Patent Application
20220117867
The present invention primarily relates to a cosmetic product comprising or consisting of a fatty acid ester, or a mixture comprising or consisting of two or more fatty acid esters. Moreover, the present invention relates to various uses of the fatty acid ester, the mixture, or the cosmetic product.
Further aspects and embodiments of the present invention will arise from the description below, in particular from the examples, as well as from the appended patent claims.
The skin is a human body's largest organ. It is colonized by diverse microorganisms, most of which are harmless or even beneficial to their host. Colonization is driven by the ecology of the skin surface, which is highly variable depending on topographical location, endogenous host factors and exogenous environmental factors. For instance, the armpits present a rather humid and nutrient-rich habitat that provides favorable conditions for growth of many microorganisms. Other habitats include sebum-rich habitats like the face and rather dry and nutrient-poor habitats like most other body regions (Barnard & Li (2017) J Physiol 595.2 pp 437-450).
Many common skin pathogens, such as Staphylococcus aureus and Streptococcus pyogenes, are inhibited by an acidic pH, thus the growth of coagulase-negative staphylococci and corynebacteria is favored. However, skin occlusion results in an elevated pH, which favors the growth of S. aureus and S. pyogenes. Areas with a high density of sebaceous glands, such as the face, chest and back, encourage the growth of lipophilic microorganisms such as Propionibacterium spp and Malassezia spp.
Many skin disorders and infections can be caused by bacteria and fungi:
Chronic wounds, affecting diabetic, elderly, and immobile individuals, are an example where commensal skin organisms invade and become pathogenic upon breach of the skin barrier. Although bacteria do not cause the initial wounding event, they are thought to contribute to the lack of healing and persistent inflammation that is associated with chronic wounds. Burn wounds commonly become infected with S. pyogenes, Enterococcus spp. or Pseudomonas aeruginosa.
A further common skin commensal is Staphylococcus epidermidis. It is also the most frequent cause of hospital-acquired infection on in-dwelling medical devices such as catheters or heart valves.
Cosmetics, soaps, hygienic products and moisturizers are potential factors contributing to the variation of skin microbiota. These products alter the conditions of the skin barrier. However, their effects on skin microbiota remain unclear.
Hence, there is a need for products capable of controlling the skin microbiota, and in particular inhibit the growth of skin pathogens.
Cleansing and degerming the skin with a soap or detergent containing an antimicrobial agent may be a useful measure to prevent or treat skin disorders and infections. Short-chain and medium-chain fatty acids display good antimicrobial activity against some microorganisms, such as Malassezia, the causative pathogen of dandruff. However, their practical use in a cosmetic product for topical application is limited by their (i) intense smell, (ii) skin irritation, (iii) lack of skin-substantiveness and (iv) the difficulties they pose during formulation into products.
Various esters of said fatty acids do not display these disadvantageous properties. It is known that some fungi are able to cleave esters of said fatty acids and to release the fatty acids, leading to a “self-kill” of the fungi. However, the hydrolysis rates of esters through the microorganism's enzymes vary strongly depending on the alcohol component of the esters.
In DE 42 37 367 A1 fatty acid esters are described as antimycotic agents. These esters are preferably selected from the group of hexyl laurate, isopropyl stearate, glyceryl monolaurate, caprylic acid triglyceride and capric acid triglyceride.
DE 42 34 188 A1 relates to ethoxylated and propoxylated organic compounds as antimycotic agents in cosmetics.
DE 10 2004 046 603 A1 describes substance mixtures comprising fatty acid esters of polyols and salts of short chain fatty acids to counteract microorganisms.
SU 1286204 A1 discloses the use of a mixture of mono- (50-60%), di- (30-35%) and triesters (10-15%) of glycerol and undecylenic acid to give antimicrobial properties to a cosmetic base.
DE 33 14 786 A1 discloses a mixture with antimycotic activity comprising mono and/or di-10-undecylenic acid glyceryl esters. The mixtures are used in the treatment of nasal cavity mycosis and onychomycosis.
In WO 2006/054110 A2, esters of 1,2,3-propanetriol with one or more C11 to C24 fatty acids are described, wherein at least one fatty acid has at least one double bond. The application field for these substances is the treatment of chronic inflammatory disorders.
WO 2007/095262 A2 discloses 1,3-propanediol esters for the purpose of dissolving botanical extracts, fragrance concentrates and oils.
In view of the prior art, it is not known whether fatty acid esters have broad antimicrobial properties against a plurality of microorganisms of the natural microbiota of mammalian skin (herein also referred to in short as skin microorganisms), and/or or have microbiota balancing or reducing properties indirectly via sebum reduction. It is further not known whether fatty acid esters are suited for use in a cosmetic product, i.e. do not have a negative impact on physicochemical and/or sensory properties of the cosmetic product.
Unpublished, pending patent application PCT/EP2019/052576, filed on 4 Feb. 2019, discloses specific fatty acid esters and their use for treating an excess of Malassezia on the skin surface of mammals, the content of which is incorporated herein in its entirety.
