil packets. Each milliliter of liquid absorbed on the wipe 
contains 10 mgm anthralin base in a vehicle consisting of alcohol (66%) 
and propylene glycol and may contain ascorbic acid to adjust pH and serve 
as an anti-oxidant. Each individual wipe is filled to contain 0.8 ml. of 
solution. 
A variety of strengths can be used for the anthralin solution in the 
liquid-absorbed wipe. For example, the anthralin can be present in a range 
spanning 0.5-10% by weight. A variety of liquid carriers and a variety of 
strengths of the liquid carriers can be used for the anthralin. For 
example, the carrier can contain a quantity of water in addition to the 
alcohol and propylene glycol. Moreover, a carrier can contain a blend of 
water, ethyl alcohol, and isopropyl alcohol such as found in the carrier 
known as "Neutrogena Vehicle N (mild)" made by Neutrogena Dermatologics 
Division of Neutrogena Corporation, Los Angeles Corporation. A wide range 
of proportions of individual carrier ingredients can be employed. 
EXAMPLE 19 
In this example, anthralin is prepared for topical administration with 
liposomes. Methods of preparing liposomes containing active ingredients 
are disclosed in U.S. Pat. No. 4,673,567, incorporated herein by 
reference. More specifically, Examples 1 and 4 (which is for the 
cephalosporin cefalexin) in U.S. Pat. No. 4,673,567 are adapted herein for 
use with the anthralin. 
More specifically, 700 mg of D,L-dipalmitoylphosphatidyl choline is 
dissolved in chloroform in a round-bottom flask. The chloroform is removed 
by a rotary-evaporator to form a thin layer of phospholipid on the inner 
wall of the round-bottom flask. The phospholipid is dried sufficiently 
under reduced pressure, to which 25 ml of water is added. The mixture is 
shaken by hand at 50 degrees Centigrade for about 7 minutes to give a 
dispersion of liposomes (multilamellar vesicles, MLV). The dispersion is 
frozen by the used of dry ice/acetone and dried by vacuum lyophilization. 
The powder obtained is collected and placed in a tube for centrifugal 
separation. A solution of anthralin (1% anthralin by weight) is dissolved 
in purified water in the tube; and 2-fold diluted aqueous isotonic sodium 
chloride solution and 0.02M phosphate buffer are added to the tube. The 
mixture is dispersed well, then warmed up and kept at 50 degrees 
Centigrade for five minutes and washed twice with an isotonic phosphate 
buffer solution (pH 7.4) at room temperature by means of ultra-centrifugal 
separation. The liposomes, containing the anthralin are dried by 
lyophilization and blended with purified water for topical administration 
to treat acne. 
The anthralin used can be in a solution in a range of 0.5% to 10% by 
weight. 
The lyophilized powder which contains the anthralin in liposomes can also 
be used in creams and gels. 
EXAMPLE 20 
A time-release patch containing anthralin is described below. The making of 
the time-release patch is adapted from U.S. Pat. No. 4,839,174, 
incorporated herein by reference, which discloses the making of nicotine 
patches. More specifically, Example 1 is adapted for use with anthralin. 
Monolithic patches containing the anthralin are made as follows. A 
solution of anthralin-loaded Pellethane 2363-80AE is made by mixing 
Pellethane pellets into tetrahydrofuran, adding anthralin to be 1% by 
weight anthralin. The mixture is agitated on a bottle roller for three 
days to form a matrix mixture. A layer of backing material grade 3M-1005 
is spread in a petri dish and covered with the matrix mixture. The petri 
dish is covered, and the matrix is left to cure for 10 days at room 
temperature to form the time-release, anthralin composition. Patches are 
cut from the finished matrix. Time-release patches can be made in a 
variety of sizes to accommodate different anatomic locations to which the 
patches are applied. The anthralin can be added in a range spanning 0.5% 
to 20% by weight. 
As mentioned above, a carrier for the anthralin can contain a blend of 
water, ethyl alcohol, and isopropyl alcohol such as found in the carrier 
known as "Neutrogena Vehicle N (mild)" made by Neutrogena Dermatologics 
Division of Neutrogena Corporation, Los Angeles Corporation. More 
generally, however, a broad range of suitable amounts of anthralin and 
respective carrier ingredients is as follows: the anthralin is present in 
an amount in a range of 0.5-10% by weight; the ethyl alcohol is present in 
a range of 35-50% by weight; the laureth-4 is present in a range of 0-1% 
by weight; the isopropyl alcohol is present in a range of 0-10% by weight; 
and the water is present in a range of 40-60% by weight. 
EXAMPLE 21 
A composition of anthralin, a film-forming material, and a solvent is as 
follows: 
______________________________________ 
anthralin 5.0% by weight 
salicylic acid 1.0% by weight 
acetone (solvent) 15.0% by weight 
collodion (film-forming material) 
79.0% by weight 
______________________________________ 
The composition is applied directly onto the warts. The acetone evaporates, 
and the collodion forms a film which provides occlusion (film occlusion) 
for the anthralin stabilized (acidified) by the salicylic acid. 
Aside from the compositions which disclose anthralin described hereinabove, 
numerous other compositions which include anthralin can be employed for 
treating warts with tape occlusion in accordance with the principles of 
the present invention. As further examples of suitable compositions 
containing anthralin, reference is made to the exemplary 
anthralin-containing compositions disclosed in U.S. Pat. Nos. 4,495,203 
and 4,504,494, both by Grollier et al, mentioned hereinabove. 
In this respect, U.S. Pat. No. 4,495,203 is incorporated herein by 
reference, and the anthralin-containing gel compositions for treating the 
skin that are disclosed in Examples 1-5 in U.S. Pat. No. 4,495,203 are 
incorporated herein by reference. Furthermore, the percentages of 
anthralin in these compositions can be altered to be in a range of from 
0.50% to 10.0% by weight. 
Also, in this respect, U.S. Pat. No. 4,504,494 is incorporated herein by 
reference, and the anthralin-containing compositions for treating the skin 
that are disclosed in Examples IV, VII, VIII, XIII, and XIV, in U.S. Pat. 
No. 4,504,494 are incorporated herein by reference. Furthermore, the 
percentages of anthralin in these compositions can be altered to be in a 
range of from 0.50% to 10.0% by weight. 
The foregoing description of the invention has been presented for purposes 
of illustration and description. It is not intended to be exhaustive or to 
limit the invention to the precise forms disclosed. Obvious modifications 
or variations of the methods and compositions of the invention are 
possible in light of the above teachings. The embodiments were chosen and 
described in order to best illustrate the principles of the invention and 
its practical application to thereby enable one of ordinary skill in the 
art to best utilize the invention in various embodiments and with various 
modifications as are suited to the particular use contemplated. It is 
intended that the scope of the invention be defined by the claims appended 
hereto.