阅读说明：本技术 作为抗马拉色菌剂的脂肪酸酯 (Fatty acid esters as anti-malassezia agents ) 是由 彼得·迈泽 曼努埃尔·佩萨罗 格哈德·施毛斯 杰西卡·格里格尔 尼古拉斯·布格丹 于 2019-02-04 设计创作，主要内容包括：本发明主要涉及脂肪酸酯或者两种或更多种脂肪酸酯的混合物或者包含一种或多种脂肪酸酯的混合物,用于治疗哺乳动物,优选地为人类的皮肤表面上过量的马拉色菌,其中所述脂肪酸酯或者一种或多种所述脂肪酸酯中的一种、两种、三种或更多种、优选地为全部选自由3-羟丙基辛酸酯、单辛酸甘油酯、3-羟丙基十一碳烯酸酯和甘油单十一碳烯酸酯组成的组。本发明进一步涉及特定混合物或产品,以及本文所定义的脂肪酸酯或包含该脂肪酸酯的混合物或产品用于减少哺乳动物,优选地为人类的皮肤表面上马拉色菌数量的美容、非治疗用途。(The present invention relates primarily to a fatty acid ester or a mixture of two or more fatty acid esters or a mixture comprising one or more fatty acid esters for use in the treatment of excess malassezia on the surface of the skin of a mammal, preferably a human, wherein said fatty acid ester or one, two, three or more, preferably all of said fatty acid esters are selected from the group consisting of 3-hydroxypropyl caprylate, glyceryl monocaprylate, 3-hydroxypropyl undecylenate and glyceryl monocaprylate. The invention further relates to a specific mixture or product, and the cosmetic, non-therapeutic use of a fatty acid ester as defined herein or a mixture or product comprising the fatty acid ester for reducing the number of malassezia bacteria on the skin surface of a mammal, preferably a human.)

1. A fatty acid ester or a mixture of two or more fatty acid esters or a mixture comprising one or more fatty acid esters for use in the treatment of excess malassezia bacteria on the skin surface, preferably the scalp, of a mammal, preferably a human, wherein said fatty acid ester or one, two, three or more, preferably all of said fatty acid esters is selected from the group consisting of 3-hydroxypropyl caprylate, glyceryl monocaprylate, 3-hydroxypropyl undecylenate and glyceryl monocaprylate, preferably wherein said fatty acid ester or one, two or three, preferably all of said fatty acid esters is selected from the group consisting of 3-hydroxypropyl caprylate, glyceryl monocaprylate and 3-hydroxypropyl undecylenate, more preferably wherein said fatty acid ester or one or two or more of said fatty acid esters, Preferably all selected from the group consisting of 3-hydroxypropyl octanoate and 3-hydroxypropyl undecanoate.

2. The mixture for use according to claim 1, further comprising one or more 1, 2-alkane diols, preferably one or more 1, 2-alkane diols selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol, and 1, 2-decanediol, more preferably one 1, 2-alkane diol selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol, and 1, 2-decanediol.

3. The fatty acid ester or mixture for use according to claim 1 or 2, wherein malassezia is one or more species selected from the group consisting of malassezia furfur, malassezia pachydermatis, malassezia symptomatica, malassezia globosa, malassezia inactive, malassezia restricta, malassezia slagoensis, malassezia dermalis, malassezia japan, malassezia na, malassezia macrocephala, malassezia caprina, malassezia margari, m.cuniculus, malassezia brasiliensis, malassezia parrot, and m.arrunakahei, preferably selected from the group consisting of malassezia globosa, malassezia furfur, malassezia globosa, and malassezia dermalis.

4. Mixture for use according to any one of the preceding claims, wherein the mixture comprising one or more fatty acid esters is a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos.

5. A mixture, preferably a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos, said mixtures or products comprising 3-hydroxypropyl caprylate and 3-hydroxypropyl undecylate, or comprising glyceryl monocaprylate and 3-hydroxypropyl undecylate, or comprising 3-hydroxypropyl caprylate and glyceryl monocaprylate, or comprising glyceryl monocaprylate and glyceryl monocaprylate, or comprising 3-hydroxypropyl caprylate and glyceryl monocaprylate.

6. The mixture or product according to claim 5, further comprising one or more 1, 2-alkane diols, preferably one or more 1, 2-alkane diols selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol, and 1, 2-decanediol, more preferably one 1, 2-alkane diol selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol, and 1, 2-decanediol.

7. A mixture, preferably a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos, said mixtures or products comprising 1, 2-pentanediol and 3-hydroxypropyl caprylate, or comprising 1, 2-pentanediol and 3-hydroxypropyl undecylate, or comprising 1, 2-hexanediol and 3-hydroxypropyl caprylate, or comprising 1, 2-hexanediol and 3-hydroxypropyl undecylate, or comprising 1, 2-octanediol and 3-hydroxypropyl caprylate, or comprising 1, 2-octanediol and 3-hydroxypropyl undecylate, or comprising 1, 2-decanediol and 3-hydroxypropyl caprylate, or comprising 1, 2-decanediol and 3-hydroxypropyl undecylate, or comprising 1, 2-pentanediol and glyceryl monocaprylate, or comprising 1, 2-pentanediol and glycerol monoundecenoate, or 1, 2-hexanediol and glycerol monocaprylate, or 1, 2-hexanediol and glycerol monoundecenoate, or 1, 2-octanediol and glycerol monocaprylate, or 1, 2-octanediol and glycerol monoundecenoate, or 1, 2-decanediol and glycerol monocaprylate, or 1, 2-decanediol and glycerol monoundecenoate.

8. Mixture or product according to any one of claims 5 to 7, for use in the treatment of an excess of malassezia on the skin surface, preferably the scalp, of a mammal, preferably a human.

9. Mixture or product for use according to claim 8, wherein malassezia is one or more species selected from the group consisting of malassezia furfur, malassezia pachydermatis, malassezia symptomatica, malassezia globosa, malassezia inactive, malassezia restricta, malassezia semiata, malassezia dermalis, malassezia japan, malassezia na, malassezia macrocephala, malassezia caprina, malassezia margari, malassezia m, cuniculi, malassezia brasiliensis, malassezia parrot and m.arnunalokei, preferably selected from the group consisting of malassezia globosa, malassezia furfur, malassezia globosa and malassezia dermalis.

10. A fatty acid ester or a mixture of two or more fatty acid esters or a mixture comprising one or more fatty acid esters, or a mixture or product according to any of claims 5 to 7, for use in avoiding and/or reducing the amount of dandruff on human skin, preferably on human scalp, wherein the fatty acid ester or one, two, three or more, preferably all of the fatty acid esters are selected from the group consisting of 3-hydroxypropyl caprylate, glyceryl monocaprylate, 3-hydroxypropyl undecylenate and glyceryl monocaprylate, preferably wherein the fatty acid ester or one, two or three, preferably all of the fatty acid esters are selected from the group consisting of 3-hydroxypropyl caprylate, glyceryl monocaprylate and glyceryl monocaprylate, preferably wherein the fatty acid ester or one, two or three, preferably all of the fatty acid esters, Glyceryl monocaprylate and 3-hydroxypropyl undecylenate, more preferably wherein the fatty acid ester or one or two, preferably all, of the fatty acid ester or one or more of the fatty acid esters is selected from the group consisting of 3-hydroxypropyl caprylate and 3-hydroxypropyl undecylenate.

11. The mixture for use according to claim 10, wherein the mixture comprising one or more fatty acid esters is a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos.

12. Cosmetic, non-therapeutic use of a fatty acid ester or a mixture of two or more fatty acid esters or a mixture comprising one or more fatty acid esters, or a mixture or product according to any of claims 5 to 7 for reducing the number of malassezia bacteria on the skin surface of a mammal, preferably a human, preferably on the scalp of a human, and/or for avoiding dandruff on the human skin, preferably on the human scalp, and/or for reducing the amount of dandruff on the human skin, preferably on the human scalp, wherein the fatty acid ester or one, two, three or more, preferably all of the fatty acid esters are selected from the group consisting of 3-hydroxypropyl caprylate, glyceryl monocaprylate, 3-hydroxypropyl undecylenate and glyceryl monoundecylenate, preferably wherein the fatty acid ester or one or more of the fatty acid esters, Two or three, preferably all selected from the group consisting of 3-hydroxypropyl caprylate, glyceryl monocaprylate and 3-hydroxypropyl undecylenate, more preferably wherein the fatty acid ester or one or two, preferably all selected from one or more of the fatty acid esters is selected from the group consisting of 3-hydroxypropyl caprylate and 3-hydroxypropyl undecylenate.

