CA2306772C - Use of c18 to c26 aliphatic alcohols for the manufacture of a medicament in the treatment of hyperproliferative skin disorders - Google Patents

Abstract

A method for treating a benign or malignant hyperprofilerative skin lesion, comprising topically administering a C18 to C26 aliphatic alcohol to the skin lesion in a pharmaceutically acceptable carrier.

Description

WO 981267"!1 PCT/US97/22945 OF A MEDICAMENT IN THE TREATMENT OF HYPERPROLIFERATIYE SKIN DISORDERS
F~Id of the Invention The present invention relates to the treatment of hyperprokf~at'rve disorders of the skin by topical adn~iatration of a composition comprising one or more C18 to C28 aliphatic alcohoh;.
Backoround of the InveM'ron Benign hyperproliferat'rve disorders of the skin result from excess keratin depos'rt'ron [hyperkeratoaia) of the corneous layer. Such hyperproliferative disorders include epidermolytic hyperkeratoais and fotiicular keratosis. One cormnon benign hyperproliferative disorder is hypertrophic scar formation (a keloidh a sharply elevated, irregutarly-shaped, progressively enlarging scar due to the formation of excessive amounts of collagen in the corium during connective tissue repair following surgical and traumatic lacerations. Wh~le such hypertrophic tissue repair is most evident at sites of external wound heating, keloid-prone individuals also manifest hypertrophic scarring internatiy.
The major conaequancea of external keloid scarring are mainly cosmetic, although keloids can also result in varying degrees of psychological and social trauma for the afflicted individuals. In such cases, surgical or laser interverrt'ron is indicated because there is currently no generally effective topical or systemic treatment for this cand'ttion. Other hypwproliferat'rve disorders are corns and calluses. Current non-surgical treatments for less acute cases of hyperkeratosia include 17% salicylic acid in collodion and 40% salicylic acid plasters. A keloid is usually treated by ejection of a corticoateroid into the base of the lesion. This treatment may flatten the kaloid, but is often areffect'rve.
Malignant hyperprotiferat'rve disorders of the skin include Kaposi's sarcoma (KS) and skin cancer. KS is a neoph~sm, often associated with AIDS patients. characterized by vascular skin tumors. KS lesions originate from muhifocal sites in the mid-dermis and extend to the epidermis. Histopathology shows spindle cetis and vascular structuros admixed to various degrees. Repeated biopsies show a progressive sarcomatous-tike appearance. In more advanced stages, the Visions appear as multiple purplish to brown subcutaneous nodular or plaque-tike dermal lesions, often w'tth a varicose surface. The characteristic histological features of KS
include the proliferation of spindle-shaped ceps (KS cells, considered the tumor element) and of endothelial cells (CDC Task Force on KS and Opportunistic Infections, New Engl. J. Med., 308:248. 1982). Thero are two types of KS: indohmt and lymphadenopathic. Indohmt KS is characterized by nodular or plaque-tike dermal lesions. Treatment options include freezing. electrocoagulation or electron beam radiotherapy. Unresponsive lesions are treated locally w'tth 1,000-2,000 reds of x-ray therapy.
Aliphatic alcohols are known to have various biological activities. U.S.
Patent No. 3.031,378 discuses that n-tetracosanol (C24), n-hexacosanol [C28), n-octacosanol (C28) and triacontanol [C30) and their esters improved physical performance of athletes and disclosed compositions comprising such alcohols and esters for oral ingestion.
U.S. Patent No. 4,870,471 discloses the use of triacontanol for treatment of inflammatory disorders such as herpes simplex, eczema, shingles, atopic dermatitis and psoriasis. U.S. Patent No.
3,592,930 discloses a medicant vehicle comprising 15 to 45 parts of saturated aliphatic alcohol having from 18 to 24 carbons as a carrier for antibiotics, wo ~~srn rc'rrcls~nz~s steroids and antihistam~es. U.S. patent No. 3,883,833 discbses a compos-ttion for topical treatment of the eye comprising 10-80% C12 to C22 surface active alcohols such as n-docosanol, n-hexadecanol, n-octadecanol and n-eicosanoL U.S. Patent No. 4,874.794 discloses a method of treating virus-induced and inflammatory diseases of the skin and membranes with a compoa-rtion comprising one or more of the aliphatic alcohols n-docosanol (C22), n-tetracosanol and n-hexacasanoL Ant-'rviral and anti-inflammatory acfrv'rties of aliphatic alcohols having from 20 to 32 carbons are disclosed in U.S. PateM No. 4.874,794, U.S. Patent No.
5,071,879, U.S. Patent No. 5,166,219, U.S.
Patent No. 5,194,451 and U.S. Patent No. 5,534,554. Related chemical compounds and compositions having therapeutic act'rv-ttiea are disclosed therea~.
A C22 aliphatic alcohol, n-docosanol, suspended in a surfactant exhibits potent ant'rviral activity against a variety of lipid emetoped viruses including herpes simplex virus and respiratory syncytial virus in cefl culture assays (Katz, 0. H., et al., Proc. Nat/. Acad. Sci. USA 88:10825-10829, 1991; U.S.
Patent No. 5,534,554). intracehular metabolic conversions of n-docosanol may account for its anfrviral activity (Pope et al., J. Lurid Has , 37:21 B7-2178, 19981. The alcohol is not cytotoxtc in concentrations up to 300 mM.
There is a need for therapeutic agents which will inhibit hyperproliferafrve skin lesions. The present invention addresses this need.
Summary of the Invention One embodiment of the present invention is a method of treating or inlu-b'tting the growth of a hyperproliferat'rve skin lesion in an individual in need thereof, comprising topically administer~g to the lesion an effective proliferation-inhib'tting amount of one or more C18 to C2B aliphatic alcohols in a pharmaceutically acceptable carrier. Preferably, the skin lesion is benign. Advantageously, the said skin lesion is hyperkeratosis or keloid.
According to another aspect of this embodiment, the skin lesion is malignant.
The skin lesion may be Kaposi's sarcoma or skin cancer. Preferably, the aliphatic alcohol is present in an amount from about 0.1 % to 20% by weight; more preferably, the aliphatic alcohol is present in an amount from about 5% to 15% by weight.
Advantageously, the aliphatic a~ohol is n-docosanol, n-tetracosanol or n-hexacosanol; more advantageously, the akphatic a~ohol is n-docosanol.
Another embodiment of the awent'ron is the use of one or more ClB to C26 aliphatic alcohols in the preparation of a medicament for the treatment or growth inhibition of a hyperproliferative skin lesion. In one aspect of this embadanent, the skin lesion is benign. Preferably, the benign lesion is keloid. Alternatively, the skin lesion is malignant. In one aspect of this preferred embodiment, the malignant skin lesion is Kaposi'a sarcoma or akin cancer. Preferably, the one or more aliphatic alcohols is present in an amount from about 0.1 % to 20% by weight.
More preferably, the one or more aliphatic alcohols is present in an amount from about 5 to 15% by weight.
Advantageously, the aliphatic alcohol is selected from the group consisting of n-docosanol, n-tetracosanol and n-hexacosanol. More advantageously, the aliphatic alcohol is n-docoaanol.
Detaged e~~r'rotion of the Preferred Embodknenta The present invention relates to the treatment or growth inhib'ttion of hyperprokferative akin Visions by topical administration of one or more aliphatic straight-chain saturated monohydric alcohols which have from 18-26, wo ~~~m rcr~s9~nZ~as preferably 22-26 carbons, in a.topicagy acceptab~ carrier. Compos'ttiona of this krvention su'ttable for use in treating or ah~iting the growth of hyperproliferat'rve akin lesions comprise an active ingredient or combination of compounds as the active ingredient, selected from a group consisting of C18 to C2B
saturated aliphatic alcohols and mono-unsaturated aliphatic alcohols. The C18 to C2B alcohols useful in the present invention include n-eicosanol (C201.
n-docoaanol (C22), n-tetracosanol (C24) and n-hexacosanot (C2B). The use of C22 aliphatic alcohols is particularly preferred. The corresponding bw molecular weight ether or ester der'rvafrves of these alcohols (e.g., methy4~, ethyl, propyN) are also contemplated for use in the present invention.
Methods of synthesis of n-docoaanol are known to those skilled in the art (e.g., see U.S. Patent No.

