Improved deposition of Anti-dandruff agent

Abstract

The present invention primarily relates to fatty acid esters of formula (I) and their use as a deposition aid for anti-dandruff agents.

Description

[0001] Improved deposition of anti-dandruff agent

[0002] The present invention lies in the field of managing Malassezia on the skin surface. In particular, the present invention provides products with improved deposition of antidandruff agents, corresponding uses and methods for managing Malassezia through application of the products. Malassezia is a genus of fungi and is naturally found on the skin surfaces of many animals, including humans. It is involved in the pathogenesis of a variety of diseases, in particular skin diseases, and undesired conditions such as, for example, in pityriasis versicolor, seborrheic dermatitis and dandruff.

[0003] Pityriasis versicolor (or tinea versicolor) is a condition characterized by a skin eruption, typically on the trunk and proximal extremities of a subject. Pityriasis versicolor is known to be caused by Malassezia, such as M. globosa.

[0004] Seborrhoeic dermatitis (or seborrhoea) is a long-term skin disorder typically characterized by red, scaly, greasy, itchy, and inflamed skin, particularly the scalp. Seborrhoeic dermatitis is known to be caused by Malassezia, such as M. globosa, M. restricta, M. pachydermatis and M. sympodialis.

[0005] Dandruff is a skin condition, which is characterized by flaking and often mild itchiness of the skin, particularly the scalp. Dandruff is often referred to as the mild form of seborrheic dermatitis, however, without an inflammation. Thus, dandruff is considered as a cosmetic skin condition. Still, dandruff negatively impacts quality of life.

[0006] The search for active ingredients to address and manage scalp dysfunctions remains one of the main objectives of shampoo developers. Among the active ingredients, piroctone olamine (INN; also known as piroctone ethanolamine, herein abbreviated as “PO”) is of particular interest. It is often used as an anti-dandruff agent as a replacement for the commonly used compound zinc pyrithione which was banned from cosmetic use in the EU in 2022.

[0007] The target for antidandruff shampoo formulations is to bring large deposits of the active ingredient to the hair surface, close to the root, and near the scalp, such that the the active ingredient can achieve its function properly. For this reason, an effective deposition of the active ingredient on the scalp is key to its anti-dandruff efficacy. Deposition of the active ingredient from hair care products requires balancing many technical parameters to achieve the desired outcome without sacrificing secondary parameters, such as cosmetic attributes.

[0008] A deposition aid for an anti-dandruff agent is a substance that helps in the deposition of the anti-dandruff agent onto the hair from a hair care product, such as a shampoo or conditioner. This improves the effectiveness of the anti-dandruff agent by ensuring it is adequately distributed and adheres to the hair and scalp. For example, EP2046453 suggests triglyceride oil as a deposition aid in a hair conditioning composition that also includes a cationic surfactant and an anti-dandruff agent. The triglyceride oil helps to improve the deposition of the anti-dandruff agent. Another example is guar hydroxypropyltrimonium chloride. It is often used as a deposition aid in hair care products. It is a quaternary ammonium derivative of guar gum and is known for its excellent conditioning and detangling benefits. It helps to deposit active ingredients, such as antidandruff agents, onto the hair and scalp, improving the effectiveness of these ingredients. It also provides other benefits such as reducing static charges and forming a protective film on the hair. WO 1998 / 023258A1 describes a hair shampoo, comprising a surfactant, polyethylenimine, and piroctone olamine. The presence of polyethylenimine in the composition is said to enhance the desposition of the active piroctone olamine onto the hair and skin.

[0009] However, the known deposition aids may not be always for all products desireable. Hence, there is a constant need for novel agents with a deposition improving effect on anti-dandruff agents. It was thus a primary object of the present invention to provide further effective and pharmaceutically and / or cosmetically compatible deposition aids for the managment of Malassezia-associated diseases and undesired conditions, preferably of dandruff, on human scalp. The primary object of the present invention is solved by the use of a fatty acid ester of formula I, in which

[0010] R1together with the carboxy group to which it is attached represents a first linear fatty acid group with 5 to 14, preferably 6 to 12, more preferably 8 to 12 carbon atoms, and

[0011] R2is selected from the group consisting of: . . . hich R3together with the carboxy group to which it is attached represents a second linear fatty acid group with 5 to 14, preferably 6 to 12, more preferably 8 to 12 carbon atoms.

