RU2792104C2 - Prebiotic-based compositions and methods for maintaining healthy skin microbiota - Google Patents

Abstract

FIELD: cosmetology.

SUBSTANCE: group of inventions relates to the field of cosmetology and medicine and can be used to provide or maintain the microbiota of healthy skin. A composition is proposed to provide or maintain the microbiota of healthy skin, containing a carrier and a means to balance the microbiota of the skin, which contains a combination of certain prebiotics. A method is also proposed to ensure or maintain the microbiota of healthy skin in the subject, providing for the introduction of this composition based on prebiotics to the subject.

EFFECT: group of inventions provides a balanced growth of commensal skin bacteria to maintain a healthy and natural microbiota of human skin, as well as the ratio of Corynebaderium to Staphylococcus, which is 1.3, the ratio of Corynebaderium to Micrococcus, which is 1.4 and the ratio of Staphylococcus to Micrococcus, which is 1.1.

5 cl, 1 dwg, 6 tbl

Description

BACKGROUND OF THE INVENTION

Human skin serves as the main physical barrier to protect the body from the external environment. This biological boundary includes many bacteria and fungi that help maintain the barrier function provided by the skin. It is believed that the skin has a low number of bacteria, but a large variety of them. Such a wide variety of bacteria creates a complex relationship between resident bacteria, transient bacteria, interaction between such bacteria, the skin and the immune system of the host. These relationships are important for healthy skin.

Healthy skin can be affected by a number of factors. Intrinsic factors, such as host genetic characteristics and biochemical properties of the skin, as well as extrinsic factors, such as hygiene practices and environmental conditions of the host, can shift the skin microbiota from its typical state to a dysbiotic state, which can lead to breakdown of the skin barrier and potentially to disease. The microbiota of healthy skin consists of several types of bacteria living in different proportions in the skin niche.

There are prebiotics that can be beneficial for various bacteria. However, the use of some existing prebiotics can lead to disproportionate growth of host skin bacteria and thus can disrupt natural relationships within the natural skin microbiota.

Thus, there is currently a need for improved compositions that can provide and maintain a healthy balance and proportion of commensal skin bacteria that result in a well-balanced skin microbiota, as well as methods for maintaining such a skin microbiota.

BRIEF DESCRIPTION OF THE INVENTION

It has now surprisingly been found that various compositions including skin microbiota balancing agents can provide a balanced growth of commensal skin bacteria to maintain a healthy and natural human skin microbiota. These compositions may be well suited for topical application to the skin of a human subject to help promote and maintain a healthy balance of the skin microbiota, and may be delivered to the skin via a variety of delivery mechanisms and methods.

Accordingly, in one embodiment, a composition for providing or maintaining healthy skin microbiota may include a carrier. The composition may also include an agent that balances the microbiota of the skin. The skin microbiota balancing agent may include at least one combination of carbohydrate sources, including a first carbohydrate source and a second carbohydrate source. The skin microbiota balancer may be configured to provide at least two of the following desired ratios: a first desired ratio of Corynebacterium to Staphylococcus, a second desired ratio of Corynebacterium to Micrococcus, and a third desired ratio of Staphylococcus to Micrococcus.

In another embodiment, a composition for providing or maintaining healthy skin microbiota may include a carrier. The composition may also include an agent that balances the microbiota of the skin. The skin microbiota balancing agent may include at least one combination of carbohydrate sources. The carbohydrate source combination may be selected from the group consisting of the following: D-alanine + 3-methylglucose, D-alanine + oxalic acid, L-alanylglycine + γ-cyclodextrin, L-alanylglycine + inulin, L-alanylglycine + sebacic acid, L -alanylglycine + 2,3-butanediol, L-alanylglycine + 3-hydroxy-2-butanone, D-sugar acid + oxalic acid + L-alanine, succinic acid + oxalic acid + L-alanine, succinic acid + pectin + L- alanine, Tween 40 + oxalic acid + L-alanine, Tween 40 + pectin + L-alanine, α-ketoglutaric acid + inulin + glycyl-L-aspartic acid, α-ketoglutaric acid + sebacic acid + glycyl-L-aspartic acid, α-ketoglutaric acid + 3-hydroxy-2-butanone + glycyl-L-aspartic acid, mesotartaric acid + oxalic acid + L-alanine, mesotartaric acid + pectin + L-alanine, brosuccinic acid + γ-cyclodextrin + D-glucosamine acid , brosuccinic acid + γ-cyclodextrin + glycyl-L-aspartic acid, brosuccinic acid ta + inulin + D-glucosamine acid, brosuccinic acid + inulin + glycyl-L-aspartic acid, brosuccinic acid + 3-methylglucose + D-glucosamine acid, brosuccinic acid + 3-methylglucose + glycyl-L-aspartic acid, brosuccinic acid + sebacic acid + D-glucosamine acid, brosuccinic acid + sebacic acid + glycyl-L-aspartic acid, brosuccinic acid + 2,3-butanediol + D-glucosamic acid, brosuccinic acid + 3-hydroxy-2-butanone + D-glucosamine acid , brosuccinic acid + pectin + D-glucosamine acid, brosuccinic acid + pectin + glycyl-L-aspartic acid, phenylethylamine + α-cyclodextrin + N-acetyl-D-galactosamine, phenylethylamine + turanose + N-acetyl-D-galactosamine, phenylethylamine + L-homoserine + N-acetyl-D-galactosamine, phenylethylamine + 2,3-butanediol + N-acetyl-D-galactosamine and phenylethylamine + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine.

In yet another embodiment, a method of providing or maintaining healthy skin microbiota in a subject may include providing a prebiotic composition configured to maintain at least one of a first desired ratio of Corynebacterium to Staphylococcus, a second desired ratio of Corynebacterium to Micrococcus, and a third desired ratio of Staphylococcus to Micrococcus. The prebiotic composition may include a carrier. The prebiotic composition may also include a skin microbiota balancing agent. The skin microbiota balancing agent may include at least a first source of carbohydrate. The first carbohydrate source may be selected to support at least one of the first desired ratio of Corynebacterium to Staphylococcus, the second desired ratio of Corynebacterium to Micrococcus, and the third desired ratio of Staphylococcus to Micrococcus. The method may further comprise providing instructions for use of the prebiotic composition to the subject.

BRIEF DESCRIPTION OF GRAPHICS

A complete and sufficient disclosure of the present invention, intended for a person skilled in the art, is set forth more specifically in the remainder of the description, which provides reference to the accompanying drawings, on which:

in fig. 1 is a graph showing the twelve exemplary carbohydrate sources from Table 3 and plotted the difference between the respective calculated ratio and the required ratio of Corynebacterium to Staphylococcus (C:S), Corynebacterium to Micrococcus (C:M), and Staphylococcus to Micrococcus (S:M) for each of twelve exemplary carbohydrate sources.

DEFINITIONS

As used herein, the term "absorbent article" refers to an article that can be placed on the body of the wearer or in close proximity (i.e., adjacent to the body) to absorb and contain various liquid, solid and semi-solid waste products emerging from organism. It should be appreciated that the present disclosure applies to a variety of disposable absorbent products, including, but not limited to, diapers, diaper briefs, potty training briefs, teen briefs, swim trunks, feminine hygiene products, including but not limited to menstrual pads or briefs, products for incontinence, medical garments, surgical pads and bandages, other personal care or health care garments, and the like, without departing from the scope of the present invention.

As used herein, the term “skin microbiota balancer” refers to any carbohydrate source or combination of carbohydrate sources that provides a calculated ratio of commensal skin bacteria within ±0.25 units of the corresponding required ratio of such commensal skin bacteria.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to compositions and methods useful in providing and maintaining a healthy skin microbiota for human subjects. The compositions are particularly well suited for topical application to the skin, and in particular to dry to semi-moist areas of the skin. The compositions can be applied directly to the skin, for example in the form of a liquid, cream or aerosol. Alternatively or additionally, the compositions may be applied to the skin via a delivery mechanism, such as, for example, a tissue paper backing, or by application to an absorbent article that can deliver the composition to the skin.

Targets for the required ratios between various commensal skin bacteria have been developed from a variety of sources providing values for the relative abundance of various commensal skin bacteria. Skin areas examined include dry and semi-moist skin areas such as arms, legs, back, buttocks, etc. For example, it has been documented that the relative abundance of Corynebacterium, Staphylococcus, and γ-proteobacteria in moist areas of the skin (e.g., inside the nostrils, armpit, inside of the elbow, between the fingers, lateral groin, gluteal fold, under the knee, navel, etc. .) may vary from about 4% to about 65%, from about 8% to about 48%, and from about 1% to about 10%, respectively. The relative abundance of Micrococcus on the shoulder blade has been documented to be approximately 40%. Based on this, the following ratios of commensal bacteria were chosen: 65% for Corynebacterium, 48% for Staphylococcus, 45% for Micrococcus, and 10% for γ-proteobacteria. These ratios were then normalized to 100% to provide the following values: Corynebacterium 38.69%, Staphylococcus 28.57%, Micrococcus 26.79% and γ-proteobacteria 5.95%. These percentages were then used to calculate the required ratios of Corynebacterium to Staphylococcus (1.3), Corynebacterium to Micrococcus (1.4), and Staphylococcus to Micrococcus (1.1) in the healthy skin microbiome. This necessary relationship was created because the bacteria Corynebacterium, Staphylococcus and Micrococcus can provide the vast majority of commensal bacteria in the microbiome of dry-semi-moist healthy skin. As will be discussed further below, the required ratios of Corynebacterium to Staphylococcus (1.3), Corynebacterium to Micrococcus (1.4), and Staphylococcus to Micrococcus (1.1) were used in a further study to model the respective carbohydrate sources and combinations of carbohydrate sources that could be applicable as a means of balancing the microbiota of the skin.

Products that balance the microbiota of the skin

After creating the necessary ratios of various commensal skin bacteria in the healthy skin microbiome, 188 different carbohydrate sources were screened as the next step in identifying potential prospects for skin microbiota balancing agents. A screening process was provided to determine which carbohydrate sources stimulate commensal and/or pathogenic bacteria, as well as to obtain single carbohydrate sources or combinations thereof that can serve as microbiota balancing agents that can provide or maintain healthy proportions of commensal skin bacteria Corynebacterium, Staphylococcus and Micrococcus. Screening was performed using a Biolog phenotypic data analysis microarray (Hayward, CA). Table 1 provides a coded list of commensal and pathogenic skin bacteria for which carbohydrate screening was performed.

Table 1. Bacterial codes for carbohydrate screening

Table 2 presents screening results for various carbohydrate sources compared to the commensal and pathogenic bacteria codes listed in Table 1. Bacteria codes B, D, E, I, and J represent commensal bacteria and are shaded in Table 2 for reference. Bacteria of each code were placed on a carbon microchip and screened using the Carbohydrate Screening Test Method as described in the Test Methods section of this document. If bacteria of a particular code used a specific carbohydrate source as described in the Carbohydrate Screening Testing Method, then the corresponding cell in Table 2 was labeled Y (short for "Yes" ("yes")). If bacteria of a particular code did not use a carbohydrate source, then the corresponding cell in Table 2 was left blank. Many carbohydrate sources have been used by both commensal and pathogenic bacteria and as such have not been advantageous for the selective growth of commensal bacteria. However, some carbohydrate sources have only been used by commensal bacteria and have been identified for further testing as described herein.

Table 2 Carbohydrate Screening Results

As shown in the results from Table 2, 154 different carbohydrate sources were used by bacteria in at least one of the tested codes. Of these 154 different carbohydrate sources, 79 were used only by commensal bacteria and 27 were used only by pathogenic bacteria. In addition, 34 additional carbohydrate sources were tested, but they were not used by any of the bacteria and therefore were not listed in Table 2. The carbohydrate sources that were not used by any of the bacteria of the codes tested were: D-serine, D-ribose , Tween 20, 2-deoxyadenosine, glycyl-L-proline, p-hydroxyphenylacetic acid, L-lyxose, glycogen, laminarin, N-acetyl-neuraminic acid, β-D-allose, L-arabitol, 2-deoxy-D- ribose, erythritol, D-fucose, L-glucose, a-methyl-D-glucoside, β-methyl-D-xyloside, sedoheptulosan, D-tagatose, xylitol, 2-hydroxybenzoic acid, γ-hydroxybutyric acid, a-ketovaleric acid , 5-keto-D-gluconic acid, sorbic acid, D-tartaric acid, glycine, hydroxy-L-proline, L-lysine, L-phenylalanine, L-valine, sec-butylamine, and 2,3-butanone.

