EP3074005A2

EP3074005A2 - Composition for dermatitis

Info

Publication number: EP3074005A2
Application number: EP14811758.3A
Authority: EP
Inventors: Flemming Licht
Original assignee: Unigroup ApS
Current assignee: Unigroup ApS
Priority date: 2013-11-25
Filing date: 2014-11-24
Publication date: 2016-10-05
Also published as: WO2015074667A2; WO2015074667A3

Abstract

The invention relates to a composition for the treatment of Diaper Dermatitis (DD) and Seborrheic Dermatitis (SD), including Infantile Seborrhoeic Dermatitis (ISD). In particular, it concerns a composition comprising ethyl lactate for the treatment of DD.

Description

Composition for Dermatitis

The present invention relates to a composition for the treatment of Dermatitis, such as Diaper Dermatitis (DD) and Seborrheic Dermatitis (SD), such as Infantile Seborrhoeic Dermatitis (ISD). In particular, it concerns a composition comprising ethyl lactate for the treatment of DD. Technical Background

The damaging potential of wearing diapers on skin integrity is a known problem in pediatric dermatology (Berg RW. Etiology and pathophysiology of diaper dermatitis. Adv Dermatol 1988;3:75- 98). The skin in the diapered area, including the buttocks, genitals, abdomen, and thighs, is prone to the development of irritant Diaper Dermatitis (commonly referred to as "diaper dermatitis" or "nappy dermatitis"), which clinically manifests with erythema (Visscher MO, Chatterjee R, Munson KA et al Changes in diapered and nondiapered infant skin over the first month of life. Pediatr

Dermatol 2000;17:45-51).

Diaper Dermatitis (DD) represents the most common dermatologic disease that affects infants (Ward DB, Fleischer AB Jr, Feldman SR et al. Characterization of diaper dermatitis in the United States. Arch Pediatr Adolesc Med 2000;154:943-946). The incidence of DD is highest in those between 8 and 12 months of age (Wolf R, Wolf D, Tuzun E, et al. Diaper Dermatitis. Clin Dermatol 2001; 18: 657-60). There are no differences in the prevalence between genders or race, although breastfed babies may have a reduced risk (Singleton JK. Pediatric dermatoses: three common skin disruptions in infancy. Nurse Pract 1997; 22: 32-50 and Levy M. Diaper rash syndrome or dermatitis. Cutis 2001; 67: 37-38). The enzymes in feces (protease and lipase) may irritate baby's tender skin. In addition, feces contain organisms that can cause skin infection. Urine further irritates the diaper area. As urine breaks down, it releases ammonia. This causes the pH of the skin to rise (in other words, to become increasingly basic, or alkaline) and the enzymes from baby's stool to become more active. This may result in tissue/skin damage and lead to diaper rash. Contributing factors to the acute inflammatory condition include skin occlusion and friction , lipolytic and proteolytic activity of fecal enzymes, and excessive moisture as well as increased pH related to the prolonged exposure to urine. The combined action of these factors may compromise the skin barrier and increase susceptibility to further attack by enzymatic activity and chemical irritants as well as to secondary bacterial or fungal infections, frequently involving Candida spp. and Staphylococcus aureus. The incidence of Diaper Dermatitis correlates with the occurrence of diarrhea and frequency of diaper changes (Stamatas GN, Zerweck C, Grove G, Martin KM. Documentation of Impaired Epidermal Barrier in Mild and Moderate Diaper Dermatitis In Vivo Using Noninvasive Methods. Pediatr Dermatol 2011; 28: 99-107).

Excessive skin hydration is of particular significance for the diaper area, because it increases skin permeability and leaves skin susceptible to frictional damage and microbial invasion (Zimmerer RE, Lawson KD, Calvert CJ. The effects of wearing diapers on skin. Pediatr Dermatol 1986; 3: 95-101). Diaper Dermatitis is characterized by compromised stratum corneum (SC) barrier function as indicated by increased transepidermal water loss (TEWL) and also by increased skin hydration.

Furthermore, high TEWL values have been associated with an increase in the activity of proteolytic enzymes in the SC such as trypsin-like kallikreins, tryptase like serine protease, plasmin, and urokinase (Voegeli R, Rawlings AV, Doppler S et al. Increased basal transepidermal water loss leads to elevation of some but not all stratum corneum serine proteases. Int J Cosmet Sci 2008; 30: 435-42). In contrast to dry skin conditions where an inverse relationship between TEWL and skin hydration values exists (Tagami H, Yoshikuni K. Interrelationship between water barrier and reservoir functions of pathologic stratum corneum. Arch Dermatol 1985; 121:642-45) Stamatas et al. reported that in Diaper Dermatitis both TEWL and skin hydration are elevated, which is approximating conditions of fresh wound.

Diaper Dermatitis causes emotional stress for infants, as indicated in a study on infant behavior during and after an episode of DD. Parents reported an increase in the frequency of crying as the first symptom of pain together with agitation. Other behavioral indicators of distress, such as facial expressions (eyes squeezed shut, deepening of the nasolabial furrow), were more prevalent, normal eating habits and sleeping patterns were disrupted, and the frequency of urination and defecation diminished. Levels of salivary Cortisol, a molecular indicator of stress, also increased in some infants during the period with DD (Stamatas GN, Tierney NK. Diaper Dermatitis: Etiology, Manifestations, Prevention, and Management. Pediatr Dermatol 2014; 31: 1-7).

The most effective treatment of Diaper Dermatitis, although not the most practical, is to discontinue use of diapers, allowing the affected skin to air out. Thorough drying of the skin before diapering is a good preventive measure because it is the excess moisture, either from urine and feces or from sweating, that sets the conditions for a diaper rash to occur. Various moisture-absorbing powders, such as talcum or starch, reduce moisture but may introduce other complications. Airborne powders of any sort can irritate lung tissue, and powders made from starchy plants (corn, arrowroot) provide food for fungi and are not recommended by the American Academy of Dermatology.

Combinations of mild to midpotency corticosteroids and antifungal drugs have been prescribed to treat Diaper Dermatitis. However, prescribing corticosteroids to infants raises concerns because the relatively higher body surface to volume ratio for young children creates the potential for suppression of the HPA axis, a complex set of direct influences and feedback interactions among three endocrine glands: the hypothalamus, the pituitary gland, and the adrenal glands. This side effect is reported to occur even with corticosteroids regarded as midpotent ("Diaper Dermatitis: A Therapeutic Dilemma. Results of a Double-Blind Placebo Controlled Trial of Miconazole Nitrate 0,25 %").