[0012] The present invention is based on the innovation that a fatty acid ester of formula I is capable to function as deposition aid for an anti-dandruff agent. It helps the anti-dandruff agent to deposit onto the hair from a composition such as a cosmetic composition, in particular a rinse off hair care product, such as a shampoo or conditioner. The fatty acid ester of formula I helps the anti-dandruff agent to properly distribute and adhere to the hair and scalp, thereby increasing the effectiveness of the anti-dandruff agent. Accordingly, the use of the fatty acid ester of formula I is as a deposition aid for an anti-dandruff agent.

[0013] The fatty acid ester of formula I encompasses the following fatty acid monoesters and fatty acid diesters: ich the first fatty acid group R1and the second fatty acid group R3are as defined above. In a preferred embodiment of the present invention, the first and / or the second fatty acid group is / are independently selected from the group consisting of n-octanoic acid (caprylic acid), n-decanoic acid (capric acid), n-undecenoic acid (undecylenic acid), and n- dodecanoic acid (lauric acid).

[0014] In particularly preferred embodiments, the fatty acid ester of formula I is selected from the group consisting of 3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate, 3- hydroxypropyl caprate, 3-hydroxypropyl laurate, propanediol dicaprylate / caprate, propylene glycol caprylate, propylene glycol undecylenate, propylene glycol caprate, and propylene glycol laurate. More preferably, the fatty acid ester of formula I is selected from the group consisting of 3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate, 3- hydroxypropyl caprate, 3-hydroxypropyl laurate, and propanediol dicaprylate / caprate. Yet more preferably, the fatty acid ester of formula I is selected from the group consisting of 3- hydroxypropyl caprylate, 3-hydroxypropyl undecylenate, 3-hydroxypropyl caprate, and 3- hydroxypropyl laurate. Most preferably, the fatty acid ester of formula I is selected from the group consisting of 3-hydroxypropyl caprylate, and 3-hydroxypropyl undecylenate.

[0015] In some embodiments, one fatty acid ester of formula I is used in the present invention. In some embodiments, two or more different fatty acid esters of formula I are used in the present invention. Preferred combinations for use in the present invention include the following:

[0016] 3-hydroxypropyl caprylate, and 3-hydroxypropyl undecylenate;

[0017] 3-hydroxypropyl caprylate, and 3-hydroxypropyl caprate;

[0018] 3-hydroxypropyl caprylate, and 3-hydroxypropyl laurate;

[0019] 3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate, and 3-hydroxypropyl caprate;

[0020] 3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate, and 3-hydroxypropyl laurate;

[0021] 3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate, 3-hydroxypropyl caprate, and 3-hydroxypropyl laurate. The fatty acid ester of formula I may impart a deposition enhancing effect on a variety of different anti-dandruff agents. Accordingly, the anti-dandruff agent may be selected from the group consisting of piroctone olamine, ciclopirox olamine, decylene glycol, 1 ,10- decanediol, climbazole, ketoconazole, salicylic acid, sodium salicylate, zinc pyrithione, pyrithione zinc, zinc gluconate, zinc glycyrrhetinate, zinc PCA, copper PCA, sulfur, selenium sulfide, selenium disulfide, o-cymen-5-ol, hexamidine diisetionate, ethyl lauroyl arginate HCI, coal tar, sodium caproyl / lauroyl lactylate, sclareolide, capryloyl glycine, undecylenoyl glycine, succinic acid, sodium usnate, usnic acid, copper usnate, terpineol, 4-terpineol, isosorbide, tea trea oil, Malus Domestica Fruit Cell Culture Extract, Epilobium Angustifolium Flower / Leaf / Stem Extract, Botrytis cinerea / Passiflora Edulis fruit extract / piceatannol ferment filtrate, Apium Graveolens (Celery) Seed Extract, and Morinda Citrifolia Callus Culture Lysate. Preferably, the anti-dandruff agent is selected from the group consisting of piroctone olamine, ciclopirox olamine, decylene glycol, climbazole, ketoconazole, salicylic acid, o-cymen-5-ol, hexamidine diisetionate, and sodium caproyl / lauroyl lactylate. More preferably, the anti-dandruff agent is selected from the group consisting of piroctone olamine, decylene glycol, climbazole, and o-cymen-5-ol. Most preferably, the anti-dandruff agent is piroctone olamine.

[0022] In preferred uses of the present invention, the fatty acid ester of formula I and the antidandruff agent are co-applied onto scalp or skin of a human. It is further preferred that both the fatty acid ester of formula I and the anti-dandruff agent are contained in the same formulation / product.