For 79 carbohydrate sources that were used only by commensal bacteria, additional analysis was performed to identify agents that ensure the balance of the skin microbiota. To do this, the corresponding data obtained from the microarray for 79 carbohydrate sources were processed using the GrowthRates 2.1 program to obtain growth parameters, such as growth rate values, and maximum yield data, as described by the Belingham Research Institute, Hall, B.G., H. Acar and M. Barlow. 2014 Growth Rates Made Easy. Mol. Biol. Evol. 31:232-238 doi:10.1093/molbev/mst197. The maximum yield parameters obtained were used to calculate the ratios of the tested commensal bacteria. The calculated ratios were compared with the required ratios defined above (corynebacterium to Staphylococcus ratio of 1.3, Corynebacterium to Micrococcus ratio of 1.4 and Staphylococcus to Micrococcus ratio of 1.1). The results of this method are shown in Table 3, with the ratios of the different genera of bacteria mentioned above reduced for formatting purposes such that Corynebacterium and Staphylococcus are given as C:S, Corynebacterium and Micrococcus are given as C:M, and Staphylococcus and Micrococcus are given as S:M. As described in the definitions section of this document, a skin microbiota balancer is any carbohydrate source or combination of carbohydrate sources that provides a calculated ratio of commensal bacteria within ±0.25 units of the corresponding required ratio of such commensal bacteria. As a reference, the cells in Table 3 were highlighted, which include the calculation of the ratio difference of the respective commensal bacteria within ±0.25.

As an example of this method used to calculate the ratios of commensal bacteria and the difference between the calculated ratios and the required ratios, an illustrative code from Table 3 will be described. C. jeikeium and M. luteus SK58 achieved maximum yields of 0.157 and 0.098, respectively, when grown in the presence of D- alanine. S. epidermidis M23864:W2 achieved a maximum yield of 0.123 in the presence of 3-methylglucose. Thus, if D-alanine and 3-methylglucose were mixed together (code no. 12 in Table 3), the mixture was expected to support the growth of all three commensal bacteria. The maximum yields were then used to calculate the ratios that the bacteria could achieve when co-cultured. The calculated ratios for this example, as well as those shown in Table 3, are as follows: Corynebacterium to Staphylococcus (1.28), Corynebacterium to Micrococcus (1.60), and Staphylococcus to Micrococcus (1.26). The difference between the required ratios and each of the respective calculated ratios is a maximum of ±0.20, since the difference between the required Corynebacterium to Staphylococcus ratio of 1.3 and the calculated Corynebacterium to Staphylococcus ratio of 1.28 is 0.02, the difference between the desired ratio of Corynebacterium to Micrococcus of 1.4 to the calculated ratio of Corynebacterium and Micrococcus of 1.6 is -0.20, and the difference between the desired ratio of Staphylococcus to Micrococcus of 1.1 and the calculated ratio of Staphylococcus to Micrococcus, component 1.26 is -0.16. Thus, the combination of D-alanine + 3-methylglucose (Code No. 12) was the preferred carbohydrate source combination as it provided all three required ratios of commensal Corynebacterium to Staphylococcus of 1.3, Corynebacterium to Micrococcus of 1.4, and Staphylococcus to Micrococcus of 1.1 if each of the calculated ratios is within ±0.25 units of the corresponding required ratio.

Table 3. Results of the method of analysis of carbohydrate sources as a means of ensuring the balance of the skin microbiota

As can be seen from Table 3, the method involved calculating the ratios for Corynebacterium to Staphylococcus, Corynebacterium to Micrococcus, and Staphylococcus to Micrococcus for 2532 unique carbohydrate sources that included one or more carbohydrates. As discussed above, a skin microbiota balancer can be considered any carbohydrate source or combination of carbohydrate sources that provides at least one of the required ratios of Corynebacterium to Staphylococcus, Corynebacterium to Micrococcus, and Staphylococcus to Micrococcus, providing a calculated ratio of commensal bacteria within ±0.25 of the respective required ratio of commensal bacteria (corynebacterium to Staphylococcus ratio of 1.3, Corynebacterium to Micrococcus of 1.4, and Staphylococcus to Micrococcus of 1.1). Through the screening process described above, the large number of carbohydrate sources analyzed in Table 3 provided at least one of the required ratios and thus could serve as a means of balancing the skin microbiota. However, far fewer carbohydrate sources tested provided two or more of the required ratios, or even more preferably all three of the required ratios.

Analyzing the results in Table 3, only 119 of the 2532 carbohydrate combinations tested provided two or more of the required ratios of Corynebacterium to Staphylococcus, Corynebacterium to Micrococcus, and Staphylococcus to Micrococcus. These skin microbiota balancers that provided the two or three required ratios of Corynebacterium to Staphylococcus, Corynebacterium to Micrococcus, and Staphylococcus to Micrococcus were: D-alanine + γ-cyclodextrin, D-alanine + sebacic acid, D-alanine + 2, 3-butanediol, D-aspartic acid + oxalic acid, D-aspartic acid + pectin, D-threonine + 3-methylglucose, D-threonine + pectin, fumaric acid + α-cyclodextrin, fumaric acid + mannan, L-alanylglycine + 3 -methylglucose, L-alanylglycine + oxalic acid, L-alanylglycine + pectin, L-malic acid + mannan, D-sugar acid + pectin + L-alanine, succinic acid + 3-methylglucose + D-glucosamine acid, succinic acid + 3 -methylglucose + L-alanine, succinic acid + 3-methylglucose + glycyl-L-aspartic acid, succinic acid + pectin + D-glucosamine acid, succinic acid + pectin + glycyl-L-aspartic acid, Tween 40 + 3-methylglucose + D-glucosamine acid, Tween 40 + 3-methylglucose + L-alanine, Tween 40 + 3-methylglucose + glycyl-L-aspartic acid, Tween 40 + pectin + D-glucosamic acid, Tween 40 + pectin + glycyl-L-aspartic acid, α-ketoglutaric acid + γ-cyclodextrin + glycyl-L-aspartic acid, α-ketoglutaric acid + inulin + D-glucosamine acid, α-ketoglutaric acid + 3-methylglucose + glycyl-L-aspartic acid, α-ketoglutaric acid + γ-aminobutyric acid + glycyl-L-aspartic acid, α-ketoglutaric acid + sebacic acid + D-glucosamine acid, α-ketoglutaric acid + 2,3-butanediol + glycyl-L-aspartic acid, α-ketoglutaric acid + 3-hydroxy-2- butanone + D-glucosamine acid, α-ketobutyric acid + α-cyclodextrin + N-acetyl-D-galactosamine, α-ketobutyric acid + inulin + D-glucosamine acid, α-ketobutyric acid + inulin + glycyl-L-aspartic acid, α-ketobutyric acid + 3-methylglucose + D-glucosamine acid, α-ketobutyric acid acid + 3-methylglucose + glycyl-L-aspartic acid, α-ketobutyric acid + oxalic acid + L-alanine, α-ketobutyric acid + sebacic acid + D-glucosamic acid, α-ketobutyric acid + sebacic acid + glycyl-L- aspartic acid, α-ketobutyric acid + L-homoserine + N-acetyl-D-galactosamine, α-ketobutyric acid + 2,3-butanediol + N-acetyl-D-galactosamine, α-ketobutyric acid + 3-hydroxy-2- butanone + N-acetyl-D-galactosamine, mesotartaric acid + pectin + D-glucosamic acid, mesotartaric acid + pectin + glycyl-L-aspartic acid, α-hydroxybutyric acid + inulin + D-glucosamic acid, α-hydroxybutyric acid + inulin + glycyl-L-aspartic acid, α-hydroxybutyric acid + 3-methylglucose + D-glucosamine acid, α-hydroxybutyric acid + 3-methylglucose + glycyl-L-aspartic acid, α-hydroxybutyric acid + oxalic acid + L-alanine, α-hydroxybutyric acid + sebacic acid + D-glucosamine acid lot, α-hydroxybutyric acid + sebacic acid + glycyl-L-aspartic acid, α-hydroxybutyric acid + 2,3-butanediol + N-acetyl-D-galactosamine, α-hydroxybutyric acid + 3-hydroxy-2-butanone + N -acetyl-D-galactosamine, citric acid + α-cyclodextrin + glycyl-L-glutamic acid, citric acid + α-cyclodextrin + tricarballic acid, citric acid + mannan + glycyl-L-glutamic acid, citric acid + mannan + tricarballylic acid , citric acid + oxalic acid + L-alanine, citric acid + pectin + L-alanine, brosuccinic acid + 2,3-butanediol + N-acetyl-D-galactosamine, brosuccinic acid + 2,3-butanediol + glycyl-L- aspartic acid, brosuccinic acid + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine, brosuccinic acid + 3-hydroxy-2-butanone + glycyl-L-aspartic acid, brosuccinic acid + pectin + L-alanine, mucic acid + inulin + D-glucosamine acid, mucic acid + inulin + glycyl-L-aspartic acid acid, mucic acid + 3-methylglucose + D-glucosamic acid, mucic acid + 3-methylglucose + glycyl-L-aspartic acid, mucic acid + oxalic acid + L-alanine, mucic acid + sebacic acid + D-glucosamic acid, mucic acid + sebacic acid + glycyl-L-aspartic acid, mucic acid + 2,3-butanediol + N-acetyl-D-galactosamine, mucic acid + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine, glyocylic acid + inulin + glycyl-L-aspartic acid, glyocylic acid + 3-methylglucose + D-glucosamine acid, glyocylic acid + 3-methylglucose + glycyl-L-aspartic acid, glyocylic acid + oxalic acid + L-alanine, glyocylic acid + sebacic acid + D-glucosamine acid, glyocylic acid + sebacic acid + glycyl-L-aspartic acid, glyocylic acid + 2,3-butanediol + N-acetyl-D-galactosamine, glyocylic acid + 3-hydroxy-2-butanone + N- acetyl-D-galactosamine, phenylethy lamin + 3-methylglucose + D-glucosamine acid, phenylethylamine + 3-methylglucose + N-acetyl-D-galactosamine, phenylethylamine + 3-methylglucose + glycyl-L-aspartic acid, phenylethylamine + oxalic acid + L-alanine, phenylethylamine + oxalic acid acid + N-acetyl-D-galactosamine, phenylethylamine + pectin + N-acetyl-D-galactosamine, D-alanine + 3-methylglucose, D-alanine + oxalic acid, L-alanylglycine + γ-cyclodextrin, L-alanylglycine + inulin , L-alanylglycine + sebacic acid, L-alanylglycine + 2,3-butanediol, L-alanylglycine + 3-hydroxy-2-butanone, D-sugar acid + oxalic acid + L-alanine, succinic acid + oxalic acid + L- alanine, succinic acid + pectin + L-alanine, Tween 40 + oxalic acid + L-alanine, Tween 40 + pectin + L-alanine, α-ketoglutaric acid + inulin + glycyl-L-aspartic acid, α-ketoglutaric acid + sebacic acid acid + glycyl-L-aspartic acid, α-ketoglutaric acid + 3-hydroxy-2-butanone + glycyl-L-aspartic acid, meso tartaric acid + oxalic acid + L-alanine, mesotartaric acid + pectin + L-alanine, brosuccinic acid + γ-cyclodextrin + D-glucosamine acid, brosuccinic acid + γ-cyclodextrin + glycyl-L-aspartic acid, brosuccinic acid + inulin + D-glucosamine acid, brosuccinic acid + inulin + glycyl-L-aspartic acid, brosuccinic acid + 3-methylglucose + D-glucosamine acid, brosuccinic acid + 3-methylglucose + glycyl-L-aspartic acid, brosuccinic acid + sebacic acid + D -glucosamine acid, brosuccinic acid + sebacic acid + glycyl-L-aspartic acid, brosuccinic acid + 2,3-butanediol + D-glucosamine acid, brosuccinic acid + 3-hydroxy-2-butanone + D-glucosamine acid, bromosuccinic acid + pectin + D-glucosamine acid, brosuccinic acid + pectin + glycyl-L-aspartic acid, phenylethylamine + α-cyclodextrin + N-acetyl-D-galactosamine, phenethylamine + turanose + N-acetyl-D-galactosam in, phenylethylamine + L-homoserine + N-acetyl-D-galactosamine, phenylethylamine + 2,3-butanediol + N-acetyl-D-galactosamine and phenylethylamine + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine.