Unpublished, pending patent application PCT/EP2019/052582, filed on 4 Feb. 2019, discloses specific fatty acid esters and their use in modifying the physicochemical properties, particularly increasing the viscosity or of the foam volume of a skin care product, the content of which is incorporated herein in its entirety.
Unpublished, pending patent application PCT/EP2019/052578, filed on 4 Feb. 2019, discloses specific fatty acid esters and their use in modifying the sensory properties of a skin care product, particularly improving the foam formation on the skin or of the skin sensation, the content of which is incorporated herein in its entirety.
It has now been further found by the inventors of the present application that the therein disclosed fatty acids exhibits activity against further microorganisms, particularly bacteria and fungi of the mammalian natural microbiota of the skin or mucosa.
It was thus an object of the present invention to provide active agents that are effective against a variety of microorganisms, in particular bacteria and/or fungi, of the natural microbiota of mammalian skin or mucosa, while at the same time meet an ingredient's requirements for inclusion into a cosmetic product for topical application. In particular, the active agents should not have an intense smell, should not cause skin irritation, should have good skin-substantiveness and should be easy to formulate. Moreover, the active agents should have a neutral, preferably positive, impact on physicochemical and/or sensory properties of the cosmetic product.
According to a first aspect of the present invention, the object is achieved by a cosmetic product comprising:
a fatty acid ester, or
a mixture comprising, or consisting of, two or more fatty acid esters,
wherein the fatty acid ester, or at least one of the two or more fatty acid esters in the mixture, are selected from the group consisting of:
3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate and glyceryl monoundecylenate, preferably from the group consisting of 3-hydroxypropyl caprylate, and 3-hydroxypropyl undecylenate, and
more preferably, wherein the fatty acid ester, or one of the fatty acid esters, is 3-hydroxypropyl caprylate.
As used herein, the term “comprising” means that the named elements are essential, but other elements may be added and is still embraced by the present invention, whereas the term “consisting of” signifies that the subject matter is closed-ended and can only include the limitations that are expressly recited. Whenever reference is made to “comprising” it is intended to cover both meanings as alternatives, that is the meaning can be either “comprising” or “consisting of”, unless the context dictates otherwise.
The present invention is based on the inventors' innovation that specific fatty acid esters confer an advantageous property profile to a cosmetic product, which has not been achieved before. First, the specific fatty acid esters have been found to exhibit antimicrobial activity against a plurality of microorganisms, in particular bacteria and/or fungi, of the natural microbiota of mammalian skin or mucosa. The cosmetic product can therefore be usefully employed in controlling the natural microbiota of the skin or mucosa. Second, the specific fatty acid esters have been found to exhibit antimicrobial activity against microorganisms that are commonly used for preservative testing. Therefore, the cosmetic product is expected to have a good shelf-life. Third, the specific fatty acid esters are associated with improved physicochemical and sensory properties. Addition of the specific fatty acid esters to a cosmetic product thus results in improved physicochemical and sensory properties of the cosmetic product, in particular in terms of an increase of the viscosity, an increase of the foam volume, an improvement of the foam formation on the skin, and an improvement of the skin sensation. In addition, it has been found that the specific fatty acid esters disclosed herein have microbiota balancing or reducing properties indirectly via sebum reduction. The specific fatty acid esters as disclosed herein are therefore a universal tool for conferring beneficial properties to a cosmetic product and can be advantageously used for different types of cosmetic products including crèmes, lotions, shampoos, etc. (further examples are given below).
The cosmetic product as disclosed herein comprises at least one of a specified fatty acid ester. Moreover, it is to be understood that the at least one specified fatty acid ester is present in an antimicrobial effective amount. An antimicrobial effective amount of a compound is an amount, which has to be added to a cosmetic product in order to observe an antimicrobial effect associated with said compound. In preferred cases, the observed antimicrobial effect may be due to a cooperation (e.g. synergism) of the at least one specified fatty acid ester with a further compound. To determine the antimicrobial effective amount of the at least one specified fatty acid ester in a cosmetic product sample, like samples may be prepared that contain different amounts of the at least one specified fatty acid ester, and at least a further like sample that does not contain the at least one specified fatty acid ester. These samples may be used in different antimicrobial tests as described in the examples section herein.
An increase of the viscosity, an increase of the foam volume, an improvement of the foam formation on the skin, and an improvement of the skin sensation can be determined by following routine methods or in analogy to PCT/EP2019/052582, and PCT/EP2019/052578.
As non-limiting examples of mixtures comprising two or more fatty acid esters, mixtures that comprise or consist of one, two, three or all of the two or more fatty acid esters in the mixture are mentioned.
Caprylate refers to an ester of caprylic acid (CAS Registry Number of caprylic acid: 124-07-2; also known as octanoic acid) and undecylenate refers to an ester of 10-undecylenic acid (CAS Registry Number of 10-undecylenic acid: 112-38-9; also known as 10-undecenoic acid).
3-Hydroxypropyl caprylate refers to the monoester of the alcohol 1,3-propanediol (CAS Registry Number: 504-63-2) with caprylic acid, and 3-hydroxypropyl undecylenate refers to the monoester of the alcohol 1,3-propanediol with 10-undecylenic acid.
