WO2022258405A1 - Topical composition for balancing microbiota of skin - Google Patents

Abstract

The present invention relates to use of zinc pyrithione or a piroctone compound in a topical composition for balancing microbiota of skin, where balancing means reducing the ratio of level of Malassezia restricta to that of Malassezia globosa, or selectively reducing microbial count of at least one genus of microbes belong to Staphylococcus; wherein said skin is scalp having dandruff; wherein the said genus of microbes belong to Staphylococcus is Staphylococcus capitis.

Description

TOPICAL COMPOSITION FOR BALANCING MICROBIOTA OF SKIN

Field of the Invention The present invention relates to a method of balancing microbiota of skin.

Background of the Invention

The skin is the largest organ of human body. It protects our body from external factors such as the environment, pollution and microbes. Our skin harbours a diverse range of microorganisms which live as a community and function as a component of skin biology. Due to the advent of next-generation sequencing technologies, we now know that the microbiome or microbiota of human skin is highly dependent on biophysical characteristics and chemical constitution of the skin. For example, sebaceous sites are dominated by Cutibacterium sp., whereas moist areas harbour Staphylococcus and Corynebacterium species. Any adverse alteration in the microbiome of our skin could lead to conditions e.g., dysbiosis, that may need at least cosmetic treatment as such seen in the case of acne, dry skin and dandruff.

The microbiome of skin can be balanced e.g. by reducing the overload microbial load or microbial count of skin but by selectively reducing some while selectively increasing the count of some others.

In some cases, balancing the microbiota of skin refers to selectively increasing the microbial count of good microbes and/or reducing the same count of bad microbes. Good microbes are said to provide benefit to their host through e.g., competing with bad microbes for available nutrients and through secretion of good metabolites.

Summary of the Invention

In accordance with a first aspect disclosed is use of zinc pyrithione or a piroctone compound in a topical composition for balancing microbiota of skin, where balancing means reducing the ratio of level of Malassezia restricta to that of Malassezia globosa, or selectively reducing microbial count of at least one genus of microbes belong to Staphylococcus; wherein said skin is scalp having dandruff; wherein the said genus of microbes belong to Staphylococcus is Staphylococcus capitis. In accordance with a second aspect disclosed is a method of balancing microbiota of skin comprising a step of applying thereto zinc pyrithione or a piroctone compound in a topical composition, where balancing means reducing the ratio of level of Malassezia restricta to that of Malassezia globosa, or selectively reducing microbial count of at least one genus of microbes belong to Staphylococcus, wherein said skin is scalp having dandruff; wherein the said genus of microbes belong to Staphylococcus is Staphylococcus capitis.

In accordance with a third aspect disclosed is at topical composition comprising zinc pyrithione or a piroctone compound for use in balancing microbiota of skin, where balancing means reducing the ratio of level of Malassezia restricta to that of Malassezia globosa, or selectively reducing microbial count of at least one genus of microbes belong to Staphylococcus, while maintain the microbial count of at least one genus of microbes belong to Cuti bacterium; wherein said skin is scalp having dandruff

In accordance with a fourth aspect disclosed is use of zinc pyrithione or a piroctone compound for balancing microbiota of skin, where balancing means reducing the ratio of level of Malassezia restricta to that of Malassezia globosa, or selectively reducing microbial count of at least one genus of microbes belong to Staphylococcus, while maintain the microbial count of at least one genus of microbes belong to Cutibacterium preferably Cutibacterium aeries ; wherein said skin is scalp having dandruff.

Detailed Description of the Invention

Any feature of one aspect of the present invention may be utilized in any other aspect of the invention. The word “comprising” is intended to mean “including” but not necessarily “consisting of’ or “composed of”. In other words, the listed steps or options need not be exhaustive. Except in the operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of material or conditions of reaction, physical properties of materials and/or use are to be understood as modified by the word “about”. Numerical ranges expressed in the format "x to y" are understood to include x and y. When for a specific feature multiple preferred ranges are described in the format "x to y", it is understood that all ranges combining the different endpoints are also contemplated. Unless specified otherwise, amounts as used herein are expressed in percentage by weight based on total weight of the composition and is abbreviated as “wt%”. The use of any and all examples or exemplary language e.g. “such as” provided herein is intended merely to better illuminate the invention and does not in any way limit the scope of the invention otherwise claimed.

