WO1998026771A1 - Utilisation d'alcools aliphatiques c18 a c26 pour preparer un medicament destine a traiter les dermatites hyperproliferantes - Google Patents

Utilisation d'alcools aliphatiques c18 a c26 pour preparer un medicament destine a traiter les dermatites hyperproliferantes Download PDF

Info

Publication number
WO1998026771A1
WO1998026771A1 PCT/US1997/022945 US9722945W WO9826771A1 WO 1998026771 A1 WO1998026771 A1 WO 1998026771A1 US 9722945 W US9722945 W US 9722945W WO 9826771 A1 WO9826771 A1 WO 9826771A1
Authority
WO
WIPO (PCT)
Prior art keywords
docosanol
cells
lesion
skin
keloid
Prior art date
Application number
PCT/US1997/022945
Other languages
English (en)
Inventor
Laura E. Pope
Mohammed N. Khalil
John F. Marcelletti
Lee R. Katz
David H. Katz
Original Assignee
Lidak Pharmaceuticals
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lidak Pharmaceuticals filed Critical Lidak Pharmaceuticals
Priority to EP97949808A priority Critical patent/EP1039885A1/fr
Priority to AU77352/98A priority patent/AU7735298A/en
Priority to CA002306772A priority patent/CA2306772C/fr
Publication of WO1998026771A1 publication Critical patent/WO1998026771A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/342—Alcohols having more than seven atoms in an unbroken chain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/28—Rubbing or scrubbing compositions; Peeling or abrasive compositions; Containing exfoliants