A preferred embodiment relates to a cosmetic product (as disclosed herein), wherein the cosmetic product is a cosmetic product for topical application on a mammal's skin or mucosa. The mammal is preferably a human. For topical application, the cosmetic products are either rinse off or leave on preparations preferably taking the form of a cleanser, an o/w or w/o emulsion, serum, scrub, lotion, soap, ointment, wax, powder, solution, emulsion, paste, suspension, tablet, gel, stick, aerosol, most preferably taking the form of an aerosol-based deo spray, deo pump spray, deo stick, deo roll on, deo cream, deo wipes, deo crystals, pickering emulsions, hydrodisperion gels, skin balms, shampoo, shower gel, foam bath, micellar water, facial cleansing solutions, cleansing wipes, intimate spray, intimate cream, intimate wash lotion, intimate wipes, aerosol-based foot spray, foot pump spray, foot bath, foot balm, mouth wash concentrate, mouth wash ready to use, and tooth paste.
According to a further preferred embodiment, the cosmetic product is selected from the group consisting of body (including foot) deodorant care products (for example deo spray aerosol based and deo pump spray, deo stick, deo roll on, deo cream, deo wipes, deo crystals, water free deo products), skin care (for example o/w emulsions, w/o emulsions, multiple emulsions, pickering emulsions, hydrodisperion gels, balms, water free products) & cleansing products (for example shampoo, shower gel, foam bath, micellar water, facial cleansing solutions, water free cleansing products, cleansing wipes), intimate care & cleansing products (for example spray, cream, lotion, fluid, surfactant based rinse off preparations, wipes), foot care & cleansing products (for example aerosol spray, pump spray, foot bath, o/w & w/o emulsion, balm), and oral care products (for example mouth wash concentrate, mouth wash ready to use, tooth paste). That is, the cosmetic product is primarily intended to be applied under the armpit, to the face, to the feet, to the intimate region or to the oral mucosa for the primary purposes of providing a hygienic and “healthy” feeling. It is advantageous to formulate the cosmetic product as disclosed herein in a way that enables users to incorporate the desired effects, in particular the desired antimicrobial effect, into their daily hygienic routine. This is achieved by, for example, providing the cosmetic product in the form of the above-mentioned (daily) care products.
A further embodiment of the invention relates to a cosmetic product as defined herein comprising 3-hydroxypropyl caprylate or 3-hydroxypropyl undecylenate or glyceryl monoundecylenate.
Another embodiment of the invention relates to a cosmetic product as defined herein comprising a mixture comprising:
3-hydroxypropyl caprylate or 3-hydroxypropyl undecylenate or glyceryl monoundecylenate, and
at least one further fatty acid ester that does not belong to the fatty acid esters specified in claim 1 (herein also referred as the specified fatty acid esters).
Another embodiment of the invention relates to a cosmetic product as defined herein comprising a mixture comprising at least two fatty acid esters, wherein at least one fatty acid ester is selected from the group consisting of:
3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate and glyceryl monoundecylenate, and at least one further fatty acid ester is selected from the group consisting of:
3-hydroxypropyl caprylate, glyceryl monocaprylate, 3-hydroxypropyl undecylenate and glyceryl monoundecylenate.
Another preferred embodiment of the invention relates to a cosmetic product as defined herein, further comprising one or more 1,2-alkane diol(s), preferably one or more 1,2-alkane diol(s) selected from the group consisting of:
(i) 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, in particular 1,2-octanediol, and/or
(ii) one or more compounds selected from the group consisting of dimethyl phenylbutanol, glyceryl caprylate and Farnesol.
Surprisingly, it was found that the addition of one or more 1,2-alkane diol(s) as defined herein, or a compound as described in item (ii) above, to one or more fatty acid ester as defined herein leads to a synergistic increase in antimicrobial activity against a plurality of microorganisms (as will be demonstrated further below). In terms of a synergistic effect, it is particularly preferred that the one or more fatty acid ester is/are caprylic acid ester(s) or undecylenic acid ester(s) as defined herein, preferably 3-hydroxypropyl caprylate.
Thus, a preferred embodiment of the invention relates to a cosmetic product comprising:
Another embodiment of the invention relates to a cosmetic product as defined herein comprising a mixture of:
Another embodiment of the invention relates to a cosmetic product as defined herein comprising a mixture of:
Another embodiment of the invention relates to a cosmetic product comprising a mixture of:
As described above, the cosmetic product according to the various embodiments described herein may further comprise one or more 1,2-alkane diol(s) as defined herein.
In some embodiment, there may be at least one further fatty acid ester that does not belong to the specified fatty acid esters. In other embodiments, the specified fatty acid ester(s) is (are) the only fatty acid esters comprised in the cosmetic product.
Another preferred embodiment of the invention relates to a cosmetic product as defined herein, wherein the cosmetic product does not comprise any diesters of caprylic acid and/or does not comprise any triesters of caprylic acid and/or does not comprise any ethoxylated variants of caprylic acid and/or does not comprise any diesters of undecylenic acid and/or does not comprise any triesters of undecylenic acid and/or does not comprise any ethoxylated variants of undecylenic acid.