4,188,2111. Methods of synthesis of aliphatic alcohola are wed known in the art (e.g., see A. Streitwieser, Jr. 8~
C.H. Heathcock, Introduction to Oroanic Chemistry. 2nd ed.. MacmiNan Publishing Co., New York, NY, 1881, at pages 160, 243-247, 303-307, 311-312. 315-317, 401-40B, 447-453, 51 B, 550-555, 604.805 and 670).
n-Docosanol exhib'tts antiproliferative activity against cultured hypertrophic ftbrobtasts. This krhib'rtory activity is specific to hyperproliferative cell poputafrons, as the growth of normal cells was unaffected under the tiawe cuhure conditions used. Reduction of cell proliferation by n-docoaanol is favored by low cell densities and longer incubation times and is concentration-dependent. Unexpectedly, n-docosanol significantly reduced hyperprolfferat'rve keloid formation in a patient for whom other treatments bad not been succeaafuL
The hyperproGferative skin lesions far troatment with the C18 to C2B aliphatic alcohola may be either bmrign or malignant. Benign lesions may arise from hyperkeratosis occurring, for example, in keloid, dermatitis papiparis capi6ti (acne keloid), fibromatosis gingivae (keloid of gums), epidermolytic hyperkeratoais and fol~ular keratosis. Malignant lesions include skin cancers (basal cell carcinoma, aquamous ceg carcinoma, melanoma) and KS.
The use of the aliphatic alcohol compositions described herein can be combined with well known treatments for akin cancer (e.g., irradiation andlor chemotherapy) to lead to total or partial remission of the cancerous skin lesion. The treatment of any such hyperproliferative skin lesion is w'tthin the scope of the invention.
The active agents and surfactants are combined with a carrier that is physiologically compatible with the skin and membrane tissue of a human or animal to which it is administered. The topically acceptable carrier is non-rcr'rtating to the skin and membranes and free from physiological effect.
Suit~la carriers include aqueous and oleaginous carriers such as, for example, white petrolatum, isopropyl myristate, lanolin or lanolin alcohols, mineral oil, aorb'rtan mono-oteate, propylene glycol, cetylstearyl alcohol (together or in various combinations). The carriers may be combined with a detergent (e.g., polyaxyl stearate or sodium lauryl aulfatel and mixed with water to form a lotion, gel, cream or semi-sorut compos'ttion. Other suitable carriers comprise matures of emulsifiers and emoUienta with sohrenta such as sucrose stearate, sucrose cocoate, sucrose distearate, mineral og, propylene glycol, 2-ethyl-1,3-hexanediol, polyoxypropylene-15-stearyl ether and water. Preservafrvea may also be included in the carrier including methylparaben, propylparaben, benryl alcohol and ethylene diamine tetraacetate salts. Preferred carraer formulations are described in U-S.
Patent No. 5,534.554.
Dilute suspensions without thickeners are moat suitable for delivery to skin surfaces as aerosol sprays, using well known methods of delivery. The compos'ttion may also include a plasticizer such as glycerol or polyethylene wo ~sr26m rc rrtrs9~n2~ts .4.
- glycol Im.w. 800 to 20.000) and penetrants such as azone. The compoa'rtion of the carrier can be varied so long as it does not interfere with the pharrnacolog~al activ'tty of the active ingredients.
The aliphatic alcohol compositions of the inventron may additionally employ adjunct components conventionaNlr found in pharmaceutical compositions in their art-estabr~shed fashion and at their art-established levels.
These pharmaceuticaNy active materials do not interfere with the efficacy of the aliphatic a~ohols. Thus, for example, the compos'ttions may include anti-microbial agents, anti-viral agents, anti-fungal agents, antioxidants, antiproritics, astringents, local anesthetics, anti-inflammatory agents, buffering agents, sunscreens and cosmetic agents such as coloring agents, fragrances. lubricants, skin penetrafron enhancers end moisturaers or drying agents.
Anti-microbial agents useful for inclusion in the compositions include, for example, polymyxin B and tetracycline.
Other anti-viral e~nts included in the formulations may be nucleoside analogs such as acyclovir or cytokines. Anti-fungal agents that may be included are miconazole or talnaftate. Antioxidants such as vitamin E may be included.
Sunscreens such as pare-aminobenzoic acid-may be included. Drying agents that may be included are weN known, such as, for example, phenol and benzyl alcohol. Lubricants such as synthetic or natural beeswax may also be included. Thickening agents to produce gels or suspensions may include puUulin, xanthan, polyvinylpyrralidone or carboxymethylcellulose. Other carriers contemplated for use in formulating the aliphatic alcohol compositions arclude creams, saHes, dispersions, suspensions, pastes and ointments. A suitable carrier may include, for example, white petrolatum, atearyl alcohol, isopropyl myriatate, aorbitan monooleate, propylene glycol, water and a detergent such as polyoxyl stearate mixed to form a stable cream. The acfrve ingredients (i.e., n-docosanop comprise about 0.1 %
to about 50% by weight of the final compoa'ttion, preferably 1 % to 10% by weight. For assistance in formulating the compositions of the present invention, one may refer to RemMgton's Pharmaceutical Sciences, 15th ed., Mack PubNshing Co, Eaaton, PA. Exemplary compositions for use in the present invention are disclosed in U.S. U.S. Patent Ne. 5,534,554.
Another anitable corr~pos'ttion for use in the present invention is formulated of stearyl alcohol, petrolatum, water and mineral of stabiNzed with a detergent such as sodium lauryl sulfate and may include a preservative such as methylparaben or propylparaben and an effective amount, typically from about 5% to 15% percent by weight of one or more C18 to C2B aliphatic alcohols.
Administration is preferably to the ska~ or a mucous membrane using a cream, lotion, gel, ointment, suspension, aerosol spray or semi-solid formulation (e.g., a suppositoryl, aU
formulated using methods well known in the art. Applications of the pharmaceutical compositions containing the active ingredient in an amount between about 0.1 % and about 20% Iwlw) effective in treating or inhibiting the growth of a hyperproliferafrve akin lesion consist of about 10 mg to 10 g of the compoa'ttion per application for between one day and one year. The compositions are typically applied between one and five times per day in an amount sufficient to completely cover the lesion. In a preferred embodiment, one to four applicat'rons of the composition per day, of about 0.1 g to 5 g per appYcation, for one to thirty days are sufficient to treat or inhibit the growth of a hyperproliferafrve skin lesion.
The compositions are preferably applied to lesions daily as soon as the lesion is detected and discontinued once the lesion has completely disappeared or exhibits no further reduction in size.
Alternatively, the compositions may be .5.
- used to manage or slow the growth of a Vision such as a tumor. Even when a particular tumor cannot be cured, there is significant value in slowing its rate of growth.
The following study addressed the toxicity and antiprokferative act'rv-rty of n-docosanol in keloid f~roblasts.
Exempla 1 AMioroliferat'rve activity of n-docoaenol in keloid cela Humwr kebid fibroblaats were obtained from the American Type Cuhure Collection (Rockville, MD) (CRL
17821, n-Docosanol 1300 mM) was suspended in the nonionic surfactant Pkrronic F-88 (12 mM) as descried previously (Katz et al., Pioc. Nato Aced Sc1 U.S.A., 88:10825-10828, 19911. A
vehicle control was prepared using the same procedure except n-docoaanol was omitted. Keloid ceNs 127 x 10' per wem were added to 18 mm wags cortta~ing DMEM supplemented w'tth 10% fetal calf serum IFCSI, sodium pyruvate, L-glutamine and peniciginlstreptomycin. n-Docosanol (15 mMl or the correapondb~p Pluronic F-88 control (O.B mMl was added (total volume - 2.0 mll. Ceaa were harvested after incubation for 72 and 188 hours at 37°C in a humidified 10% COi incubator. Tho number of viable cells was determined by trypan blue ata~ing.
The reaufts are shown in Table 1.
Table 1 72 hours 188 hours Condition cegslwell % control" celblwell % control' no addition 3.2 x 10' 100 4.2 x 10' 100 control soapenaion 2.9 x 10' 81 2.9 x 10' B9 15 mM n-dacos~ol 3.3 x 10' i03 1.0 x 10' 24 "Compared to cells incubated with no addition In view of the ~itial cep inoculum, the ceg number after a 72 hour incubation indicates that cultured keloids are slow-growing relative to other cell types. After 168 hours, cells without addition were at 1.5 x the initial cell density. The growth of n-docosanol-treated ceaa was inh~itad 78% compared to no addition, whc~e control (Pluronic F-68 treated) ceg growth was only inhib'tted 31 % compared to no addition.
Thus, n-docosanol treatment resuhod in a dramatic inhi~'rtion of keloid ceg growth ~ vitro.
The experiment described in Example 1 was repeated. However, human fetal lung cells were also subjected to the same treatments as the keloid fibroblasts and growth resuhs were compared.