Zinc oxide-based ointments may be effective in certain cases, especially in prevention of diaper dermatitis, because they have both a drying and an astringent effect on the skin, being mildly antiseptic without necessarily causing irritation. Unfortunately treatment with zinc oxide-based ointments introduces a risk of drying out the skin and thus does not provide an optimal treatment of diaper dermatitis.

Zinc oxide-based sprays suffer from the drawback of having a thick viscosity, requiring subsequent distribution by rubbing in on the sensitive skin. Further, such existing sprays require shaking of the spray container before use, and the spray leaves a white residual after use.

In addition hereto not all patients respond to skin protective agents, like zinc oxide ("Diaper Dermatitis: A Therapeutic Dilemma. Results of a Double-Blind Placebo Controlled Trial of Miconazole Nitrate 0,25 %").

According to "Adult Seborrheic Dermatitis - A Status Report on Practical Topical Management" (J Clin Aesthet Dermatol. 2011 May; 4(5): 32-38, by James Q. Del Rosso) Seborrheic dermatitis (SD) is a chronic inflammatory skin disorder characterized in immunocompetent adult patients by periods of exacerbation and remission. The reported prevalence of SD in the overall adult population ranges from 1 to 5 percent, and the disorder can affect any ethnicity. There is a transient infantile form of SD that presents and resolves within the first 3 to 4 months of life; however, some cases may be more persistent with recurrences over several months. Infantile SD may be limited to scalp involvement ("cradle cap") or may be more diffuse. The adult form of SD, which is far more common than infantile SD and appears to affect men more than women, may present first around puberty, correlating with the increase in cutaneous lipids resulting from androgen-driven sebaceous gland development and sebum secretion. The course of adult SD in affected individuals is variable throughout adulthood with some noting only occasional periods of exacerbation and others experiencing greater chronicity with more frequent recurrences.

Seborrheic dermatitis is a common complaint brought to pediatricians. Also known as "cradle cap" in infants and "dandruff" in adolescents, the condition is believed to be triggered by Malassezia yeasts ("Use of Olive Oil for the Treatment of Seborrheic Dermatitis in Children" by Elaine Siegfried and Erica Glenn, Arch Pediatr Adolesc Med. 2012;166(10):967, citing "The role of sebaceous gland activity and scalp microfloral metabolism in the etiology of seborrheic dermatitis and dandruff" by o Bl, Dawson TL, J Investig Dermatol Symp Proc. 2005;10(3):194-197). While oil application may be risk free, a potential concern arises when considering a possible Malassezia virulence factor regulated by its metabolic lipid pathways. In vivo, Malassezia digests sebum into saturated and unsaturated fatty acids. Only the saturated molecules are essential while the unsaturated fatty acids are a by-product. Organic oils (such as olive oil) contain both saturated and unsaturated lipids and may be

counterproductive to treat a condition whose etiology is linked to Malassezia. In fact, olive oil is a standard in vitro culture media for Malassezia. Saturated fatty acids likely encourage Malassezia overgrowth and excess unsaturated fatty acids may induce inflammation and scaling (Siegfried, supra).

In contrast to this, the letter "Borage oil, an effective new treatment for infantile seborrhoeic dermatitis" (Br J Dermatol. 1993 Jul;129(l):95, Tollesson A and Frithz A) describes treatment of Infantile Seborrhoeic Dermatitis (ISD) with borage oil. The authors note that "The finding that the dermatitis also cleared from areas not treated with the oil suggests that it was absorbed". The article "Transepidemal Water Loss and Water Content in the Stratum Corneum in Infantile Seborrhoeic Dermatitis", Acta Derm Venereol (Stockh) 1993, 73, 18-20 describes treatment of Infantile Seborrhoeic Dermatitis with topically applied borage oil (containing 24% gamma-linolenic acid).

According to Wikipedia, borage seed oil is derived from the seeds of the Borago officinalis (borage). Borage seed oil has one of the highest amounts of gamma-linolenic acid (GLA) of seed oils— higher than blackcurrant seed oil or evening primrose oil, to which it is considered similar. The oil comprises around 24% of GLA typically. GLA is converted to dihomo-gamma-linolenic acid, a precursor to a variety of the 1-series prostaglandins and the 3-series leukotrienes.

Summary of the invention As noted, existing treatments of dermatitis, such as DD, is associated with drawbacks. According to an aspect the present invention concerns a composition comprising ethyl lactate, for use in the treatment, prophylaxis or alleviation of symptoms of dermatitis. Without being bound by theory, it is speculated that ethyl lactate may stabilize the pH of the skin, thereby alleviating symptoms of dermatitis, in particular DD.

It appears the use of ethyl lactate provides a number of advantages as compared to existing treatments. The skin does not become dry; rather, ethyl lactate provides a natural level of moisture. Further, ethyl lactate provides a barrier against contaminants leading to DD. In addition, the application of ethyl lactate does not leave a visible residual after use.

Known treatment of dermatitis such as ISD with borage oil suffer from the drawback that borage oil is greasy, leading to problems with patient compliance and inconvenience upon application. It has now surprisingly been discovered that compositions according to the present invention provide improved penetration, as well as a less greasy texture of the composition as compared to borage oil. This leads to improved ease of application as well as improved patient compliance. It has further surprisingly been discovered that compositions according to the present invention reduces, inhibits and/or does not allow proliferation of strains of Malassezia. It appears that Squalane dissolves glue formed by dry sebum. Squalane has similar properties as liquid sebum, meaning it dissolves dry sebum at the scalp so it can be washed away. Without being bound by theory it is speculated that a mixture of Squalane and borage oil provides improved and faster penetration of borage oil and improved dissolution of dry sebum. It may further be speculated that the combination of Squalane and borage oil provides an increased reduction of TEWL. Thus, the combination may provide a synergy effect.

It has been speculated that ISD is caused by the lack of or non-function of the enzyme delta-6- desaturase (D-6-D). Thus, GLA has been proposed used to circumvent this lack or non-function. However, after applying GLA, the metabolism of GLA takes time. In order to restore the balance of the skin faster and provide more immediate relief of symptoms, the present compositions are provided.

It seems that borage oil has not been used successfully for the oral treatment of ISD. It is not known whether this is due to lack of clinical experimentation, or because GLA administered orally is broken down or accompanied by side effects, or its metabolism is too fast to provide effective treatment.

Without being bound by theory, it is speculated that compositions of the present invention may act as depot formulations, slowly releasing any actives from the skin.

According to an aspect, the present invention concerns a composition comprising Squalane and gamma-linolenic acid (GLA).

According to an aspect, the present invention concerns a method of manufacture of a composition, comprising mixing Squalane, gamma-linolenic acid (GLA) and vitamin E. The addition of vitamin E surprisingly appears to prevent precipitate in forming upon mixing Squalane and borage oil. According to an aspect, the present invention concerns a use of Squalane and GLA for the manufacture of a medicament for the treatment, prophylaxis or alleviation of symptoms of

Dermatitis, such as Diaper Dermatitis (DD) and Seborrheic Dermatitis (SD).