Definitions

  • the present invention relates to the treatment of hyperproliferative disorders of the skin by topical administration of a composition comprising one or more C18 to C26 aliphatic alcohols.
  • Benign hyperproliferative disorders of the skin result from excess keratin deposition (hyperkeratosis) of the corneous layer.
  • hyperproliferative disorders include epidermolytic hyperkeratosis and follicular keratosis.
  • hypertrophic scar formation a keloid
  • keloid-pro ⁇ e individuals While such hypertrophic tissue repair is most evident at sites of external wound healing, keloid-pro ⁇ e individuals also manifest hypertrophic scarring internally.
  • keloid scarring The major consequences 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 intervention is indicated because there is currently no generally effective topical or systemic treatment for this condition.
  • Other hyperproliferative disorders are corns and calluses. Current non-surgical treatments for less acute cases of hyperkeratosis include 17% salicylic acid in collodion and 40% salicylic acid plasters. A keloid is usually treated by injection of a corticosteroid into the base of the lesion. This treatment may flatten the keloid, but is often ineffective.
  • Malignant hyperproliferative disorders of the skin include Kaposi's sarcoma (KS) and skin cancer.
  • KS is a neoplasm, often associated with AIDS patients, characterized by vascular skin tumors. KS lesions originate from multifocal sites in the mid-dermis and extend to the epidermis. Mistopathology shows spindle cells and vascular structures admixed to various degrees. Repeated biopsies show a progressive sarcomatous-like appearance, in more advanced stages, the lesions appear as multiple purplish to brown subcutaneous nodular or plaque-like dermal lesions, often with a varicose surface.
  • KS cells spindle- shaped cells
  • endothelial cells CDC Task Force on KS and Opportunistic Infections, New Engl. J. Med., 306:248, 1982.
  • KS spindle- shaped cells
  • endothelial cells CDC Task Force on KS and Opportunistic Infections, New Engl. J. Med., 306:248, 1982.
  • indolent and lymphadenopathic Indolent KS is characterized by nodular or plaque-like dermal lesions. Treatment options include freezing, electrocoagulation or electron beam radiotherapy. Unresponsive lesions are treated locally with 1,000-2,000 rads of x-ray therapy.
  • Aliphatic alcohols are known to have various biological activities.
  • U.S. Patent No. 3,031,376 discloses that n-tetracosanol (C24), n-hexacosanol (C26), n-octacosanol (C28) and triaco ⁇ tanol (C30) and their esters improved physical performance of athletes and disclosed compositions comprising such alcohols and esters for oral ingestion.
  • U.S. Patent No. 4,670,471 discloses the use of triacontanol for treatment of inflammatory disorders such as herpes simplex, eczema, shingles, atopic dermatitis and psoriasis.
  • 3,592,930 discloses a medicant vehicle comprising 15 to 45 parts of saturated aliphatic alcohol having from 16 to 24 carbons as a carrier for antibiotics, steroids and antihistami ⁇ es.
  • U.S. patent No. 3,863,633 discloses a composition 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- eicosa ⁇ ol.
  • 4,874,794 discloses a method of treating virus-induced and inflammatory diseases of the skin and membranes with a composition comprising one or more of the aliphatic alcohols n-docosanol (C22), n- tetracosanol and n-hexacosanol.
  • Antiviral and anti-inflammatory activities of aliphatic alcohols having from 20 to 32 carbons are disclosed in U.S. Patent 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 activities are disclosed therein.
  • a C22 aliphatic alcohol, /7-docosanol, suspended in a surfactant exhibits potent antiviral activity against a variety of lipid enveloped viruses including herpes simplex virus and respiratory syncytial virus in cell culture assays (Katz, D. H., et al., Proc. Natl. Acad. Sci. USA 88:10825-10829, 1991; U.S. Patent No. 5,534,554).
  • Intracellular metabolic conversions of /7-docosanol may account for its antiviral activity (Pope et al., J. Lipid Res., 37:2167-2178, 1996).
  • the alcohol is not cytotoxic in concentrations up to 300 mM.
  • One embodiment of the present invention is a method of treating or inhibiting the growth of a hyperproliferative skin lesion in an individual in need thereof, comprising topically administering to the lesion an effective proliferation-inhibiting amount of one or more C18 to C26 aliphatic alcohols in a pharmaceutically acceptable carrier.
  • the skin lesion is benign.
  • the said skin lesion is hyperkeratosis or keloid.
  • the skin lesion is malignant.
  • the skin lesion may be Kaposi's sarcoma or skin cancer.
  • 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.
  • the aliphatic alcohol is n-docosanol, n-tetracosanol or n-hexacosanol; more advantageously, the aliphatic alcohol is n-docosanol.
  • the skin lesion is benign.
  • the benign lesion is keloid.
  • the skin lesion is malignant.
  • the malignant skin lesion is Kaposi's sarcoma or skin cancer.
  • 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.
  • the aliphatic alcohol is selected from the group consisting of n-docosanol, n-tetracosanol and n- hexacosa ⁇ ol. More advantageously, the aliphatic alcohol is n-docosanol.
  • compositions of this invention suitable for use in treating or inhibiting the growth of hyperproliferative skin lesions comprise an active ingredient or combination of compounds as the active ingredient, selected from a group consisting of C18 to C26 saturated aliphatic alcohols and mono- unsaturated aliphatic alcohols.
  • the C18 to C26 alcohols useful in the present invention include n-eicosanol (C20), n-docosanol (C22), n-tetracosanol (C24) and n-hexacosanol (C26).
  • C20 n-eicosanol
  • C22 n-docosanol
  • C24 n-tetracosanol
  • C26 n-hexacosanol
  • the use of C22 aliphatic alcohols is particularly preferred.