13. Use according to claim 12, wherein in addition to the fatty acid ester or a mixture of two or more fatty acid esters or a mixture comprising one or more fatty acid esters, one or more 1, 2-alkane diols are used, preferably one or more 1, 2-alkane diols selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol and 1, 2-decanediol, more preferably one 1, 2-alkane diol selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol and 1, 2-decanediol.

14. Use according to claim 12 or 13, wherein malassezia is one or more species selected from the group consisting of malassezia furfur, malassezia pachydermatis, malassezia symptomatica, malassezia globosa, malassezia inactive, malassezia restricta, malassezia sfiella, malassezia dermalis, malassezia japonica, malassezia na, malassezia macrocephala, malassezia caprina, malassezia margaria, m.cuniculi, malassezia brasiliensis, malassezia parrot and m.arroakoei, preferably selected from the group consisting of malassezia globosa, malassezia furfur, malassezia globosa and malassezia dermalis.

15. Use according to any one of claims 12 to 14, wherein the mixture comprising one or more fatty acid esters is a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos.

Technical Field

The invention relates primarily to fatty acid esters as defined herein or a mixture or product comprising such fatty acid esters for use in the treatment of excess malassezia on the skin surface of a mammal, preferably a human. The invention further relates to a specific mixture or product, and the cosmetic, non-therapeutic use of a fatty acid ester as defined herein or a mixture or product comprising the fatty acid ester for reducing the number of malassezia bacteria on the skin surface of a mammal, preferably a human.

Further aspects of the invention will emerge from the description below, in particular from the examples, and from the appended patent claims.

Background

Malassezia is a genus of fungi that occur naturally on the skin surfaces of many animals, including humans. It is involved in the pathogenesis of various diseases, in particular skin diseases, and undesirable conditions such as, for example, tinea versicolor (sweat stains), seborrheic dermatitis and dandruff.

Short-chain and medium-chain fatty acids exhibit good antibacterial activity against malassezia. However, their practical application in topical treatment is limited by the following limitations: (i) strong odor, (ii) skin irritation, (iii) lack of skin substantivity and (iv) difficulties in formulating into products.

The various esters of the fatty acids do not exhibit these disadvantageous characteristics. Malassezia is known to break down such esters and release fatty acids, resulting in "suicide" of the fungus. However, the rate of hydrolysis of esters by malassezia enzymes varies greatly depending on the alcohol component of the ester.

Fatty acid esters are described as antifungal agents in DE 4237367 a 1. These esters are preferably selected from the group of hexyl laurate, isopropyl stearate, glycerol monolaurate, caprylic triglyceride and capric triglyceride. 1, 3-propanediol esters and monoglycerides are not disclosed.

DE 4234188 a1 relates to ethoxylated and propoxylated organic compounds as antifungal agents in cosmetics.

DE 102004046603 a1 describes substance mixtures comprising fatty acid esters of polyhydric alcohols and salts of short-chain fatty acids for combating microorganisms. There is no disclosure of any 1, 3-propanediol esters and monoglycerides.

SU 1286204 a1 discloses the use of a mixture of mono (50-60%), di (30-35%) and tri (10-15%) esters of glycerol and undecylenic acid to impart antimicrobial properties to cosmetic substrates. 1, 3-propanediol esters and activity against malassezia are not disclosed.

DE 3314786A 1 discloses mixtures with antifungal activity which comprise glycerol mono-and/or di-10-undecenoate. The mixture is used for treating nasal mycosis and onychomycosis. Its use for reducing the number of malassezia on the skin surface, preferably the scalp, of a mammal is not disclosed.

In WO 2006/054110 a2, esters of 1, 2, 3-glycerol with one or more C11 to C24 fatty acids are described, wherein at least one fatty acid has at least one double bond. The field of application of these substances is the treatment of chronic inflammatory diseases.

WO2007/095262 a2 discloses 1, 3-propanediol esters for solubilizing plant extracts, flavor concentrates and oils. The antimicrobial effect or benefit of 1, 3-propanediol esters on skin and scalp is not disclosed.

It is therefore an object of the present invention to provide more effective and compatible active agents for the treatment of malassezia related diseases and undesirable conditions, preferably for the treatment of dandruff on the human scalp.

Disclosure of Invention

According to a first aspect of the invention, said object is achieved by the use of a fatty acid ester or a mixture of two or more fatty acid esters or a mixture comprising one or more fatty acid esters for the treatment of excess malassezia on the skin surface, preferably the scalp, of a mammal, preferably a human, wherein said fatty acid ester or one, two, three or more, preferably all of said fatty acid esters is selected from the group consisting of 3-hydroxypropyl octanoate, glyceryl monocaprylate, 3-hydroxypropyl undecanoate and glyceryl monoundecanoate, preferably wherein said fatty acid ester or one, two or three, preferably all of said fatty acid esters is selected from the group consisting of 3-hydroxypropyl octanoate, glyceryl monocaprylate and 3-hydroxypropyl undecanoate, more preferably wherein the fatty acid ester or one or two, preferably all of the fatty acid ester or esters is/are selected from the group consisting of 3-hydroxypropyl octanoate and 3-hydroxypropyl undecanoate.

Within the framework of the present text, the term "malassezia" refers to one or more species of the malassezia genus, preferably one, two, three, four, five or more species of the malassezia genus (defined below).

Malassezia are naturally present on the skin surfaces of many animals, including humans. Since these fungi require fatty acids to grow, they are most commonly found in areas with high sebaceous glands, i.e. the scalp, face and upper body. However, when the fungus grows too fast, the natural renewal of the cells is disturbed and, for example, dandruff and the accompanying itching sensation appear on the scalp.

Within the framework of the present invention, an excessive amount of malassezia on the skin surface, preferably the scalp, of a mammal, preferably a human, is thus associated with the fact that the total amount of malassezia cells present on said skin surface leads to symptoms of skin diseases such as, for example, redness, itching, dryness, flaking, greasiness, hypopigmentation and/or pigmentation of the skin. The treatment of excessive malassezia on the skin surface preferably involves measures that result in the total amount of malassezia cells present on the skin surface not causing the symptoms of the dermatological condition or at least alleviating one, more or preferably all of the symptoms.

Thus, preferably, the use according to the invention (as described herein) is selected from or comprises the treatment and/or prevention of one, more or all of the symptoms selected from the group consisting of redness, itching, dryness, flaking, greasiness, hypopigmentation and pigmentation of the skin.

Within the framework of the present text, the term "on the skin surface" also includes, if applicable, areas of the hair infundibulum, junction area and/or sebaceous glands where an excess of malassezia might be present.

Caprylate refers to the ester of caprylic acid (CAS registry number for caprylic acid: 124-07-2; also known as caprylic acid) and undecylenate refers to the ester of 10-undecylenic acid (CAS registry number for 10-undecylenic acid: 112-38-9; also known as 10-undecylenic acid).

3-hydroxypropyl octanoate refers to the monoester of alcohol 1, 3-propanediol (CAS registry number: 504-63-2) with octanoic acid, and 3-hydroxypropyl undecylenate refers to the monoester of alcohol 1, 3-propanediol with 10-undecylenic acid. Glyceryl monocaprylate refers to the monoester of (mono) glycerol (CAS registry No. 56-81-5; also known as 1, 2, 3-propanetriol) and caprylic acid, and glyceryl monoundecenoate refers to the monoester of (mono) glycerol and undecylenic acid.

The basic study of the present invention surprisingly demonstrates the rapid enzymatic release of octanoic acid and undecylenic acid from fatty acid esters as defined herein by malassezia strains involved in various adverse skin conditions, such as dandruff. The expert in the field is particularly surprised that malassezia strains readily accept the fatty acid esters defined herein as substrate, since the fatty acids octanoic acid and undecylenic acid are not found in sebum of human skin. Furthermore, since the rate of hydrolysis of esters by malassezia enzymes varies greatly depending on the alcohol component of the ester, it has also been surprisingly found that fatty acid esters of 1, 3-propanediol and glycerol are efficiently hydrolyzed by malassezia.

A preferred embodiment of the invention relates to 3-hydroxypropyl caprylate or monocaprylate or 3-hydroxypropyl undecylenate or glyceryl monoundecylenate or to a mixture comprising 3-hydroxypropyl caprylate or monocaprylate or 3-hydroxypropyl undecylenate or glyceryl monoundecylenate (as the only malassezia active ingredient in the mixture) for use in the treatment of excess malassezia on the skin surface, preferably the scalp, of a mammal, preferably a human.