According to an aspect, the present invention concerns the treatment, prophylaxis or alleviation of symptoms of DD and SD comprising application of a composition according to the invention.

Detailed Disclosure

According to an embodiment, the invention concerns a composition comprising ethyl lactate, for use in the treatment, prophylaxis or alleviation of symptoms of dermatitis. Without being bound by theory, it is speculated that ethyl lactate may stabilize the pH of the skin, thereby alleviating symptoms of dermatitis.

According to another embodiment, the invention concerns the composition, wherein said use is for treatment, prophylaxis or alleviation of symptoms of an indication selected among Diaper Dermatitis (DD), Atopic Dermatitis and Seborrheic Dermatitis (SD).

According to an embodiment, the invention concerns the composition for use in the treatment, prophylaxis or alleviation of symptoms of Diaper Dermatitis (DD). Without being bound by theory, it is speculated that ethyl lactate may counteract the pH effect of urine and feces.

According to an embodiment, the invention concerns the composition for use in the treatment, prophylaxis or alleviation of symptoms of Seborrheic Dermatitis (SD).

According to an embodiment, the invention concerns the composition for use in the treatment, prophylaxis or alleviation of symptoms of Infantile Seborrheic Dermatitis (ISD).

According to an embodiment, the invention concerns the composition for use in the treatment, prophylaxis or alleviation of symptoms of an indication selected among the group consisting of dandruff and cradle cap.

According to an embodiment, the invention concerns the composition comprising 1% - 50%, preferably 2% - 40%, more preferred 3% - 30%, preferably 4% - 25%, more preferred 5% - 20%, preferably 7% - 15%, more preferred about 10% ethyl lactate.

According to an embodiment, the invention concerns the composition further comprising kigelia.

According to an embodiment, the invention concerns the composition further comprising kigelia oil.

According to an embodiment, the invention concerns the composition comprising 1% - 50%, preferably 2% - 40%, more preferred 3% - 35%, preferably 5% - 30%, more preferred 7% - 25%, preferably 10% - 20%, more preferred about 15% kigelia oil.

According to an embodiment, the invention concerns the composition comprising 0.5% - 15%, preferably 1% - 10%, more preferred 2% - 5%, preferably 2.5% - 4%, more preferred about 3% kigelia.

According to another embodiment, the invention concerns ethyl lactate for use in the treatment, prophylaxis or alleviation of symptoms of dermatitis. According to an embodiment, the invention concerns the ethyl lactate, wherein said use is for treatment, prophylaxis or alleviation of symptoms of an indication selected among Diaper Dermatitis (DD), Atopic Dermatitis and Seborrheic Dermatitis (SD).

According to an embodiment, the invention concerns the ethyl lactate for use in the treatment, prophylaxis or alleviation of symptoms of Diaper Dermatitis (DD).

According to an embodiment, the invention concerns a composition comprising Squalane and gamma-linolenic acid (GLA).

GLA may be obtained from vegetable oils such as GLA safflower oil (Carthamus tinctorius), evening primrose (Oenothera biennis) oil, blackcurrant seed oil, borage oil, and hemp seed oil. GLA is also found in edible hemp seeds, oats, barley, and spirulina. Each contains varying amounts of the fatty acid, with GLA safflower oil at 40% GLA being a concentrated form. This is a genetically modified oil. It should be noted that conventional safflower oils have zero GLA. Borage oil ranges from 15% to 20% and evening primrose oil ranges from 8% to 10% GLA.

According to an embodiment, the invention concerns a composition, further comprising at least one fat-soluble ingredient.

According to an embodiment, the invention concerns a composition, further comprising vitamin E.

According to Wikipedia, Vitamin E refers to a group of eight fat-soluble compounds that include both tocopherols and tocotrienols. The eight compounds are alpha-tocopherol, beta-tocopherol, gamma- tocopherol, delta-tocopherol, alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, and delta- tocotrienol.

It has been discovered that Squalane and GLA upon mixing may lead to a precipitate or a phase different from the mixture of Squalane and GLA. Surprisingly, it has been discovered that this precipitate or different phase tends not to form in the presence of Vitamin E.

According to an embodiment, the invention concerns a composition, further comprising Rosemary Extract. Rosemary Extract is also known as rosmarinus officinalis I. extract, with CAS Number: 84604- 14-8.

According to an embodiment, the invention concerns a composition, further comprising vitamin E and Rosemary Extract. Using vitamin E and Rosemary Extract appears to provide a synergy effect on the stability of the composition. According to an embodiment, the invention concerns a composition comprising gamma-linolenic acid (GLA), vitamin E and Rosemary Extract, and optionally at least one fat-soluble ingredient. Vitamin E and Rosemary Extract appear to stabilize GLA.

According to an embodiment, the invention concerns a composition, further comprising Sunflower oil. According to an embodiment, the invention concerns a composition, further comprising Rosemary Extract and Sunflower Oil. Sunflower oil is a suitable carrier for Rosemary Extract. According to an embodiment, the invention concerns a composition, comprising at least one compound selected among a tocopherol and a tocotrienol, or a pharmaceutically acceptable salt thereof.

According to an embodiment, the invention concerns a composition, comprising at least one compound selected among the group consisting of alpha-tocopherol, beta-tocopherol, gamma- tocopherol, delta-tocopherol, alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, and delta- tocotrienol, or a pharmaceutically acceptable salt thereof.

According to an embodiment, the invention concerns a composition, comprising at least one tocopherol selected among a natural tocopherol and a synthetic form of tocopherol. According to an embodiment, the invention concerns a composition, comprising an ingredient selected among safflower oil, evening primrose oil, blackcurrent seed oil, borage oil, and hemp seed oil.

According to an embodiment, the invention concerns a composition comprising an ingredient selected among borage oil, evening primrose oil and blackcurrant oil. According to an embodiment, the invention concerns a composition comprising borage oil.

Borage oil is a preferred source of GLA. Borage seed oil is a particularly preferred source of GLA. Other suitable sources of GLA may be utilized.

According to an embodiment, the invention concerns a composition comprising 1% - 99%, preferably 5% - 95%, more preferred 10% - 90%, preferably 20% - 80%, more preferred 30% - 70%, preferably 40% - 60%, more preferred 50 % borage oil.

According to an embodiment, the invention concerns a composition comprising 1% - 99%, preferably 5% - 95%, more preferred 10% - 90%, preferably 20% - 80%, more preferred 30% - 70%, preferably 40% - 60%, more preferred 50 % Squalane.