  • the corresponding low molecular weight ether or ester derivatives of these alcohols e.g., methyl-, ethyl, prop ⁇ l ) are also contemplated for use in the present invention.
  • n-Docosanol exhibits antiproliferative activity against cultured hypertrophic fibroblasts.
  • This inhibitory activity is specific to hyperproliferative cell populations, as the growth of normal cells was unaffected under the tissue culture conditions used. Reduction of cell proliferation by n-docosanol is favored by low cell densities and longer incubation times and is concentration-dependent. Unexpectedly, n-docosanol significantly reduced hyperproliferative keloid formation in a patient for whom other treatments had not been successful.
  • the hyperproliferative skin lesions for treatment with the C18 to C26 aliphatic alcohols may be either benign or malignant.
  • Benign lesions may arise from hyperkeratosis occurring, for example, in keloid, dermatitis papillaris capilliti (acne keloid), fibromatosis gingivae (keloid of gums), epider olytic hyperkeratosis and follicular keratosis.
  • Malignant lesions include skin cancers (basal cell carcinoma, squamous cell carcinoma, melanoma) and KS.
  • aliphatic alcohol compositions described herein can be combined with well known treatments for skin cancer (e.g., irradiation and/or chemotherapy) to lead to total or partial remission of the cancerous skin lesion.
  • treatments for skin cancer e.g., irradiation and/or chemotherapy
  • the treatment of any such hyperproliferative skin lesion is within 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- irritating to the skin and membranes and free from physiological effect.
  • Suitable carriers include aqueous and oleaginous carriers such as, for example, white petrolatum, isopropyl myristate, lanolin or lanolin alcohols, mineral oil, sorbitan mono-oleate, propylene glycol, cetylstearyl alcohol (together or in various combinations).
  • the carriers may be combined with a detergent (e.g., polyoxyl stearate or sodium lauryl sulfate) and mixed with water to form a lotion, gel, cream or semi-solid composition.
  • a detergent e.g., polyoxyl stearate or sodium lauryl sulfate
  • suitable carriers comprise mixtures of emulsifiers and emollients with solvents such as sucrose stearate, sucrose cocoate, sucrose distearate, mineral oil, propylene glycol, 2-ethyl-1,3-hexanediol, polyoxypropylene-15-stearyl ether and water.
  • solvents such as sucrose stearate, sucrose cocoate, sucrose distearate, mineral oil, propylene glycol, 2-ethyl-1,3-hexanediol, polyoxypropylene-15-stearyl ether and water.
  • Preservatives may also be included in the carrier including methylparaben, propylparaben, benzyl alcohol and ethylene diamine tetraacetate salts.
  • Preferred carrier formulations are described in U.S. Patent No. 5,534,554. Dilute suspensions without thickeners are most suitable for delivery to skin surfaces as aerosol sprays, using well known methods of delivery.
  • the composition may also include a plasticizer such as glycerol or polyethylene glycol ( .w. 800 to 20,000) and penetrants such as azo ⁇ e.
  • a plasticizer such as glycerol or polyethylene glycol ( .w. 800 to 20,000) and penetrants such as azo ⁇ e.
  • the composition of the carrier can be varied so long as it does not interfere with the pharmacological activity of the active ingredients.
  • compositions of the invention may additionally employ adjunct components conventionally found in pharmaceutical compositions in their art-established fashion and at their art-established levels. These pharmaceutically active materials do not interfere with the efficacy of the aliphatic alcohols.
  • the compositions may include anti microbial agents, anti-viral agents, anti-fungal agents, antioxidants, antipruritics, astringents, local anesthetics, anti-inflammatory agents, buffering agents, sunscreens and cosmetic agents such as coloring agents, fragrances, lubricants, skin penetration enhancers and moisturizers or drying agents.
  • Anti microbial agents useful for inclusion in the compositions include, for example, polymyxin B and tetracycline.
  • anti-viral agents included in the formulations may be nucleoside analogs such as acyclovir or cytokines.
  • Anti- fungal agents that may be included are miconazole or tolnaftate.
  • Antioxidants such as vitamin E may be included.
  • Sunscreens such as para-aminobenzoic acid may be included.
  • Drying agents that may be included are well 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 pullulin, xanthan, polyvinylpyrrolidone or carboxymethylcellulose.
  • a suitable carrier may include, for example, white petrolatum, stearyl alcohol, isopropyl myristate, sorbitan monooleate, propylene glycol, water and a detergent such as polyoxyl stearate mixed to form a stable cream.
  • the active ingredients i.e., n-docosanol
  • compositions of the present invention For assistance in formulating the compositions of the present invention, one may refer to Remington's Pharmaceutical Sciences, 15th ed., Mack Publishing Co, Easton, PA. Exemplary compositions for use in the present invention are disclosed in U.S. U.S. Patent No. 5,534,554.
  • compositions for use in the present invention is formulated of stearyl alcohol, petrolatum, water and mineral oil stabilized with a detergent such as sodium lauryl sulfate and may include a preservative such as meth ⁇ lparaben or propylparaben and an effective amount, typically from about 5% to 15% percent by weight of one or more C1B to C26 aliphatic alcohols.
  • Administration is preferably to the skin or a mucous membrane using a cream, lotion, gel, ointment, suspension, aerosol spray or semi-solid formulation (e.g., a suppository), all 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% (w/w) effective in treating or inhibiting the growth of a hyperproliferative skin lesion consist of about 10 mg to 10 g of the composition 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.
  • one to four applications of the composition per day are sufficient to treat or inhibit the growth of a hyperproliferative 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.