Another preferred embodiment of the invention relates to a mixture of 3-hydroxypropyl caprylate and 3-hydroxypropyl undecylenate, or of glycerol monocaprylate and 3-hydroxypropyl undecylenate, or of 3-hydroxypropyl caprylate and glycerol monocaprylate or glycerol monocaprylate and glycerol monocaprylate, or of 3-hydroxypropyl caprylate and glycerol monocaprylate, or to a mixture comprising 3-hydroxypropyl caprylate and 3-hydroxypropyl undecylenate, or glycerol monocaprylate and 3-hydroxypropyl undecylenate, or 3-hydroxypropyl caprylate and glycerol monocaprylate or glycerol monocaprylate and glycerol monocaprylate, or 3-hydroxypropyl caprylate and glycerol monocaprylate (as the only active component of the Malasse in the mixture), for the treatment of an excess of malassezia bacteria on the skin surface, preferably the scalp, of a mammal, preferably a human.

Another preferred embodiment of the invention relates to a mixture of 3-hydroxypropyl caprylate, glyceryl monocaprylate and 3-hydroxypropyl undecylenate, or to a mixture comprising 3-hydroxypropyl caprylate, glyceryl monocaprylate and 3-hydroxypropyl undecylenate (as the only malassezia active ingredient in the mixture) for use in the treatment of excess malassezia on the skin surface, preferably the head, of a mammal, preferably a human.

Another preferred embodiment of the invention relates to a mixture of 3-hydroxypropyl caprylate, glyceryl monocaprylate, 3-hydroxypropyl undecylenate and glyceryl monoundecylenate, or to a mixture comprising 3-hydroxypropyl caprylate, glyceryl monocaprylate, 3-hydroxypropyl undecylenate and glyceryl monoundecylenate (as the only malassezia active ingredient in the mixture) for use in the treatment of excess malassezia on the skin surface, preferably the scalp, of a mammal, preferably a human.

Another preferred embodiment of the invention relates to a fatty acid ester or a mixture of two or more fatty acid esters or a mixture comprising one or more fatty acid esters for use in the treatment of excess malassezia on the skin surface, preferably the scalp, of a mammal, preferably a human, wherein one, two or three, preferably all of the fatty acid ester or fatty acid ester is selected from the group consisting of 3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate and glycerol monoundecylenate.

More preferably, the fatty acid ester or mixture used according to the invention is (further) not or not comprising any diester of octanoic acid and/or not comprising any triester of octanoic acid and/or not comprising any ethoxylated variant of octanoic acid and/or not comprising any diester of undecylenic acid and/or not comprising any triester of undecylenic acid and/or not comprising any ethoxylated variant of undecylenic acid.

Advantageously, the fatty acid esters or mixtures for use as defined herein show a particularly high antibacterial activity against malassezia. In particular, the binary combination of fatty acid esters of caprylic acid and fatty acid esters of undecylenic acid (as defined above) as well as mixtures comprising the same ingredients show a synergistic enhancement of the antibacterial activity against malassezia (as will be further demonstrated below).

Another preferred embodiment of the present invention relates to a mixture for use as defined herein, said mixture further comprising one or more 1, 2-alkane diols, preferably one or more 1, 2-alkane diols selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol, 1, 2-decanediol, more preferably one 1, 2-alkane diol selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol and 1, 2-decanediol.

A preferred alternative embodiment relates to a fatty acid ester as defined herein for use as defined herein in combination with one or more 1, 2-alkane diols, preferably one or more 1, 2-alkane diols selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol 1, 2-decanediol, more preferably one 1, 2-alkane diol selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol and 1, 2-decanediol.

Surprisingly, it was found that the addition of one or more 1, 2-alkane diols as defined herein to one or more octanoates or one or more undecanoate esters as defined herein results in a synergistic increase in antibacterial activity against malassezia (as will be further demonstrated below).

Thus, another preferred embodiment of the invention relates to a mixture comprising 1, 2-pentanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-pentanediol and 3-hydroxypropyl undecanoate, or comprising 1, 2-hexanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-octanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-hexanediol and 3-hydroxypropyl undecanoate, or comprising 1, 2-octanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-octanediol and 3-hydroxypropyl undecanoate, or comprising 1, 2-decanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-decanediol and 3-hydroxypropyl undecanoate, or comprises 1, 2-pentanediol and glycerol monocaprylate, or comprises 1, 2-pentanediol and glycerol monoundecenoate, or comprises 1, 2-hexanediol and glycerol monocaprylate, or comprises 1, 2-hexanediol and glycerol monoundecenoate, or comprises 1, 2-octanediol and glycerol monocaprylate, or comprises 1, 2-octanediol and glycerol monoundecenoate, or comprises 1, 2-decanediol and glycerol monocaprylate, or comprises 1, 2-decanediol and glycerol monoundecenoate.

Another preferred embodiment of the invention relates to a fatty acid ester or mixture for use as defined herein, wherein malassezia is one or more species selected from the group consisting of malassezia furfur, malassezia pachydermatis, malassezia symptomatica, malassezia globosa, malassezia inactive, malassezia restricted, malassezia slae, malassezia dermalis, malassezia japan, malassezia na, malassezia major and malassezia, malassezia ovis, malassezia margari, m.cuniculi, malassezia brasiliensis, malassezia parrot, malassezia furfur, malassezia globosa and m.arralankei, preferably selected from the group consisting of malassezia restricted, malassezia globosa, malassezia furfur, malassezia globosa and malassezia dermalis.

Another embodiment of the present invention relates to a mixture for use as defined herein, wherein the mixture comprising one or more fatty acid esters is a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos.

Advantageously, the mixture for use as defined herein can be formulated in a manner that allows the user to incorporate the treatment of excess malassezia on the surface of their skin into their daily hair or skin care regimen. This is achieved, for example, by formulating the mixture into a hair or skin care product. By creating a hair or skin care product, such as an anti-dandruff shampoo, comprising one or more fatty acid esters for use as defined herein, the user can save time, money and energy by combining the treatment of the excess malassezia on the skin surface with its standard hair or skin care, such as shampooing. A rinse-off skin care product as defined herein may also be, for example, a body wash, while a leave-on skin care product may be, for example, a body cream or body lotion.

Another preferred embodiment of the present invention relates to a mixture for use as defined herein, the mixture comprising one or more additional active agents, preferably one or more antibacterial agents, more preferably one or more agents selected from the group consisting of clotrimazole (CAS registry No. 23593-75-1), bifonazole (CAS registry No. 60628-96-8), miconazole (CAS registry No. 22916-47-8), ketoconazole (CAS registry No. 65277-42-1), fluconazole (CAS registry No. 86386-73-4), climbazole (CAS registry No. 38083-17-9), itraconazole (CAS registry No. 84625-61-6), terbinafine (CAS registry No. 91161-71-6), nystatin (CAS registry No. 1400-61-9), amorolfine (CAS registry No. 78613-35-1), Ciclopirox olamine (CAS registry No. 29342-05-0), piroctone olamine (CAS registry No. 68890-66-4) and undecylenic acid (CAS registry No. 112-38-9).

A preferred alternative embodiment relates to a fatty acid ester for use as defined herein in combination with one or more additional active agents, preferably in combination with one or more antibacterial agents, more preferably in combination with one or more active agents selected from the group consisting of clotrimazole, bifonazole, miconazole, ketoconazole, fluconazole, climbazole, itraconazole, terbinafine, nystatin, amorolfine, ciclopirox olamine, piroctone olamine, and undecylenic acid.

Another aspect of the invention relates to a mixture, preferably a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos, comprising 3-hydroxypropyl caprylate and 3-hydroxypropyl undecylenate, or comprising glyceryl monocaprylate and 3-hydroxypropyl undecylenate, or comprising 3-hydroxypropyl caprylate and glyceryl monocaprylate, or comprising glyceryl monocaprylate and glyceryl monocaprylate, or comprising 3-hydroxypropyl caprylate and glyceryl monocaprylate.

According to a preferred embodiment, the total amount of the one or more fatty acid esters (as defined herein) comprised in the mixture or product as defined herein is 0.02 to 5wt. -%, more preferably 0.05 to 2wt. -%, most preferably 0.1 to 1wt. -%, relative to the total weight of the mixture or product.

According to another preferred embodiment, the mixture or product as defined herein comprises two fatty acid esters as defined herein in a weight ratio of from 10: 1 to 1: 10, more preferably from 5: 1 to 1: 5, most preferably from 3: 1 to 1: 3.

Advantageously, the mixture or product comprising the binary combination of fatty acid ester of caprylic acid and fatty acid ester of undecylenic acid as defined above exhibits a particularly high antibacterial activity against malassezia (as will be further demonstrated hereinafter).