Advantageously, the specified fatty acid esters show particularly high antimicrobial activity against a variety of microorganisms of the natural microbiota of mammalian skin and mucosa. Particularly, binary mixtures of fatty acid esters display a synergistic increase in antimicrobial activity (as will be demonstrated further below). Of particular value in this respect are binary mixtures of a fatty acid ester as disclosed herein and at least one of an 1,2-alkanediol, dimethyl phenylbutanol, glyceryl caprylate and Farnesol. Preferably, in the binary mixtures, the fatty acid ester is 3-hydroxypropyl caprylate. Further preferred is that the 1,2-alkanediol, if present in a binary mixture as disclosed herein, is 1,2-pentanediol, 1-2, hexanediol, or 1,2-octanediol, preferably 1,2 octanediol.
Another preferred embodiment of the present invention relates to a cosmetic product as defined herein, comprising one or more additional active agent(s), preferably one or more antimicrobial agent(s), more preferably one or more active agent(s) selected from the group consisting of clotrimazole (CAS Registry Number 23593-75-1), bifonazole (CAS Registry Number 60628-96-8), miconazole (CAS Registry Number 22916-47-8), ketoconazole (CAS Registry Number 65277-42-1), fluconazole (CAS Registry Number 86386-73-4), climbazole (CAS Registry Number 38083-17-9), itraconazole (CAS Registry Number 84625-61-6), terbinafine (CAS Registry Number 91161-71-6), nystatin (CAS Registry Number 1400-61-9), amorolfine (CAS Registry Number 78613-35-1), ciclopirox (CAS Registry Number 29342-05-0), octopirox (CAS Registry Number 68890-66-4) and undecylenic acid (CAS Registry Number 112-38-9).
A preferred alternative embodiment relates to a cosmetic product as defined herein, which is used in combination with one or more additional active agent(s), preferably with one or more antimicrobial agent(s), more preferably with one or more active agent(s) selected from the group consisting of 2-Methyl 5-cyclohexylpentanol, Dimethyl phenylbutanol, Di methyl phenylpropanol, 2-benzylheptanol, Ethylhexylglycerin, Triethyl citrate, Polyglyceryl-3 caprylate, Polyglyceryl-10 Laurate, glyceryl caprate, polyglyceryl-2 caprate, Zinc ricinoleate, Farnesol, bisabolol, Glyceryl laurate, glyceryl caprylate, Xylityl Sesquicaprylate, decylene glycol, caprylyl glycol, phenylpropanol, lauryl alcohol, o-cymen-5-ol, Octenidine HCl, Undecylenoyl Glycine, Sodium Caproyl/Lauroyl Lactylate, Ethyl Lauroyl, Arginate Laurate, PCA, Ethyl Cocoyl Arginate, Salvia officinalis (Sage) Oil, tropolone, piroctone olamine, triclosan, triclocarban, chloroxylenol, chlorocresol, benzalkonium chloride, benzalkonium bromide, benzalkonium saccharinate, benzethonium chloride, chlorphenesin, alkyl (C12-22) trimethyl ammonium bromide and chloride, zinc pyrithione, climbazole, chlorhexidine, chlorhexidine diacetate, chlorhexidine digluconate, chlorhexidine dihydrochloride, hexamidine, hexamidine diisethionate, silver chloride, and silver citrate.
According to a preferred embodiment, the total amount of the fatty acid ester(s) (as defined herein) comprised in the cosmetic product as defined herein is from 0.01 to 5 wt.-%, more preferably from 0.05 to 2 wt.-%, most preferably from 0.1 to 1 wt.-%, relative to the total weight of said product.
According to another preferred embodiment, in cosmetic products comprising a mixture of two fatty acid esters, the weight ratio between the two fatty acid esters as defined herein is from 10:1 to 1:10, more preferably from 5:1 to 1:5 and most preferably from 3:1 to 1:3.
According to a preferred embodiment, the total amount of the fatty acid ester(s) (as defined herein) and 1,2-alkane diol(s) (as defined herein) comprised in the cosmetic product as defined herein is from 0.1 to 10 wt.-%, more preferably from 0.2 to 5 wt.-%, most preferably from 0.3 to 3 wt.-%, relative to the total weight of said product.
According to another preferred embodiment, the weight ratio between the fatty acid ester(s) (as defined herein) and the 1,2-alkane diol(s) (as defined herein) comprised in the cosmetic product as defined herein is from 20:1 to 1:20, more preferably from 10:1 to 1:10 and most preferably from 5:1 to 1:5.
A second aspect of the present invention relates to the use of a fatty acid ester, or a mixture comprising two or more fatty acid esters, in a cosmetic product for:
(i) inhibiting growth of microorganisms on a mammal's skin or mucosa; and/or
(ii) preserving the cosmetic product, and
optionally:
(iii) modifying physicochemical properties of the cosmetic product, and/or
(iv) improving sensory properties of the cosmetic product on a mammal's skin or mucosa, and/or
(v) balancing and/or reducing sebum production,
wherein the fatty acid ester, or at least one of the two or more fatty acid esters in the mixture, are selected from the group consisting of:
3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate and glyceryl monoundecylenate, preferably from the group consisting of 3-hydroxypropyl caprylate, and 3-hydroxypropyl undecylenate, and
more preferably, wherein the fatty acid ester, or one of the fatty acid esters, is 3-hydroxypropyl caprylate.
