A method and a product to reduce and treat problems associated with tinea pedis

Background of the invention

According to the principle of hydrophobicity in the laws of nature, the system will always strive for the lowest possible energy consumption. When two hydrophobic molecules touch each other, they will increase entropy and create disorder. The water molecules that surround the two hydrophobic molecules will force them to be brought together by hydrogen bonds between the water molecules, despite the absence of any attraction force between the hydrophobic molecules, and the water molecules will be pushed away.

Numerous studies over the past few decades have shown that the bacteria, yeast Candida albicans and the fungus Trichophyton rubrum commonly show deep cell surface hydrophobicity. Several structures have been defined that make the cell surface hydrophobic, such as Escherichia coli fimbria, which affect adhesion to the intestinal wall, proteins on C. albicans and T. rubrum, which are called "hydrophobins", and lipoteichoic acid in the cell wall of Gram-positive bacteria.

The initial stage in skin and mucosal surface infections is the adhesion of microorganisms to wounded tissues. Several microbiological components have been identified that bind adhesively to specific receptors. Initial adhesion can be regulated by hydrophobic interactions between microorganisms and host tissue structures, as well as by

EP 2 326 296 impacts of charges. Binding of extracellular matrix and serum proteins like fibronectin, collagen and fibrinogen may further increase the colonization of deeper wound tissues. Using the SORBACT® principle described in patent application W02006062470, assigned to the same group as the invention, products such as the SORBACT® insert consist of complex acetate gas and cotton gauze treated with a DACC fatty acid ester (dialkyl carbamoyl chloride). This provides SORBACT® insoles with strong hydrophobic properties. When the SORBACT® insert comes into contact with pathogenic microorganisms on the wound surface, the microorganisms adhere to the insert due to hydrophobic interactions. The method is based on the principle that two hydrophobic surfaces bond together when physically in contact with each other. The SORBACT® insert consists of two components. The first component has one or more liquid-permeable layers of a hydrophobic, bacteria-absorbing, physiologically harmless material containing a woven or non-woven hydrophilic structure. The structure was made hydrophobic by chemical treatment with a compound containing hydrophobic groups. The second component consists of one or more layers of hydrophilic, fluid absorbing, physiologically harmless material. The hydrophilic, fluid-absorbing material affects the flow of fluid by aspirating exudate from the wound. If the microorganisms have hydrophobic surface structures, they will accompany this flow of fluid, will come into contact with the hydrophobic component and bind to it.

Another antimicrobial property of SORBACT® is its cationic activity. The outer membranes of the outer membranes of mammalian cells are usually neutral. Hence, the positively charged SORBACT® material preferentially binds to the membranes of microorganisms (negatively charged) and lifts them together. US patent application SN 10 / 559.464 (publication number 2006/0163149) relates to an absorption product in which the hydrophobic unit and the positively charged unit are connected to a support matrix. In this way, the hydrophobic unit can be connected using polyethyleneimine. Preferred areas of application according to the prior art are filters, face masks, wound dressings, nasal sprays and drapes for use during surgical interventions, etc. However, in contrast to the present invention, no mention is made of the treatment of interdigital foot fungus or the attachment of hydrophobic material to foam or the like.

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Athlete's foot (interdigital mycosis stop) is a common name given to skin fungal infections that occur primarily between toes, but can occur anywhere on the foot. The term 'athlete's foot' is a very misleading word, as the condition is not only found in athletes. It is caused by one of four dermatophytes, most often it is Trichophyton rubrum, which is a microscopic fungus that lives on dead hair tissue, toenails and outer layers of the skin. The mushroom likes warm, humid environments, including shoes, socks, public shower floors, changing rooms and swimming pools. The athlete's foot is transmitted by contact with injury or abrasion on the bottom surface (bottom) of the foot. Infection causes raised, round pimples or blisters.

There are four common forms of athlete's foot. The most common is persistent itching of the skin on the soles of the feet or between the toes. As the infection progresses, the skin becomes soft. The central area of ​​infection is inflamed and sensitive to touch. Gradually, the edges of the infected area become milky white and the skin begins to peel. Slight watery exudate may also occur.

The second form is ulcerative. In this form, exfoliation of the skin worsens. Large cracks appear in the skin, making the patient susceptible to secondary bacterial infections. Infection can spread to other parts of the body through scratches or contamination of clothing and bedding.

The third type of infection is often referred to as "moccasin mycosis". In this type, the red rash spreads across the bottom of the foot, creating a moccasin pattern. The skin in this area gradually becomes coherent, white and scaly.