Table 3 also describes that only 32 carbohydrate source combinations out of 2352 combinations tested provided all three required ratios of Corynebacterium to Staphylococcus, Corynebacterium to Micrococcus, and Staphylococcus to Micrococcus. These Skin Microbiota Balancers are even more preferred because they provide a more complete skin microbiota balancer by providing and maintaining three different ratios of commensal bacteria in healthy skin microbiota. These agents that ensure the balance of the skin microbiota were: D-alanine + 3-methylglucose, D-alanine + oxalic acid, L-alanylglycine + γ-cyclodextrin, L-alanylglycine + inulin, L-alanylglycine + sebacic acid, L-alanylglycine + 2,3-butanediol, L-alanylglycine + 3-hydroxy-2-butanone, D-sugar acid + oxalic acid + L-alanine, succinic acid + oxalic acid + L-alanine, succinic acid + pectin + L-alanine, Tween 40 + Oxalic Acid + L-Alanine, Tween 40 + Pectin + L-Alanine, α-Ketoglutaric Acid + Inulin + Glycyl-L-Aspartic Acid, α-Ketoglutaric Acid + Sebacic Acid + Glycyl-L-Aspartic Acid, α-Ketoglutaric Acid acid + 3-hydroxy-2-butanone + glycyl-L-aspartic acid, mesotartaric acid + oxalic acid + L-alanine, mesotartaric acid + pectin + L-alanine, brosuccinic acid + γ-cyclodextrin + D-glucosamine acid, bromosuccinic acid + γ-cyclodextrin + glycyl-L-aspartic acid, brosuccinic acid + inulin + D-gluco saminic acid, brosuccinic acid + inulin + glycyl-L-aspartic acid, brosuccinic acid + 3-methylglucose + D-glucosamine acid, brosuccinic acid + 3-methylglucose + glycyl-L-aspartic acid, brosuccinic acid + sebacic acid + D-glucosamine acid, brosuccinic acid + sebacic acid + glycyl-L-aspartic acid, brosuccinic acid + 2,3-butanediol + D-glucosamine acid, brosuccinic acid + 3-hydroxy-2-butanone + D-glucosamine acid, brosuccinic acid + pectin + D-glucosamine acid, brosuccinic acid + pectin + glycyl-L-aspartic acid, phenylethylamine + α-cyclodextrin + N-acetyl-D-galactosamine, phenylethylamine + turanose + N-acetyl-D-galactosamine, phenylethylamine + L-homoserine + N -acetyl-D-galactosamine, phenethylamine + 2,3-butanediol + N-acetyl-D-galactosamine and phenethylamine + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine.

In FIG. 1 presents a set of sample data from the experimental analysis described above and documented in Table 3 and provides a visual indication of a set of sample codes from Table 3 that provide agents that provide skin microbiota balance, as well as some of the codes from Table 3 that do not provide agents to balance the microbiota of the skin. As shown in FIG. 1, the twelve codes from Table 3 are shown on the horizontal axis, and their respective difference for the calculated and required ratios for Corynebacterium to Staphylococcus (C:S), Corynebacterium to Micrococcus (C:M) and Staphylococcus to Micrococcus (S:M) is shown by vertical axis. Skin microbiota balancers are carbohydrate sources that provide at least one of the required ratios described above, or, in other words, have at least one ratio difference that is within ±0.25 of the corresponding desired ratio. relationship.

Some of the carbohydrate sources did not provide any of the required ratios of Corynebacterium to Staphylococcus (C:S), Corynebacterium to Micrococcus (C:M), and Staphylococcus to Micrococcus (S:M), and thus do not serve as agents to balance the microbiota. skin. For example, Code Nos. 2, 5, and 7 from Table 3 are shown in FIG. 1 as unable to provide any of the three necessary ratios. An analysis of Table 3 shows that a significant number of tested codes do not provide any of the three required ratios and thus cannot provide a means to balance the skin microbiota.

As described above, some carbohydrate sources provided at least one desired ratio of Corynebacterium to Staphylococcus (C:S), Corynebacterium to Micrococcus (C:M), and Staphylococcus to Micrococcus (S:M). Exemplary Code Nos. 12, 508, 688, 2113, 2208, 2334, 1213, 1554, and 2022 from Table 3 are shown in FIG. 1 and provide such a result. A review of Table 3 shows that several hundred carbohydrate source codes out of 2532 tested codes provided at least one required ratio and thus could serve as a means to balance the skin microbiota.

However, only 119 of the 2532 carbohydrate sources tested provided two or more of the required ratios of Corynebacterium to Staphylococcus, Corynebacterium to Micrococcus, and Staphylococcus to Micrococcus. This represents only 4.7% of the tested carbohydrate sources providing this result. Exemplary Code Nos. 12, 508, 688, 2113, 2208, and 2334 from Table 3 illustrate such a result in FIG. 1. Carbohydrate sources that provide at least two of the required ratios are more preferred than carbohydrate sources that provide none of the required ratios or provide only one of them.

Even more surprising was the result that the carbohydrate source provided all three required ratios of codes Corynebacterium to Staphylococcus, Corynebacterium to Micrococcus, and Staphylococcus to Micrococcus. Exemplary Code Nos. 12, 508, and 688 from Table 3 illustrate such an unexpected result in FIG. 1. Carbohydrate sources in Table 3 that provide all of the required ratios (and as illustrated by exemplary codes Nos. 12, 508, and 688 in Figure 1) are preferred over carbohydrate sources that provide none, provide only one, or even two of the necessary relationships. These combinations of carbohydrates accounted for only 32 specific codes out of 2532 tested and thus represent only approximately 1.3% of the codes tested.

The composition may be in a wide variety of forms, such as, for example, simple solutions (water or oil based), solid forms (eg gels or sticks), lotions, suspensions, creams, milks, balms, ointments, sprays, emulsions, oil gums, aerosols, and the like. Preferably, the compositions useful in the present invention are soluble in order to facilitate the introduction of their composition to the consumer.

Carrier

The compositions may include a carrier. The carrier may be any dermatologically acceptable carrier. As used herein, the term "dermatologically acceptable carrier" generally refers to a carrier that is suitable for topical application to the skin and compatible with a skin microbiota balancing agent. Suitable liquid carrier materials for use in the present invention include those commonly known for use in the cosmetic, pharmaceutical and medical fields as a base for ointments, lotions, creams, soothing agents, aerosols, gels, suspensions, sprays, foams, rinses, etc., and can be applied at their prescribed levels. In some embodiments, the carrier may comprise from about 0.01% to about 99.98% (by total weight of the composition) depending on the carrier used.

Preferred carrier materials include polar solvent materials such as water. Other contemplated carriers include emollients, humectants, polyols, surfactants, esters, perfluorocarbons, silicones, and other pharmaceutically acceptable carrier materials. In one embodiment, the carrier is volatile to allow immediate application of the antimicrobial ingredient to the desired surface while improving the overall feel of the product by reducing dry time. Non-limiting examples of these volatile carriers include dimethicone, cyclomethicone, methylperfluoroisobutyl ether, methylperfluorobutyl ether, ethylperfluoroisobutyl ether and ethylperfluorobutyl ether, 5c5t.

If the composition forms a wetting composition, such as described below for use with a wet wipe, then the composition will typically contain water. The compositions may suitably contain water in an amount ranging from about 0.01% (based on the total weight of the composition) to about 99.98% (based on the total weight of the composition), or from about 1.00% (based on the total weight of the composition) to about 99.98% (based on the total weight of the composition), or from about 50.00% (based on the total weight of the composition) to about 99.98% (based on the total weight of the composition), or from about 75.00% (based on the total weight of the composition) up to about 99.98% (based on the total weight of the composition). In some embodiments, the amount of water may be from about 50.00% (based on the total weight of the composition) to about 70.00% (based on the total weight of the composition). In some embodiments, the amount of water may be greater than 90.00% (based on the total weight of the composition).

Emollients

In one embodiment, the compositions may optionally contain one or more emollients that are typically used to soften, soothe and otherwise smooth and/or moisturize the skin. Suitable emollients that can be included in the compositions include oils such as alkyl dimethicones, alkyl methicones, alkyl dimethicone copolyols, phenyl silicones, alkyl trimethylsilanes, dimethicone, dimethicone crosspolymers, cyclomethicone, lanolin and its derivatives, fatty acid esters, fatty acids, glycerol esters and their derivatives, propylene glycol esters and derivatives thereof, alkoxylated carboxylic acids, alkoxylated alcohols, fatty alcohols, and combinations thereof.

Some embodiments of the compositions may include one or more emollients in an amount ranging from about 0.01% (by total weight of the composition) to about 20% (by total weight of the composition), or from about 0.05% (by total weight of the composition). ) to about 10% (based on the total weight of the composition), or from about 0.10% (based on the total weight of the composition) to about 5% (based on the total weight of the composition).

Esters

In some embodiments, the compositions include one or more esters. Esters may be selected from cetyl palmitate, stearyl palmitate, cetyl stearate, isopropyl laurate, isopropyl myristate, isopropyl palmitate, and combinations thereof. Fatty alcohols include octyldodecanol, lauryl, myristyl, cetyl, stearyl, behenyl alcohols, and combinations thereof. Fatty acids may include, without limitation, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, arachidic acid, and behenic acid. Esters such as eucalyptol, cetearyl glucoside, dimethylisosorbide, polyglyceryl-3-cetyl ether, polyglyceryl-3-decyltetradecanol, propylene glycol myristyl ether, and combinations thereof can also be suitably used as emollients. Other ester compounds suitable for use in antimicrobial compositions or the present invention are listed in the International Cosmetic Ingredient Dictionary and Handbook , 11th Edition, CTFA, (January 2006) ISBN-10: 1882621360, ISBN-13: 978 -1882621361, and in 2007 Cosmetic Bench Reference , Allured Pub. Corporation (July 15, 2007) ISBN-10: 1932633278, ISBN-13: 978-1932633276, both of which are incorporated herein by reference to the extent that they are consistent with this document.

Hygroscopic substances

Hygroscopic substances which are suitable as carriers in the compositions of the present invention include, for example, glycerol, glycerol derivatives, hyaluronic acid, hyaluronic acid derivatives, betaine, betaine derivatives, amino acids, amino acid derivatives, glycosaminoglycans, glycols, polyols, sugars, sugar alcohols, hydrogenated starch hydrolysates, hydroxy acids, hydroxy acid derivatives, PCA salts, and the like. and their combinations. Specific examples of suitable humectants include honey, sorbitol, hyaluronic acid, sodium hyaluronate, betaine, lactic acid, citric acid, sodium citrate, glycolic acid, sodium glycolate, sodium lactate, urea, propylene glycol, butylene glycol, pentylene glycol, ethoxydiglycol, methyl glucet-10 , methyl glucet-20, polyethylene glycols (as listed in the International Cosmetic Ingredient Dictionary and Handbook , such as PEG-2 to PEG 10), propanediol, xylitol, maltitol, or combinations thereof.

The compositions of the present invention may include one or more humectants in an amount of from about 0.01% (by total weight of the composition) to about 20% (by total weight of the composition), or from about 0.05% (by total weight of the composition). ) to about 10% (by total weight of the composition), or from about 0.1% (by total weight of the composition) to about 5.0% (by total weight of the composition).

Surfactants

In some embodiments, the implementation of the composition may include one or more surfactants. In one embodiment, where the composition is included in a tissue, the composition may also be expected to contain one or more surfactants. They can be selected from anionic, cationic, nonionic, zwitterionic and amphoteric surfactants. The amounts of surfactants may range from 0.01% to 30%, or 10% to 30%, or 0.05% to 20%, or 0.10% to 15%, based on the total weight of the composition. In some embodiments, for example where the wetting composition is applied via a wipe, the surfactant may comprise less than 5% by total weight of the wetting composition.