WO 98IZbTl1 PCT/US97/22945 .g.
- Example 2 Comparison of n-docoaanol effect between keloid and normal cells Human fetal lung cells (HFI; ATCC CCL 1531 and keloid cells 15 x 10' cegalwelll were separately added to 16 mm weNs and frosted as described in Example 1. The results are shown in Tables 2 (keloid rags) and 3 (human fetal kmg regal.
Tabts 2 72 hours 168 hours Condition cell:<well % control' cegslwell % control' no addition 1.7 x 10' 100 2.7 x 10' 100 control suspension 1.2 x 10' 71 2.1 x 10' 78 mM n-docasanol 1.1 x 10' 84 0.4 x 10' 15 'Compared to cells ~cubated w'tth no addition Table 3 72 hours 168 hours C~dition celh~Iwell- % co~rol' cell~well % control' no additan 5.0 x 10' t00 8.0 x 10' 100 control suspension 4.2 x 1Q' 84 2.3 x 10' 30 15 mM n-docosa~l 5.8 x 10' 118 20 x 10' 250 'Compared to ceps ~cubated w'tth no add'tt'ron As shown in Table 2, n-docoaanol inhibited the number of keloid cells per well by 38% at 72 hours end by 85% at 168 hours. The vehicht control inhibited 29% at 72 hours and 22% at 168 hours. In contrast, at both time intervals ttm number of human fetal lung cells was significantly increased in the n-docosanol frosted group, while the control suspension inhibited lung cell growth by 70%. These rosuhs show that the inhibition of cell proliferation mediated by n-docosanol is not a generelaed phenomena, but is specific for hyperproliferative cells.
The fogowing experiment examined the effect of n-docosanol on ceg proliferation and quantitation of n-[1-"C]docosanol binding to keloid, Yero (normal African green monkey kidney; ATCC
CCL 81) and normal skin fibroblast (ATCC CRL 1900) cogs.