The fatty acid ester(s) and the cosmetic product of the second aspect are identical to the fatty acid ester(s) and the cosmetic product of the first aspect. That is, the various embodiments described in the context of the first aspect form corresponding embodiments of the second aspect.
According to a preferred embodiment, the use of a fatty acid ester, or a mixture comprising two or more fatty acid esters, in a cosmetic product as disclosed herein is for:
(i) inhibiting growth of microorganisms on a mammal's skin or mucosa; and
(ii) optionally preserving the cosmetic product; and
(iii) optionally modifying physicochemical properties of the cosmetic product; and
(iv) optionally improving sensory properties of the cosmetic product on a mammal's skin or mucosa; and
(v) optionally balancing and/or reducing sebum production.
According to a further preferred embodiment, the use of a fatty acid ester, or a mixture comprising two or more fatty acid esters, in a cosmetic product as disclosed herein is for:
(i) inhibiting growth of microorganismson a mammal's skin or mucosa; and
(ii) optionally preserving the cosmetic product; and
(iii) modifying physicochemical properties of the cosmetic product, and
(iv) optionally improving sensory properties of the cosmetic product on a mammal's skin or mucosa; and
(v) optionally balancing and/or reducing sebum production.
According to a further preferred embodiment, the use of a fatty acid ester, or a mixture comprising two or more fatty acid esters, in a cosmetic product as disclosed herein is for:
(i) inhibiting growth of microorganisms on a mammal's skin or mucosa; and
(ii) optionally preserving the cosmetic product; and
(iii) optionally modifying physicochemical properties of the cosmetic product, and
(iv) improving sensory properties of the cosmetic product on a mammal's skin or mucosa; and
(v) optionally balancing and/or reducing sebum production.
According to a further preferred embodiment, the use of a fatty acid ester, or a mixture comprising two or more fatty acid esters, in a cosmetic product as disclosed herein is for:
(i) inhibiting growth of microorganisms on a mammal's skin or mucosa; and
(ii) optionally preserving the cosmetic product; and
(iii) modifying physicochemical properties of the cosmetic product, and
(iv) improving sensory properties of the cosmetic product on a mammal's skin or mucosa; and
(v) optionally balancing and/or reducing sebum production.
According to a further preferred embodiment, the use of a fatty acid ester, or a mixture comprising two or more fatty acid esters, in a cosmetic product as disclosed herein is for:
(i) inhibiting growth of microorganisms on a mammal's skin or mucosa; and
(ii) preserving the cosmetic product; and
(iii) modifying physicochemical properties of the cosmetic product, and
(iv) improving sensory properties of the cosmetic product on a mammal's skin or mucosa; and
(v) optionally balancing and/or reducing sebum production.
According to a further preferred embodiment, the use of a fatty acid ester, or a mixture comprising two or more fatty acid esters, in a cosmetic product as disclosed herein is for:
(i) inhibiting growth of microorganisms on a mammal's skin or mucosa; and
(ii) preserving the cosmetic product; and
(iii) modifying physicochemical properties of the cosmetic product, and
(iv) improving sensory properties of the cosmetic product on a mammal's skin or mucosa; and
(v) balancing and/or reducing sebum production.
Preferably, the use is a cosmetic use and/or a non-therapeutic use. This means, it is desirable to use the fatty acid ester or mixture as defined herein cosmetically/non-therapeutically to inhibit the growth of microorganisms on the mammal's skin or mucosa, in particular before a condition or infection of the skin develops, or before any disease symptoms can be observed. It is, for example, possible to use the fatty acid ester(s) or mixtures as defined herein to improve unpleasant conditions associated with excessive sebum production, redness, itching, dryness, flaking, greasiness, hypopigmentation and/or hyperpigmentation of the skin or mucosa, which would not (yet) be categorized as a disease condition.
A preferred embodiment relates to a use, wherein the inhibition of the growth of microorganisms is a reduction of the microorganisms' growth rate, and/or a stagnation or reduction of the number of living microorganisms. A further preferred embodiment of the invention relates to a use, wherein the modification of the sensory properties is an improvement of the foam formation on the skin or mucosa, and/or of the skin or mucosa sensation of the cosmetic product. A further preferred embodiment of the invention relates to a use, wherein the modification of the physicochemical properties is an increase of the viscosity and/or of the foam volume of the cosmetic product.
A use is further preferred, wherein the microorganismsare selected from the group consisting of microorganisms, in particular bacteria and/or fungi, of the natural microbiota of mammalian skin or mucosa. Preferably, the microorganismsare selected from the group consisting of microorganisms from the genus; Staphylococcus; Corynebacterium; Aspergillus; Candida; Escherichia; Peptoniphilus; Streptococcus; Lactobacillus; Gardnerella; Fannyhessea; Epidermophyton; Trichophyton; Fusobacterium, and combinations threreof. Preferably, the microorganisms are selected from the group consisting of: S. epidermidis; Staphylococcus hominis; Corynebacterium xerosis; Aspergillus brasiliensis; Candida albicans; Escherichia coli; Staphylococcus aureus; Peptoniphilus lacrimalis; Streptococcus agalactiae; Lactobacillus acidophilus; Gardnerella vaginalis; Fannyhessea vaginae (Atopobium vaginae); Epidermophyton floccosum; Trichophyton rubrum; Streptococcus mutans; Fusobacterium nucleatum, and combinations threreof. The cosmetic product as disclosed herein showed excellent antimicrobial activities against these microorganisms.