Suitable anionic surfactants include, without limitation, C ₈ -C ₂₂ alkane sulfates, sulfuric acid esters, and sulfonates. Suitable sulfonates include primary C ₈ -C ₂₂ alkane sulfonate, primary C ₈ -C ₂₂ alkane disulfonate, C ₈ -C ₂₂ alkene sulfonate, C ₈ -C ₂₂ hydroxyalkane sulfonate, or alkyl glycerol ester sulfonic acid. Конкретные примеры анионных поверхностно-активных веществ включают лаурилсульфат аммония, лауретсульфат аммония, лаурилсульфат триэтиламина, лауретсульфат триэтиламина, лаурилсульфат триэтаноламина, лауретсульфат триэтаноламина, лаурилсульфат моноэтаноламина, лауретсульфат моноэтаноламина, лаурилсульфат диэтаноламина, лауретсульфат диэтаноламина, лауриновый моноглицерид сульфата натрия, лаурилсульфат натрия, лауретсульфат натрия, лауретсульфат sodium lauryl sarcosinate, sodium lauroyl sarcosinate, potassium lauryl sulfate, sodium trideceth sulfate, sodium methyl lauroyl taurate, sodium lauroyl isethionate, sodium lauryl sulfosuccinate, sodium lauroyl sulfosuccinate, sodium tridecylbenzenesulfonate, sodium dodecylbenzenesulfonate, sodium lauryl amphoacetate and mixtures thereof. Other anionic surfactants include C ₈ -C ₂₂ acylglycinate salts. Suitable glycinate salts include sodium cocoyl glycinate, potassium cocoyl glycinate, sodium lauroyl glycinate, potassium lauroyl glycinate, sodium myristoyl glycinate, potassium myristoyl glycinate, sodium palmitoyl glycinate, potassium palmitoyl glycinate, sodium stearoyl glycinate, potassium stearoyl glycinate, ammonium cocoyl glycinate, and mixtures thereof. Cationic counterions to form the glycinate salt may be selected from sodium, potassium, ammonium, alkanolammonium, and mixtures of these cations.

Suitable cationic surfactants include, without limitation, alkyldimethylamines, alkylamidopropylamines, alkylimidazoline derivatives, quaternized amine ethoxylates, and quaternary ammonium compounds.

Suitable non-ionic surfactants include, without limitation, alcohols, acids, amides, or alkylphenols reactive with alkylene oxides, especially ethylene oxide, either alone or with propylene oxide. Specific non-ionic substances are condensates of C ₆ -C ₂₂ alkylphenols and ethylene oxide, condensation products of C ₈ -C ₁₃ aliphatic primary or secondary straight or branched alcohols with ethylene oxide, and products obtained by the condensation of ethylene oxide with the reaction products of propylene oxide and ethylenediamine. Other non-ionic materials include long chain tertiary amine oxides, long chain tertiary phosphine oxides and dialkyl sulfoxides, alkyl polysaccharides, amine oxides, block copolymers, castor oil ethoxylates, cetoolyl alcohol ethoxylates, cetostearyl alcohol ethoxylates, decyl alcohol ethoxylates, dinonylphenol ethoxylates, dodecylphenol ethoxylates, and terminal dodecylphenol ethoxylates. amine ester derivatives, ethoxylated alkanolamides, ethylene glycol esters, fatty acid alkanolamides, fatty alcohol alkoxylates, lauryl alcohol ethoxylates, monobranched alcohol ethoxylates, natural alcohol ethoxylates, nonylphenol ethoxylates, octylphenol ethoxylates, oleylamine ethoxylates, random copolymer sorbalkoxylates, sorbitanium ethoxylates , stearic acid ethoxylates, stearyl amine ethoxylates, synthetic alcohol ethoxylates, tallow fatty acid ethoxylates, solid amine ethoxylates, and tridecanol tride ethoxylates.

Suitable zwitterionic surfactants include, for example, alkylamine oxides, alkylhydroxysultaines, siliconamine oxides, and combinations thereof. Specific examples of suitable zwitterionic surfactants include, for example, 4-[N,N-di(2-hydroxyethyl)-N-octadecylammonio]-butane-1-carboxylate, S-[S-3-hydroxypropyl-S- hexadecylsulfonio]-3-hydroxypentane-1-sulfate, 3-[P,P-diethyl-P-3,6,9-trioxatetradexoptylphosphonio]-2-hydroxypropane-1-phosphate, 3-[N,N-dipropyl-N- 3-dodecoxy-2-hydroxypropylammonio]-propane-1-phosphonate, 3-(N,N-dimethyl-N-hexadecylammonio)propane-1-sulfonate, 3-(N,N-dimethyl-N-hexadecylammonio)-2- hydroxypropane-1-sulfonate, 4-[N,N-di(2-hydroxyethyl)-N-(2-hydroxydodecyl)ammonio]-butane-1-carboxylate, 3-[S-ethyl-S-(3-dodecoxy- 2-hydroxypropyl)sulfonio]-propane-1-phosphate, 3-[P,P-dimethyl-P-dodecylphosphonio]-propane-1-phosphonate, 5-[N,N-di(3-hydroxypropyl)-N-hexadecylammonio ]-2-hydroxy-pentane-1-sulfate, laurylhydroxysultaine and combinations thereof.

Suitable amphoteric surfactants include, but are not limited to, derivatives of aliphatic quaternary ammonium, phosphonium, and sulfonium compounds wherein the aliphatic radicals may be straight or branched chain, and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one substituent contains an anionic a group such as a carboxyl, sulfonate, sulfate or phosphate group. Illustrative amphoteric substances are cocodimethylcarboxymethylbetaine, cocamidopropylbetaine, cocobetaine, oleylbetaine, cetyldimethylcarboxymethylbetaine, lauryl bis-(2-hydroxyethyl)carboxymethylbetaine, stearyl-bis-(2-hydroxypropyl)carboxymethylbetaine, oleyldimethyl-gamma-carboxypropylbetaine, lauryl-bis-(2-hydroxyethyl)carboxymethylbetaine, hydroxypropyl)alpha-carboxyethylbetaine, cocoamphoacetates, and combinations thereof. Sulfobetaines may include stearyldimethylsulfopropyl betaine, lauryldimethylsulfoethyl betaine, lauryl bis-(2-hydroxyethyl)sulfopropyl betaine, and combinations thereof.

Rheology Modifiers

Optionally, one or more rheology modifiers, such as thickeners, may be added to the composition. Suitable rheology modifiers are compatible with the skin microbiota balancing agent. As used herein, "compatible" refers to a compound that, when mixed with a skin microbiota balancer, does not adversely affect the properties of the skin microbiota balancer.

The thickening system is used in compositions to control the viscosity and stability of the compositions. In particular, thickening systems prevent the composition from running off the hands or body during distribution and application of the composition. If the composition is used with a tissue product, then a thicker formulation may be used to prevent movement of the composition out of the tissue substrate.

The thickening system must be compatible with the compounds used in the present invention; that is, the thickening system, when used in combination with a skin microbiota balancer, should not precipitate, form a coacervate, or prevent the user from experiencing the conditioning benefits (or other desired benefits) that are obtained from the composition. The thickening system may contain a thickening agent that can provide both the thickening effect desired from the thickening system and the conditioning effect on the user's skin.

Thickeners may include cellulosic polymers, gums, acrylates, starches, and various polymers. Suitable examples include, without limitation, hydroxyethyl cellulose, xanthan gum, guar gum, potato starch and corn starch. In some embodiments, PEG-150 stearate, PEG-150 distearate, PEG-175 diisostearate, polyglyceryl-10 behenate/eicosandioate, disteareth-100 IPDI, polyacrylamidomethylpropane sulfonic acid, butylated PVP, and combinations thereof may be suitable.

Although the viscosity of the compositions will generally depend on the thickener used and other components of the compositions, composition thickeners suitably provide a composition having a viscosity ranging from greater than 1 centipoise to about 30,000 centipoise or greater. In another embodiment, the thickeners provide compositions having a viscosity ranging from about 100 centipoise to about 20,000 centipoise. In yet another embodiment, the thickeners provide compositions having a viscosity ranging from about 200 cps to about 15,000 cps. In embodiments where the compositions are included in a wipe, the viscosity may range from about 1 centipoise to about 2000 centipoise. In some embodiments, it is preferred that the viscosity of the composition is less than 500 centipoise.

When a thickening system is included, the compositions of the present invention may include a thickening system in an amount of no more than about 20% (by total weight of the composition) or from about 0.01% (by total weight of the composition) to about 20% (by total weight of the composition). ). In another aspect, the thickening system is present in the antimicrobial composition in an amount ranging from about 0.10% (by total weight of the composition) to about 10% (by total weight of the composition), or from about 0.25% (by total weight of the composition) to about 5% (based on the total weight of the composition), or from about 0.5% (based on the total weight of the composition) to about 2% (based on the total weight of the composition).

In one embodiment, the compositions may include hydrophobic and hydrophilic ingredients such as a lotion or cream. Typically, these emulsions have a continuous phase and a continuous phase and are usually formed by the addition of a surfactant or a combination of surfactants with varying hydrophilic-lipophilic balance (HLB) values. Suitable emulsifiers include surfactants having HLB values of 0 to 20 or 2 to 18. Suitable non-limiting examples include ceteareth-20, cetearyl glucoside, cetet-10, cetet-2, cetet-20, cocamide MEA, glyceryl laurate, Glyceryl Stearate, PEG-100 Stearate, Glyceryl Stearate, Glyceryl Stearate SE, Glycol Distearate, Glycol Stearate, Isosteareth-20, Laureth-23, Laureth-4, Lecithin, Methyl Glucose Sesquistearate, Olet-10, Olet-2, Olet-20, PEG-100 Stearate, PEG-20 Almond Oil Glycerides, PEG-20 Methyl Glucose Sesquistearate, PEG-25 Hydrogenated Castor Oil, PEG-30 Dipolyhydroxystearate, PEG-4 Dilaurate, PEG-40 Sorbitan Peroleate, PEG-60 Almond Oil Glycerides, PEG-7 Olivate, PEG-7 glyceryl cocoate, PEG-8 dioleate, PEG-8 laurate, PEG-8 oleate, PEG-80 sorbitan laurate, polysorbate 20, polysorbate 60, polysorbate 80, polysorbate 85, propylene glycol isostearate, sorbitan anisostearate, sorbitan laurate, sorbitan monostearate, sorbitan oleate, sorbitan sesquioleate , sorbitan stearate, sorbitan trioleate, MEA stearamide, steareth-100, steareth-2, steareth-20, steareth-21. The compositions may additionally contain surfactants or combinations of surfactants that create ordered structures of liquid crystals or ordered structures of liposomes. Suitable non-limiting examples include OLIVEM 1000 (INCI: Cetearyl Olivate (and) Sorbitan Olivate available from HallStar Company (Chicago, IL)); ARLACEL LC (INCI: sorbitan stearate (and) sorbityl laurate, commercially available from Croda (Edison, NJ)); CRYSTALCAST MM (INCI: beta-sitosterol (and) sucrose stearate (and) sucrose distearate (and) cetyl alcohol (and) stearyl alcohol, commercially available from MMP Inc. (South Plainfield, NJ)); UNIOX CRISTAL (INCI: cetearyl alcohol (and) polysorbate 60 (and) cetearyl glucoside, commercially available from Chemyunion (São Paulo, Brazil)). Other suitable emulsifiers include lecithin, hydrogenated lecithin, lysolecithin, phosphatidylcholine, phospholipids, and combinations thereof.