According to an alternative embodiment, the invention relates to a mixture, preferably a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and a rinse-off skin care product, preferably a shampoo, more preferably an anti-dandruff shampoo, comprising a fatty acid ester or a mixture of two or more fatty acid esters or a mixture of one or more fatty acid esters, wherein the fatty acid ester or one, two, three or more, preferably all of the fatty acid esters are selected from the group consisting of 3-hydroxypropyl octanoate, glyceryl monocaprylate, 3-hydroxypropyl undecanoate and glyceryl monoundecanoate, preferably wherein the fatty acid ester or one, two or three, preferably all of the fatty acid esters are selected from the group consisting of 3-hydroxypropyl octanoate, glyceryl monocaprylate and 3-hydroxypropyl undecanoate, more preferably wherein the fatty acid ester or one or two or more of the fatty acid esters, Preferably all selected from the group consisting of 3-hydroxypropyl octanoate and 3-hydroxypropyl undecanoate.

According to a preferred alternative embodiment, the invention relates to a mixture, preferably a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos, comprising 3-hydroxypropyl caprylate, glyceryl monocaprylate, and 3-hydroxypropyl undecylenate.

According to a particularly preferred alternative embodiment, the invention relates to a mixture, preferably a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos, comprising 3-hydroxypropyl caprylate, glyceryl monocaprylate, 3-hydroxypropyl undecylenate, and glyceryl monocarbenoate.

A preferred embodiment relates to a mixture or product as defined herein, further comprising one or more 1, 2-alkane diols, preferably one or more 1, 2-alkane diols selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol, 1, 2-decanediol, more preferably one 1, 2-alkane diol selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol, and 1, 2-decanediol.

According to a preferred embodiment, the total amount of the one or more fatty acid esters (as defined herein) and the one or more 1, 2-alkanediols (as defined herein) comprised in the mixture or product as defined herein is between 0.1 and 10wt. -%, more preferably between 0.2 and 5wt. -%, most preferably between 0.3 and 3wt. -%, relative to the total weight of the mixture or product.

According to another preferred embodiment, the weight ratio of the one or more fatty acid esters (as defined herein) and the one or more 1, 2-alkane diols (as defined herein) comprised in the mixture or product as defined herein is from 20: 1 to 1: 20, more preferably from 10: 1 to 1: 10, most preferably from 5: 1 to 1: 5.

Another preferred embodiment relates to a mixture, preferably a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos, comprising 1, 2-pentanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-pentanediol and 3-hydroxypropyl undecanoate, or comprising 1, 2-hexanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-hexanediol and 3-hydroxypropyl undecanoate, or comprising 1, 2-octanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-octanediol and 3-hydroxypropyl undecanoate, or comprising 1, 2-decanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-decanediol and 3-hydroxypropyl undecanoate, or comprising 1, 2-pentanediol and glycerol monocaprylate, or 1, 2-hexanediol and glycerol monocaprylate, or 1, 2-hexanediol and glycerol monoundecenoate, or 1, 2-octanediol and glycerol monocaprylate, or 1, 2-octanediol and glycerol monoundecenoate, or 1, 2-decanediol and glycerol monocaprylate.

Surprisingly, it was found that the addition of a1, 2-alkane diol as defined herein to an octanoate or undecanoate ester as defined herein results in a synergistic increase in antibacterial activity against malassezia. Thus, the mixture or product as defined herein exhibits a particularly high antibacterial activity against malassezia (as will be further demonstrated below).

Another preferred embodiment of the present invention relates to a mixture or product as defined herein comprising one or more additional active agents, preferably one or more antibacterial agents, more preferably one or more active agents selected from the group consisting of clotrimazole, bifonazole, miconazole, ketoconazole, fluconazole, climbazole, itraconazole, terbinafine, nystatin, amorolfine, ciclopirox olamine, piroctone olamine, and undecylenic acid.

Another aspect of the invention relates to a mixture or product as defined herein for use in the treatment of excess malassezia on the skin surface, preferably the scalp, of a mammal, preferably a human.

As defined above, an excessive amount of malassezia on the skin surface, preferably the scalp, of a mammal, preferably a human, is thus associated with the fact that the total amount of malassezia present on said skin surface leads to symptoms of skin diseases such as, for example, redness, itching, dryness, flaking, greasiness, hypopigmentation and/or pigmentation of the skin.

A preferred embodiment relates to a mixture or product for use as defined herein, wherein malassezia is one or more species selected from the group consisting of malassezia furfur, malassezia pachydermatis, malassezia symptomatica, malassezia globosa, malassezia inactive, malassezia restricta, malassezia sflorescens, malassezia dermalis, malassezia japan, malassezia na, malassezia macrocephala, malassezia caprina, malassezia margari, m.cunicululi, malassezia brasiliensis, malassezia parrot, and m.arralanoehei, preferably selected from the group consisting of malassezia furfur, malassezia globosa and malassezia dermalis.

Another preferred embodiment of the present invention relates to a mixture or product for use as defined herein comprising one or more additional active agents, preferably one or more antibacterial agents, more preferably one or more active agents selected from the group consisting of clotrimazole, bifonazole, miconazole, ketoconazole, fluconazole, climbazole, itraconazole, terbinafine, nystatin, amorolfine, ciclopirox olamine, piroctone olamine, and undecylenic acid.

Another aspect of the invention relates to a fatty acid ester or a mixture of two or more fatty acid esters or a mixture comprising one or more fatty acid esters, or a mixture or product as defined above, for avoiding dandruff on human skin, preferably on human scalp, and/or reducing the amount of dandruff on human skin, preferably on human scalp, wherein said fatty acid ester or one, two, three or more, preferably all of said fatty acid esters are selected from the group consisting of 3-hydroxypropyl caprylate, glyceryl monocaprylate, 3-hydroxypropyl undecylenate and glyceryl monocaprylate, preferably wherein said fatty acid ester or one, two or three, preferably all of said fatty acid esters are selected from the group consisting of 3-hydroxypropyl caprylate, glyceryl monocaprylate, and glyceryl monocaprylate, Glyceryl monocaprylate and 3-hydroxypropyl undecylenate, more preferably one or two, preferably all, of said fatty acid ester or one or more of said fatty acid esters is selected from the group consisting of 3-hydroxypropyl caprylate and 3-hydroxypropyl undecylenate.

Within the framework of this document, the term "protection against dandruff on human skin, preferably on human scalp", relates to a preventive measure in which the first appearance or the second appearance of dandruff on a defined area of human skin, preferably on human scalp, is avoided by applying a fatty acid ester or mixture as defined herein to said defined area of human skin at one time or repeatedly. As a result, no dandruff is visible on said defined area of human skin when examined with the naked eye (by a professional trained in the art, such as for example a dermatologist).

Within the framework of this document, the term "reducing the amount of dandruff on human skin, preferably on human scalp" relates to a measure in which the total amount of dandruff on a defined area of human skin, preferably of human scalp, observed by the naked eye after a one-time or repeated treatment of said defined area with a fatty acid ester or mixture as defined herein is reduced by more than 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% or 90%.

A preferred embodiment relates to 3-hydroxypropyl caprylate or glyceryl monocaprylate or 3-hydroxypropyl undecylenate or glyceryl monoundecylenate or to a mixture comprising 3-hydroxypropyl caprylate or glyceryl monocaprylate or 3-hydroxypropyl undecylenate or glyceryl monoundecylenate (as the only malassezia active ingredient in the mixture) for avoiding dandruff and/or reducing the amount of dandruff on human skin, preferably on human scalp.

Another preferred embodiment of the invention relates to a mixture of 3-hydroxypropyl caprylate and 3-hydroxypropyl undecylenate, or of glycerol monocaprylate and 3-hydroxypropyl undecylenate, or of 3-hydroxypropyl caprylate and glycerol monocaprylate or glycerol monocaprylate and glycerol monocaprylate, or of 3-hydroxypropyl caprylate and glycerol monocaprylate, or to a mixture comprising 3-hydroxypropyl caprylate and 3-hydroxypropyl undecylenate, or glycerol monocaprylate and 3-hydroxypropyl undecylenate, or 3-hydroxypropyl caprylate and glycerol monocaprylate or glycerol monocaprylate and glycerol monocaprylate, or 3-hydroxypropyl caprylate and glycerol monocaprylate (as the only active component of the Malasse in the mixture), for avoiding and/or reducing the amount of dandruff on human skin, preferably on human scalp.

Another preferred embodiment of the invention relates to a mixture of 3-hydroxypropyl caprylate, glyceryl monocaprylate and 3-hydroxypropyl undecylenate, or to a mixture comprising 3-hydroxypropyl caprylate, glyceryl monocaprylate and 3-hydroxypropyl undecylenate (as the only malassezia active ingredient in the mixture) for avoiding and/or reducing the amount of dandruff on human skin, preferably on human scalp.