According to an embodiment, the invention concerns a composition comprising 0.1% - 25%, preferably 0.5% - 20%, more preferred 1% - 15%, preferably 3% - 10%, more preferred 5% vitamin E.

According to a preferred embodiment, the invention concerns a composition, comprising 0.05% - 10%, preferably 0.1% - 5%, more preferred 0.2% - 2%, preferably 0.3% - 1%, more preferred 0.5% vitamin E.

According to an embodiment, the invention concerns a composition, comprising 0.001% - 10%, preferably 0.005% - 5%, more preferred 0.007% - 2%, preferably 0.01% - 1%, more preferred 0.02% - 0.5%, preferably 0.03% - 0.2%, more preferred 0.05% - 0.1% Rosemary Extract.

According to an embodiment, the invention concerns a composition, comprising 10 - 50000, preferably 50 - 10000, more preferred 100 - 5000, preferably 300 - 2000, more preferred 500 -1000 ppm (w/w) Rosemary Extract. According to an embodiment, the invention concerns a composition, comprising 0.1% - 25%, preferably 0.2% - 10%, more preferred 0.3% - 5%, preferably 0.5% - 2%, more preferred 0.9-0.95% Sunflower oil. According to an embodiment, the invention concerns a composition comprising 500 - 250000, preferably 1000 - 100000, more preferred 3000 - 50000, preferably 5000 - 20000, more preferred 9000 - 9500 ppm (w/w) Sunflower oil.

According to an embodiment, the invention concerns a composition comprising 1% - 50%, preferably 2% - 40%, more preferred 3% - 30%, preferably 4% - 25%, more preferred 5% - 20%, preferably 7% - 15%, more preferred about 10% ethyl lactate. Ethyl lactate may stabilize, adjust and/or lower the pH to a value suitable for skin treatment.

According to an embodiment, the invention concerns a composition comprising 1% - 50%, preferably 2% - 40%, more preferred 3% - 35%, preferably 5% - 30%, more preferred 7% - 25%, preferably 10% - 20%, more preferred about 15% kigelia oil. Kigelia oil is a mixture of about 80% olive oil and about 20% Kigelia. Kigelia may provide antifungal, anti bacteriological, antioxidant and anti quorum sensing properties.

According to an embodiment, the invention concerns a composition comprising 0.5% - 15%, preferably 1% - 10%, more preferred 2% - 5%, preferably 2.5% - 4%, more preferred about 3% kigelia. According to an embodiment, the invention concerns a composition for use as a medicament.

According to an embodiment, the invention concerns a composition for use in the treatment, prophylaxis or alleviation of symptoms of a skin disorder, such as Dermatitis.

According to an embodiment, the invention concerns a composition for use in the treatment, prophylaxis or alleviation of symptoms of an indication selected among Diaper Dermatitis (DD), Atopic Dermatitis and Seborrheic Dermatitis (SD).

Diaper Dermatitis, also known as "Irritant diaper dermatitis" and "napkin dermatitis" and commonly known as diaper rash or nappy rash, is a generic term applied to skin rashes in the diaper area that are caused by various skin disorders and/or irritants.

Seborrheic Dermatitis is an inflammatory skin disorder affecting the scalp, face, and torso. Typically, Seborrheic Dermatitis presents with scaly, flaky, itchy, and red skin. It particularly affects the sebaceous-gland-rich areas of skin. It is also known as "cradle cap" in infants and "dandruff" in adolescents.

According to an embodiment, the invention concerns a composition for use in the treatment, prophylaxis or alleviation of symptoms of Diaper Dermatitis (DD). According to an embodiment, the invention concerns a composition for use in the treatment, prophylaxis or alleviation of symptoms of Seborrheic Dermatitis (SD).

According to an embodiment, the invention concerns a composition for use in the treatment, prophylaxis or alleviation of symptoms of infantile Seborrheic Dermatitis (ISD).

According to an embodiment, the invention concerns a composition for use in the treatment, prophylaxis or alleviation of symptoms of an indication selected among the group consisting of dandruff and cradle cap. Further potential indications for the present compositions comprise anti-inflammatory disorders, arthritis, eczema, atopic eczema, atopic dermatitis, and psoriasis. Additional envisaged indications comprise hyperactive gastrointestinal, respiratory and cardiovascular disorders, such as

gastrointestinal (colic, cramps, diarrhea), airways (asthma, bronchitis), cardiovascular, (cardiotonic, antihypertensive and blood purifier), and urinary (diuretic and kidney/bladder disorders).

Furthermore, envisaged indications or uses comprise acute respiratory distress syndrome, periodontitis (gum disease)/ gingivitis, rheumatoid arthritis, alcohol-induced hangover, cystic fibrosis, hyperlipidemia, infant development / neonatal care, malnutrition (inflammation complex syndrome), stress, supplementation in preterm and very low birthweight infants. According to an embodiment, the invention concerns a composition, wherein said composition reduces, inhibits and/or does not allow proliferation of Malassezia. This may be tested by comparing with a negative control. Malassezia (formerly known as Pityrosporum) is a genus of fungi. Many researchers and clinicians believe that Malassezia play a pivotal role in the pathogenesis of

Seborrheic Dermatitis (SD), according to the article "Seborrheic Dermatitis and Malassezia species - How Are They Related?" by Grace K. Kim et al., J Clin Aesthet Dermatol. 2009 November; 2(11): 14- 17.

According to an embodiment, the invention concerns a composition, wherein said composition reduces, inhibits and/or does not allow proliferation of Malassezia strains MRL 821 and 822.

According to an embodiment, the invention concerns a composition, wherein said composition does not form precipitate upon storage. According to this embodiment, no precipitate is formed within 1 week, preferably 1 month, more preferred 3 months, preferably 6 months, more preferred 12 months.

While the compositions of the present invention are intended for human use, animal use is also envisaged. According to an embodiment, the invention concerns a composition for use in the treatment, prophylaxis or alleviation of symptoms, comprising topical administration of said composition.

According to an embodiment, the invention concerns a composition for use in the treatment, prophylaxis or alleviation of symptoms, wherein 0.001 - 5 mg, preferably 0.005 - 1 mg, more preferred 0.01-0.5 mg, preferably 0.02-0.1 mg, more preferred 0.05 mg GLA/kg body weight is administered.

According to an embodiment, the invention concerns a composition for use in the treatment, prophylaxis or alleviation of symptoms, comprising at least daily administration of said composition.

According to an embodiment, the invention concerns a composition for use in the treatment, prophylaxis or alleviation of symptoms, comprising administering said composition at a site affected by DD or SD.