Gelling agents

In some embodiments in which the composition is in the form of a gel, the discontinuous phase of the gel may be formed from any of a number of different gelling agents, including temperature sensitive ("thermogel") compounds, ion sensitive compounds, and the like. For example, thermogel systems respond to a change in temperature (eg, an increase in temperature) by converting from a liquid to a gel. In general, the temperature range of interest is from about 25°C to about 40°C, in some embodiments from about 35°C to about 39°C, and in one specific embodiment at human body temperature (about 37°C). In some cases, thermal gel block copolymers, graft copolymers and/or homopolymers can be used. For example, in some embodiments of the present invention, polyoxyalkylene block copolymers can be used to form a thermal gel composition. Suitable thermogel compositions may include, for example, homopolymers such as poly(N-methyl-N-n-propylacrylamide), poly(N-n-propylacrylamide), poly(N-methyl-N-isopropylacrylamide), poly(N-n -propylmethacrylamide), poly(N-isopropylacrylamide), poly(N,n-diethylacrylamide); poly(N-isopropylmethacrylamide), poly(N-cyclopropylacrylamide), poly(N-ethylmethylacrylamide), poly(N-methyl-N-ethylacrylamide), poly(N-cyclopropylmethacrylamide) and poly(N-ethylacrylamide). Still other examples of suitable thermogel polymers may include cellulose ether derivatives such as hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose and ethylhydroxyethylcellulose. In addition, thermogel polymers can be obtained by forming copolymers with (from) monomers or by combining such homopolymers with other water-soluble polymers, such as acrylic monomers (for example, acrylic or methacrylic acid, acrylate or methacrylate, acrylamide or methacrylamide and their derivatives) .

Ion sensitive compounds

The compositions of the present invention may also include an ion-sensitive compound. Typically, such compounds are well known in the art and tend to gel in the presence of certain ions or at a certain pH. For example, one suitable class of ion-sensitive compounds that can be used in the present invention are anionic polysaccharides. Anionic polysaccharides can form a three-dimensional network of polymers that acts as a dispersed phase of a gel. In general, anionic polysaccharides include polysaccharides having an overall anionic charge as well as neutral polysaccharides that contain anionic functional groups.

Antimicrobials

In some embodiments, the implementation of the composition may include one or more antibacterial agents to increase the shelf life. Some suitable antimicrobial agents that can be used in the present invention include conventional antimicrobial agents. As used in this document, the term "traditional antimicrobials" means compounds that were previously known to regulatory authorities to provide an antimicrobial effect, such as those listed in Annex V of the European Union Regulation in the list of preservatives allowed in cosmetic products. Traditional antimicrobial agents include, without limitation, propionic acid and its salts; salicylic acid and its salts; sorbic acid and its salts; benzoic acid and its salts and esters; formaldehyde; paraformaldehyde; orthophenylphenol and its salts; zinc pyrithione; inorganic sulfites; hydrogen sulfites; chlorobutanol; benzoic parabens such as methylparaben, propylparaben, butylparaben, ethylparaben, isopropylparaben, isobutylparaben, benzylparaben, sodium methylparaben and sodium propylparaben; dehydroacetic acid and its salts; formic acid and its salts; dibromohexamidine isethionate; thiomersal; salts of phenylmercury; undecylenic acid and its salts; hexetidine; 5-bromo-5-nitro-1,3-dioxane; 2-bromo-2-nitropropane-1,3,-diol; dichlorobenzyl alcohol; triclocarban; p-chloro-m-cresol; triclosan; chloroxylenol; imidazolidinyl urea; polyaminopropyl biguanide; phenoxyethanol, mezathemamine; quaternium-15; climbazole; DMDM hydantoin; benzyl alcohol; pyroctonolamine; bromchlorophene; ortho-cymen-5-ol; methylchloroisothiazolinone; methylisothiazolinone; chlorophene; chloroacetamide; chlorhexidine; chlorhexidine diacetate; chlorhexidine digluconate; chlorhexidine dihydrochloride; phenoxyisopropanol; alkyl(C12-C22)trimethylammonium bromide and chlorides; dimethyloxazolidine; diazolidinylurea; hexamidine; hexamidine diisethionate; glutaral; 7-ethylbicyclooxazolidine; chlorphenesin; sodium hydroxymethylglycinate; silver chloride; benzethonium chloride; benzalkonium chloride; benzalkonium bromide; benzylhemiformal; iodopropynyl butylcarbamate; ethyl lauroylarginate HCl; citric acid and silver citrate.

Other antimicrobials that can be added to the compositions of the present invention include non-traditional antimicrobials known to exhibit antimicrobial activities in addition to their primary functions, but which were not previously known as antimicrobials to regulatory authorities (such as in list of Annex V of the European Union Regulation). Examples of these non-traditional antimicrobials include, without limitation, hydroxyacetophenone, caprylyl glycol, coco-PG-dimonium chloride sodium phosphate, phenylpropanol, lactic acid and its salts, capryl hydroxamic acid, levulinic acid and its salts, sodium lauroyl lactylate, phenethyl alcohol, sorbitan caprylate, glyceryl caprate, glyceryl caprylate, ethylhexylglycerin, p-anisic acid and its salts, gluconolactone, decylene glycol, 1,2-hexanediol, glucose oxidase and lactoperoxidase, leuconostoc/fermented radish root filtrate, and glyceryl laurate.

The amount of antimicrobial agents in the compositions depends on the relative amounts of other components present in the composition. For example, in some embodiments, the antimicrobial agent may be present in the compositions in an amount of from about 0.001% to about 5% (by total weight of the composition), in some embodiments from about 0.01 to about 3% (by total weight of the composition) and in some embodiments, from about 0.05% to about 1.0% (based on the total weight of the composition). In some embodiments, the antimicrobial agent may be present in the composition in an amount of less than 0.2% (based on the total weight of the composition). However, in some embodiments, the composition may be substantially free of any antimicrobial agents. Thus, in some embodiments, the composition does not contain a conventional antimicrobial agent or a non-traditional antimicrobial agent.

Auxiliary ingredients

The compositions of the present invention may further comprise auxiliary ingredients conventionally found in cosmetic, pharmaceutical, medical, household, industrial compositions/products or personal care compositions/products in the prescribed manner and at prescribed levels. For example, the compositions may contain additional compatible pharmaceutically active and compatible combination therapy materials such as antioxidants, antiparasitic agents, antipruritic agents, antifungal agents, antiseptic active agents, biologically active agents, astringents, keratolytic active agents, topical anesthetics, agents anti-burning agents, anti-redness agents, skin emollients, topical analgesics, film formers, dead skin exfoliators, sunscreens, and combinations thereof.

Other suitable additives that may be included in the compositions of the present invention include compatible colorants, deodorants, emulsifiers, defoamers (if foam is not required), lubricants, skin conditioners, skin protectants, and skin benefit agents. (e.g. aloe vera and tocopheryl acetate), solvents (e.g. water-soluble glycol and glycol ethers, glycerin, water-soluble polyethylene glycols, water-soluble polyethylene glycol ethers, water-soluble polypropylene glycols, water-soluble polypropylene glycol ethers, dimethyl isosorbide), solubilizing agents, suspending agents, detergent components, ( e.g., alkali and alkaline earth metal salts, which are carbonate, bicarbonate, phosphate, hydrogen phosphate, dihydrogen phosphate, hydrogen sulfate), wetting agents, pH adjusting ingredients (a suitable pH range of the compositions may be b from about 3.5 to about 8), chelating agents, propellants, colorants and/or pigments, and combinations thereof.

Another component that may be suitable for addition to the compositions is a perfume. Any compatible perfume may be used. Typically, the fragrance is present in an amount of from about 0% (by weight of the composition) to about 5% (by weight of the composition) and more typically from about 0.01% (by weight of the composition) to about 3% (by weight of the composition) . In one desirable embodiment, the perfume will have a clean, fresh and/or neutral fragrance to create an attractive delivery vehicle for the end user.

Organic sunscreens that may be present in the compositions include ethylhexylmethoxycinnamate, avobenzone, octocrylene, benzophenone-4, phenylbenzimidazole sulfonic acid, homosalate, oxybenzone, benzophenone-3, ethylhexyl salicylate, and mixtures thereof.

As previously noted herein, compositions of the present disclosure may be applied to a delivery mechanism, such as a backing, which in turn may be used to deliver and/or apply the prebiotic composition to the user's skin. Suitable supports include a web, such as a wet-spun or air-spun fabric, gauze, cotton swab, transdermal patch, container, or holder. The various webs onto which the composition can be applied can provide products in the form of wipes, wipes, toilet paper, paper towels, diapers, diapers, diaper briefs, feminine hygiene products (tampons, pads), gloves, socks, masks, or their combinations. In some embodiments, the substrate on which the composition is applied may form part of an absorbent article. For example, the composition may be applied to a substrate, which may form at least a portion of the bodyside liner of an absorbent article. Particularly preferred applicators include fibrous webs, including flushable and non-drainage cellulosic webs and synthetic fiber nonwoven webs. Suitable webs may be wet-laid, air-laid, melt-blown, or spunbond. Suitable synthetic fibrous material includes meltblown polyethylene, polypropylene, copolymers of polyethylene and polypropylene, bicomponent fibers including polyethylene or polypropylene, and the like. Suitable nonwoven webs may be meltblown, coform, spunbond, fabrics obtained by dry-air molding; water jet bonded nonwovens, spunlaced webs, bonded carded webs.

In certain embodiments, especially those in which the composition is applied to a web, it may be desirable for the composition to provide certain physical properties such as a smooth, lubricious, non-greasy feel; the ability to at least partially be transferred from the web to the skin of the user; the ability to remain on the web at about room temperature; or the ability to be compatible with the method of production of the web. In some embodiments, it is preferred that at least a portion of the composition is transferred from the tissue to the skin of the user upon application.

The composition can be applied to the web during formation of the web or after the web has been formed and dried, often referred to as off-line or post-processing. Suitable methods for applying the composition to the web include methods known in the art such as gravure printing, flexographic printing, spraying, WEKO™, slot die application, or electrostatic spraying. One particularly preferred off-line application method is rotogravure printing.

Where the composition is added to the web during formation of the web and prior to drying, an application method may preferably be used in which the composition is incorporated onto the surface of the web. One way to add a prebiotic to the surface of the web is to apply the composition during creping of the fabric web. Surprisingly, the composition itself can be used as a creping composition or can be combined with other well known creping compositions to apply the composition to a fabric web without significantly compromising important web properties such as strength, stiffness, or friability.

In some embodiments in which the composition is applied to a delivery mechanism such as a support, the composition may be applied in an addition amount ranging from about 1% to about 500%, or from about 30% to about 400%, or from about 100%. up to about 350%. Of course, it is contemplated that the composition can be applied to a delivery agent outside of this range and is still within the scope of the present disclosure.

Fibrous webs containing the composition obtained in accordance with the present invention can be incorporated into products with multiple layers. For example, in one aspect, a fibrous web made in accordance with the present invention can be combined with one or more other fibrous webs to form a wiping product having the desired characteristics. Other webs laminated to the fibrous web of the present invention may be, for example, wet creped web; calendered canvas; embossed canvas; air-dried canvas; fabric creped by air-dry method; non-creped fabric, air-dried; air-blown fabric and the like, and may or may not contain any skin microbiota balancing agent.

Methods for producing air-blown nonwoven backing sheets are described, for example, in US Published Application No. 2006/0008621, incorporated herein by reference to the extent that it is consistent with this document.

TESTING METHODS

Carbohydrate Screening Method

В исследовании использовали 10 иллюстративных кожных бактерий: Staphylococcus epidermidis ATCC 14990, Staphylococcus epidermidis M23864:W2, Staphylococcus aureus ATCC 6538, Staphylococcus aureus ATCC 25904 (Newman), Pseudomonas aeruginosa ATCC 9027, Micrococcus luteus ATCC 48732, Micrococcus luteus SK58, Klebsiella pneumoniae ATCC BAA -2146, Corynebacterium amycolatum SK46 and Corynebacterium minutissimum ATCC 23348. Cultivation was started from frozen pellets by placing one pellet in 20 ml of trypsin soy broth (TSB) for all organisms except C. amycolatum SK46 and C. minutissimum ATCC 23348, which were placed in brain heart extract (BHI) broth. Cultures were grown for approximately 24 hours at 37°C, except for M. luteus ATCC 49732 and M. luteus SK58, which were grown at 30°C. Subculturing cultures were performed using a sterile swab and streaked onto two M9*2 agar plates to obtain an incubated microarray culture for analysis of phenotypic data according to Table 4. The plates were incubated for approximately 24 hours at 37°C, except for M. luteus ATCC 49732 and M. luteus SK58, which were incubated at 30°C for 24 hours.