A third aspect of the present invention relates to a cosmetic product as disclosed herein for use in a method of antimicrobial therapy of a mammal by topical application of the cosmetic product on the mammal's skin or mucosa in at least a region of the skin or mucosa infested with microorganisms. Again, the various embodiments described in the context of the first aspect form corresponding embodiments of the third aspect.
For the purposes of the present invention, the term “therapy” encompasses prevention of a condition of the skin or mucosa, or a prevention of symptoms associated with said condition, or a restoral of the health of a mammal having a condition of the skin or mucosa, or relief of symptoms associated with said condition. Prevention can be achieved by applying the cosmetic product as defined herein in repeated time intervals such as once in a week, once every other day, or once daily, to regions of the skin or mucosa, where occurrence of a condition should be avoided. Treatment can be achieved by applying the cosmetic product once or repeatedly to a region of the skin or mucosa, which shows symptoms of a condition of the skin or mucosa.
According to a preferred embodiment, the antimicrobial therapy is a therapy of a condition or infection of the skin or mucosa involving an excess of the microorganisms in at least the region of the skin or mucosa. As defined herein, an excess of microorganisms on the skin or mucosa of a mammal, preferably a human, relates to a situation where the total amount of cells of a given microbial species present on said skin or mucosa leads to symptoms of conditions or infections of the skin or mucosa such as, for example, redness, itching, dryness, flaking, greasiness, hypopigmentation and/or hyperpigmentation of the skin.
According to a further preferred embodiment, the microorganisms are selected from the group consisting of microorganisms, in particular bacteria and/or fungi, of the natural microbiota of mammalian skin or mucosa. Preferably, the microorganisms are selected from the group consisting of microorganisms from the genus Staphylococcus; Corynebacterium; Aspergillus; Candida; Escherichia; Peptoniphilus; Streptococcus; Lactobacillus; Gardnerella; Fannyhessea; Epidermophyton; Trichophyton; Fusobacterium, and combinations threreof. Preferably, the microorganisms are selected from the group consisting of: S. epidermidis; Staphylococcus hominis; Corynebacterium xerosis; Aspergillus brasiliensis; Candida albicans; Escherichia coli; Staphylococcus aureus; Peptoniphilus lacrimalis; Streptococcus agalactiae; Lactobacillus acidophilus; Gardnerella vaginalis; Fannyhessea vaginae (Atopobium vaginae); Epidermophyton floccosum; Trichophyton rubrum; Streptococcus mutans; Fusobacterium nucleatum, and combinations threreof.
In some embodiments, the microorganisms do not belong to the genus of Malassezia.
A method for reducing the growth of microorganisms on the skin or mucosa of mammals, preferably humans, in particular of humans in need thereof (i.e. of humans showing one or more symptoms of a (unpleasant or disease) condition of the skin or mucosa (such as, for example, body or scalp malodor, redness, itching, dryness, flaking, greasiness, hypopigmentation and/or hyperpigmentation of the skin) comprising the step of applying a cosmetic product as disclosed herein to a region of the skin or mucosa, is further disclosed herein. The cosmetic product is preferably selected from the group consisting of body (including foot) deodorant care products (for example deo spray aerosol based and deo pump spray, deo stick, deo roll on, deo cream, deo wipes, deo crystals, water free deo products), skin care (for example o/w emulsions, w/o emulsions, multiple emulsions, pickering emulsions, hydrodisperion gels, balms, water free products), cleansing products (for example shampoo, shower gel, foam bath, micellar water, facial cleansing solutions, water free cleansing products, cleansing wipes), intimate care & cleansing products (for example spray, cream, lotion, fluid, surfactant based rinse off preparations, wipes) foot care & cleansing products (for example aerosol spray, pump spray, foot bath, o/w & w/o emulsion, balm) and oral care products (for example mouth wash concentrate, mouth wash ready to use, tooth paste). Accordingly, the method as disclosed herein is particularly useful for the purpose of improving body odor, hygiene and/or cleansing.
The present disclosure also relates to a cosmetic product as disclosed herein, wherein the fatty acid ester is glyceryl monocaprylate in place of 3-hydroxypropyl caprylate, 3-hydroxypropyl undecylenate and/or glyceryl monoundecylenate.
The various aspects and embodiments described herein are meant to be combinable with each other unless the context dictates otherwise.
In the following drawings:
The invention will now be described in more detail hereinafter with references to selected examples.
1. Methods
A) Minimum Inhibitory Concentration (MIC) Method A
The MIC test is a test on growth inhibition. Estimation of Minimum Inhibitory Concentration (MIC) is executed in 96 well plates. Through the comparison of bacterial growth curves with positive and negative controls via optical density (OD), different concentrations of given test substances are evaluated.