According to an embodiment, the invention concerns a composition for use in the treatment, prophylaxis or alleviation of symptoms, comprising administering said composition at a site not affected by DD or SD. According to an embodiment, the invention concerns the composition in an administration form selected among a liquid, solution, topical solution, shake lotion, shampoo, oil, gel, ointment, cream, lotion, liquid, aerosol, spray, skin patch, transdermal patch, foam, solid, powder, sponge, tape, paste, and tincture; preferably a spray.

A spray comprising ethyl lactate may provide a viscosity suitable for application without requiring subsequent rubbing on the sensitive skin.

According to an embodiment, the invention concerns a method of manufacture of a composition, comprising mixing Squalane, gamma-linolenic acid (GLA) and vitamin E.

According to an embodiment, the invention concerns a use of vitamin E and Rosemary Extract for stabilizing gamma-linolenic acid (GLA). Vitamin E and Rosemary Extract may stabilize GLA for example using the amounts of vitamin E and Rosemary Extract indicated in the claims, embodiments and examples.

According to an embodiment, the invention concerns the use of Squalane and GLA for the manufacture of a medicament for the treatment, prophylaxis or alleviation of symptoms of Diaper Dermatitis (DD) or Seborrheic Dermatitis (SD).

According to an embodiment, the invention concerns a use, wherein borage oil is used as a source of GLA.

According to an embodiment, the invention concerns a use, wherein said medicament is for topical application.

According to an embodiment, the invention concerns a use, wherein said medicament is for a treatment, prophylaxis or alleviation of symptoms, wherein 0.001 - 5 mg, preferably 0.005 - 1 mg, more preferred 0.01-0.5 mg, preferably 0.02-0.1 mg, more preferred 0.05 mg GLA/kg body weight is administered.

According to an embodiment, the invention concerns a use, wherein said medicament is for a treatment, prophylaxis or alleviation of symptoms, wherein said composition is administered at least daily.

According to an embodiment, the invention concerns a use, wherein said medicament is for a treatment, prophylaxis or alleviation of symptoms, wherein said composition is administered at a site affected by DD or SD.

According to an embodiment, the invention concerns a use, wherein said medicament is for a treatment, prophylaxis or alleviation of symptoms, wherein said composition is administered at a site not affected by DD or SD.

According to an embodiment, the invention concerns the treatment, prophylaxis or alleviation of symptoms of DD or SD comprising application of a composition according to the invention.

According to an embodiment, the invention concerns the treatment, prophylaxis or alleviation of symptoms, wherein said application is topical. According to an embodiment, the invention concerns the treatment, prophylaxis or alleviation of symptoms, wherein 0.001 - 5 mg, preferably 0.005 - 1 mg, more preferred 0.01-0.5 mg, preferably 0.02-0.1 mg, more preferred 0.05 mg GLA/kg body weight is administered.

According to an embodiment, the invention concerns the treatment, prophylaxis or alleviation of symptoms, wherein said composition is administered at least daily.

According to an embodiment, the invention concerns the treatment, prophylaxis or alleviation of symptoms, wherein said composition is administered a number of times selected among 1, 2, 3, 4, 5, and 6 times daily.

According to an embodiment, the invention concerns the treatment, prophylaxis or alleviation of symptoms, wherein said composition is administered a number of times selected among 1, 2, 3, 4, 5, 6 and 7 times weekly.

According to an embodiment, the invention concerns the treatment, prophylaxis or alleviation of symptoms, wherein said composition is administered at a site affected by DD or SD.

According to an embodiment, the invention concerns the treatment, prophylaxis or alleviation of symptoms, wherein said composition is administered at a site not affected by DD or SD.

According to an embodiment, the invention concerns the treatment, prophylaxis or alleviation of symptoms of DD or SD comprising administration of Squalane and GLA.

Compositions of the invention may provide advantages selected among, but not limited to: 1. Adjusting the pH (ethyl lactate).

2. Providing an adequate level of skin hydration (squalane/borage oil and/or ethyl lactate).

3. Providing a semi permeable barrier against friction and moisture from the diaper

(squalane/borage oil and/or ethyl lactate, and possibly other ingredients).

4. Reducing TEWL (squalane/borage oil and possibly other ingredients).

5. Provides healing properties (borage oil and/or vitamin E, and possibly other ingredients).

6. Regulates the barrier function of the skin (squalane/borage oil and possibly other

ingredients).

7. Soften the skin/acts as an emollient (oils).

8. Improves antimicrobial defense (kigelia).

All cited references are incorporated by reference.

The accompanying Figures and Examples are provided to explain rather than limit the present invention. It will be clear to the person skilled in the art that aspects, embodiments and claims of the present invention may be combined. Unless otherwise mentioned, all percentages and ppm are weight/weight (w/w). Figures

Figure 1 shows Malassezia growth on LNA with various agents 3 days post inoculation. Figure 2 shows Malassezia growth on LNA with various agents 11 days post inoculation. Figure 3 shows Malassezia growth on LNA with various agents 21 days post inoculation. Figure 4 shows the induction time of different compositions of the invention. Figure 5 shows the protection factor of different compositions of the invention.

Examples

Example 1 Evaluation of the Ability of Malassezia Spp. to Utilize Squalane/Borage oil mixture

The Malassezia strains M L 821 and 822 were tested.

Standardized inocula of 10² yeast cells were prepared in sterile saline, inoculated onto modifications of Leeming-Notman (LNA) agar plates, and incubated for up to 3 weeks. The formulation of LNA is as follows: To 1 L distilled water add:

10 g Peptone (Oxoid)

5 g glucose

0.1 g Yeast Extract (Oxoid)

- 8 g Ox bile (Oxoid)

- 0.5 g glycerol monostearate

0.5 mL Tween 60

l mL glycerol

12 g Agar (Oxoid)

0.05 g chloramphenicol

- 0.03 g gentamicin

The following modified agar plates were inoculated with each test strain

LNA without glycerol monostearate, with 0.5 g Squalane/borage oil formulation

LNA without glycerol, with 0.5 g Squalane/borage oil formulation

LNA without glycerol monostearate or glycerol, with 0.5 g Squalane/borage oil formulation - LNA without glycerol monostearate, glycerol, or glucose, with 0.5 g Squalane/borage oil formulation

LNA (growth control)

LNA without glycerol monostearate, glycerol, or glucose (negative control)

Growth was determined by colony size and colony forming units (CFU) on each medium was evaluated for each strain. The Squalane/borage oil formulation comprised 30% Squalane, 65% Borage oil and 5% vitamin E.

Figure 1 shows Malassezia growth of strain M L 822 on LNA with various agents 3 days post inoculation. The following symbols are used.