Table 4. Obtaining an incubated culture for a microarray for the analysis of phenotypic data

Scheme for a microarray for the analysis of phenotypic data

All cultures were harvested and washed prior to inoculation into a carbon phenotypic data analysis microarray (BiOLOG, Hayward, CA), with each of the Biolog PM1 and PM2 chips characterized by a particular carbon source. Bacteria on M9*2 agar were suspended by seed loop mixing in 1 ml of M9*1 collection medium in a 1.7 ml microcentrifuge tube as indicated in Table 4. Bacteria were resuspended in M9*1 medium, shaken and collected in the same 1.7 ml microcentrifuge tube used in the previous step. The tube was centrifuged for 5 minutes at 4000 X G, the supernatant was decanted, the pellet was resuspended in 1 ml of M9*1 medium and vortexed. The washing process was repeated a total of 4 times.

A 10-fold dilution was performed in M9*1 medium using 1 ml of the washed bacterial culture. From the 10-fold dilution, 200 μl was placed in an untreated 96-well plate (Falcon, Pasadena, TX) to read the initial optical density (OD) at 600 nm. OD was used to correlate with colony forming units (CFU) per milliliter using linear regression lines for each organism. See Appendix B for the equations used for each organism. Using the output of the linear regression lines, all organisms were diluted to reach 10 ⁴ cfu/ml.

The inoculation medium was supplemented with 0.75% (w/v) BHI for S. epidermidis M23864:W2, S. epidermidis ATCC 14990, and C. minutissimum ATCC 23348. For S. aureus ATCC 6538 and S. aureus ATCC 25904, the inoculation medium was supplemented with 0 .25% (w/v) BHI (Table 5). M9*1 medium was used as inoculation medium for P. aeruginosa ATCC 9027, M. luteus ATCC 49732, M. luteus SK58 and K. pneumoniae BAA-2146. A multichannel pipette was used to place 100 μl of inoculum into each well, directing approximately 10 ³ CFU/well into the microarray for analysis of phenotypic data. The plate lid was treated with an anti-fog agent (Xodus Medical Inc., New Kensington, PA) to reduce condensation. The microarray for analysis of phenotypic data was placed in a Gemini 3M plate reader (Molecular Devices, Sunnyvale, CA) with SoftMax Pro 6.3 software (Molecular Devices, Sunnyvale, CA). The following settings were used: kinetic reading every 20 minutes for 36 hours, wavelength 600 nm and temperature 33°C.

Table 5. Inoculation media for S. epidermis M23864:W2, S. epidermis ATCC 14990, C. minutissimum ATCC 23348, S. aureus ATCC 6538, and S. aureus ATCC 25904

Controls for microarray for analysis of phenotypic data

An untreated 96-well plate was used as a control. All wells were loaded with 200 μl of the medium described in Table 6. The control plate contained empty medium as all media used in the control plate and the same medium inoculated with bacteria to provide approximately 10 ⁴ cfu/well in the plate. M9*1 was used as a negative growth control. TSB was used as a positive growth control, except for C. minutissimum ATCC23348 and C. amycolatum SK46, for which BHI was used. Microchip inoculation medium for analysis of phenotypic data (without carbon) was used as a background control. No growth should have been observed in this environment. Microchip inoculation medium containing carbon for analysis of phenotypic data served as the final control. There must have been growth in this environment. The control plate was incubated at 37°C for 36 hours except for M. luteus ATCC 49732 and M. luteus SK58. They were incubated at 33°C for 36 hours. After incubation, endpoint absorbance readings were performed at OD 600 nm. If several organisms used the same inoculation medium, one empty plate was sufficient for these organisms.

Table 6. Schematic of the control plate

The surface culture method was used to confirm the concentration of bacteria in the inoculum. Dilutions were plated on TSA in duplicate, except for C. minutissimum ATCC23348 and C. amycolatum SK46, which were plated on BHI agar. All plates were incubated at 37°C for 36 hours except M. luteus ATCC 49732 and M. luteus SK58. They were incubated at 33°C for 36 hours.

Control plate analysis

The mean OD of empty media (wells A1-D1, A2-D2, A3-D3 and A4-D4) was expected to have low OD values. The mean OD of wells E1-H1 was expected to be similar to A1-D1 (inoculum without carbon). The average OD for E2-H2 (carbon seed) was expected to be high compared to A2-D2. It was assumed that the average OD for E3-H3 (environment without carbon and nitrogen) would have a value similar to the average OD for A3-D3. Finally, the mean OD for E4-H4 (positive growth control) was expected to have the highest value.

Microarray analysis for phenotypic data analysis

Biochemical usage samples were analyzed using SoftMax Pro 6.3 software. The background was removed by subtracting the negative control (well A1) from all other wells. To do this, SoftMax chose the "matrix editor", clicked cell A1, chose the "blank tablet" and clicked "OK". All curves were normalized for better comparison by pressing the "decrease" button, number 2 "set first data point to zero" was selected and "OK" was pressed. Wells were selected seven at a time and were clicked twice as they were selected. All seven curves were displayed on the screen. The maximum ODs were observed when hovering over the highest part of the curve, the second number displayed was the OD. Charts that reached less than 0.05 OD units above zero, fell below zero, or did not show traditional growth curve trends were considered negative to maintain growth. Charts showing traditional growth curve trends and reaching more than 0.05 OD units above zero were considered positive and supportive of growth. Positive results were not sorted in any way.

Embodiments

In light of the foregoing description and examples, the present invention provides for the following embodiments.

Embodiment 1. A composition for providing or maintaining a healthy skin microbiota, comprising a carrier and a skin microbiota balancing agent, wherein the skin microbiota balancing agent comprises at least one combination of carbohydrate sources, including a first carbohydrate source and a second carbohydrate source, wherein the skin microbiota balancer is configured to provide at least two of the following desired ratios: a first desired ratio of Corynebacterium to Staphylococcus, a second desired ratio of Corynebacterium to Micrococcus, and a third desired ratio of Staphylococcus to Micrococcus.

Embodiment 2 The composition of Embodiment 1 wherein the first desired ratio of Corynebacterium to Staphylococcus is 1.3, the second desired ratio of Corynebacterium to Micrococcus is 1.4, and the third desired ratio of Staphylococcus to Micrococcus is 1.1.

Embodiment 3 The composition of Embodiment 1 or 2 wherein at least one combination of carbohydrate sources is selected from the group consisting of the following: D-alanine + γ-cyclodextrin, D-alanine + sebacic acid, D-alanine + 2.3 -butanediol, D-aspartic acid + oxalic acid, D-aspartic acid + pectin, D-threonine + 3-methylglucose, D-threonine + pectin, fumaric acid + α-cyclodextrin, fumaric acid + mannan, L-alanylglycine + 3- methylglucose, L-alanylglycine + oxalic acid, L-alanylglycine + pectin, L-malic acid + mannan, D-sugar acid + pectin + L-alanine, succinic acid + 3-methylglucose + D-glucosamine acid, succinic acid + 3- methylglucose + L-alanine, succinic acid + 3-methylglucose + glycyl-L-aspartic acid, succinic acid + pectin + D-glucosamine acid, succinic acid + pectin + glycyl-L-aspartic acid, Tween 40 + 3-methylglucose + D -glucosamine acid, Tween 40 + 3-methylglucose + L-alanine, Tween 4 0 + 3-methylglucose + glycyl-L-aspartic acid, Tween 40 + pectin + D-glucosamine acid, Tween 40 + pectin + glycyl-L-aspartic acid, α-ketoglutaric acid + γ-cyclodextrin + glycyl-L-aspartic acid . + sebacic acid + D-glucosamine acid, α-ketoglutaric acid + 2,3-butanediol + glycyl-L-aspartic acid, α-ketoglutaric acid + 3-hydroxy-2-butanone + D-glucosamine acid, α-ketobutyric acid + α-cyclodextrin + N-acetyl-D-galactosamine, α-ketobutyric acid + inulin + D-glucosamine acid, α-ketobutyric acid + inulin + glycyl-L-aspartic acid, α-ketobutyric acid + 3-methylglucose + D-glucosamine acid, α-ketobutyric acid + 3-methylglucose + glycyl-L-asparagino oic acid, α-ketobutyric acid + oxalic acid + L-alanine, α-ketobutyric acid + sebacic acid + D-glucosamic acid, α-ketobutyric acid + sebacic acid + glycyl-L-aspartic acid, α-ketobutyric acid + L- homoserine + N-acetyl-D-galactosamine, α-ketobutyric acid + 2,3-butanediol + N-acetyl-D-galactosamine, α-ketobutyric acid + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine, mesotartaric acid + pectin + D-glucosamic acid, mesotartaric acid + pectin + glycyl-L-aspartic acid, α-hydroxybutyric acid + inulin + D-glucosamic acid, α-hydroxybutyric acid + inulin + glycyl-L-aspartic acid, α- hydroxybutyric acid + 3-methylglucose + D-glucosamine acid, α-hydroxybutyric acid + 3-methylglucose + glycyl-L-aspartic acid, α-hydroxybutyric acid + oxalic acid + L-alanine, α-hydroxybutyric acid + sebacic acid + D- glucosamine acid, α-hydroxybutyric acid + sebacic i acid + glycyl-L-aspartic acid, α-hydroxybutyric acid + 2,3-butanediol + N-acetyl-D-galactosamine, α-hydroxybutyric acid + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine, citric acid + α-cyclodextrin + glycyl-L-glutamic acid, citric acid + α-cyclodextrin + tricarballic acid, citric acid + mannan + glycyl-L-glutamic acid, citric acid + mannan + tricarballylic acid, citric acid + oxalic acid + L-alanine, citric acid + pectin + L-alanine, brosuccinic acid + 2,3-butanediol + N-acetyl-D-galactosamine, brosuccinic acid + 2,3-butanediol + glycyl-L-aspartic acid, bromosuccinic acid + 3 -hydroxy-2-butanone + N-acetyl-D-galactosamine, brosuccinic acid + 3-hydroxy-2-butanone + glycyl-L-aspartic acid, brosuccinic acid + pectin + L-alanine, mucic acid + inulin + D-glucosamine acid, mucic acid + inulin + glycyl-L-aspartic acid, mucic acid + 3-methylglucose + D-Glucosamic Acid, Mucinic Acid + 3-Methylglucose + Glycyl-L-Aspartic Acid, Mucinic Acid + Oxalic Acid + L-Alanine, Mucinic Acid + Sebacic Acid + D-Glucosamic Acid, Mucinic Acid + Sebacic Acid + Glycyl-L- aspartic acid, mucic acid + 2,3-butanediol + N-acetyl-D-galactosamine, mucic acid + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine, glyocylic acid + inulin + glycyl-L-aspartic acid , Glyocylic Acid + 3-Methylglucose + D-Glucosamic Acid, Glyocylic Acid + 3-Methylglucose + Glycyl-L-Aspartic Acid, Glyocylic Acid + Oxalic Acid + L-Alanine, Glyocylic Acid + Sebacic Acid + D-Glucosamic Acid, Glyocylic Acid + sebacic acid + glycyl-L-aspartic acid, glyocylic acid + 2,3-butanediol + N-acetyl-D-galactosamine, glyocylic acid + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine, phenylethylamine + 3 -methylglucose + D-glucosamine acid lota, phenylethylamine + 3-methylglucose + N-acetyl-D-galactosamine, phenylethylamine + 3-methylglucose + glycyl-L-aspartic acid, phenylethylamine + oxalic acid + L-alanine, phenylethylamine + oxalic acid + N-acetyl-D-galactosamine , phenylethylamine + pectin + N-acetyl-D-galactosamine, D-alanine + 3-methylglucose, D-alanine + oxalic acid, L-alanylglycine + γ-cyclodextrin, L-alanylglycine + inulin, L-alanylglycine + sebacic acid, L -alanylglycine + 2,3-butanediol, L-alanylglycine + 3-hydroxy-2-butanone, D-sugar acid + oxalic acid + L-alanine, succinic acid + oxalic acid + L-alanine, succinic acid + pectin + L- alanine, Tween 40 + oxalic acid + L-alanine, Tween 40 + pectin + L-alanine, α-ketoglutaric acid + inulin + glycyl-L-aspartic acid, α-ketoglutaric acid + sebacic acid + glycyl-L-aspartic acid, α-ketoglutaric acid + 3-hydroxy-2-butanone + glycyl-L-aspartic acid, mesotartaric acid + oxalic acid + L-alanine , mesotartaric acid + pectin + L-alanine, brosuccinic acid + γ-cyclodextrin + D-glucosamine acid, brosuccinic acid + γ-cyclodextrin + glycyl-L-aspartic acid, brosuccinic acid + inulin + D-glucosamine acid, bromosuccinic acid + inulin + glycyl-L-aspartic acid, brosuccinic acid + 3-methylglucose + D-glucosamine acid, brosuccinic acid + 3-methylglucose + glycyl-L-aspartic acid, brosuccinic acid + sebacic acid + D-glucosamine acid, brosuccinic acid + sebacic acid + glycyl-L-aspartic acid, brosuccinic acid + 2,3-butanediol + D-glucosamine acid, brosuccinic acid + 3-hydroxy-2-butanone + D-glucosamic acid, brosuccinic acid + pectin + D-glucosamine acid, brosuccinic acid + pectin + glycyl-L-aspartic acid, phenylethylamine + α-cyclodextrin + N-acetyl-D-galactosamine, phenylethylamine + turanose + N-acetyl-D-galactosamine, phenylethylamine + L-homoserine + N-acetyl-D- galactosamine, phenethylamine + 2,3-butanediol + N-acetyl-D-galactosamine and phenethylamine + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine.