By ‘a cosmetic composition’ as used herein, is meant to include a composition for topical application to skin, hair and/or scalp of mammals, especially human beings. Such a composition is generally applied on to the desired topical surface of the body for a period of time from a few seconds to up to 24 hours. When the period of time of application is low say of the order of a few seconds to a few minutes after which the composition is rinsed off with water or wiped away, such a composition is known as a cleansing composition or a wash-off composition. On the other hand, When the composition is applied for longer period of time say from several minutes to up to 24 hours and washed off usually during the process of normal personal cleaning, such a composition is known as a leave-on composition. The composition as per the present invention includes any product applied to a human body for also improving appearance, cleansing, odor control or general aesthetics.

By "hair care composition" as used herein, is meant to include a composition for topical application to hair or scalp of mammals, especially humans. By topical is meant that the composition is applied to the external surface of the body. In the present invention this is achieved by applying the composition on the hair or scalp. Such a composition may be generally classified as leave-on or rinse off, and includes any product applied for improving the appearance, cleansing, odor control or general aesthetics of scalp and hair. The hair care composition of the present invention could be in the form of a liquid, lotion, cream, foam, scrub, gel, shampoo, conditioner, shower gel or bar. The haircare composition of the present invention is preferably a leave-on composition. Alternatively, the hair care composition of the present invention is a wash-off composition. Compositions for achieving the desired benefits by way of ingestion into the human body are excluded from the scope of the present invention.

The term balancing means selectively reducing the ratio of level of one species of microbes considered to be harmful to that of at least one genus of microbes considered to be beneficial, or reducing microbial count of at least one genus of microbes considered to be harmful or of at least one genus of microbes that exhibit growth which is not representation of a normal healthy skin, while selectively increasing microbial count of at least one genus of microbes considered to be beneficial or of at least one genus of microbes whose numbers have reduced which is also not representation of a normal healthy skin.

Wherein the term “normal healthy skin” preferably refers to skin which is free from any infection.

Sometimes it might not be easy to distinguish between beneficial and harmful microbes because it might vary depending on circumstances. Therefore, for dysbiotic conditions like dandruff, balancing means reducing or increasing the count of those microbes that have significantly changed in a condition as against healthy state. Such change could either be an abnormal increase or an abnormal decrease in their count.

A microbe can be described as a tiny living organism, such as bacterium, fungus, or virus. A microbiome or microbiota refers collectively to all the microbes on or in the human body. In other words, a microbiome is a community of microbes. A balanced microbiota containing diversity of organisms helps to maintain health and is essential for human development, immunity, health and wellbeing. Each of our individual microbiomes adapts throughout our lifetime and people can achieve a healthy microbiome in different ways. One way to regulate microbiome balance is via boosting skin’s own mechanisms of innate immunity, e.g. via boosting the activity of antimicrobial lipids or peptides.

According to one aspect of the present invention, amenable skin means the scalp which has dandruff.

Dandruff is a common scalp condition, characterized by excessive flaking and itch. It is generally accepted that the presence of dandruff is associated with changes in microbe ecology, altered lipid composition, inflammation and abnormal epidermal barrier function. The Malassezia yeast has long been considered as one of the main microbial drivers for dandruff. Severity of dandruff is generally associated with an increased abundance of Malassezia restricta.

The recent development of next generation sequencing (NGS) technology supplemented by quantitative polymerase chain reaction (qPCR) of the key fungal and bacterial community members, makes it possible to understand the microbiome composition with more details. It is demonstrated by Sally G. Grimshaw et al. that the major component of the fungal microbiome of both healthy and dandruff scalp is Malassezia restricta. The level of Malassezia restricta as quantified by qPCR is higher on dandruff scalp compared to healthy scalp, which is in consensus with the association of the yeast with dandruff condition. However, one of the other Malassezia species, namely Malassezia globosa, does not show the same trend as Malassezia restricta.