Another preferred embodiment of the invention relates to a mixture of 3-hydroxypropyl caprylate, glyceryl monocaprylate, 3-hydroxypropyl undecylenate and glyceryl monoundecylenate, or to a mixture comprising 3-hydroxypropyl caprylate, glyceryl monocaprylate, 3-hydroxypropyl undecylenate and glyceryl monoundecylenate (as the only malassezia active ingredient in the mixture) for avoiding dandruff and/or reducing the amount of dandruff on human skin, preferably on human scalp.

Another preferred embodiment of the invention relates to a fatty acid ester or a mixture of two or more fatty acid esters or a mixture comprising one or more fatty acid esters for avoiding dandruff on human skin, preferably on human scalp, and/or reducing the amount of dandruff on human skin, preferably on human scalp, wherein one, two or three, preferably all of said fatty acid ester or one or more of said fatty acid esters are selected from the group consisting of 3-hydroxypropyl octanoate, 3-hydroxypropyl undecanoate and glyceryl monoundecanoate.

More preferably, the fatty acid ester or mixture for use according to the invention is (further) not or not comprising any diester of octanoic acid and/or not comprising any triester of octanoic acid and/or not comprising any ethoxylated variant of octanoic acid and/or not comprising any diester of undecylenic acid and/or not comprising any triester of undecylenic acid and/or not comprising any ethoxylated variant of undecylenic acid.

Another embodiment of the present invention relates to a mixture for use as defined above, wherein the mixture comprising one or more fatty acid esters is a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos.

Another preferred embodiment of the present invention relates to a mixture for use as defined herein, which mixture comprises one or more additional active agents, preferably one or more antibacterial agents, more preferably one or more active agents selected from the group consisting of clotrimazole, bifonazole, miconazole, ketoconazole, fluconazole, climbazole, itraconazole, terbinafine, nystatin, amorolfine, ciclopirox olamine, piroctone olamine, and undecylenic acid.

A preferred alternative embodiment relates to a fatty acid ester for use as defined herein in combination with one or more additional active agents, preferably in combination with one or more antibacterial agents, more preferably in combination with one or more active agents selected from the group consisting of clotrimazole, bifonazole, miconazole, ketoconazole, fluconazole, climbazole, itraconazole, terbinafine, nystatin, amorolfine, ciclopirox olamine, piroctone olamine, and undecylenic acid.

Another aspect of the invention relates to the cosmetic, non-therapeutic use of a fatty acid ester or a mixture of two or more fatty acid esters or a mixture comprising one or more fatty acid esters, or a mixture or product as defined above, for reducing the amount of malassezia on the skin surface of a mammal, preferably a human scalp, and/or for avoiding dandruff on a human skin, preferably a human scalp, and/or for reducing the amount of dandruff on a human skin, preferably a human scalp. Wherein the fatty acid ester or one, two, three or more, preferably all of the fatty acid esters is selected from the group consisting of 3-hydroxypropyl octanoate, glyceryl monocaprylate, 3-hydroxypropyl undecanoate and glyceryl monocaprylate, preferably wherein the fatty acid ester or one, two or three, preferably all of the fatty acid esters is selected from the group consisting of 3-hydroxypropyl octanoate, glyceryl monocaprylate and 3-hydroxypropyl undecanoate, more preferably wherein the fatty acid ester or one or two, preferably all of the fatty acid esters is selected from the group consisting of 3-hydroxypropyl octanoate and 3-hydroxypropyl undecanoate.

As defined above, an excessive amount of malassezia on the surface of the skin of a mammal, preferably a human, is related to the situation where the total amount of malassezia present on the surface of the skin causes symptoms of skin diseases, such as redness, itching, dryness, flaking, greasiness, hypopigmentation and/or pigmentation of the skin.

However, it may also be desirable to use the fatty acid esters or mixtures as defined herein in a cosmetic/non-therapeutic manner to reduce the total amount of malassezia on the surface of mammalian, preferably human, skin, preferably the scalp, particularly before the occurrence of severe skin disorders as described above. For example, the fatty acid esters or mixtures defined herein may be used to improve the mild symptoms of redness, itching, dryness, flaking, greasiness, hypopigmentation and/or pigmentation of the skin, which symptoms have not (yet) been classified as skin disorders.

The term "reducing the number of malassezia bacteria on the skin" as used herein is defined as a significant reduction of the total number of malassezia bacteria in a specific area of the surface of the mammalian, preferably human, skin, i.e. preferably a reduction of the number of malassezia cells over a defined area of the skin surface of more than 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% or 90%.

Within the framework of this document, the term "protection against dandruff on human skin, preferably on human scalp", relates to a preventive measure in which the first appearance or the second appearance of dandruff on a defined area of human skin, preferably on human scalp, is avoided by applying a fatty acid ester or mixture as defined herein to said defined area of human skin at one time or repeatedly. As a result, no dandruff is visible on said defined area of human skin when examined with the naked eye (by a professional trained in the art, such as for example a dermatologist).

Within the framework of this document, the term "reducing the amount of dandruff on human skin, preferably on human scalp" relates to a preventive measure wherein the total amount of dandruff on human skin, preferably on a defined area of human scalp, is reduced by more than 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% or 90% upon visual inspection (by a trained professional in the art) after one or repeated treatments of said defined area with a fatty acid ester or mixture as defined herein.

Another embodiment of the invention relates to a cosmetic, non-therapeutic use as defined herein, wherein in addition to the fatty acid ester or a mixture of two or more fatty acid esters or a mixture comprising one or more fatty acid esters, one or more 1, 2-alkane diols are used, preferably one or more 1, 2-alkane diols selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol and 1, 2-decanediol, more preferably one 1, 2-alkane diol selected from the group consisting of 1, 2-pentanediol, 1, 2-hexanediol, 1, 2-octanediol and 1, 2-decanediol.

As mentioned above, it has surprisingly been found that the addition of a1, 2-alkane diol as defined herein to an octanoate or undecanoate ester as defined herein results in a synergistic increase in antibacterial activity against malassezia.

Thus, another preferred embodiment of the invention relates to the cosmetic, non-therapeutic use of a mixture comprising 1, 2-pentanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-pentanediol and 3-hydroxypropyl undecanoate, or comprising 1, 2-hexanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-hexanediol and 3-hydroxypropyl undecanoate, or comprising 1, 2-octanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-decanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-octanediol and 3-hydroxypropyl undecanoate, or comprising 1, 2-decanediol and 3-hydroxypropyl octanoate, or comprising 1, 2-decanediol and 3-hydroxypropyl undecanoate, or comprises 1, 2-pentanediol and glycerol monocaprylate, or comprises 1, 2-pentanediol and glycerol monoundecenoate, or comprises 1, 2-hexanediol and glycerol monocaprylate, or comprises 1, 2-hexanediol and glycerol monoundecenoate, or comprises 1, 2-octanediol and glycerol monocaprylate, or comprises 1, 2-octanediol and glycerol monoundecenoate, or comprises 1, 2-decanediol and glycerol monocaprylate, or comprises 1, 2-decanediol and glycerol monoundecenoate.

Another embodiment of the invention relates to a cosmetic, non-therapeutic use as defined herein, wherein malassezia is one or more species selected from the group consisting of malassezia furfur, malassezia pachydermatis, malassezia symptomatica, malassezia globosa, malassezia inactive, malassezia restricta, malassezia slaensis, malassezia dermalis, malassezia japan, malassezia na, malassezia macrocephala, malassezia capriana, malassezia margari, m.cunicululi, malassezia brasiliensis, malassezia parrot and m.arrunalokei, preferably selected from the group consisting of malassezia furfur, malassezia globosa and malassezia dermalis.

Another embodiment of the present invention relates to a cosmetic, non-therapeutic use as defined herein, wherein said mixture comprising one or more fatty acid esters is a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos.

Another embodiment of the present invention relates to a cosmetic, non-therapeutic use as defined herein, in addition to or in a mixture of two or more fatty acid esters, and optionally in addition to the one or more 1, 2-alkane diols, using one or more additional active agents, preferably one or more antibacterial agents, more preferably one or more active agents selected from the group consisting of clotrimazole, bifonazole, miconazole, ketoconazole, fluconazole, climbazole, itraconazole, terbinafine, nystatin, amorolfine, ciclopirox olamine, piroctone olamine, and undecylenic acid.