Embodiment 4 The composition of Embodiment 1 or 2 wherein the skin microbiota balancer is configured to provide a first desired ratio of Corynebacterium to Staphylococcus, a second desired ratio of Corynebacterium to Micrococcus, and a third desired ratio of Staphylococcus to Micrococcus.

Embodiment 5 The composition of Embodiment 4 wherein at least one combination of carbohydrate sources is selected from the group consisting of the following: D-alanine + 3-methylglucose, D-alanine + oxalic acid, L-alanylglycine + γ-cyclodextrin, L -alanylglycine + inulin, L-alanylglycine + sebacic acid, L-alanylglycine + 2,3-butanediol, L-alanylglycine + 3-hydroxy-2-butanone, D-sugar acid + oxalic acid + L-alanine, succinic acid + oxalic acid acid + L-alanine, succinic acid + pectin + L-alanine, Tween 40 + oxalic acid + L-alanine, Tween 40 + pectin + L-alanine, α-ketoglutaric acid + inulin + glycyl-L-aspartic acid, α- ketoglutaric acid + sebacic acid + glycyl-L-aspartic acid, α-ketoglutaric acid + 3-hydroxy-2-butanone + glycyl-L-aspartic acid, mesotartaric acid + oxalic acid + L-alanine, mesotartaric acid + pectin + L- alanine, brosuccinic acid + γ-cyclodextrin + D-glucosamine acid, brosuccinic acid + γ-cyclodextrin + glycyl-L-aspartic acid, brosuccinic acid + inulin + D-glucosamine acid, brosuccinic acid + inulin + glycyl-L-aspartic acid, brosuccinic acid + 3-methylglucose + D-glucosamine acid, bromosuccinic acid + 3-methylglucose + glycyl-L-aspartic acid, brosuccinic acid + sebacic acid + D-glucosamine acid, brosuccinic acid + sebacic acid + glycyl-L-aspartic acid, brosuccinic acid + 2,3-butanediol + D-glucosamine acid, bromosuccinic acid + 3-hydroxy-2-butanone + D-glucosamine acid, brosuccinic acid + pectin + D-glucosamine acid, brosuccinic acid + pectin + glycyl-L-aspartic acid, phenethylamine + α-cyclodextrin + N-acetyl-D-galactosamine , phenylethylamine + turanose + N-acetyl-D-galactosamine, phenylethylamine + L-homoserine + N-acetyl-D-galactosamine, phenylethylamine + 2,3-butanediol + N-acetyl-D-galactosamine and phenylethylamine + 3-hydroxy-2 -butanone + N-acetyl-D -galactosamine.

Embodiment 6. A composition according to any of the previous embodiments wherein the composition is applied to a component of an absorbent article or to a tissue.

Embodiment 7. A composition according to any of the previous embodiments wherein the composition is in the form of a liquid or cream.

Embodiment 8. A composition for providing or maintaining a healthy skin microbiota, comprising a carrier and a skin microbiota balancing agent, wherein the skin microbiota balancing agent comprises at least one combination of carbohydrate sources, wherein the combination of carbohydrate sources is selected from the group, consisting of the following: D-alanine + 3-methylglucose, D-alanine + oxalic acid, L-alanylglycine + γ-cyclodextrin, L-alanylglycine + inulin, L-alanylglycine + sebacic acid, L-alanylglycine + 2,3-butanediol, L-alanylglycine + 3-hydroxy-2-butanone, D-sugar acid + oxalic acid + L-alanine, succinic acid + oxalic acid + L-alanine, succinic acid + pectin + L-alanine, Tween 40 + oxalic acid + L -alanine, Tween 40 + pectin + L-alanine, α-ketoglutaric acid + inulin + glycyl-L-aspartic acid, α-ketoglutaric acid + sebacic acid + glycyl-L-aspartic acid, α-ketoglutaric acid + 3-hydroxy- 2-butanone + glycyl-L-aspartic acid, mesotartaric acid + oxalic acid + L-alanine, mesotartaric acid + pectin + L-alanine, brosuccinic acid + γ-cyclodextrin + D-glucosamine acid, bromosuccinic acid + γ-cyclodextrin + glycyl-L- aspartic acid, brosuccinic acid + inulin + D-glucosamine acid, brosuccinic acid + inulin + glycyl-L-aspartic acid, brosuccinic acid + 3-methylglucose + D-glucosamic acid, brosuccinic acid + 3-methylglucose + glycyl-L-aspartic acid , brosuccinic acid + sebacic acid + D-glucosamine acid, brosuccinic acid + sebacic acid + glycyl-L-aspartic acid, brosuccinic acid + 2,3-butanediol + D-glucosamine acid, brosuccinic acid + 3-hydroxy-2-butanone + D-glucosamine acid, brosuccinic acid + pectin + D-glucosamine acid, brosuccinic acid + pectin + glycyl-L-aspartic acid, phenylethylamine + α-cyclodextrin + N-acetyl-D-galactosamine, phenylethyl min + turanose + N-acetyl-D-galactosamine, phenylethylamine + L-homoserine + N-acetyl-D-galactosamine, phenylethylamine + 2,3-butanediol + N-acetyl-D-galactosamine and phenylethylamine + 3-hydroxy-2- butanone + N-acetyl-D-galactosamine.

Embodiment 9 The composition of Embodiment 8 wherein the skin microbiota balancer is configured to provide a first desired ratio of Corynebacterium to Staphylococcus, a second desired ratio of Corynebacterium to Micrococcus, and a third desired ratio of Staphylococcus to Micrococcus.

Embodiment 10 The composition of Embodiment 9 wherein the first desired ratio of Corynebacterium to Staphylococcus is 1.3, the second desired ratio of Corynebacterium to Micrococcus is 1.4, and the third desired ratio of Staphylococcus to Micrococcus is 1.1.

Embodiment 11. The composition of any one of Embodiments 8-10, wherein the composition is applied to a component of an absorbent article or to a tissue.

Embodiment 12 A composition according to any one of Embodiments 8-11 wherein the composition is in the form of a liquid or cream.

Embodiment 13. A method of providing or maintaining a healthy skin microbiota in a subject, the method comprising providing a prebiotic composition configured to maintain at least one of a first desired ratio of Corynebacterium to Staphylococcus, a second desired ratio of Corynebacterium to Micrococcus, and a third desired ratio Staphylococcus to Micrococcus, wherein the composition based on prebiotics contains a carrier and an agent that provides a balance of the skin microbiota, containing at least a first carbohydrate source, while the first carbohydrate source is selected to maintain at least one of the first necessary ratio of Corynebacterium to Staphylococcus, the second necessary the ratio of Corynebacterium to Micrococcus and the third required ratio of Staphylococcus to Micrococcus; and providing instructions for use of the prebiotic composition to the subject.

Embodiment 14. The method of Embodiment 13 further comprising administering the prebiotic composition to a subject to provide or maintain a healthy skin microbiota in the subject.

Embodiment 15. The method of Embodiment 13 or 14, wherein the first desired ratio of Corynebacterium to Staphylococcus is 1.3, the second desired ratio of Corynebacterium to Micrococcus is 1.4, and the third desired ratio of Staphylococcus to Micrococcus is 1.1.

Embodiment 16. The method of any one of embodiments 13-15, wherein the prebiotic composition is configured to maintain at least two of a first desired ratio of Corynebacterium to Staphylococcus, a second desired ratio of Corynebacterium to Micrococcus, and a third desired ratio of Staphylococcus to Micrococcus.

Embodiment 17. The method of any one of Embodiments 13-16, wherein the skin microbiota balancing agent comprises at least one combination of carbohydrate sources, wherein the at least one combination of carbohydrate sources comprises a first carbohydrate source and a second carbohydrate source.