While association of fungal mycobiome with dandruff condition are well accepted, recent studies have suggested a possible contribution from dysbiosis of the scalp bacterial microbiome. The two most abundant bacterial genera found on the scalp surface were Cutibacterium and Staphylococcus as assessed by NGS. Quantitative assessment of the bacterial species on both dandruff and healthy scalps revealed that dandruff was correlated with a higher incidence Staphylococcus spp. compared to the healthy population. In addition, the increase in levels of Staphylococcus capitis was of sufficient magnitude to drive an overall increase in absolute Staphylococcus species abundance at a dandruff lesional site.

For Cutibacterium aeries, the other dominant bacterial species on scalp, it was found that the relative abundance was decreased in dandruff conditions comparing with healthy. By absolute quantification of the species using qPCR, it was demonstrated that there was no significant association of the level with dandruff conditions, indicating the commensal role of this bacterial species on scalp.

In accordance with the present invention, the microbes are bacteria or fungi the bacteria or fungi is dandruff associated.

At least one genus of harmful microbes is Staphylococcus. It is further preferred that upon use of the present invention, total count of bacteria belonging to genus Staphylococcus is reduced to the level normally indicative of healthy skin. Such levels are within the domain knowledge of persons skilled in the art of cosmetics and pharmaceutical products.

The harmful microbe is Staphylococcus capitis. It is reported by Sally G. Grimshaw et al. that the major component of the fungal mycrobiome of both healthy and dandruff scalp is Malassezia restricta. The level of Malassezia restricta as quantified by qPCR is higher on dandruff scalp compared to healthy scalp, which is in consensus with the association of the yeast with dandruff condition. However, one of the other Malassezia species, namely Malassezia globosa, does not show the same trend as Malassezia restricta. A further analysis on the Malassezia dysbiosis index, characterized by the ratio of Malassezia restricta / Malassezia globosa, indicated the association of disrupted Malassezia balance between the two species with dandruff conditions, that the Malassezia dysbiosis index is higher in dandruff conditions comparing with heathy.

Upon use of the present invention, ratio of Malassezia restricta / Malassezia globosa is reduced to the level normally indicative of healthy skin. Such levels are within the domain knowledge of persons skilled in the art of cosmetics and pharmaceutical products.

In accordance with the present invention, the use of zinc pyrithione or a piroctone compound in a topical composition balances microbiota of skin, where balancing means reducing the ratio of level of Malassezia restricta to that of Malassezia globosa, or selectively reducing microbial count of at least one genus of microbes belong to Staphylococcus. It is preferred that upon use of the present invention, the microbial count of at least one genus of microbes belong to commensal of skin, more preferably commensal of scalp is maintained. Preferably the commensal is Cutibacterium, more preferably Cutibacterium aeries.

It is preferred that such balancing is progressive, preferably takes at least 4 weeks.

It is preferred that the antimicrobial active is a piroctone compound, more preferably piroctone olamine.

Zinc pyrithione (ZPTO) which is shorthand for zinc 1-hydroxy-2-pyridinethione is polyvalent metal salt of pyrithione.

The polyvalent metal salt of pyrithione is represented by the following general formula(l):

In the case of zinc pyrithione, M is the metal cation zinc.

Piroctone Olamine is an olamine salt of the hydroxamic acid derivative piroctone. It is commonly known as piroctone ethanolamine with the trade name Octopirox^®.

The piroctone olamine according to the present invention is a 1:1 compound of 1- hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1 H)-pyridinone with 2-aminoethanol and is also designated 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H) pyridinone monoethanolamine salt. The CAS number is 68890-66-4 and the compound has the general formula (II) as below:

The Composition It is preferred that the topical composition comprises 0.01 to 5.0 wt% of zinc pyrithione or a piroctone compound.

In one aspect of the invention the composition preferably comprises a piroctone compound, more preferably piroctone olamine. When the composition comprises a piroctone compound, it preferably comprises 0.01 to 5%, more preferably 0.05 to 2%, still more preferably 0.5 to 1% of piroctone compound by weight of the total composition.

Alternatively, the topical composition comprises zinc pyrithione.