Finally, the fourth form of foot mycosis is inflammatory or follicular in which a series of raised bumps or thickening of the skin develops on the lower foot, typically in the head region of the metatarsal bone. Itching is intense and there is less peeling of the skin.

In people with acute fungal infections, similar foci may occur on the hands, usually on the hands. The Trichophyde reaction, also known as tineas manuum, is the immune system's response to fungal antigens (antibodies that fight fungal infection).

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Ringworm has proved difficult to remove and often recurs. Infections may disappear on their own or persist for years. The best results are obtained with early treatment before the fungal infection is well established. Antifungal drugs have been used in the past. In the early "mild" cases, imidazole class drugs were used to combat fungal infections, which attack the fungal cell wall enzymes and inhibit growth and multiplication. Examples of such drugs include clotrimazole (LOTRIMIN®) and miconazole (contained in LOTRIMIN® and ABSORBINE JR®). They are applied topically and rubbed into the skin. They must be reused every few hours during the weeks.

More difficult cases may require the use of allylamines. These drugs contain terbinafine (contained in the preparation LAMISIL®) and naphthephine (NAFTIN®) and are available without a prescription. The most difficult cases should be treated with drugs such as griseofulvin (FULVICIN® and GRISACTIN®) and concentrated forms of terbinafine and itraconazole. Griseofulvin can cause side effects such as headaches, nausea and numbness, so it is used as a last resort.

These therapies are not without flaws. Topical treatment requires many days, if not weeks. Often, the ailments occur in those areas of the skin of the feet that are in frequent contact with the friction with the patient's clothing or other skin surfaces. As a result of this frictional contact, topically applied drugs may be easier removed from the affected areas of the patient's foot. In addition, topical medications are more susceptible to moisture that is present on the surface of the affected skin. These difficulties mean that treatment is significantly reduced because the medicine does not stay in place for a sufficient period of time. As a result, the effectiveness of treatment is significantly reduced, and the patient often has to re-apply the drug so that the area receives the correct treatment. In addition, the discomfort associated with bandages, due to the constant or frequent movement and bending of the skin, the small surface that is usually affected (such as toes), friction and humidity make bandages impractical to minimize the contact of the type of friction that occurs in the affected diseased areas of the foot in place for extended periods of time. In other words, topical drugs mean troublesome creams and lotions. As for internal medicine, a problem

EP 2 326 296 is that they can cause side effects including headaches, nausea and in extreme cases organ damage.

Overlays for the treatment of athlete's foot have not previously been described in the literature, while patches with dressing are known for the treatment of fungal infections of the toes and nails, e.g. WO-A-99/40955, US Patent No. 5,753,256 and US Patent Applications US20040265362, US20040161452 and US5464610.

The invention described in US Patent Application 20030068331 relates to biological dressings based on rubber resins or other film-forming agents that adhere to the skin and contain one or more pharmacologically active agents to treat symptoms associated with the athlete's foot. The biological dressing contains an adhesive film, rubber resin or other agent that forms a film on the skin and a pharmacologically active agent. This is in contrast to the present invention, in which the dressing is in the shape of a dog's ring or bone, does not stick and is removed. In addition, the invention does not contain any pharmacologically active substances, as the effectiveness is the result of a hydrophobic action in combination with the separation of the toes.

There are many different types of foot toe splitters commercially available from foot care manufacturers. They are usually made of differently shaped pieces of silicone, felt or foam material that can be impregnated with soothing oils or aromatic substances. They are inserted separately between the toes that rub against each other to prevent friction between the toes. They may have the shape of a ring, as in the invention, but toe separators are only used to separate toes. They only give a drying effect, not both a drying effect and removal of the fungus.

Round cushions for placement on the prints are known, for example "Round Callus Cushions" sold by DR. SCHOLL. In contrast to the present invention, such cushions do not attach foam material with a hydrophobic fabric attached thereto, nor are they intended to be placed around the finger.

There are many patents and patent applications describing dehumidifying devices to prevent the occurrence of an athlete's foot, e.g. DE10020989, US3943922 A and US5497789. However, unlike the invention, it works

Antifungal activity is caused by drying of the surface separators between the toes of the foot and not the removal of microorganisms by means of a hydrophobic action.

Patent application W02004017881 discloses a moisture absorbing soft sleeve for applying to the toe for the treatment of an athlete's foot.

The sleeve is made of wood or cotton. The disadvantage of the invention is that the sleeve is only effective when it is dry. Unfortunately, under conditions of humidity, microorganisms can multiply.

Consequently, there is a need for alternative treatment of the athlete's feet without the use of antimicrobial substances, such that, due to their perfect fit, remains at the treatment site for a sufficient period of time, which reduces the spread or transmission of a fungal infection, and which provides quick, effective relief of foot symptoms the athlete.