WO 98/267?1 PCT/US97/22945 .7.
Examphs 3 n-loco ~anol bindino and orogferafron studies Human kekbd fgrroblasts, normal control skin fibroblaats and Vero cells were obtained from ATCC. n Docosanol (30 mM) was suspended in Pluronic F-88 (1.2 mM) as descr'bed previously (Katz et sl., ~idl. A vehicle control was prepared using the same procedure except for the omiss'ron of n-docosanol. Radiolabeled n-[1-"C]
docosanol suspension was prepared as deacr~ed by Katz at al. (bid 1. Cells were reauspended ~ 1.2 x 10' cegslml in DMEM supplemented with 10% fetal calf serum, sodium pyruvate, L-glutamine and penicglin-streptomycin. Cell suspension (0.5 ml1 was added to each 35 mm well containing 1.3 ml media, followed by addition of 0.2 ml rad~labeled n-docosanol auspenaien (final n-docoaanol concentration - 3 mMl.
After 24 hours at 37°C in humidified 10% COr, the suspension was removed, welts were washed extensively w'tth saline and tags were aolubBzed for scintglation taunting by incubafron w-'tth 0.5 ml trypsin for 15 min at 37°C. Solubilized cells were counted in a Beckman LSW00 scintBation counter. Samples were corrected for nonspecific binding to plates by subtracting values obtained in control wags lacking cells. To determine cell number, duplicate plates were treated w'tth non-radrolabe~d n-docoaanol or control suspension at the same concentration or were left untreated. The number of viable cabs wss determined by trypan bhie staining. The resuhs are summarized in Table 4.
Tabs 4 Ksloid CRL-1800 Vero Addition No. cells % ctrl No. cells % ctrl No. Cells % cM
none 3.7 x 105 100 5.5 x 105 100 3.9 x 106 100 control 2.3 x 105 82 5.2 x 106 95 5.1 x 106 131 n-docosanol 1.B x 105 43 5.4 x 106 98 5.9 x 106 151 (3mM) Binding per 45.5 fug 15.8 ~ 8.9 fug 10~ cells 'Compared to tags incubated w'tth no addition Aa shown in Table 4, n-docosanol reduced the number of keloid cells by 57%
after a one day incubation, while the control suspension reduced the number of keloid cells by 38%.
Conversely, the numbers of CRL-1900 normal skin fibroblaats and Vero cells were not decreased in the presence of n-docosanol. About three fold greater amounts of radiolab~ed n-docosanol bound to keloid sa compared to CRL 1900 or Vero cage. The increased binding and subsequent uptake of n-docosanol in keloid tags iguatrates the setecfrve toxic'tty of the compound to hyperproliferat'rve ceg types.
The case report described below igustrates the clinical use of n-docosanol (LIDAKOL'""I in treatment of keloid scar format-ion.