[0023] According to a further preferred use, the fatty acid ester of formula I is applied in an amount effective to enhance the deposition of the anti-dandruff agent by at least 10%, preferably at least 15%, more preferably at least 20%, yet more preferably at least 25%, yet more preferably at least 30%, most preferably at least 35%, as compared to a corresponding application lacking the fatty acid ester of formula I. The enhancement of the deposition of an anti-dandruff agent through the co-application of the fatty acid ester of formula I can be quantified experimentally using an appropriate skin model. An exemplary test method comprises the steps applying a defined amount of the fatty acid ester and the anti-dandruff agent (both contained in a common formulation, e.g., the exemplified shampoo formulation) on a surface of a skin model substrate, distributing the fatty acid ester and the anti-dandruff agent on the surface for 30 seconds, rinsing the surface after 3 minutes using 200 mL water at 37°C, and extracting the skin model substrate for 6 hours with a 1 :1 solution of acetonitril and ethanol. The higher the amount of the anti-dandruff agent extracted, the better the deposition effect of the fatty acid ester of formula I. In accordance with the above, the fatty acid ester of formula I is parrticulary preferably used in an amount effective to enhance the deposition of the anti-dandruff agent when tested on a skin model substrate involving the aforementioned steps.

[0024] Moreover, the fatty acid ester of formula I may be contained in a personal care or pharmaceutical product, preferably in admixture with the anti-dandruff agent. Preferably, the personal care or pharmaceutical product is a rinse-off product. Yet preferably, the rinse- off product is selected from the group consisting of shampoos, conditioners, shower gels, cleansers, micellar waters, solid formats, and concentrates.

[0025] Another aspect of the present invention pertains to a method of improving deposition of an anti-dandruff agent. The method comprises the following steps: providing a fatty acid ester of formula I as defined herein, and an anti-dandruff agent, applying the fatty acid ester of formula I and the anti-dandruff agent onto scalp or skin of a human, and optionally rinsing the scalp or skin on which the fatty acid ester of formula I and the anti-dandruff agent have been applied.

[0026] According to a related aspect of the present invention, a method of managing Malassezia comprises the steps: providing a fatty acid ester of formula I and an anti-dandruff agent, applying the fatty acid ester of formula I and the anti-dandruff agent onto scalp or skin of a human, and optionally rinsing the scalp or skin on which the fatty acid ester of formula I and the anti-dandruff agent has been applied.

[0027] In the above methods, the fatty acid ester of formula I is applied in an amount effective to enhance the deposition of the anti-dandruff agent by at least 10%, preferably at least 15%, more preferably at least 20%, yet more preferably at least 25%, yet more preferably at least 30%, most preferably at least 35%, as compared to a corresponding application lacking the fatty acid ester of formula I. Prefereably, the enhancement of the deposition of the antidandruff agent is tested on a skin model substrate using the steps described further above.

[0028] According to preferred embodiments of the invention, the fatty acid ester of formula I and the anti-dandruff agent are co-applied onto the scalp or skin. To this end, both the fatty acid ester of formula I and the anti-dandruff agent may be contained in a, i.e. the same, rinse- off product. Preferably, the rinse-off product is selected from the group consisting of shampoos, conditioners, shower gels, cleansers, micellar waters, solid formats, and concentrates.

[0029] According to another aspect, a personal care product or pharmaceutical product comprises a fatty acid ester of formula I as defined herein and an anti-dandruff agent, wherein the fatty acid ester of formula I is contained in an amount effective to enhance the deposition of the anti-dandruff agent by at least 10%, preferably at least 15%, more preferably at least 20%, yet more preferably at least 25%, yet more preferably at least 30%, most preferably at least 35%, as compared to a corresponding product lacking the fatty acid ester of formula I. As mentioned above, the fatty acid ester of formula I is contained in an amount effective to enhance the deposition of the anti-dandruff agent when tested on a skin model by the test method described herein. The personal care or pharmaceutical product is preferably a rinse-off product, in particular being selected from the group consisting of shampoos, conditioners, shower gels, cleansers, micellar waters, solid formats, and concentrates.

[0030] Examples:

[0031] 1 . Tested materials

[0032] 2. Tested formulation Shampoo formulations pH 5.8 (amounts in wt.-percent) The formulations #01 (without fatty acid ester of formula i) and #02 (with propanediol caprylate as fatty acid ester according to formula I) have been prepared as follows: Phase A materials were blended involving gentle stirring slowly with a glass stirrer. Stirring was stopped when foaming started. Ucare Polymer JR-400 was swelled in water by stirring and warming up to 50°C. Components reflecting phases B, C and D were added to phase A one after the other under gentle stirring.

[0033] 3. Substantivity test

[0034] The depositioning effect of the fatty acid esters of formula I has been tested with the help of a commercial skin model substrate. To this end, VITRO-SKIN substrate, offered by IMS, has been used. The substrate is an advanced testing substrate that effectively mimics the surface properties of human skin. It has been formulated to have topography, pH, critical surface tension, chemical reactivity and ionic strength that is similar to human skin.