Applicants have surprisingly found that the ring-shaped toe pad, consisting of a hydrophobic material with a foam layer, described in patent application US2008 / 0177214, meets this need. The invention is not limited only to a ring-shaped product, but applies to all toe pads consisting of a hydrophobic material with a foam layer, trimmed to give a perfect fit around the area affected by athlete's foot, e.g. bone-shaped toe caps for a dog.

Due to the perfect fit, the product according to the invention may come in close contact with the affected area for effective treatment. Simultaneously with the removal of the fungus, it acts as a toe separator, providing space between the toes of the foot so that the affected area will be ventilated and dried. The use of moisture-absorbing foam attached to a hydrophobic material increases the drying effect. This material was disclosed by applicants and described in US 2008/0177214. Unlike commercially available topical medications that are more susceptible to moisture, the invention provides a significantly more effective treatment for the athlete's foot.

The product is held in place by ordinary socks and can be used with ordinary footwear. Accordingly, the patient may be charged with 7

EP 2 326 296 save the discomfort of bandages associated with displacement, friction and moisture.

In addition, because the treatment and prevention methods of the invention provide a stronger physical barrier to affected skin areas, the risk of spreading or transmitting a fungal infection to other areas of the patient's body or to other persons is significantly reduced. The invention therefore provides significant public health benefits.

Short description of the drawings

Figure 1 is a perspective view of the ring-shaped toe cap of the present invention.

Brief description of the invention

The invention provides treatment that helps reduce foot mycosis and is safe and easy to use. Another object of the invention is to provide treatment using a round toe pad made of rubber foam attached to a hydrophobic material for removing the T. rubrum fungus. The toe cap of the invention according to claim 1 has the shape of a ring and has notches extending deep into the toe from the center wheel in the toe cap.

The objects and features of the invention will become more apparent from the following disclosure and the appended claims.

Detailed description of the invention and its preferred embodiments The product according to the invention is ideal for treating athlete's foot.

Reduces the number of T. rubrum without the use of antimicrobial substances. The product of the invention consists of two combined layers: a woven hydrophobic cellulose acetate that binds microorganisms and an attached layer of rubber foam.

The article of the toe cap according to the invention for the treatment and prevention of onychomycosis includes a hydrophobic layer made of a material selected from the group consisting of: a hydrophobic fabric, a hydrophobic nonwoven which has been made hydrophobic by chemical treatment with a compound containing hydrophobic groups or a hydrophobic perforated film; attached to the foam layer to create a toe cap. Each toe cap is round with an outer diameter and has a central circle cut from the hydrophobic layer and the attached foam layer. A number of incisions extend deep into 8

EP 2 326 296 foot pads, each with incisions extending from the central circle at regular intervals around the central circle.

Referring to the figure, Fig. 1 shows the hydrophobic layer (1), the foam layer (2) and the cuts (3). The cuts are preferably made in 6 positions, at regular intervals. Each cut (3) is preferably 6 mm long. When placed on the toe, the cuts allow the toe cap to be left in closer contact with the skin. The incisions also make the product adapt to different thicknesses of the toes.

The hydrophobic layer (1) is directed towards the infection area. Hydrophobic fabrics and nonwovens can be made of synthetic fibers or fibers such as polyamide, polypropylene and polytetrafluoroethylene, or carbon fibers. To obtain a hydrophobic material from a hydrophilic fabric or nonwoven, such as a cotton fabric or nonwoven, the fabric can be chemically treated, e.g., in a known manner, with a hydrophobic group containing compound, e.g. DACC (carbamoyl dialkyl chloride), such as dihexadecyl carbamoyl chloride or dioctadecyl carbamoyl chloride, or alkyl ketene dimer (AKD).

A preferred hydrophobic layer according to the invention is made of green cellulose acetate, to which dialkyl carbamoyl chloride has been used, as discussed in the example.

The hydrophobic layer is attached to the foam layer with a suitable adhesive, for example 9L8 (Protechnic Sweden). Other adhesives known in the art can also be used. The foam can be based on, for example, polyether, polyester and cellulose.

Mushrooms will be removed when changing the dressing. Hence, the number of microorganisms decreases over time to a number that the body can control and the wound can heal. As microbes adhere to the dressing due to hydrophobic interactions, the spread of microorganisms into the environment is limited when the dressing changes. In this way, the load on the affected surface of the fungus is quickly and effectively reduced. The body's defense mechanism can then take control, and natural healing processes can be continued. The use of a hydrophobic layer, even without systemic antibiotic therapy, reduces the number of attacking fungi, but does not remove all bacteria, which is an advantage because a small number of microorganisms

EP 2 326 296 stimulates healing. The invention replaces the use of topical drugs and thereby reduces the spread of resistant organisms.