Embodiment 18. The method of Embodiment 17 wherein at least one combination of carbohydrate sources is selected from the group consisting of the following: D-alanine + γ-cyclodextrin, D-alanine + sebacic acid, D-alanine + 2,3-butanediol , D-aspartic acid + oxalic acid, D-aspartic acid + pectin, D-threonine + 3-methylglucose, D-threonine + pectin, fumaric acid + α-cyclodextrin, fumaric acid + mannan, L-alanylglycine + 3-methylglucose, L-alanylglycine + oxalic acid, L-alanylglycine + pectin, L-malic acid + mannan, D-sugar acid + pectin + L-alanine, succinic acid + 3-methylglucose + D-glucosamine acid, succinic acid + 3-methylglucose + L-alanine, succinic acid + 3-methylglucose + glycyl-L-aspartic acid, succinic acid + pectin + D-glucosamine acid, succinic acid + pectin + glycyl-L-aspartic acid, Tween 40 + 3-methylglucose + D-glucosamine acid, Tween 40 + 3-methylglucose + L-alanine, Tween 40 + 3-me tilglucose + glycyl-L-aspartic acid, Tween 40 + pectin + D-glucosamine acid, Tween 40 + pectin + glycyl-L-aspartic acid, α-ketoglutaric acid + γ-cyclodextrin + glycyl-L-aspartic acid, α-ketoglutaric acid + inulin + D-glucosamine acid, α-ketoglutaric acid + 3-methylglucose + glycyl-L-aspartic acid, α-ketoglutaric acid + γ-aminobutyric acid + glycyl-L-aspartic acid, α-ketoglutaric acid + sebacic acid + D-glucosamine acid, α-ketoglutaric acid + 2,3-butanediol + glycyl-L-aspartic acid, α-ketoglutaric acid + 3-hydroxy-2-butanone + D-glucosamic acid, α-ketobutyric acid + α-cyclodextrin + N-acetyl-D-galactosamine, α-ketobutyric acid + inulin + D-glucosamine acid, α-ketobutyric acid + inulin + glycyl-L-aspartic acid, α-ketobutyric acid + 3-methylglucose + D-glucosamine acid, α- ketobutyric acid + 3-methylglucose + glycyl-L-aspartic acid ota, α-ketobutyric acid + oxalic acid + L-alanine, α-ketobutyric acid + sebacic acid + D-glucosamic acid, α-ketobutyric acid + sebacic acid + glycyl-L-aspartic acid, α-ketobutyric acid + L-homoserine + N-acetyl-D-galactosamine, α-ketobutyric acid + 2,3-butanediol + N-acetyl-D-galactosamine, α-ketobutyric acid + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine, mesotartaric acid + pectin + D-glucosamic acid, mesotartaric acid + pectin + glycyl-L-aspartic acid, α-hydroxybutyric acid + inulin + D-glucosamic acid, α-hydroxybutyric acid + inulin + glycyl-L-aspartic acid, α-hydroxybutyric acid acid + 3-methylglucose + D-glucosamine acid, α-hydroxybutyric acid + 3-methylglucose + glycyl-L-aspartic acid, α-hydroxybutyric acid + oxalic acid + L-alanine, α-hydroxybutyric acid + sebacic acid + D-glucosamine acid, α-hydroxybutyric acid + sebacic acid a + glycyl-L-aspartic acid, α-hydroxybutyric acid + 2,3-butanediol + N-acetyl-D-galactosamine, α-hydroxybutyric acid + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine, citric acid + α-cyclodextrin + glycyl-L-glutamic acid, citric acid + α-cyclodextrin + tricarballic acid, citric acid + mannan + glycyl-L-glutamic acid, citric acid + mannan + tricarballylic acid, citric acid + oxalic acid + L -alanine, citric acid + pectin + L-alanine, brosuccinic acid + 2,3-butanediol + N-acetyl-D-galactosamine, brosuccinic acid + 2,3-butanediol + glycyl-L-aspartic acid, bromosuccinic acid + 3- hydroxy-2-butanone + N-acetyl-D-galactosamine, brosuccinic acid + 3-hydroxy-2-butanone + glycyl-L-aspartic acid, brosuccinic acid + pectin + L-alanine, mucic acid + inulin + D-glucosamine acid , mucic acid + inulin + glycyl-L-aspartic acid, mucic acid + 3-methylglucose + D-gluco saminic acid, mucic acid + 3-methylglucose + glycyl-L-aspartic acid, mucic acid + oxalic acid + L-alanine, mucic acid + sebacic acid + D-glucosamic acid, mucic acid + sebacic acid + glycyl-L-aspartic acid , mucic acid + 2,3-butanediol + N-acetyl-D-galactosamine, mucic acid + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine, glyocylic acid + inulin + glycyl-L-aspartic acid, glyocylic acid + 3-methylglucose + D-glucosamine acid, glyocylic acid + 3-methylglucose + glycyl-L-aspartic acid, glyocylic acid + oxalic acid + L-alanine, glyocylic acid + sebacic acid + D-glucosamine acid, glyocylic acid + sebacic acid + glycyl-L-aspartic acid, glyocylic acid + 2,3-butanediol + N-acetyl-D-galactosamine, glyocylic acid + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine, phenylethylamine + 3-methylglucose + D-glucosamine acid, fe nylethylamine + 3-methylglucose + N-acetyl-D-galactosamine, phenylethylamine + 3-methylglucose + glycyl-L-aspartic acid, phenylethylamine + oxalic acid + L-alanine, phenylethylamine + oxalic acid + N-acetyl-D-galactosamine, phenylethylamine + pectin + N-acetyl-D-galactosamine, D-alanine + 3-methylglucose, D-alanine + oxalic acid, L-alanylglycine + γ-cyclodextrin, L-alanylglycine + inulin, L-alanylglycine + sebacic acid, L-alanylglycine + 2,3-butanediol, L-alanylglycine + 3-hydroxy-2-butanone, D-sugar acid + oxalic acid + L-alanine, succinic acid + oxalic acid + L-alanine, succinic acid + pectin + L-alanine, Tween 40 + oxalic acid + L-alanine, Tween 40 + pectin + L-alanine, α-ketoglutaric acid + inulin + glycyl-L-aspartic acid, α-ketoglutaric acid + sebacic acid + glycyl-L-aspartic acid, α- ketoglutaric acid + 3-hydroxy-2-butanone + glycyl-L-aspartic acid, mesotartaric acid + oxalic acid + L-alanine, meso acid + pectin + L-alanine, brosuccinic acid + γ-cyclodextrin + D-glucosamine acid, brosuccinic acid + γ-cyclodextrin + glycyl-L-aspartic acid, brosuccinic acid + inulin + D-glucosamine acid, brosuccinic acid + inulin + glycyl-L-aspartic acid, brosuccinic acid + 3-methylglucose + D-glucosamine acid, brosuccinic acid + 3-methylglucose + glycyl-L-aspartic acid, brosuccinic acid + sebacic acid + D-glucosamine acid, brosuccinic acid + sebacic acid + glycyl-L-aspartic acid, brosuccinic acid + 2,3-butanediol + D-glucosamine acid, brosuccinic acid + 3-hydroxy-2-butanone + D-glucosamic acid, brosuccinic acid + pectin + D-glucosamine acid, brosuccinic acid + pectin + glycyl-L-aspartic acid, phenylethylamine + α-cyclodextrin + N-acetyl-D-galactosamine, phenylethylamine + turanose + N-acetyl-D-galactosamine, phenylethylamine + L-homoserine + N-acetyl-D-galactose amine, phenylethylamine + 2,3-butanediol + N-acetyl-D-galactosamine and phenylethylamine + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine.

Embodiment 19 The method of Embodiment 17 wherein the skin microbiota balancer is configured to provide a first desired ratio of Corynebacterium to Staphylococcus, a second desired ratio of Corynebacterium to Micrococcus, and a third desired ratio of Staphylococcus to Micrococcus.

Embodiment 20. The method of Embodiment 19 wherein at least one combination of carbohydrate sources is selected from the group consisting of the following: D-alanine + 3-methylglucose, D-alanine + oxalic acid, L-alanylglycine + γ-cyclodextrin, L -alanylglycine + inulin, L-alanylglycine + sebacic acid, L-alanylglycine + 2,3-butanediol, L-alanylglycine + 3-hydroxy-2-butanone, D-sugar acid + oxalic acid + L-alanine, succinic acid + oxalic acid acid + L-alanine, succinic acid + pectin + L-alanine, Tween 40 + oxalic acid + L-alanine, Tween 40 + pectin + L-alanine, α-ketoglutaric acid + inulin + glycyl-L-aspartic acid, α- ketoglutaric acid + sebacic acid + glycyl-L-aspartic acid, α-ketoglutaric acid + 3-hydroxy-2-butanone + glycyl-L-aspartic acid, mesotartaric acid + oxalic acid + L-alanine, mesotartaric acid + pectin + L- alanine, brosuccinic acid + γ-cyclodextrin + D-glucosamine acid, brosuccinic acid acid + γ-cyclodextrin + glycyl-L-aspartic acid, brosuccinic acid + inulin + D-glucosamine acid, brosuccinic acid + inulin + glycyl-L-aspartic acid, brosuccinic acid + 3-methylglucose + D-glucosamine acid, bromosuccinic acid + 3-methylglucose + glycyl-L-aspartic acid, brosuccinic acid + sebacic acid + D-glucosamine acid, brosuccinic acid + sebacic acid + glycyl-L-aspartic acid, brosuccinic acid + 2,3-butanediol + D-glucosamine acid, bromosuccinic acid + 3-hydroxy-2-butanone + D-glucosamine acid, brosuccinic acid + pectin + D-glucosamine acid, brosuccinic acid + pectin + glycyl-L-aspartic acid, phenethylamine + α-cyclodextrin + N-acetyl-D-galactosamine , phenylethylamine + turanose + N-acetyl-D-galactosamine, phenylethylamine + L-homoserine + N-acetyl-D-galactosamine, phenylethylamine + 2,3-butanediol + N-acetyl-D-galactosamine and phenylethylamine + 3-hydroxy-2 -butanone + N-acetyl-D- galactosamine.

Claims (6)

1. A composition for providing or maintaining healthy skin microbiota, comprising a carrier and a skin microbiota balancing agent, wherein the skin microbiota balancing agent contains at least one combination selected from the group consisting of the following: D-alanine + 3 -methylglucose, D-alanine + oxalic acid, L-alanylglycine + γ-cyclodextrin, L-alanylglycine + inulin, L-alanylglycine + sebacic acid, L-alanylglycine + 2,3-butanediol, L-alanylglycine + 3-hydroxy-2 -butanone, D-sugar acid + oxalic acid + L-alanine, succinic acid + oxalic acid + L-alanine, succinic acid + pectin + L-alanine, Tween 40 + oxalic acid + L-alanine, Tween 40 + pectin + L -alanine, α-ketoglutaric acid + inulin + glycyl-L-aspartic acid, α-ketoglutaric acid + sebacic acid + glycyl-L-aspartic acid, α-ketoglutaric acid + 3-hydroxy-2-butanone + glycyl-L-aspartic acid acid, mesotartaric acid + oxalic acid + L-ala nin, mesotartaric acid + pectin + L-alanine, brosuccinic acid + γ-cyclodextrin + D-glucosamine acid, brosuccinic acid + γ-cyclodextrin + glycyl-L-aspartic acid, brosuccinic acid + inulin + D-glucosamine acid, bromosuccinic acid + inulin + glycyl-L-aspartic acid, brosuccinic acid + 3-methylglucose + D-glucosamine acid, brosuccinic acid + 3-methylglucose + glycyl-L-aspartic acid, brosuccinic acid + sebacic acid + D-glucosamine acid, brosuccinic acid + sebacic acid + glycyl-L-aspartic acid, brosuccinic acid + 2,3-butanediol + D-glucosamine acid, brosuccinic acid + 3-hydroxy-2-butanone + D-glucosamic acid, brosuccinic acid + pectin + D-glucosamine acid, bromosuccinic acid + pectin + glycyl-L-aspartic acid, phenylethylamine + α-cyclodextrin + N-acetyl-D-galactosamine, phenylethylamine + turanose + N-acetyl-D-galactosamine, phenylethylamine + L-homoserine + N-acetyl l-D-galactosamine, phenylethylamine + 2,3-butanediol + N-acetyl-D-galactosamine and phenylethylamine + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine. 2. The composition of claim 1, wherein the skin microbiota balancer is configured to provide a first desired ratio of Corynebacterium to Staphylococcus, a second desired ratio of Corynebacterium to Micrococcus, and a third desired ratio of Staphylococcus to Micrococcus, where the first desired ratio of Corynebacterium to Staphylococcus is 1 3, the second required ratio of Corynebacterium to Micrococcus is 1.4 and the third required ratio of Staphylococcus to Micrococcus is 1.1. 3. A composition according to claim 1 or 2, wherein the composition is applied to a component of the absorbent article or to a tissue. 4. The composition according to any one of paragraphs. 1-3, where the composition is in the form of a liquid or cream. 5. A method of providing or maintaining a healthy skin microbiota in a subject, the method comprising administering a prebiotic composition to a subject, wherein the prebiotic composition comprises a carrier and a skin microbiota balancing agent comprising at least one combination selected from the group consisting of the following: D-alanine + 3-methylglucose, D-alanine + oxalic acid, L-alanylglycine + γ-cyclodextrin, L-alanylglycine + inulin, L-alanylglycine + sebacic acid, L-alanylglycine + 2,3-butanediol, L-alanylglycine + 3-hydroxy-2-butanone, D-sugar acid + oxalic acid + L-alanine, succinic acid + oxalic acid + L-alanine, succinic acid + pectin + L-alanine, Tween 40 + oxalic acid + L-alanine, Tween 40 + pectin + L-alanine, α-ketoglutaric acid + inulin + glycyl-L-aspartic acid, α-ketoglutaric acid + sebacic acid + glycyl-L-aspartic acid, α-ketoglutaric acid + 3-hydroxy-2-butanone + glycyl-L-aspartic acid, mesotartaric acid + oxalic acid + L-alanine, mesotartaric acid + pectin + L-alane in, brosuccinic acid + γ-cyclodextrin + D-glucosamine acid, brosuccinic acid + γ-cyclodextrin + glycyl-L-aspartic acid, brosuccinic acid + inulin + D-glucosamine acid, brosuccinic acid + inulin + glycyl-L-aspartic acid, brosuccinic acid + 3-methylglucose + D-glucosamine acid, brosuccinic acid + 3-methylglucose + glycyl-L-aspartic acid, brosuccinic acid + sebacic acid + D-glucosamine acid, brosuccinic acid + sebacic acid + glycyl-L-aspartic acid, brosuccinic acid + 2,3-butanediol + D-glucosamine acid, brosuccinic acid + 3-hydroxy-2-butanone + D-glucosamic acid, brosuccinic acid + pectin + D-glucosamic acid, brosuccinic acid + pectin + glycyl-L-aspartic acid acid, phenylethylamine + α-cyclodextrin + N-acetyl-D-galactosamine, phenylethylamine + turanose + N-acetyl-D-galactosamine, phenylethylamine + L-homoserine + N-acetyl-D-galactosamine, phenylethylamine + 2,3-but andiol + N-acetyl-D-galactosamine and phenethylamine + 3-hydroxy-2-butanone + N-acetyl-D-galactosamine.

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