  • the compositions may be used to manage or slow the growth of a lesion such as a tumor. Even when a particular tumor cannot be cured, there is significant value in slowing its rate of growth.
  • Human keloid fibroblasts were obtained from the American Type Culture Collection (Rockville, MD) (CRL 1762). n-Docosanol (300 mM) was suspended in the nonio ⁇ ic surfactant Pluronic F-68 (12 mM) as described previously (Katz et al., Proc. Natl. Acad. Sci. U.S.A., 88:10825-10829, 1991). A vehicle control was prepared using the same procedure except n-docosanol was omitted.
  • Keloid cells (2.7 x 10 4 per well) were added to 16 mm wells containing DMEM supplemented with 10% fetal calf serum (FCS), sodium pyruvate, L-glutamine and penicillin/streptomycin.
  • FCS fetal calf serum
  • n-Docosanol 15 mM
  • Pluronic F-68 control 0.6 mM
  • Cells were harvested after incubation for 72 and 168 hours at 37°C in a humidified 10% C0 2 incubator. The number of viable cells was determined by trypan blue staining. The results are shown in Table 1.
  • the cell number after a 72 hour incubation indicates that cultured keloids are slow-growing relative to other cell types.
  • cells without addition were at 1.5 x the initial cell density.
  • the growth of n-docosanol-treated cells was inhibited 76% compared to no addition, while control (Pluronic
  • F-68 treated cell growth was only inhibited 31% compared to no addition.
  • n-docosanol treatment resulted in a dramatic inhibition of keloid cell growth in vitro.
  • Example 2 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 results were compared.
  • Example 2 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 results were compared.
  • n-docosanol inhibited the number of keloid cells per well by 36% at 72 hours and by 85% at 168 hours.
  • the vehicle control inhibited 29% at 72 hours and 22% at 168 hours.
  • the number of human fetal lung cells was significantly increased in the n-docosanol treated group, while the control suspension inhibited lung cell growth by 70%.
  • Docosa ⁇ ol (30 mM) was suspended in Pluronic F-68 (1.2 mM) as described previously (Katz et al., ibid.).
  • a vehicle control was prepared using the same procedure except for the omission of n-docosanol.
  • Radiolabeled n-[1- 1 C] docosanol suspension was prepared as described by Katz et al. (ibid.). Cells were resuspended in 1.2 x 10 6 cells/ml in DMEM supplemented with 10% fetal calf serum, sodium pyruvate, L-glutamine and penicillin-streptomycin.
  • Cell suspension (0.5 ml) was added to each 35 mm well containing 1.3 ml media, followed by addition of 0.2 ml radiolabeled n-docosanol suspension (final n-docosanol concentration - 3 M). After 24 hours at 37°C in humidified 10% C0 2 , the suspension was removed, wells were washed extensively with saline and cells were solubilized for scintillation counting by incubation with 0.5 ml trypsin for 15 min at 37° C. Solubilized cells were counted in a
  • 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%.
  • the numbers of CRL-1900 normal skin fibroblasts and Vero cells were not decreased in the presence of n-docosanol.
  • the increased binding and subsequent uptake of n-docosanol in keloid cells illustrates the selective toxicity of the compound to hyperproliferative cell types.
  • the case report described below illustrates the clinical use of n-docosanol (LIDAKOLTM) in treatment of keloid scar formation.
  • the injuries first appeared as ulcerating wounds at the temple mark on each side of the face and extended progressively downward along the mandibular lines, usually erupting as ulcerated sores which, as they healed, resulted in keloid scarring at the affected sites.
  • cream containing either 15% or 10% n-docosanol as active ingredient was to be applied to the affected areas.
  • These topical cream formulations are described in U.S. Patent No. 5,534,554. Initially, 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 percent).
  • cream containing 10% n-docosanol was changed to cream containing 10% n-docosanol and the application frequency was reduced to two times daily, after showering in the morning and just before bed in the evening.
  • This cream composition contained, in addition to 10% n-docosanol, 5.0% sucrose stearates, 8.0% mineral oil NF, 5.0% propylene glycol USP, 2.7% benzyl alcohol NF and 69.3% purified water.
  • the patient reported a significant diminution in pain around the lesions, and within 48 hours the inventors observed a significant reduction in swelling on the right side 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 face.
  • the patient could perceive a diminution in tightness and thickness of the keloids and a greater suppleness of the overlying dermis.
  • Example 6 The treatment described in Example 4 is repeated with other C18 to C26 aliphatic alcohols.
  • 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-docosanol. Similar improvements in the condition are observed.
  • Example 6 The treatment described in Example 4 is repeated with other C18 to C26 aliphatic alcohols.
  • 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-docosanol. Similar improvements in the condition are observed.
  • Example 6 Example 6
  • Kaposi's sarcoma HIV-positive male patients presenting with treatment-resistant cutaneous Kaposi's sarcoma were treated for 28 days, 5 times daily with the 10% n-docosanol cream formulation described in Example 4. Response to treatment was evaluated according to lesion dimensions, color of the lesion and the type of lesion (hard, 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.
  • Target lesion dimensions represent the product of two measured perpendicular diameters.
  • Example 6 The treatment described in Example 6 is repeated with other C18 to C26 aliphatic alcohols.
  • the active compounds are used in the therapeutic regimen described in Example 6 in patients with Kaposi's sarcoma, substituting the appropriate alcohol for n-docosanol. Similar improvements in the condition are observed.

