WO1994005278A1

WO1994005278A1 - X-hydroxy saturated fatty acids for the treatment of corns and calluses

Info

Publication number: WO1994005278A1
Application number: PCT/US1993/007720
Authority: WO
Inventors: Michael L. Caswell
Original assignee: Schering-Plough Healthcare Products, Inc.
Priority date: 1992-09-02
Filing date: 1993-08-20
Publication date: 1994-03-17
Also published as: CA2143629A1; AU5016393A; EP0658108A1; JPH08500603A; MX9305345A

Abstract

A medicament and a method for treating corns and calluses is claimed. The medicament contains an effective amount of at least one saturated α-hydroxy fatty acid having 12 to 22 carbon atoms, or salts or esters thereof. The medicament can be in the form of a liquid preparation or a medicated device which contains the saturated α-hydroxy fatty acid.

Description

X-HYDROXY SATURATED FATTY ACIDS FOR THE TREATMENT OF CORNS AND CALLUSES

BACKGROUND Corns and calluses are examples of hyperkeratosis.

Hyperkeratosis is hypertrophy of the stratum corneum (ie., outer layer of the skin) caused by excess production of keratinized tissue relative to shedding of keratinized tissue. Essentially, hyperkeratotic tissue forms where more stratum corneum is being made than is being lost. According to the Handbook of Nonprescription Drugs, Eighth

Edition, American Pharmaceutical Association, 1986, Chapter 33 Footcare Products, pp. 655-687, corns and calluses are strikingly similar in one respect: each has a marked hypertrophy of the stratum corneum. Beyond this feature, however, there are marked differences. A corn (clavus) is a small, sharply demarcated, hyperkeratotic lesion having a central core. It is raised, has a yellowish gray color, and ranges from a few millimeters to one centimeter or more in diameter. The apex of the corn points inward and presses on the nerve endings in the dermis, causing pain. A callus is different from a corn in that it has no central core, has more diffuse thickening of the skin and generally occurs in different locations on the body. It has indefinite borders and can range from a few millimeters to several centimeters in diameter. It is usually raised, yellow and has a normal pattern of skin ridges on its surface. Besides joints, calluses form on weight-bearing areas, such as the palms of the hands and sides and soles of the feet.

U.S. Patent 5,091 ,171 discloses generically, that amphoteric compositions containing the dimeric or polymeric forms of hydroxyacids may be useful in treating cosmetic conditions and dermatologic disorders in human and animals, including dry skin, dandruff, acne, keratoses, psoriasis, eczema, pruitus, age spots, lentigines, melasmas, wrinkles, warts, blemished skin, hyperpigmented skin, hyperkeratotic skin, inflammatory dermatoses, skin changes associated with aging and as skin cleaners. U.S. Patent 4,824,865 discloses that 2-hydroxyoctanoic acid, 2-ketooctanoic acid and their C2 to C& alkyl esters are useful in treating callous-forming disorders, notably palmar and plantar hyperkeratosis, including corns. A number of other agents have been taught for treating corns or calluses such as glacial acetic acid, lactic acid, salicylic acid, phenoxyacetic acid, zinc chloride, ascorbic acid, calcium pantothenate, cantharidin, podophyllum and bleomycin sulfate. It would be desirable, however, to provide undiscovered alternative methods as effective or even more so for treating corns and calluses.

SUMMARY OF THE INVENTION In one embodiment, the present invention is directed towards a medicament for treating corns and calluses containing an effective amount of at least one saturated α-hydroxy fatty acid having 12 to 22 carbon atoms, or salts or esters thereof. The medicament can be in the form of a liquid preparation or a medicated device which contains the saturated α- hydroxy fatty acid. The amount of saturated α-hydroxy fatty acid in the liquid preparation can range from about 5 to about 25 percent by weight of the liquid preparation. The medicated device can comprise at least one saturated α-hydroxy fatty acid having 12 to 22 carbon atoms, or salts or esters thereof, admixed into a plaster preparation, wherein the plaster preparation is attached to a carrier. The saturated α-hydroxy fatty acid can be present in the plaster preparation in an amount ranging from about 15 to about 80 percent (%) by weight of the plaster preparation. Preferably, the saturated α-hydroxy fatty acid is α-hydroxy palmitic acid. Also preferred is that the α-hydroxy fatty acid has an even number of carbon atoms.

In another embodiment, the present invention is directed toward a method for treating corns and calluses, comprising contacting the affected area with the liquid preparation or the medicated device containing an effective amount of at least one saturated α-hydroxy fatty acid having 12 to 22 carbon atoms, or salts or esters thereof, to effect softening or loosening of the corn or callus for removal thereof.

The present invention has the advantage of providing compounds which can rapidly penetrate corn and callus tissues to facilitate rapid softening or loosening thereof, for removal from the body.