A. LNA without glycerol monostearate, with 0.5 g Squalane/borage oil formulation, B. LNA without glycerol, with 0.5 g Squalane/borage oil formulation, C. LNA without glycerol monostearate or glycerol, with 0.5 g Squalane/borage oil formulation, D. LNA without glycerol monostearate, glycerol, or glucose, with 0.5 g Squalane/borage oil formulation, E. LNA (growth control), F. LNA without glycerol monostearate, glycerol, or glucose (negative control)

Figure 2 shows Malassezia growth of strain M L 822 on LNA with various agents 11 days post inoculation. The following symbols are used.

Figure 3 shows Malassezia growth of strain MRL 822 on LNA with various agents 21 days post inoculation. The following symbols are used.

As can be seen in Figure 1, on day three post inoculation all media show colony growth. Overall, LNA without glycerol with 0.5 g Squalane/borage oil formulation had the largest colonies.

1. LNA without glycerol monostearate with 0.5 g Squalane/borage oil formulation, LNA without glycerol monostearate or glycerol with 0.5 g Squalane/borage oil formulation and unmodified LNA (growth control) demonstrated similar Malassezia colony growth and size.

2. LNA without glycerol monostearate, glycerol, or glucose with 0.5 g Squalane/borage oil formulation, and LNA without glycerol monostearate, glycerol, glucose or Squalane/borage oil formulation (negative control) had smaller colony growth.

As can be seen in Figure 2, on day 11 post inoculation (the results are summarized in Table 1 below):

1. LNA without glycerol monostearate with 0.5 g Squalane/borage oil formulation, LNA without glycerol with 0.5 g Squalane/borage oil, LNA without glycerol monostearate or glycerol, with 0.5 g Squalane/borage oil formulation, and unmodified LNA (growth control) all had similar large Malassezia colonies.

2. In contrast the Malassezia colonies grown on LNA without glycerol monostearate, glycerol, or glucose with 0.5 g Squalane/borage oil formulation, and LNA without glycerol monostearate, glycerol, glucose or Squalane/borage oil (negative control) were smaller and grew more slowly.

The same pattern of growth can be seen again in Figure 3, 21 days post inoculation.

Table 1 - Summary of test results 11 days post inoculation

The symbol "÷" indicates that the ingredient was excluded from the usual LNA mixture. The symbol "+" indicates that the ingredient was added to the LNA mixture.

"LC" means large colonies. "SG" means slow growth.

Table 2 below shows the colony counts for the 2 strains of Malassezia tested on each media.

Media with glycerol monostearate and glycerol added produce large colonies similar to the unmodified LNA. When glycerol monstearate and glycerol, alone or in combination, were removed from LNA media and replaced with 0.5 g Squalane/borage oil formulation, the Malassezia produced large colonies similar to those on unmodified LNA (growth control). However, when glycerol monostearate, glycerol and glucose were all removed and 0.5 g of Squalane/borage oil formulation added, the growth rate was slower and overall colony size similar to that of the LNA without glycerol monostearate, glycerol or glucose (negative control).

From Samples D and F, it is seen that The Malassezia strains were not able to break down or use the Squalane/borage oil formulation as a feed source. Table 2

Leeing-Notman Agar M L MRL

821 822 w/o glycerol monostearate, w/ Squalane/borage oil formulation 124 129 w/o glycerol, w/ Squalane/borage oil formulation 144 175 w/o glycerol monostearate or glycerol, w/ Squalane/borage oil 120 165

formulation

LNA (growth control) 111 151 w/o glycerol monostearate, glycerol, or glucose (negative control) 105 133

These test show that a composition according to the invention, (used in sample D), surprisingly provided less growth than the negative control, (sample F). Thus, a composition according to the invention is able to reduce the growth of Malassezia strains. This is evidenced by Fig. 1, Fig. 2 and Fig. 3, as well as by the data of Table 2.

Further, the experiments indicate ingredients such as glycerol, monostearate glycerol, and glucose may enhance the growth of Malassezia.

Example 2

Testing of af Borage oil/Squalane mixture on subjects suffering from Seborrhoeic Dermatitis

Subjects suffering from Seborrhoeic Dermatitis or Infantile Seborrhoeic Dermatitic are topically administered a composition according to the invention containing 65% Borage oil, 30% Squalane and 5% vitamin E (w/w) to the affected areas. This administration is conducted once daily for four weeks.

Example 3

Various Borage oil/Squalane mixtures

Table 3 below provides examples of manufactured as well as envisaged embodiments of

compositions of the present invention. Table 3

Example 4

Precipitation experiment A mixture of Squalane and Borage oil was produced, as noted in Table 3, example XII. A similar mixture was produced, containing 47.5% w/w Squalane, 47.5% w/w Borage oil, and 5% w/w Vitamin E. In the former mixture, precipitate was formed in the absence of vitamin E, while no precipitate formed in the latter mixture, in the presence of vitamin E. Other experiments have shown that in the presence of 0.5% w/w vitamin E no precipitate was formed. Example 5

Rosemary Mixture is a mixture comprising Sunflower oil (90-95%) and Rosemary Extract (5-10%).

The following compositions were tested, with and without Rosemary Mixture (The compositions prepared without Rosemary Mixture had additional borage oil):

Composition A (w/w %) Borage oil 69% Squalane 30% Vit E 0.5 % [Rosemary Mixture 0.5%]

Composition B (w/w%) Borage oil 68.5% Squalane 30% Vit E 0.5 %

[Rosemary Mixture 1%]

Composition C (w/w%) Borage oil 65% Squalane 30% Vit E 5 %

Rosemary Mixture: 0%

Composition D (w/w%) Borage oil 69% Squalane 30% [Rosemary Mixture 1%] Composition E (w/w%) Borage oil 65% Squalane 30% Vit E 4% [Rosemary Mixture 1%]

Oxidative Stability Index

Protection factor of each treatment was calculated by measuring the oxidative stability of samples using an Omnion Oxidative Stability Instrument (Rockland, MA). The Oxidative Stability Instrument (OSI) provides a rapid instrumental determination of the oxidative stability of fats, oils and other organic materials by measuring the induction period (length of time before rapid acceleration of oxidation occurs. The induction period, as indicated by the OSI, is positively correlated with antioxidant efficacy and the subsequent oxidative stability of the substrate. The OSI results are then converted to Protection Factor (PF) by the equation of [PF= Induction Time (treatment) / Induction Time (Control without antioxidant treatment)] to show the percentage increase (or decrease) in stability when the various treatments are added. Induction Time (hours) and Protection Factor (%) are provided in figure 4 and 5. The compositions A, B, C, D and E were tested with and without Rosemary Mixture.

Temperature of measurement: 100 °C. Figure 4 shows the Induction Time results for all the Formulas treatments. Rosemary Mixture showed excellent effect in increasing the induction time of formula A, B, D and E relative to the untreated control.