An alternative way to lift microbes, e.g. from a wound, is an electrostatic solution, e.g. a positively charged unit, such as described in US Patent Application No. 2006/0163149. The positively charged unit is used together with the foam layer. A further way to lift microbes is to use a hydrophobic method in combination with an electrostatic method along with a foam layer.

Other objects and features of the invention will become more apparent from the following examples and the appended claims.

Example 1

Manufacture of a wound dressing product with foam as a moisturizing matrix.

In this example, a ring-shaped foot pad according to the invention is produced in the following manner:

materials:

<td>LAYER</td><td>COMMERCIAL NAME PRODUCT</td><td>MANUFACTURER</td>

<td>1. Hydrophobic layer</td><td>Green cellulose acetate fabric (Green Cellulose acetate) obtained according to US 4,617,326</td><td>ABIGO MED ICAL AB Sweden</td>

<td>2. Glue</td><td>9L8</td><td>Protechnic, France</td>

<td>3. Moisturizing foam</td><td>Vivo PCF 03</td><td>Corpura, the Netherlands</td>

The hydrophobic layer is preferably produced according to US Patent No. 4,617,326 by treating cellulose acetate fabric with some amount of carbamoyl dialkyl chloride as disclosed in this patent to form a covalent bond between materials.

Acetate fabric comes in rolls with a width of 1 m, and as such goes to the next stage.

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The adhesive component is applied to the foam material under pressure (maximum 5 bar) at a maximum temperature of 90 ° C and in an amount of &lt;30 g / m2², preferably at 20 g / m2².

The hydrophobic layer (1) and foam layer (2) currently bonded together are cut into suitable pieces having the dimensions of the final product. The foot pad is punched out in the form of a circle, preferably in diameter

4.2 cm. In the center of the round overlay, a circle is cut out, 1.2 cm, which gives the overlay the shape of a ring. From the inside, the ring is cut in 6 positions, which gives 6 cuts (3) at regular intervals. Each cut (3) is 6 mm long 10 guests. The product is sterilized (Isotron Gamma Irradiation, The Netherlands).

Example 2

A prospective study of the topical treatment of fungal infections between the fingers in diabetic patients.

Twenty patients with diabetes were enrolled in the open prospective study, with the help of a diabetic leg specialist in a diabetic foot clinic at the NAL hospital in Sweden. Patients were scheduled for regular follow-up visits to a leg disease specialist. Inclusion criteria were clinically identified local fungal infections between the fingers. Patients were treated once a day using a ring-shaped toe cap manufactured by Abigo Medical AB, Sweden.

During the patients' first visit to the clinic, infection was assessed in hospitalized patients, swabs were collected for breeding, and photographs of infected areas were taken. The researcher put an overlay on the toe, and patients were carefully instructed in the application and self-hygiene of the foot between controls. Patients were re-admitted to the clinic on days 5 and 10 in connection with the assessment in the conditions of hospitalization, fungal culture and photographic control.

Results:

The photos were evaluated by an independent observer under the blank conditions, according to the protocol. Clinical and visual evaluation was carried out in the conditions of hospitalization and using images consistent with the previously developed evaluation protocol. All twenty patients completed the study. No side effects have been reported.

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Microbiology. Samples for fungal culture were collected on days 1, 5 and 10. Microbiological findings showed wide variability for the different fungi present in the treated area:

Trichophyton, Penicillium, Fusarium, Trichosporon, Dermathophyta and Candida.

Photo rating. Photographs of the changes were taken by the researcher on days 1, 5 and 10, and the blind assessment was carried out by an independent researcher, shown in Table 1.

Table 1

<td>Rating</td><td>Day 5</td><td>Day 10. (%)</td>

<td>Deterioration</td><td>2 patients</td><td>1 patient (5)</td>

<td>No change</td><td>7 patients</td><td>4 patients (20)</td>

<td>Improvement</td><td>11 patients</td><td>5 patients (25)</td>

<td>healing</td><td>0 patients</td><td>10 patients (50)</td>

<td>Not subject to evaluation</td><td>0 patients</td><td>0 patients (0)</td>

Seventy-five percent (75%) of patients had right or healing after ten days of treatment. Twenty percent (20%) showed no change, and five percent (5%) worsened. Table 1. After 10 days, the cured patients had negative mushroom cultures.

The researcher found that the ring-shaped foot pad was very easy to use in all patients.

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