DETAILED DESCRIPTION OF THE INVENTION

Saturated α-hydroxy fatty acids, salts or esters thereof suitable for use in the present method include α-hydroxy lauric acid (C-12), α-hydroxy myristic acid (C-14), α-hydroxy palmitic acid (C-16), α-hydroxy stearic acid (C-18), α-hydroxy arachidic acid (C-20) or α-hydroxy behenic acid (C-22). Alternatively, mixtures of the above α-hydroxy fatty acids can be employed. Suitable pharmacologically acceptable salts include various inorganic acids and bases such as ammonium salts, alkali metal salts, eg. sodium and potassium salts, and alkaline earth metal salts, eg. calcium and magnesium salts. Salts with organic bases may also be employed, eg. N-methylglucamine, lysine and arginine, as well as salts of organic and inorganic acids, eg. HCI, HBr, H2SO4, H₃PO₄, methanesulfonic acid, toluenesulfonic acid, maleic acid, fumaric acid and camphorsulfonic acid. Suitable esters include the C2 to C-β alkyl esters, diglyceride and triglyceride esters and mixtures thereof.

The term "medicament" includes liquid preparations and medicated devices. Typical liquid preparations include those pharmaceutical forms in which the compound is applied locally or topically by direct contact with the external surface to be treated. Conventional liquid pharmaceutical forms for this purpose include ointments, waxes, lotions, pastes, jellies, sprays, aerosols, colloidal suspensions and the like in aqueous or non- aqueous formulations. The term "ointment" refers to formulations including creams which are oleaginous, absorbative or water soluble, and include emulsion type bases such as petrolatum, lanolin, polyethylene glycols as well as mixtures thereof. Non-aqueous formulations include solutions containing solvents such as monoalcohols of from two to ten carbon atoms including ethanol and isopropanol, and diols such as ethylene glycol or propylene glycol. The liquid preparation can also include polymeric resins which upon evaporation of the solvent, will form films which hold the α-hydroxy fatty acid(s) against the corn or callus. The liquid preparation containing the α-hydroxy fatty acid compound can be administered by spraying, dabbing, swabbing or other means of applying the preparation to the corn or callus tissue.

The term "medicated device" refers to a combination of at least one α-hydroxy fatty acid, or salts, esters or mixtures thereof in a suitable delivery system where the active ingredient is dissolved or dispersed in a vehicle affixed to the skin. One of the more common medicated devices include plaster preparations attached to a carrier or backing material. The term "vehicle" broadly refers to any inert medium in which the active ingredient is administered, including but not limited to film-solvents, plasters, carriers or binders for the active ingredient.

The term "plaster" refers to any non-liquid vehicle which can be applied to the skin and which can hold an α-hydroxy fatty acid(s) against a corn or callus. Suitable plaster vehicles include plasters or preformed films based upon rubbers, acrylics, polysiloxanes, polyvinylalkylethers, gels or impregnated microporous membranes.

The term "plaster preparation" refers to a preparation of at least one α-hydroxy fatty acid, or salts, esters or mixtures thereof in a plaster vehicle. Preferably, the plaster preparation is self-adhering to the corn or callus. Alternatively, the plaster preparation can be cut to the size of the corn or callus and held in place with waterproof or water resistant tapes or bandages. In the most preferred embodiment, the plaster preparation containing an α-hydroxy fatty acid(s) and the plaster vehicle is attached to a carrier to form a medicated device. In the medicated device, the carrier or backing material, can impart occlusive properties and dimensional strength to the plaster preparation. The carrier can also provide dimensional stability to the plaster preparation against disintegration and/or tearing by external forces, such as shear forces exerted on the plaster from normal handling or from rubbing of the limb afflicted with the corn or callus. The carrier can be selected from a wide range of materials, especially those which can promote occlusion and hydration of the corn or callus, such as moleskin, cotton, a resin-impregnated woven cloth, flexible polyvinyl chloride film or a flexible polyester film. However, the plaster preparation can be designed to be highly occlusive without the need for the carrier to possess substantial occlusive properties. The carrier can be attached to the plaster preparation by lamination techniques, by coextrusion or by bonding the carrier onto the plaster preparation using adhesives.

The α-hydroxy fatty acid(s) are employed in amounts effective to treat the corn or callus tissue. The amount of α-hydroxy fatty acid(s) in a liquid can range from about 5 to about 25 percent (%) by weight, preferably from about 5 to about 15%. Where a medicated device is employed, the amount of α-hydroxy fatty acid(s) can range from about 15 to about 80 percent, more preferably from about 30 to 50 percent. The medicament can be topically applied according to a regimen effective to soften or loosen the corn or callus tissue for removal thereof from the body. Generally, the medicament can be applied to the tissue one or two times daily or for intermittent intervals such as for two to three times per week until the corn or callus is softened or loosened sufficiently for removal. Optionally, the corn or callus can be soaked in water or bathed before application of a medicament containing the α-hydroxy fatty acid.