[0035] Before use the substrate was treated in a humidity chamber. A defined amount of the formulation to be tested was applied to the skin and distributed for 30 seconds. After 3 minutes the formulation was rinsed with 200ml 37°C water. The skin substrate was extracted for 6h with Acetonitril / Ethanol (1 :1).

[0036] As a control for the success of the extraction, a corresponding test was carried out without rinsing.

[0037] 4. Results

[0038] Deposition of Piroctone Olamine on skin (Recovery rate)

[0039] The relative amount of piroctone olamine recovered from the skin model substrate using the methodology set forth above is depicted in Fig. 1. As shown, the recovery rate of the anti-dandruff agent was found to be significantly increased when a fatty acid ester according to formula I was co-applied (formulation #02), as compared to a corresponding test without fatty acid ester of formula I (formulation #01). 5. Formulation examples

[0040] Cosmetic formulations (compositions) - amounts are indicated as % by weight for all formulations.

[0041] 5.1 Shampoo 5.1.1 Anti Oil Shampoo

[0042] .1 .2 Refreshing Green Body Jello .1.3 Shampoo Sulfate-Free .1.4 Antidandruff Shampoo .1.5 All Natural Shower Jelly .1.6 Aloe Shower Cream .1.7 Fresh Hair shampoo .2 Conditioner .2.1 Detox Refreshing Spray for Hair .2.2 Scalp soothing hair conditioner with UV-B / UV-A protection, rinse off .2.3 Refreshing conditioning Foam .2.4 Hair Refresher Mist

Claims

Claims:1 . Use of a fatty acid ester of formula I as a deposition aid for an anti-dandruff agent,whichR1together with the carboxy group to which it is attached represents a first linear fatty acid group with 5 to 14, preferably 6 to 12, carbon atoms,R2is selected from the group consisting of: .h .ic .hR3together with the carboxy group to which it is attached represents a second linear fatty acid group with 5 to 14, preferably 6 to 12, carbon atoms.

2. Use of claim 1 , wherein the first and / or second fatty acid group is independently selected from the group consisting of n-octanoic acid (caprylic acid), n-decanoic acid(capric acid), n-undecenoic acid (undecylenic acid), and n-dodecanoic acid (lauric acid).

3. Use of claim 1 or 2, wherein the fatty acid ester of formula I is selected from the group consisting of 3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate, 3- hydroxypropyl caprate, 3-hydroxypropyl laurate, propanediol dicaprylate / caprate, propylene glycol caprylate, propylene glycol undecylenate, propylene glycol caprate, and propylene glycol laurate, preferably the fatty acid ester of formula I is selected from the group consisting of 3- hydroxypropyl caprylate, 3-hydroxypropyl undecylenate, 3-hydroxypropyl caprate, 3- hydroxypropyl laurate, and propanediol dicaprylate / caprate; more preferably the fatty acid ester of formula I is selected from the group consisting of 3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate, 3-hydroxypropyl caprate, and 3-hydroxypropyl laurate; most preferably the fatty acid ester of formula I is selected from the group consisting of 3-hydroxypropyl caprylate, and 3-hydroxypropyl undecylenate.

4. Use of any of claims 1 to 3, wherein the anti-dandruff agent is selected from the group consisting of piroctone olamine, ciclopirox olamine, decylene glycol, 1 ,10- decanediol, climbazole, ketoconazole, salicylic acid, sodium salicylate, zinc pyrithione, pyrithione zinc, zinc gluconate, zinc glycyrrhetinate, zinc PCA, copper PCA, sulfur, selenium sulfide, selenium disulfide, o-cymen-5-ol, hexamidine diisetionate, ethyl lauroyl arginate HCI, coal tar, sodium caproyl / lauroyl lactylate, sclareolide, capryloyl glycine, undecylenoyl glycine, succinic acid, sodium usnate, usnic acid, copper usnate, terpineol, 4-terpineol, isosorbide, tea trea oil, Malus Domestica Fruit Cell Culture Extract, Epilobium Angustifolium Flower / Leaf / Stem Extract, Botrytis cinerea / Passiflora Edulis fruit extract / piceatannol ferment filtrate, Apium Graveolens (Celery) Seed Extract, and Morinda Citrifolia Callus Culture Lysate, preferably the anti-dandruff agent is selected from the group consisting of piroctone olamine, ciclopirox olamine, decylene glycol, climbazole, ketoconazole, salicylic acid, o-cymen-5-ol, hexamidine diisetionate, and sodium caproyl / lauroyl lactylate,more preferably the anti-dandruff agent is selected from the group consisting of piroctone olamine, decylene glycol, climbazole, and o-cymen-5-ol, most preferably the anti-dandruff agent is piroctone olamine.