Also disclosed in the framework herein is a method for reducing the number of malassezia on the skin surface, preferably the scalp, of a mammal, preferably a human, particularly a human in need thereof (i.e. a human exhibiting one or more symptoms of a skin disorder, e.g. redness, itching, dryness, flaking, greasiness, hypopigmentation and/or pigmentation of the skin), comprising or consisting of the steps of: applying a fatty acid ester or a mixture of two or more fatty acid esters or a mixture comprising one or more fatty acid esters, wherein the fatty acid ester or one, two, three or more, preferably all of the fatty acid esters is selected from the group consisting of 3-hydroxypropyl caprylate, glyceryl monocaprylate, 3-hydroxypropyl undecylenate and glyceryl monocaprylate, or the mixture or product as defined herein to the skin surface, preferably the scalp, of a mammal, preferably a human.

A preferred embodiment relates to the method as defined above, wherein the administered fatty acid ester or one, two or three, preferably all of the one or more fatty acid esters is selected from the group consisting of 3-hydroxypropyl caprylate, glyceryl monocaprylate and 3-hydroxypropyl undecylenate.

Another preferred embodiment relates to the method as defined above, wherein the administered fatty acid ester or one, two or three, preferably all of the one or more fatty acid esters is selected from the group consisting of 3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate and glycerol mono undecylenate.

Another preferred embodiment relates to the method as defined above, wherein the administered fatty acid ester or one or two, preferably all of the one or more fatty acid esters is selected from the group consisting of 3-hydroxypropyl caprylate and 3-hydroxypropyl undecylenate.

Another preferred embodiment relates to the method as defined above, wherein the fatty acid ester administered is 3-hydroxypropyl caprylate or monocaprylin-yl or 3-hydroxypropyl undecylenate or glyceryl monoundecylenate, or wherein the mixture administered comprises 3-hydroxypropyl caprylate or monocaprylin-yl or 3-hydroxypropyl undecylenate or glyceryl monoundecylenate (as the only malassezia active ingredient in the mixture).

Another preferred embodiment relates to the method as defined above, wherein the mixture applied is 3-hydroxypropyl octanoate and 3-hydroxypropyl undecanoate, or monocaprylate and 3-hydroxypropyl undecanoate, or 3-hydroxypropyl octanoate and glycerol monocaprylate, or monocaprylate and glycerol monocaprylate, or 3-hydroxypropyl octanoate and glycerol monocaprylate, or wherein the applied mixture comprises 3-hydroxypropyl octanoate and 3-hydroxypropyl undecanoate, or comprises glyceryl monocaprylate and 3-hydroxypropyl undecylenate, or comprises 3-hydroxypropyl caprylate and glyceryl monocaprylate, or comprises glyceryl monocaprylate and glyceryl monoundecenoate, or 3-hydroxypropyl caprylate and glyceryl monocaprylate (as the only malassezia active ingredient in the mixture).

Another preferred embodiment relates to the method as defined above, wherein the applied mixture is 3-hydroxypropyl octanoate, glycerol monocaprylate and 3-hydroxypropyl undecanoate, or wherein the applied mixture comprises 3-hydroxypropyl octanoate, glycerol monocaprylate and 3-hydroxypropyl undecanoate (as the only malassezia active ingredient in the mixture).

Another preferred embodiment relates to the method as defined above, wherein the mixture applied is 3-hydroxypropyl octanoate, glyceryl monocaprylate, 3-hydroxypropyl undecanoate and glyceryl monoundecenoate, or wherein the mixture applied comprises 3-hydroxypropyl octanoate, glyceryl monocaprylate, 3-hydroxypropyl undecenoate and glyceryl monoundecenoate (as the only malassezia active ingredient in the mixture).

More preferably, the fatty acid ester or mixture administered in the method as defined above is (further) not or not comprising any diester of octanoic acid and/or not comprising any triester of octanoic acid and/or not comprising any ethoxylated variant of octanoic acid and/or not comprising any diester of undecylenic acid and/or not comprising any triester of undecylenic acid and/or not comprising any ethoxylated variant of undecylenic acid.

Another embodiment relates to the method as defined above, wherein malassezia is one or more species selected from the group consisting of malassezia furfur, malassezia pachydermatis, malassezia symptomatica, malassezia globosa, malassezia inactive, malassezia restricta, malassezia sfiella, malassezia dermalis, malassezia japonica, malassezia na, malassezia macrocephala, malassezia ovis, malassezia margari, m.cunicululi, malassezia brasiliensis, malassezia parrot and m.arroakei, preferably selected from the group consisting of malassezia globosa, malassezia furfur, malassezia globosa and malassezia dermalis.

Another embodiment relates to the method defined above, wherein the mixture comprising one or more fatty acid esters is a product selected from the group consisting of: leave-on skin care products, preferably oil-in-water or water-in-oil emulsions; and rinse-off skin care products, preferably shampoos, more preferably anti-dandruff shampoos.

Another embodiment relates to the method as defined herein above, wherein the mixture or product as defined herein administered comprises one or more additional active agents, preferably one or more antibacterial agents, more preferably one or more active agents selected from the group consisting of clotrimazole, bifonazole, miconazole, ketoconazole, fluconazole, climbazole, itraconazole, terbinafine, nystatin, amorolfine, ciclopirox olamine, piroctone olamine, and undecylenic acid.

A preferred alternative embodiment relates to the method as defined above, wherein the fatty acid ester as defined herein is used in combination with one or more additional active agents, preferably in combination with one or more antibacterial agents, more preferably in combination with one or more active agents selected from the group consisting of clotrimazole, bifonazole, miconazole, ketoconazole, fluconazole, climbazole, itraconazole, terbinafine, nystatin, amorolfine, ciclopirox olamine, piroctone olamine, and undecylenic acid.

The (preferred) embodiments of the fatty acid ester or mixture or product for use according to the invention correspond to or are derivable from the (preferred) embodiments of the mixture or product or use according to the invention or from the (preferred) embodiments of the method as described herein, as already explained above, or vice versa.

The invention will be described in more detail hereinafter with reference to selected examples.

Detailed Description

Example (b):

1.microorganism test strains

Growth inhibition tests against malassezia were performed on fatty acid esters and mixtures thereof. The following reference strains were included:

malassezia furfur var malassezia furfur	CBS 1878，CBS 7019
		Malassezia septoria	CBS 7222，CBS 7979，ATCC 42132，DSM 6171
Malassezia globosa (berk.) Kuntze	CBS 7966，PM1，CBS 7705
		Limiting Malassezia spp	CBS 7877
Malassezia pachydermatis (Fr.) kummer	CBS 1879，1892

Table 1: CBS ═ dutch culture collection (Centraalbureau voor Schimmelcultures), sydney branch, dutch; the malassezia globosa wild-type strain PM1 was isolated and deposited by professor p.mayser, university of giseng.

2.Preparing the test plate

The experiments were performed on solid media using agar dilution experiments. Stock solutions of the test substances were prepared in mDixon-Agar (see table 2). Lower assay concentrations were obtained by diluting the stock solutions with fresh agar.

Liquid agar was prepared in a warm water bath. The required amount of test substance was weighed into 130ml Dixon Agar and mixed with fresh Dixon Agar to achieve the required test substance concentration. The agar solution containing the test substance was then poured into 24-well plates. The pH was maintained at 5.5 for all experiments. Test substances were prepared as weights per volume of matrix. All results are expressed in parts per million (1ppm ═ 0.0001%).

Table 2: composition of mDixon-Agar (for 350ml)

3.Inoculation of test strains

Microbial test strains were prepared according to the protocol described by Mayser (Mayser P., Medium chain efficiency acid esters-activation of antimicrobial effects by Malassezia enzymes 2015; 58: 215-9). Briefly, malassezia strains were cultured on selective agar (Merck) of the pathogenic fungus and covered with a thin layer of cold-sterilized olive oil. Cell counts were determined in a Neubauer test cabinet and 1.75X10 suspended in 20. mu.l olive oil⁶The individual cells were transferred to a test plate (equivalent to 10)⁶Individual cell/cm²). The incubation was carried out at 32 ℃ for a maximum of 14 days, and the growth state was checked and recorded periodically. The Minimum Inhibitory Concentration (MIC) was determined as the lowest concentration of test compound with no visible growth. Each experiment was repeated to confirmAnd (6) recognizing the result.

4.Results

4.1Antifungal Activity

The minimum inhibitory concentrations of the test substances were determined for the different test strains (tables 3, 4, 5). Pure octanoic acid and undecylenic acid were used as control substances.

Table 3: minimum Inhibitory Concentrations (MICs) against the Malassezia test strain (the term "test substance" relates to the compounds listed in the following column; the numbers in the row to the right of the term "test substance" relate to the respective Malassezia test strain)

The results in table 3 show that the monoesters of caprylic acid and undecylenic acid with 1, 3-propanediol or glycerol are highly active against a broad spectrum of malassezia strains present on human and animal skin.