WO 9$/6771 PCT/US97/22945 .$.
Example 4 Treatment of keloid scar formation whh n-docoaanol LL., a 34 year old black male, presented with a one year history of progressive bgateral facial keloid scarring. The precise cause of injury is unknown, but appears to have been initiated as a resuh of work-related exposure to some aerosolized irrhant at a high rise budding construction site.
During the time of exposure, the patiern was working in an area in which noxious fumes were known to exist, and he was wearing a f'ttratron face mask for protection against inhalation exposure. Since the resuhing wounds occurred in a pattern which appeared to out~e the edges of the protecfrve face mask, the injury may reflect some type of chemical bum resuhing from concentration of aerosokZed irritants w'tth perspiration at the edge of the face mask. The injuries first appeared as idcenting wounds at the temple mark on each aide of the face and extended progresairely downward along the mandib~ar lines, usually erupting as ulcerated sores which, as they healed, resulted in keloid scarring at the affected shea.
During the ensuing year after onset of this process, the patient was seen on ~veral occas'rona in the dennatobgy division of a major local hosphal and attempts were made to arrest the process by intradermal steroid injections at the affected a'rtes. This treatment approach was ineffective.
When the patient was first seen by the inventors, he had extens'roe and d'~sfiguring bilateral scars on the face and a large ulcerated lesion at the ewer end of the process on the rpht aide of the face. There was keloid scarring on both the right and left aides of the face manifested as typical "ropey and cord-like" tissue deposhion and depigmentation. The right side of the face was noticeably swollen prewmably as a resuh of the active u~eration process at the lower end of the lesions. The patient complained of pain along both areas of scarring, particularly at the more distal ends of the lesions. He a~nitted to social w'tthdrawai as a result of embarrassment about his appearance and extreme frustration about the apparent futil-tty of obtaining any help to arrest or reverse the process.
Aher thoroughly explaining the experimental aspects of the therapeutic repanen, the patient volunteered to enter a study in which cream containing ehher 15% or 10% n-docosanol as acfrve ingredient was to be applied to the affected areas. These topical cream formulations are described in U.S.
Patent No. 5,534,554. InitiaAy, applications of cream containing 15% n-docosanol were made three times daily.
This cream formulation contained, in addition to 15% n-docosanol, 11.0% sucrose stearates, 5.0% sucrose cocoate, 8.0% mineral oil NF, 5.0%
propylene glycol USP, 2-ethyl-1,3-hexanediol and 58.3% purified water (all weight percentl. After one month on this reganen, the patient was changed to cream containing 10% n-docosanol and the application frequency was reduced to two times da5y, after showering in the morning and just before bed in the evening. This cream compoa'rtion contained, in addition to 10% n-docoaanol, 5.0% sucrose stearates, 8.0%
mineral oil NF, 5.0% propylene glycol USP, 2.7% benzyl alcohol NF and 89.3% purified water.
Almost innnediately after onset of therapy, the patient reported a significant d><n~ution in pain around the lesions, and whhin 48 hours the inventors observed a significant reduction in swelling on the right aide of the face and onset of granulation within the ulcerated lesion at the distal end of the affected area in the right side of the .g.
- face. By the end of the second week of therapy, the patient could perceive a dim~ution in tightness and thickness of the kaloids and a greater suppleness of the overlying dermia.
After three months of therapy there was a clear reduction in the extent of elevation of the keloid scarring and a considerable anpravement in skin pigmentation. At the site of the healed ulcerated lesion on the rpht side of the face, the resulting wound repair left a much amaBer scar defect compared to the large scarred area at the right temple line which was the site of hea4ng of the initial ulcer at the onset of this process. After one year of therapy, there was a significant reduction of scar tissue, a flattening of tho prev'rously ropey and cord-like elevations end almost complete return to normal pigmentation in the affected areas. The patient exhib'tted ne adverse reactions during the course of treatment.
Exempla 5 The treatment described in Example 4 is repeated with other C18 to C28 aliphatic a~ohols. The active compounds are used in the therapeutic regimen described in Example 4 in a patient with excessive keloid formation, substituting the appropriate alcohol for n-docoaanol. Similar ~rovements in the condition are observed.
Exempts B
Treatment of Kaoosi's sarcoma HiY-pos'tt'rve male patients presenting with treatment-resistant cutaneous Kaposi's sarcoma were treated for 28 days, 5 times dagy w'tth the 10% n-docosanol cream formulation described in Example 4. Response to treatment was evaluated accard~g to lesion dimensions, color of the lesion and the type of lesion chard, soft or nodule!- The data were recorded on intermittent days throughout the 28 days of the study and values were compared to baseline observations made on Day 1. Three target lesions were evaluated in each patient. Thus far, five patients have completed the study.
Oats on lesion size and color for Day 1 (baseline) and Oay 28 are indicated in Table 5. In three out of five patients a response to the treatment was indicated by a reduction in the size of the lesions at Day 28 compared to the baseline measurements of Day 1. A reduction in lesion sae was observed in 2 out of 3 lesions in one patient and in 3 out of 3 leaiona in two patients. One lesion completely disappeared by Day 3. Art increase in lesion size was not observed for any of the 15 lesions studied. In all five patients, color changes in all lesions to a lighter color suggested that treatment caused a docroase in lesion sever-'tty. One patient who reported painful lesions on Day 1 reported that the lesions were case painful on Day 15 and thereafter, and this was accompanied by a decrease in the cbnicaHy observed aweging.