5. Use of any of claims 1 to 4, wherein the fatty acid ester of formula I and the antidandruff agent are co-applied onto scalp or skin of a human.

6. Use of claim 5, wherein the fatty acid ester of formula I is applied in an amount effective to enhance the deposition of the anti-dandruff agent by at least 10%, preferably at least 15%, more preferably at least 20%, yet more preferably at least 25%, yet more preferably at least 30%, most preferably at least 35%, as compared to a corresponding application lacking the fatty acid ester of formula I, preferably the fatty acid ester of formula I is applied in an amount effective to enhance the deposition of the anti-dandruff agent when tested on a skin model substrate using the steps applying a defined amount of the fatty acid ester and the anti-dandruff agent on a surface of the skin model substrate, distributing the fatty acid ester and the anti-dandruff agent on the surface for 30 seconds, rinsing the surface after 3 minutes using 200 mL water at 37°C, and extracting the skin model substrate for 6 hours with a 1 :1 solution of acetonitril and ethanol.

7. Use of any of claims 1 to 6, wherein the fatty acid ester of formula I is contained in a personal care or pharmaceutical product.

8. Use of claim 7, wherein the personal care or pharmaceutical product is a rinse-off product.

9. Use of claim 8, wherein the rinse-off product is selected from the group consisting of shampoos, conditioners, shower gels, cleansers, micellar waters, solid formats, and concentrates.

10. Method of managing Malassezia and / or improving deposition of an anti-dandruff agent, comprising: providing a fatty acid ester of formula I as defined in any of claims 1 to 3, and an antidandruff agent, preferably being selected from the group recited in claim 4,applying the fatty acid ester of formula I and the anti-dandruff agent onto scalp or skin of a human, and optionally rinsing the scalp or skin on which the fatty acid ester of formula I and the anti-dandruff agent has been applied, wherein the fatty acid ester of formula I is applied in an amount effective to enhance the deposition of the anti-dandruff agent by at least 10%, preferably at least 15%, more preferably at least 20%, yet more preferably at least 25%, yet more preferably at least 30%, most preferably at least 35%, as compared to a corresponding application lacking the fatty acid ester of formula I.11 . Method of claim 10, wherein the fatty acid ester of formula I is applied in an amount effective to enhance the deposition of the anti-dandruff agent when tested on a skin model substrate using the steps applying a defined amount of the fatty acid ester and the anti-dandruff agent on a surface of the skin model substrate, distributing the fatty acid ester and the anti-dandruff agent on the surface for 30 seconds, rinsing the surface after 3 minutes using 200 mL water at 37°C, and extracting the skin model substrate for 6 hours with a 1 :1 solution of acetonitril and ethanol.

12. Method of claim 10 or 11 , wherein the fatty acid ester of formula I and the antidandruff agent are co-applied onto the scalp or skin.

13. Method of any of claims 10 to 12, wherein both the fatty acid ester of formula I and the anti-dandruff agent are contained in a rinse-off product, preferably the rinse-off product is selected from the group consisting of shampoos, conditioners, shower gels, cleansers, micellar waters, solid formats, and concentrates.

14. Personal care or pharmaceutical product, preferably rinse-off product, in particular being selected from the group consisting of shampoos, conditioners, shower gels, cleansers, micellar waters, solid formats, and concentrates, comprising: a fatty acid ester of formula I as defined in any of claims 1 to 9, and an anti-dandruff agent, preferably being selected from the group recited in claim 4, wherein the fatty acid ester of formula I is contained in an amount effective to enhance the deposition of the anti-dandruff agent by at least 10%, preferably at least15%, more preferably at least 20%, yet more preferably at least 25%, yet more preferably at least 30%, most preferably at least 35%, as compared to a corresponding product lacking the fatty acid ester of formula I.

15. Personal care or pharmaceutical product of claim 14, wherein the fatty acid ester of formula I is contained in an amount effective to enhance the deposition of the antidandruff agent when tested on a skin model substrate using the steps applying a defined amount of the fatty acid ester and the anti-dandruff agent on a surface of the skin model substrate, distributing the fatty acid ester and the anti-dandruff agent on the surface for 30 seconds, rinsing the surface after 3 minutes using 200 mL water at 37°C, extracting the skin model substrate for 6 hours with a 1 :1 solution of acetonitril and ethanol.

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