Abstract

L'invention porte sur un procédé de traitement des dermatites hyparproliférantes bénignes ou malignes qui consiste à appliquer sur les lésions cutanées un alcool aliphatique C18 à C26 dans un excipient pharmacocompatible.
PCT/US1997/022945 1996-12-17 1997-12-05 Utilisation d'alcools aliphatiques c18 a c26 pour preparer un medicament destine a traiter les dermatites hyperproliferantes WO1998026771A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP97949808A EP1039885A1 (fr) 1996-12-17 1997-12-05 Utilisation d'alcools aliphatiques c18 a c26 pour preparer un medicament destine a traiter les dermatites hyperproliferantes
AU77352/98A AU7735298A (en) 1996-12-17 1997-12-05 Use of C18 to C26 aliphatic alcohols for the manufacture of medicament in the t reatment of hyperproliferative skin disorders
CA002306772A CA2306772C (fr) 1996-12-17 1997-12-05 Utilisation d'alcools aliphatiques c18 a c26 pour preparer un medicament destine a traiter les dermatites hyperproliferantes

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US76772296A 1996-12-17 1996-12-17
US08/767,722 1996-12-17

Publications (1)

Publication Number Publication Date
WO1998026771A1 true WO1998026771A1 (fr) 1998-06-25

Family

ID=25080353

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/022945 WO1998026771A1 (fr) 1996-12-17 1997-12-05 Utilisation d'alcools aliphatiques c18 a c26 pour preparer un medicament destine a traiter les dermatites hyperproliferantes

Country Status (4)

Country Link
EP (1) EP1039885A1 (fr)
AU (1) AU7735298A (fr)
CA (1) CA2306772C (fr)
WO (1) WO1998026771A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998036776A2 (fr) * 1997-02-20 1998-08-27 Matrix Pharmaceutical, Inc. Vehicules d'administration en gel pour agents s'opposant a la proliferation cellulaire
EP1436006A2 (fr) * 2001-10-16 2004-07-14 Avanir Pharmaceuticals Inhibition virale par n-docosanol

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1988008294A1 (fr) * 1987-04-29 1988-11-03 Patrick Martel Composition emolliente pour ongles
US5534554A (en) * 1993-12-13 1996-07-09 Lidak Pharmaceuticals Sucrose ester-C20 to C28 alcohol formulations

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1988008294A1 (fr) * 1987-04-29 1988-11-03 Patrick Martel Composition emolliente pour ongles
US5534554A (en) * 1993-12-13 1996-07-09 Lidak Pharmaceuticals Sucrose ester-C20 to C28 alcohol formulations