Figure 5 shows the Protection Factor imparted by the different treatments. Rosemary Mixture addition improved the oxidative stability of formulas significantly. Rosemary Mixture added at 1.0% resulted in a 310% improvement in formula B, 250% in E and 244% in D. Rosemary Mixture added at 0.5% also resulted in a 171% improvement in formula A.

It is noted that by comparing composition B comprising Rosemary Mixture and composition D comprising Rosemary Mixture, that vitamin E and Rosemary Mixture together provide a synergy effect. However, this synergy effect appears only to be present at lower vitamin E levels. This is seen by comparing compositions D and E, both with Rosemary Mixture. The synergy effect appears to be absent or very small in composition E with Rosemary Mixture.

For the compositions comprising Rosemary Mixture, composition B provided the best storage stability of the tested compositions, while the storage stability of Composition D and E were about the same. This may indicate that for these compositions, 1% Rosemary Mixture provides superior storage stability compared to 0.5% Rosemary Mixture. The optimum vitamin E contents may be between 0 and 5% (all percentages by weight) when mixed with Rosemary Mixture, for the storage stability. Table 4 below provides examples of manufactured as well as envisaged embodiments compositions of the present invention.

Table 4

Example 6

Additional compositions

Further compositions have been developed, which may be particularly effective in the treatment or alleviation of symptoms of Dermatitis, in particular Diaper Dermatitis.

Such compositions are provided in Table 5 below.

Table 5

Kigelia oil is a mixture, comprising 20% Kigelia and 80% olive oil.

Alternatively, canola oil may be replaced with borage oil, as indicated in Composition N.

The compositions may be manufactured by mixing the ingredients. Compositions of this example have shown good efficacy and safety in the treatment of Diaper Dermatitis using a spray for application. The spray has been used morning and evening for 1 - 4 weeks, with good results.

Claims

1. A composition comprising ethyl lactate, for use in the treatment, prophylaxis or alleviation of symptoms of dermatitis.

2. The composition according to claim 1, wherein said use is for treatment, prophylaxis or alleviation of symptoms of an indication selected among Diaper Dermatitis (DD), Atopic Dermatitis and Seborrheic Dermatitis (SD).

3. The composition according to any of the preceding claims, for use in the treatment,

prophylaxis or alleviation of symptoms of Diaper Dermatitis (DD).

4. The composition according to any of the preceding claims, for use in the treatment,

prophylaxis or alleviation of symptoms of Seborrheic Dermatitis (SD).

5. The composition according to any of the preceding claims, for use in the treatment,

prophylaxis or alleviation of symptoms of Infantile Seborrheic Dermatitis (ISD).

6. The composition according to any of the preceding claims, for use in the treatment,

prophylaxis or alleviation of symptoms of an indication selected among the group consisting of dandruff and cradle cap.

The composition according to any of the preceding claims, comprising 1% - 50%, prefi 2% - 40%, more preferred 3% - 30%, preferably 4% - 25%, more preferred 5% - 20%, preferably 7% - 15%, more preferred about 10% ethyl lactate.

8. The composition according to any of the preceding claims, further comprising kigelia.

9. The composition according to any of the preceding claims, further comprising kigelia oil.

10. The composition according to any of the preceding claims, comprising 1% - 50%, prefi 2% - 40%, more preferred 3% - 35%, preferably 5% - 30%, more preferred 7% - 25%, preferably 10% - 20%, more preferred about 15% kigelia oil.

The composition according to any of the preceding claims, comprising 0.5% - 15%, preferal: 1% - 10%, more preferred 2% - 5%, preferably 2.5% - 4%, more preferred about 3% kigelia.

12. A composition comprising Squalane and gamma-linolenic acid (GLA).

The composition according to claim 12, further comprising at least one fat-soluble ingredient.

The composition according to any of the preceding claims, further comprising vitamin E.

The composition according to any of the preceding claims, further comprising Rosemary Extract.

16. The composition according to any of the preceding claims, comprising vitamin E and

Rosemary Extract.

17. A composition comprising gamma-linolenic acid (GLA), vitamin E and Rosemary Extract, and optionally at least one fat-soluble ingredient.

The composition according to any of the preceding claims, further comprising Sunflower oil

The composition according to any of the preceding claims, further comprising Rosemary Extract and Sunflower Oil.

The composition according to any of the preceding claims, comprising at least one compound selected among a tocopherol and a tocotrienol, or a pharmaceutically acceptable salt thereof.

21. The composition according to any of the preceding claims, comprising at least one compound selected among the group consisting of alpha-tocopherol, beta-tocopherol, gamma- tocopherol, delta-tocopherol, alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, and delta-tocotrienol, or a pharmaceutically acceptable salt thereof.

The composition according to any of the preceding claims, comprising at least one tocopherol selected among a natural tocopherol and a synthetic form of tocopherol

23. The composition according to any of the preceding claims, comprising an ingredient selected among the group consisting of safflower oil, evening primrose oil, blackcurrent seed oil, borage oil, and hemp seed oil.

24. The composition according to any of the preceding claims, comprising an ingredient selected among the group consisting of borage oil, evening primrose oil and blackcurrant oil.

25. The composition according to any of the preceding claims, comprising borage oil.

26. The composition according to any of the preceding claims, comprising 1% - 99%, preferably 5% - 95%, more preferred 10% - 90%, preferably 20% - 80%, more preferred 30% - 70%, preferably 40% - 60%, more preferred 50 % borage oil.

27. The composition according to any of the preceding claims, comprising 1% - 99%, preferably 5% - 95%, more preferred 10% - 90%, preferably 20% - 80%, more preferred 30% - 70%, preferably 40% - 60%, more preferred 50 % Squalane.

28. The composition according to any of the preceding claims, comprising 0.05% - 10%,

preferably 0.1% - 5%, more preferred 0.2% - 2%, preferably 0.3% - 1%, more preferred 0.5% vitamin E.

29. The composition according to any of the preceding claims, comprising 0.001% - 10%,

preferably 0.005% - 5%, more preferred 0.007% - 2%, preferably 0.01% - 1%, more preferred 0.02% - 0.5%, preferably 0.03% - 0.2%, more preferred 0.05% - 0.1% Rosemary Extract.

30. The composition according to any of the preceding claims, comprising 10 - 50000, preferably 50 - 10000, more preferred 100 - 5000, preferably 300 - 2000, more preferred 500 -1000 ppm (w/w) Rosemary Extract.

31. The composition according to any of the preceding claims, comprising 0.1% - 25%, preferably 0.2% - 10%, more preferred 0.3% - 5%, preferably 0.5% - 2%, more preferred 0.9-0.95% Sunflower oil.