Bacteria are cultivated under adjusted conditions based on information of the German Collection of Microorganisms and Cell Cultures (DSMZ) and stored in 50% Glycerol prior to use. Afterwards, the following method was applied:
Adding growth medium (according to microorganism) to each well of the microplate.
Adding the test-substances in different concentrations, positive controls (water controls only with medium) and negative controls (benchmarks according to organism).
Adding the microorganism in a concentration of 106 CFU/ml (CFU=colony forming units). Incubation of the microplates at appropriate conditions.
Aerobic microorganism: optical density is continuously measured (microplate reader) during incubation.
Anaerobic microorganism: incubation in an anaerobic chamber, measurement of the optical density at the end of the incubation, comparison of the results with positive and negative controls.
According to resulting growth curves, substance concentrations are labelled either as inhibiting or normal growth and MIC is defined as the lowest concentration where a clear inhibition is visible. Experiments at concentration limits (highest concentration labelled as growth and lowest concentration labelled as inhibiting) are performed at least twice.
B) Minimum Inhibitory Concentration (MIC) Method B
Test conditions: Evaluation of bactericidal and fungicidal activity in qualitative suspension test (VAH-standard methods, 04-2015). 5 ml of the appropriate dilution of the test product is mixed with 0.1 ml of test suspension and mixed well. After the required action times, the mixture was mixed again. Each 0.1 ml were removed and placed in 5 ml of CSL-bouillon without neutralizing agents.
C) Preservative Efficacy Test
Test conditions: Sample (1% test substance in adequate formulation (o/w emulsion)) was inoculated with 0.1 ml of the microbial suspensions, homogenized, and incubated at 20° C.-25° C. Colony count was determined after 2, 7, 14, and 28 days of incubation through plating on adequate solid medium.
2. Results
3-hydroxypropyl caprylate (Error! Reference source not found.), 3-hydroxypropyl undecylenate (Table 2), and glyceryl monoundecylenate (Table 3) were tested on several bacterial and fungal reference strains for application in different body regions using methods A and B (page 16). Obtained results indicate a potential use of both 3-hydroxypropyl caprylate and 3-hydroxypropyl undecylenate in Deodorant-, Skin-, Intimate-, Foot-, and Oral care products. Likewise, several reference strains for preservation showed low MIC values. Likewise, glyceryl monoundecylenate shows low MIC against C. xerosis, indicating at least a compareable application.
Corynebacterium xerosis
Staphylococcus epidermidis
Staphylococcus hominis
Aspergillus brasiliensis
Candida albicans
Escherichia coli
Staphylococcus aureus
Peptoniphilus lacrimalis
Streptococcus agalactiae
Gardnerella vaginalis
Fannyhessea vaginae
Epidermophyton floccosum
Trichophyton rubrum
Streptococcus mutans
Porphyromonas gingivalis
Fusobacterium nucleatum
Prevotella intermedia
Staphylococcus epidermidis
Corynebacterium xerosis
Aspergillus brasiliensis
Staphylococcus aureus
Corynebacterium xerosis
3-hydroxypropyl caprylate was tested in a potential formulation against the microorganisms Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans using method C. Resulting colony counts are depicted in Table 4.
E. coli
P. aeruginosa
S. aureus
C. albicans
E. coli
P. aeruginosa
S. aureus
C. albicans
The synergistic activity of 3-hydroxypropyl caprylate and antimicrobial diols against Epidermophyton floccosum was determined by measuring minimum inhibitory concentrations (MIC values) according to DIN 58940 and method B (method section above). The results are shown in Table 5,
Table 6, and Table 7.
In order to calculate the synergy index with MIC values, the Kull equation (I) was used as follows:
SI=(MICmixture×PA)/MICA+(MICmixture×PB)/MICB (I)
wherein
SI is the Synergy Index according to Kull
MICA is the MIC value for Substance A
MICB is the MIC value for Substance B
MICmixture is the MIC value for the mixture of substances A and B
PA is the proportion of the substance A in the mixture
PB is the proportion of the substance B in the mixture
Epidermophyton floccosum
Epidermophyton floccosum
Epidermophyton floccosum
The Synergy Index for the combination of 3-hydroxypropyl caprylate with different antimicrobial diols against Epidermophyton floccosum, calculated according to Kull's equation (I) is below 1 for all cases, indicating a synergism between 3-hydroxypropyl caprylate and 1,2-Pentanediol, 1,2-Hexanediol, or 1,2-Octanediol.
To verify that the tested combinations act synergistically against other microorganisms of the natural microbiota of mammalian skin, a corresponding experiment was conducted with Corynebacterium xerosis using the combination of 3-hydroxypropyl caprylate and 1,2-octanediol as an example. The MIC values of 3-hydroxypropyl caprylate and 1,2-octanediol against Corynebacterium xerosis are 500 ppm and 2500 ppm, respectively. For a 1:1 mixture of 3-hydroxypropyl caprylate and 1,2-octanediol a MIC value of 500 ppm was determined, resulting in a Synergy Index of 0.600.