Table 4: minimum Inhibitory Concentrations (MICs) against the Malassezia test strains (the term "test substance" relates to the compounds listed in the following column; the numbers in the row to the right of the term "test substance" relate to the respective Malassezia test strain)

The results in table 4 show that the diester or ethoxylated variant of caprylic acid is not or only partially active against malassezia strains.

Table 5: minimum Inhibitory Concentrations (MICs) against the Malassezia test strains (the term "test substance" relates to the compounds listed in the following column; the numbers in the row to the right of the term "test substance" relate to the respective Malassezia test strain)

The results in table 5 indicate that the di-ester, tri-ester or ethoxylated variants of undecylenic acid are not or only partially active against malassezia strains.

In addition, MIC values for various alkane diols were also determined (table 6).

Table 6: minimum Inhibitory Concentrations (MICs) of alkanediols against the Malassezia test strains (the term "test substance" relates to the compounds listed in the following column; the numbers in the row to the right of the term "test substance" relate to the respective Malassezia test strains)

Subsequently, a binary mixture of octanoate and undecanoate was prepared (table 7) and MIC values were determined as described above (table 8).

Synergistic antibacterial action is determined by calculating the Synergy Index (SI) according to Kull equation (I) (Kull, F.C., Eismann, P.C., Sylvestrowicz, H.D., and R.L.Mayer (1961) Mixtends Quaternary Ammonium Compounds and Long-chain Fatty Acids as antibacterial Agents applied Microbiology 9, 538-541.Steinberg, D.C. (2000). Measuring synergy. cosmetics & Toiletries 115(11), 59-62).

(I)SI＝(C_{Mixture of}×P_A)/C_A+(C_{Mixture of}×P_B)/C_B

Wherein

SI is the synergy index according to Kull

C_AIs the cell count of substance A

C_BIs cell count of substance B

C_{Mixture of}Cell count of mixture of substances A and B

P_AIs the proportion of substance A in the mixture

P_BIs the proportion of substance B in the mixture.

SI values below 1 indicate synergistic activity of the test substances.

Table 7: binary mixtures comprising caprylate and undecylenate in the tested ratios

¹⁾For SI calculation, MIC-value < 100 was set to 50

Table 8: minimum Inhibitory Concentrations (MICs) and calculated SI index of a binary mixture of caprylate and undecylenate on Malassezia test strains (the term "test mixture" relates to the compounds listed in the following column; the numbers in the row to the right of the term "test mixture" relate to the individual Malassezia test strains)

In another test, binary mixtures of octanoate and undecanoate, respectively, with alkane diol were prepared (table 9) and MIC values determined as described above (table 10). The synergistic antibacterial effect is determined by calculating the Synergy Index (SI) according to the Kull equation.

Name of mixture	Test articleRatio of matter	Test substance
			5a	3∶1	1, 2-pentanediol/3-hydroxypropyl octanoate
5b	3∶1	1, 2-pentanediol/3-hydroxypropyl undecylenate
			6a	3∶1	1, 2-hexanediol/3-hydroxypropyl octanoate
6b	3∶1	1, 2-hexanediol/3-hydroxypropyl undecylenate
			7a	2∶1	1, 2-octanediol/3-hydroxypropyl octanoate
7b	2∶1	1, 2-octanediol/3-hydroxypropyl undecylenic acid ester
			8a	1∶2	1, 2 decanediol/3-hydroxypropyl octanoate
8b	1∶2	1, 2 decanediol/3-hydroxypropyl undecaneCarbonic acid ester

Table 9: binary mixtures of octanoate and undecanoate, respectively, and alkane diol were included in the ratios tested.

¹⁾For SI calculation, MIC-value < 100 was set to 50

Table 10: minimum Inhibitory Concentrations (MICs) and calculated SI index for Malassezia test strains of binary mixtures of caprylate and undecylenate, respectively, with alkane diols (the term "test mixture" relates to the compounds listed in the following columns; the numbers in the row on the right hand side of the term "test mixture" relate to the test strain of Lawsonia, respectively)

4.2Ester cleavage

The two substances 3-hydroxypropyl octanoate and 3-hydroxypropyl undecylenate show excellent activity against different malassezia species and strains. For both substances, ester cleavage and subsequent release of free fatty acids by malassezia globosa and malassezia limited lipase and hydrolase were confirmed.

It is well known in the art that free short and medium chain saturated fatty acids, such as capric acid (C10: 0), caprylic acid (C8: 0) and caproic acid (C6: 0), exhibit antibacterial activity. The use of these free fatty acids in cosmetic or medical products for the treatment of malassezia related diseases is hampered by their strong negative sensory odor and their irritancy at higher concentrations.

Surprisingly, it was found that similar antibacterial effects against malassezia, but not against candida, can be obtained when monoesters of these fatty acids are used. This highly specific action is facilitated by malassezia lipase and hydrolase, which cleave the esters, thereby releasing the active component of the fatty acid. This results in targeted activation of the antimicrobial molecules only in localized areas of the skin where the malassezia is dense.

For esters of monohydric alcohols, lysis of malassezia has previously been demonstrated. However, esters of monohydric alcohols (e.g. methanol, ethanol, propanol, isopropanol, etc.) are less active against different malassezia species and also have the serious disadvantage of a strong odour, which limits their use at low concentrations.

Experimental evidence of ester cleavage of 3-hydroxypropyl octanoate and 3-hydroxypropyl undecylenate was demonstrated for both species malassezia globosa and malassezia restricta during the basic study of the present invention (see table 11). These two species are the most common species on human scalp and skin, and their hydrolytic/lipolytic activity on fatty acid esters has not been studied before.

Limiting Malassezia spp	CBS*7877
		Malassezia globosa (berk.) Kuntze	CBS*7705

Reference strain of the Netherlands culture Collection, Udele Branch, Netherlands

Table 11: malassezia strains for ester lysis experiments

4.2.1.Method

The malassezia strains were cultured on selective agar (Merck) of the pathogenic fungus and covered with a thin layer of cold-sterilized olive oil. After 3 to 5 days, the fungal cells were collected and resuspended in the corresponding test substance. Cell number was determined using Neubauer counting plates (see table 12). Sterile petri dishes (diameter: 3cm) containing selective agar for the pathogenic fungus were prepared, covered with 100. mu.l of the test suspension, and incubated at 32 ℃.

	3-hydroxypropyl octanoate	3-hydroxypropyl undecylenic acid ester
			Malassezia globosa CBS7705	20500	26500
Limiting malassezia CBS7877	12500	5550

Table 12: the number of Malassezia cells per μ l was determined for each assay

After the specified incubation time (0, 3, 6, 12, 24, 48 and 72 hours), the test suspension was removed from the agar surface by rinsing with 1ml chloroform and stored in an airtight tube under cooling conditions before analysis. The chloroform was removed by evaporation in a fume hood at 30 ℃ and the remaining liquid was mixed with 1ml isopropanol, transferred into an Eppendorf tube and centrifuged. The supernatant was transferred to a new Eppendorf tube.

To analytically quantify the esters and free fatty acids produced by malassezia enzymatic cleavage, gas chromatography was used.

For quantification (range 0, 1 wt-% to 10 wt-%), a multistage calibration method with an internal standard (ISTD, docosane [ C22 ]; 500mg in MtBE) was used. Equal amounts of the corresponding acid, ester and possible by-products [0, 2-50mg/10mL ] were mixed with ISTD, diluted to the appropriate concentration and used directly with 1 μ L of [ split 1: 50] GC analysis was carried out: GC Agilent 6890 with a 20m ZB-Wax column [0, 20mm 0, 20 μm ], injector temperature 250 ℃, detector temperature 275 ℃ and flowing gas 1, 3mL/min hydrogen [ constant ]. For the temperature profile, 60 ℃ to 240 ℃ was used, with a heating rate of 9 ℃/min.

4.2.2.Results

3-hydroxypropyl octanoate is rapidly cleaved by two malassezia species to octanoic acid and 1, 3-propanediol. With malassezia globosa CBS7705, 75% of the esters were cleaved after 6 hours and 90% after 12 hours (fig. 1). On the other hand, the limiting malassezia CBS7877 was able to cleave 21% of the esters after 6 hours and 65% after 12 hours (fig. 2). In the test without malassezia cells, caprylic acid was not detected after 72 hours until the end of the experiment.

Malassezia enzymes also use 3-hydroxypropyl undecylenate as a preferred substrate, resulting in the rapid production of undecylenic acid. Incubation of malassezia globosa CBS7705 with this material resulted in 95% lysis after 6 hours and 99.5% lysis after 12 hours (figure 3). When using the limiting malassezia CBS7877, 56% lysis was observed after 6 hours and 96% lysis was observed after 12 hours (figure 4). In the absence of malassezia cells, undecenoic acid was not detected after 72 hours until the end of the experiment.