W0.98I26771 PCT/US97/22945 Tabls 5 Day 1 Day 28 Patient Lean Diameter Color Diameter Color percent Number (mm) (mm) reduction in lesion sae WEB 1 100 purple 25 pale 75 WEB 2 54 deep gone gone gone p~k WEB 3 380 purple 100 pale pink74 DMS 2 400 purple 324 very pale19 pink OMS 3 500 purpk~ 380 pale pink20 DMS 4 100 purple 100 pale pink0 CKW 1 170 deep 170 pink 0 burgundy CKW 4 289 deep 289 pink 0 burgundy CKW 7 121 deep 121 pink 0 burgundy SHC 8 198 purple 1B0 tan 19 SHC 7 500 purple 380 tan 28 SHC 8 1200 purple , 1080 tan 10 TLM 5 9 pink 9 lighter 0 pink TLM B 250 pink 250 lighter 0 perk TlM 7 380 pink 380 lighter 0 pink 'Target lesion dimensions represent the product of two measured perpendicular diameters.
Example 7 The treatment described in Example B is repeated w'tth other C18 to C2fi aliphatic alcohols. The active compounds are used in the therapeutic regimen described in Example fi in patients with Kaposi'a sarcoma, subst'ttuting the appropriate a~ohol for n-docosanol. Similar improvements in the cond'ttion are observed.
It should ba noted that the present invention is not I~n'tted to only those embodiments described in the Detailed Description. Any embodiment which retains the spirit of the present invention should be considered to be within its scope. However, the invention is only limited by the scope of the following claims.