32. The composition according to any of the preceding claims, comprising 500 - 250000,

preferably 1000 - 100000, more preferred 3000 - 50000, preferably 5000 - 20000, more preferred 9000 - 9500 ppm (w/w) Sunflower oil.

33. The composition according to any of the preceding claims, comprising 1% - 50%, prefi

2% - 40%, more preferred 3% - 30%, preferably 4% - 25%, more preferred 5% - 20%, preferably 7% - 15%, more preferred about 10% ethyl lactate.

34. The composition according to any of the preceding claims, comprising 1% - 50%, prefi

2% - 40%, more preferred 3% - 35%, preferably 5% - 30%, more preferred 7% - 25%, preferably 10% - 20%, more preferred about 15% kigelia oil.

The composition according to any of the preceding claims, for use as a medicament.

The composition according to any of the preceding claims, for use in the treatment, prophylaxis or alleviation of symptoms of a skin disorder, such as Dermatitis.

38. The composition according to any of the preceding claims, for use in the treatment,

prophylaxis or alleviation of symptoms of an indication selected among Diaper Dermatitis (DD), Atopic Dermatitis and Seborrheic Dermatitis (SD).

39. The composition according to any of the preceding claims, for use in the treatment,

prophylaxis or alleviation of symptoms of Diaper Dermatitis (DD).

40. The composition according to any of the preceding claims, for use in the treatment, prophylaxis or alleviation of symptoms of Seborrheic Dermatitis (SD).

The composition according to any of the preceding claims, for use in the treatment, prophylaxis or alleviation of symptoms of Infantile Seborrheic Dermatitis (ISD).

42. The composition according to any of the preceding claims, for use in the treatment,

43. The composition according to any of the preceding claims, wherein said composition reduces inhibits and/or does not allow proliferation of Malassezia.

44. The composition according to any of the preceding claims, wherein said composition reduces inhibits and/or does not allow proliferation of Malassezia strains M L 821 and 822.

The composition according to any of the preceding claims, wherein said composition does not form precipitate upon storage.

46. The composition according to any of the preceding claims, for use in the treatment,

prophylaxis or alleviation of symptoms, comprising topical administration of said

composition.

47. The composition according to any of the preceding claims, for use in the treatment,

prophylaxis or alleviation of symptoms, wherein 0.001 - 5 mg, preferably 0.005 - 1 mg, more preferred 0.01-0.5 mg, preferably 0.02-0.1 mg, more preferred 0.05 mg GLA/kg body weight is administered.

48. The composition according to any of the preceding claims, for use in the treatment,

prophylaxis or alleviation of symptoms, comprising at least daily administration of said composition.

49. The composition according to any of the preceding claims, for use in the treatment, prophylaxis or alleviation of symptoms, comprising administering said composition at a site affected by DD or SD.

50. The composition according to any of the preceding claims, for use in the treatment,

prophylaxis or alleviation of symptoms, comprising administering said composition at a site not affected by DD or SD.

51. The composition according to any of the preceding claims, in an administration form selected among a liquid, solution, topical solution, shake lotion, shampoo, oil, gel, ointment, cream, lotion, liquid, aerosol, spray, skin patch, transdermal patch, foam, solid, powder, sponge, tape, paste, and tincture; preferably a spray.

52. Ethyl lactate for use in the treatment, prophylaxis or alleviation of symptoms of dermatitis.

53. Ethyl lactate according to claim 52, wherein said use is for treatment, prophylaxis or

alleviation of symptoms of an indication selected among Diaper Dermatitis (DD), Atopic Dermatitis and Seborrheic Dermatitis (SD).

54. Ethyl lactate according to claim 52 or 53, for use in the treatment, prophylaxis or alleviation of symptoms of Diaper Dermatitis (DD).

55. A method of manufacture of a composition according to any of the preceding claims,

comprising mixing Squalane, gamma-linolenic acid (GLA) and vitamin E.

56. A use of vitamin E and Rosemary Extract for stabilizing gamma-linolenic acid (GLA).

57. The use according to claim 56, wherein borage oil is used as a source of GLA.

58. A use of Squalane and GLA for the manufacture of a medicament for the treatment,

prophylaxis or alleviation of symptoms of Diaper Dermatitis (DD) or Seborrheic Dermatitis (SD).

59. The use according to claim 58, wherein said medicament is for topical application.

60. The use according to any of the claims 58 - 59, wherein said medicament is for a treatment, prophylaxis or alleviation of symptoms, wherein 0.001 - 5 mg, preferably 0.005 - 1 mg, more preferred 0.01-0.5 mg, preferably 0.02-0.1 mg, more preferred 0.05 mg GLA/kg body weight is administered.

61. The use according to any of the claims 58 - 60, wherein said medicament is for a treatment, prophylaxis or alleviation of symptoms, wherein said composition is administered at least daily.

62. The use according to any of the claims 58 - 61, wherein said medicament is for a treatment, prophylaxis or alleviation of symptoms, wherein said composition is administered at a site affected by DD or SD.

63. The use according to any of the claims 58 - 62, wherein said medicament is for a treatment, prophylaxis or alleviation of symptoms, wherein said composition is administered at a site not affected by DD or SD.

64. A treatment, prophylaxis or alleviation of symptoms of DD or SD comprising application of a composition according to any of the claims 1 - 51.

65. The treatment, prophylaxis or alleviation of symptoms according to claim 64, wherein said application is topical.

66. The treatment, prophylaxis or alleviation of symptoms according to any of the claims 64 - 65, wherein 0.001 - 5 mg, preferably 0.005 - 1 mg, more preferred 0.01-0.5 mg, preferably 0.02- 0.1 mg, more preferred 0.05 mg GLA/kg body weight is administered.

67. The treatment, prophylaxis or alleviation of symptoms according to any of the claims 64 - 66, wherein said composition is administered at least daily.

68. The treatment, prophylaxis or alleviation of symptoms according to any of the claims 64 - 67, wherein said composition is administered a number of times selected among 1, 2, 3, 4, 5, and 6 times daily.

69. The treatment, prophylaxis or alleviation of symptoms according to any of the claims 64 - 68, wherein said composition is administered a number of times selected among 1, 2, 3, 4, 5, 6 and 7 times weekly.

70. The treatment, prophylaxis or alleviation of symptoms according to any of the claims 64 - 69, wherein said composition is administered at a site affected by DD or SD.

71. The treatment, prophylaxis or alleviation of symptoms according to any of the claims 64 - 70, wherein said composition is administered at a site not affected by DD or SD.

72. The treatment, prophylaxis or alleviation of symptoms of DD or SD comprising administration of Squalane and GLA.