Example: Guinea Pig Footpad Assay

The guinea pig is used as a model because the guinea pig footpad is composed of hyperkeratotic tissue. Three Hartley guinea pigs are used per treatment group. Either the right or left rear callused footpad is treated, and the opposite footpad serves as the untreated control. Within a treatment group, the same footpad is treated on the same animal. A small cotton pledget is saturated with 200 μl of 12% w/w of an α-hydroxy fatty acid in a colloidian based vehicle and then applied once to the treated footpad. For comparison, a commercially available, liquid corn/callus remover product containing 12.6% salicylic acid in the same colloidian based vehicle used for the α-hydroxy fatty acid, is used as a positive control for keratolytic action in this assay. No additional applications of the active ingredient are made to the footpad. The cotton pledget is occluded with several wrappings of a nonirritating tape and secured in place with an outer wrapping of a securing tape. The animals are housed unrestrained three to a cage in polycarbonate cages with contact bedding. The animals have free access to food and water throughout the entire experiment. Eighteen to twenty-four hours post-application, the bandages are removed with surgical scissors and the footpads examined for gross appearance of keratolytic activity. Daily examinations are made for one week after removal of the bandages. Vehicle control and sham (bandage only) control groups are included in the analyses. The Keratolytic Indices of the controls are between 0-1. Keratolysis was scored daily using the following subjective scoring scale:

0 = no visible difference between treated and control footpads. 0.5 = slight fine cracks in the callus of the treated footpads.

1 = large cracks and peeling on the edge of treated footpads.

2 = obvious separation of the stratum corneum over a small area of the treated footpad. 3 = separation of the footpad over a large area (greater than 1/2 the foot pad area) of the treated footpad. 4 = complete removal of stratum corneum from the treated footpad callus revealing new undamaged skin beneath. Daily scores are given to each animal. The average daily scores are then calculated for each treatment group. At the conclusion of the seven day evaluation period, the Keratolytic Index (Kl) is calculated using the following formula:

Kl = Maximum Average Daily Score X 10

Number of Days Required for the Average Score to Equal or Exceed Two

The Keratolytic Index can range from zero to 20. A Kl of zero indicates that the callus is unaffected by the treatment. A Kl of 10 indicates a strong keratolytic effect within 72 to 96 hours. A Kl of 20 indicates an extremely strong keratolytic effect within 48 hours. The data above indicates that the α-hydroxy fatty acids of the prevent invention exhibit a Kl between 6.7 to 11. Thus, the α-hydroxy fatty acids demonstrate a strong keratolytic effect by clear separation of the stratum corneum over a portion of the treated footpad area within 3 to 4 days. By comparison, salicylic acid, the commercial standard, with a Kl of 2.4, exhibits only a moderate keratolytic effect and is significantly less effective than the α-hydroxy fatty acids of the present invention.

Claims

CLAIMS:

1. A medicament for treating corns and calluses containing an effective amount of at least one saturated α-hydroxy fatty acid having 12 to 22 carbon atoms, or salts or esters thereof.

2. A medicament as claimed in claim 1 wherein the saturated α-hydroxy fatty acid is applied in a liquid preparation.

3. A medicament as claimed in claims 1-2 wherein the amount of saturated α-hydroxy fatty acid in the liquid preparation ranges from about 5 to about 25 percent by weight of the liquid preparation.

4. A medicament as claimed in claim 1 which is a medicated device comprising at least one saturated α-hydroxy fatty acid having 12 to 22 carbon atoms, or salts or esters thereof, admixed into a plaster preparation.

5. A medicament as claimed in claim 4 wherein the saturated α-hydroxy fatty acid is present in the plaster preparation in an amount ranging from about 15 to about 80 percent by weight of the plaster preparation.

6. A medicament as claimed in claims 1-5 wherein the saturated α-hydroxy fatty acid is α-hydroxy lauric acid (C-12), α-hydroxy myristic acid (C-14) or α-hydroxy stearic acid (C-18).

7. A method for treating corns and calluses, comprising contacting the affected area with a liquid preparation or medicated device containing an effective amount of at least one saturated α-hydroxy fatty acid having 12 to 22 carbon atoms, or salts or esters thereof, to effect softening or loosening of the corn or callus for removal thereof.

8. The method of claim 7 wherein the saturated α-hydroxy fatty acid is applied in a liquid preparation in an amount ranging from about 5 to about

25 percent by weight of the liquid preparation.

9. The method of claim 7 wherein the medicated device comprises at least one saturated α-hydroxy fatty acid having 12 to 22 carbon atoms, or salts or esters thereof in a plaster preparation.

10 . The method of claims 7-9 wherein the saturated α-hydroxy fatty acid isα-hydroxy lauric acid (C-12), α-hydroxy myristic acid (C-14) or α-hydroxy stearic acid (C-18).