Claims (15)

The embodiments of the invention, on which an exclusive property or privilege is claimed, are defined as follows:

1. Use of one or more C20 to C26 aliphatic alcohols in the preparation of a medicament for the treatment or growth inhibition of a hyperproliferative skin lesion.

2. Use according to claim 1, wherein said skin lesion is benign.

3. Use according to claim 2, wherein said skin lesion is keloid.

4. Use according to claim 1, wherein said skin lesion is malignant.

5. Use according to claim 3, wherein said skin lesion is Kaposi's sarcoma or skin cancer.

6. Use according to claims 1 to 5, wherein said one or more aliphatic alcohols is present in an amount from about 0.1% to 20% by weight.

7. Use according to claim 6, wherein said one or more aliphatic alcohols is present in an amount from 5% to 15% by weight.

8. Use according to claim 1, wherein the aliphatic alcohol is selected from the group consisting of n-docosanol, n-tetracosanol and n-hexacosanol.

9. Use according to claim 8, wherein the aliphatic alcohol is n-docosanol.

10. Use according to claim 9, wherein said skin lesion is benign.

11. Use according to claim 10, wherein said skin lesion is keloid.

12. Use according to claim 9, wherein said skin lesion is malignant.

13. Use according to claim 12, wherein said skin lesion is Kaposi's sarcoma or skin cancer.

14. Use according to any of claims 9 to 13, wherein said n-docosanol is present in an amount from about 0.1% to 20% by weight.

15. Use according to any of claims 9 to 13, wherein said n-docosanol is present in an amount from 5 to 15% by weight.