The synergistic activity of 3-hydroxypropyl caprylate and dimethyl phenylbutanol on several bacterial and fungal reference strains for application in either Deodorant application or as preservative was determined by measuring minimum inhibitory concentrations (MIC values) according to DIN 58940 and method A (method section above). The results are shown in Table 8,
Table 9, and Table 10.
S. epidermidis
A. brasiliensis
E. coli
S. aureus
S. epidermidis
A. brasiliensis
E. coli
S. aureus
S. epidermidis
A. brasiliensis
E. coli
S. aureus
The Synergy Index SI for the combination of 3-hydroxypropyl caprylate and dimethyl phenylbutanol against the strain related to deodorant applications (Staphylococcus epidermidis) and strains related to preservative function (Aspergillus brasiliensis, Escherichia coli, Staphylococcus aureus) calculated according to Kull's equation (I) is below 1 in all cases tested, indicating a synergism between both substances.
The synergistic activity of 3-hydroxypropyl caprylate and glyceryl caprylate on several bacterial and fungal reference strains for application in either Deodorant application or as preservative was determined by measuring minimum inhibitory concentrations (MIC values) according to DIN 58940 and method B (method section above).
The results are shown in Table 11, Table 12, and Table 13.
S. hominis
C. xerosis
A. brasiliensis
E. coli
S. hominis
C. xerosis
A. brasiliensis
E. coli
S. hominis
C. xerosis
A. brasiliensis
E. coli
The Synergy Index SI for the combination of 3-hydroxypropyl caprylate and glyceryl caprylate against the strain related to deodorant applications (Staphylococcus hominis) and Aspergillus brasiliensis as a strain related to preservative function, calculated according to Kull's equation (I), is below 1 in all cases tested, indicating a synergism between both substances.
The synergistic activity of 3-hydroxypropyl caprylate and Farnesol on Corynebacterium xerosis for application in deodorant was determined by measuring minimum inhibitory concentrations (MIC values) according to DIN 58940 and method B (method section above).
The results are shown in Table 14, Table 15, and Table 16.
C. xerosis
C. xerosis
C. xerosis
The Synergy Index SI for the combination of 3-hydroxypropyl caprylate and Farnesol against the test strain related to deodorant applications, calculated according to Kull's equation (I) is 0.516 for Corynebacterium xerosis, indicating synergism between both substances.
Additional tests were performed with human sebaceous glands in order to verify the modulatory activity of a compound on sebum secretion. For this sebaceous glands had been micro-dissected and cultured with medium. The medium without any supplement served as untreated control. Medium with 5 μM Capsaicin served as positive control. Additionally, culture medium was supplemented with different concentrations of 3-hydroxypropyl caprylate. After six days the sebaceous glands were collected and lipids and proteins quantified. The total lipid amount being representative of sebum production was obtained by normalizing the quantified lipids upon the quantified proteins (i.e. mg of lipids/mg of proteins).
As shown in
The perfume oils PO1, PO2, PO3, PO4, or PO5 from the above examples were worked separately in each case into the formulations presented below.
Cosmetic formulations (compositions)—amounts are indicated as % by weight for all formulations.
Mauritia Flexuosa Fruit Oil
Theobroma Cacao (Cocoa) Seed Butter
Butyrospermum Parkii (Shea) Butter
Echinacea Purpurea Extract
Alba)
Virginiana (Witch Hazel) Water,
Helianthus Annuus (Sunflower) Seed
Prunus dulcis
Zingiber Officinale (Ginger) Root
Cera Alba
Prunus Dulcis
Butyrospermum Parkii
Rosmarinus officinalis
Sinensis Leaf Extract
officinalis (Rosemary) Leaf Extract
Theobroma Grandiflorum Seed Butter
Simmondsia Chinensis (Jojoba) Seed Oil
Calophyllum Inophyllum Seed Oil
Triticum Vulgare (Wheat) Germ Oil
Avena Sativa (Oat)
Zingiber Officinale
Bertholletia Excelsa Seed Oil
Simmondsia Chinensis (Jojoba) Seed Oil
Persea Gratissima
Butyrospermum Parkii (Shea) Butter
Persea Gratissima (Avocado) Oil
Butyrospermum Parkii (Shea)
Aurantium Dulcis (Orange) Juice,
Citrus Paradisi (Grapefruit) Juice,
Pyrus Malus (Apple) Juice,
Dulcis (Sweet Almond) Seed Extract
Camellia Sinensis Leaf
Avena Sativa (Oat) Kernel
Rosmarinus Officinalis (Rosemary)
Aloe Barbadensis Leaf Juice
Echinacea Purpurea Extract
Fucus Vesiculosus Extract)
Sativa (Oat) Kernel Extract
Hamamelis Virginiana (Witch Hazel)
Pelargonium Graveolens
| Number | Date | Country | Kind |
|---|---|---|---|
| PCT/EP2019/052576 | Feb 2019 | EP | regional |
| PCT/EP2019/052578 | Feb 2019 | EP | regional |
| PCT/EP2019/052582 | Feb 2019 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2020/051507 | 1/22/2020 | WO | 00 |