5.Formulation examples

Table 13: composition of essential oil 1(PO1, amount expressed in ‰ b.w.)

Table 14: composition of essential oil 2(PO2, amount expressed in ‰ b.w.)

Table 15: composition of essential oil 3(PO3, amount expressed in ‰ b.w.)

Table 16: composition of essential oil 4(PO4, amount expressed in ‰ b.w.)

Table 17: composition of essential oil 5(PO5, amount expressed in ‰ b.w.)

The essential oils PO1, PO2, PO3, PO4 or PO5 in the above examples were in each case acting alone in the formulations presented below.

Cosmetic preparations (compositions) — the amount of all preparations is expressed in wt. -%.

Table 18: cream o/w

Table 19: hand and body cream

Table 20: daily face cream SPF 20

Table 21: w/o night cream

Table 22: body lotion

Composition (I)	Measurement of
		Cetostearyl alcohol	2.0
Ethylhexyl isononanoate	5.0
		Cetearyl ethylhexanoate, isopropyl myristate	3.0
Glyceryl oleate citrate, caprylic/capric triglyceride	4.0
		Water (of water)	To 100 of
Carbomer	0.3
		Sodium benzoate	0.1
Propylene glycol	5.0
		30% sodium hydroxide solution	0.3
Essential oils PO1, PO2, PO3, PO4 or PO5	0.3
		Triethylene glycol, imidazolidinyl urea, methyl paraben, propyl paraben, dehydroacetic acid	0.3
3-hydroxypropyl octanoate	0.2
		3-hydroxypropyl undecylenic acid ester	0.2

Table 23: antibacterial body lotion, spray-on type

Table 24: aseptic wound ointment

Composition (I)	Measurement of
		Sorbitan isostearate, hydrogenated castor oil, gluten, beeswax (Cera alba)	6.0
Vaseline	21.0
		Cera Alba	5.0
Cetostearyl alcohol	7.0
		Almond	7.0
Lanolin	5.0
		Petrolatum	12.0
Essential oils PO1, PO2, PO3, PO4 or PO5	0.3
		Water (of water)	To 100 of
Panthenol	7.0
		Magnesium sulfate	0.7
Pentanediol	1.0
		Tocopherol acetate	1.0
Octenidine dihydrochloride	0.1
		Phenoxyethanol	0.5
3-hydroxypropyl octanoate	0.4
		Glyceryl monocaprylate	0.2

Table 25: anti-acne ointment

Table 26: moisturizing repair cream

Table 27: skin moistening lotion

Table 28: baby diaper rash cream w/o

Table 29: skin-brightening day cream o/w

Table 30: shampoo compositions

Table 31: anti-dandruff shampoo

Table 32: two-in-one shampoo

Table 33: bath foam

Table 34: shower gel

Table 35: private part cleaning fluid

Table 36: transparent liquid soap

Table 37: liquid synthetic soap

Table 38: anti-acne lotion

Composition (I)	Measurement of
		Water (of water)	To 100 of
Polyquaternium-7	0.5
		Cocoamidopropyl betaine	9.0
Coco glucosyl anhydride	2.0
		Polysorbate 80, glycerol, seed oil of grass cotton (cotton), and water	1.0
Tridecyl alcohol polyether-9, PEG-5 ethyl hexanoate, water (of water)	1.0
		Glyceryl polyether-90 isostearate and laureth-2	0.5
Sodium laureth sulfate	37.0
		Glycerol, wheat (wheat) gluten, water (watery)	1.0
Sodium chloride	0.3
		Essential oils PO1, PO2, PO3, PO4 or PO5	1.0
SymOcide BHO (hydroxyacetophenone, benzyl alcohol, caprylyl glycol, water)	1.0
		3-hydroxypropyl octanoate	0.25
3-hydroxypropyl undecylenic acid ester	0.15

Table 39: mineral cleansing and cleansing gel

Table 40: aftershave

Table 41: hair conditioner with ganbaosu, rinse-off type

Table 42: scalp soothing conditioner with UV-B/UV-A protection, rinse-off type

Table 43: hair conditioner with UV protection

Table 44: hair conditioner, leave-on type

Table 45: itching-relieving hair conditioner, no-wash type

Table 46: spray type hair conditioner containing zinc shikone and no-clean type

Table 47: hair spray

Table 48: deodorization rod

Table 49: zirconium suspension gel antiperspirant stick

Table 50: antiperspirant/deodorant ball

Table 51: deodorant preparation in the form of a roll ball gel

Composition (I)	Measurement of
		1, 3-butanediol	2.0
PEG-40-hydrogenated Castor oil	2.0
		Hydroxyethyl cellulose	0.5
Essential oils PO1, PO2, PO3, PO4 or PO5	0.3
		1, 3-propanediol	0.5
SymGuard CD (3-phenylpropanol, o-cymene-3-ol, decanediol)	0.4
		Ethyl hexyl glycerol	0.1
3-hydroxypropyl octanoate	0.3
		Glyceryl monocaprylate	0.15
3-hydroxypropyl undecylenic acid ester	0.1
		Water (W)	To 100 of

Table 52: transparent deodorizing and sweat-stopping ball

Table 53: pump spray of deodorant containing SymClariol

Table 54: deodorant spray

Table 55: sunscreen emulsion (o/w, broad band protection)

Table 56: emulsion with UV-A/B-broadband protection

Table 57: sun protection light cream (w/o), SPF 40

Table 58: sunscreen emulsion (w/o)

Table 59: sunscreen spray with UV-A/B-broad band protection with low oil content

Table 60: sunscreen spray o/w, SPE 15-20

Table 61: gel after sun drying

Table 62: after-sun emulsion

Composition (I)	Measurement of
		acrylate/C10-30 alkyl acrylate crosspolymer	0.4
Cetearyl ethyl hexanoate	15.0
		Bisabolol	0.2
Tocopherol acetate	1.0
		Panthenol	1.0
Alcohol(s)	15.0
		Glycerol	3.0
Essential oils PO1, PO2, PO3, PO4 or PO5	0.30
		1, 2-hexanediol	1.0
4-hydroxyacetophenones	0.3
		Pentanediol	4.0
Demineralized water	To 100 of
		Triethanolamine	0.2
3-hydroxypropyl octanoate	0.2
		3-hydroxypropyl undeceneAcid esters	0.1

Example 63: synthetic antibacterial soap bars

Table 64: synthetic soap bars

Table 65: antibacterial toilet bar

Composition (I)	Measurement of
		Sodium tallow soap	60.0
Palm oil sodium soap	27.0
		Glycerol	2.0
Sodium chloride	0.5
		1-hydroxyethane-1, 1-diphosphonic acid tetrasodium salt	0.3
Alpha-tocopherol	0.1
		Pigment yellow 1	0.02
Water (W)	To 100 of
		Essential oils PO1, PO2, PO3, PO4 or PO5	3.0
Farnesol	0.2
		3-hydroxypropyl octanoate	0.1
Glyceryl monocaprylate	0.1
		3-hydroxypropyl undecylenic acid ester	0.05
Mono-undecenoic acid glycerol ester	0.05

Table 66: shaving foam

Table 67: spray type disinfecting gel

Table 68: solution for wet tissues

6) In vivo studies

An in vivo study was conducted to investigate the potential of 3-hydroxypropyl caprylate for dandruff removal efficacy on the scalp. Efficacy was assessed based on a dandruff score according to Pi rerard-Franchimont, which assessed dandruff intensity in the range of 0-10 for 8 individual fractions on the scalp (0: none; 1-2: mild; 3-4: moderate; 5-6: significant; 7-8: severe; 9-10: severe). 22 participants with a visual dandruff score of 32 or more (total score of all 8 fractions) were included in the study.

The active ingredient was provided in a leave-on pump spray (0.5 wt. -% formulation of 3-hydroxypropyl octanoate in ethanol/water 70/30 vol/vol). After two weeks of shampooing with the inactive shampoo, the test product was applied to the scalp once a day (30 sprays per night, leave-on overnight) for four weeks while the shampooing continued with the inactive shampoo during the first two weeks of shampooing.

Dandruff scoring was performed after two weeks of shampooing with an inactive shampoo by trained technicians on day 1 (before first applying an active-containing leave-on pump spray) and on day 29 of treatment with a leave-on pump spray, and is depicted in fig. 5. As shown in fig. 5, the average dandruff score according to Pi rerard Franchimont decreased significantly (p 0.004) from significant (4.78) to moderate (4.38).