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BERKOW ET AL: "The 16th Merck Manual", MERCK RESEARCH LAB., 1992, XP002064741 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998036776A2 (fr) * 1997-02-20 1998-08-27 Matrix Pharmaceutical, Inc. Vehicules d'administration en gel pour agents s'opposant a la proliferation cellulaire
WO1998036776A3 (fr) * 1997-02-20 1998-11-26 Matrix Pharma Vehicules d'administration en gel pour agents s'opposant a la proliferation cellulaire
US6630168B1 (en) 1997-02-20 2003-10-07 Biomedicines, Inc. Gel delivery vehicles for anticellular proliferative agents
US6669958B1 (en) 1997-02-20 2003-12-30 Biomedicines, Inc. Gel delivery vehicles for anticellular proliferative agents
EP1436006A2 (fr) * 2001-10-16 2004-07-14 Avanir Pharmaceuticals Inhibition virale par n-docosanol
EP1436006A4 (fr) * 2001-10-16 2006-06-07 Avanir Pharmaceuticals Inhibition virale par n-docosanol

Also Published As

Publication number Publication date
CA2306772A1 (fr) 1998-06-25
EP1039885A1 (fr) 2000-10-04
AU7735298A (en) 1998-07-15
CA2306772C (fr) 2004-10-12

Similar Documents

Publication Publication Date Title
US4826830A (en) Topical application of glyciphosphoramide
US20180008557A1 (en) Use of two botanicals with complementary activities for improvement of skin
US5476664A (en) Treatment of warts using anthralins and occlusion
EP0980243B1 (fr) Procede de traitement des alterations de la peau dues a l'exposition a la lumiere au moyen de retinoides hautes doses
KR100264829B1 (ko) 좌창 또는 위스염모낭 염의 치료
JP2505983B2 (ja) 炎症性又はホルモン性脱毛症の治療剤
US5948822A (en) Treatment of hyperproliferative skin disorders with C18 to C26 alphatic alcohols
EP0793489B1 (fr) Utilisation de statin pour le traitement des maladies de la peau
JPH01151522A (ja) 皮膚疾患の局所治療
US20100068161A1 (en) Topical composition for the protection and/or treatment of radiation related skin damages
EP0462964B1 (fr) Compositions topiques contenant des amines aliphatiques pour le traitement de maladies de la peau
JP2002506801A (ja) 哺乳類の皮膚のセルライトを軽減する方法
US5795575A (en) Topical medicament which increases the number of capillaries in damaged skin
CA2273960C (fr) Inhibition virale au moyen d'alcools, alcanes, acides gras et amides a chaine longue
EP0387756B1 (fr) Utilisation de 5'-déoxy-5'-méthylthioadénosine S-adénosylméthionine et ses sels pour la préparation de compositions pharmaceutiques diminuant la séborrhée
EP1637135A1 (fr) Compositions comportant le diméthylsulfoxyde et le tretinoin pour le traitement des désordres de la peau
HU226065B1 (hu) Egy diol és egy alfa-hidroxisav keverékének alkalmazása hiperkeratózisos bõrbetegségek kezelésére szolgáló gyógyszer elõállítására
CN116209425A (zh) 用于防止脱发和促进生发的组合物
JPH04500824A (ja) 光老化の作用を回復させるための皮膚の治療方法
US20020176876A1 (en) Topical therapeutic skin care system
WO1998026771A1 (fr) Utilisation d'alcools aliphatiques c18 a c26 pour preparer un medicament destine a traiter les dermatites hyperproliferantes
US4520132A (en) Use of undecylenic acid to treat herpes labialis
JP2640597B2 (ja) 創傷治癒促進剤
WALDORF et al. Inhibition of wound epithelialization by topical 5-fluorouracil
EP3348307B1 (fr) Composition comprenant de la carnitine, du cholate de sodium, de l'acétate de sodium et éventuellement de l'argent pour utilisation dans le traitement du psoriasis

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG UZ VN YU ZW AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH KE LS MW SD SZ UG ZW AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

ENP Entry into the national phase

Ref document number: 2306772

Country of ref document: CA

Ref country code: CA

Ref document number: 2306772

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 1997949808

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1997949808

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1997949808

Country of ref document: EP