When the composition comprises zinc pyrithione it preferably comprises 0.01 to 5%, more preferably 0.02 to 3%, still more preferably 0.05 to 1% by weight of the composition.

Alternatively, the composition comprises zinc pyrithione and a piroctone compound. It is preferred that the piroctone compound is piroctone olamine.

It is preferred that the topical composition is a cosmetic composition. Alternatively, the topical composition is a medicament or a pharmaceutical composition.

The cosmetic composition is preferably in the form of a wash-off or a leave-on composition, more preferably a wash-off composition. Alternatively, it is a wash-off cosmetic composition, more preferably a hair care composition comprising 0.01 to 5.0 wt% antimicrobial active selected from zinc pyrithione or a piroctone compound or a mixture thereof.

Leave-on composition preferably means a composition which is not required to be removed or washed off from the human body after the application of the composition. When the composition is in the form of a leave-on composition, the composition is preferably a deodorant (stick, roll-on or spray), a hand sanitizer, a body lotion, a skin cream or body spray. Leave-on compositions are to be distinguished from compositions which are applied to the skin and subsequently removed, either by washing, rinsing, wiping, or the like either soon after or during the application of the product. Surfactants typically used for rinse-off compositions have physico-chemical properties giving them the ability to generate foam/lather in-use with ease of rinse; they can consist of mixtures of anionic, cationic, amphoteric, and nonionic surfactants. Wash-off composition preferably means a composition which is intended/required to be removed from the body by washing with solvent preferably water after the application of said composition like e.g. a shampoo, a hand wash composition and a face wash composition. In case of wash-off compositions, a cosmetically acceptable base preferably further comprises a surfactant.

For example, if the composition is in the form of a shampoo, in addition to water, the cosmetically acceptable base preferably comprises an anionic surfactant e.g. an alkyl sulphate and/or ethoxylated alkyl sulfate surfactant. These anionic surfactants are preferably present at a level of from 1 to 20 wt%, more preferably from 2 to 16 wt%, even more preferably from 3 to 16 wt%. Preferred alkyl sulfates are C8 to 18 alkyl sulfates, more preferably C12 to 18 alkyl sulfates, preferably in the form of a salt with a solubilizing cation such as sodium, potassium, ammonium or substituted ammonium.

It is preferred that the topical composition comprises a cosmetically acceptable base. Examples of ingredients that may be used as cosmetically acceptable base includes water, fatty acids, soaps (salts of fatty acids), alcohols and mixtures thereof.

When the composition for use in the invention is a hair care composition, it preferably is a wash-off composition, especially shampoo or a conditioner.

The preferred use of the cosmetic composition is in a shampoo. The cosmetic composition may suitably comprise from 50 to 90%, preferably from 60 to 80% water by weight of the total shampoo composition.

Shampoo compositions for use in the invention will typically comprise one or anionic surfactants such as sodium laureth sulfate, sodium oleyl succinate, ammonium lauryl sulfosuccinate, ammonium lauryl sulphate, sodium dodecylbenzene sulphonate, triethanolamine dodecylbenzene sulfonate, sodium cocoyl isethionate, sodium lauryl isethionate, sodium N-lauryl sarcosinate, sodium lauryl sulfate, sodium lauryl ether sulfate (n) EO, (where n ranges from 1 to 3), ammonium lauryl sulfate and ammonium lauryl ether sulfate (n) EO, (where n ranges from 1 to 3) .

Mixtures of any of the above described materials may also be used.

The total amount of anionic surfactant in shampoo compositions for use in the invention generally ranges from 5 to 30%, preferably from 8 to 20% by weight of the total weight of the composition. Shampoo compositions for use in the invention may also include co-surfactants such as nonionic surfactants, which can be included in an amount ranging from 0.5 to 8%, preferably from 2 to 5% (by weight based on the total weight of the composition) and/or amphoteric or zwitterionic surfactants, which can be included in an amount ranging from 0.5 to 8%, preferably from 1 to 4% by weight based on the total weight of the composition. Representative nonionic surfactants include alkanolamides such as cocamide monoethanolamide and cocamide monoisopropanolamide; alkyl polyglucosides such as cocoglucoside and lauryl glucoside; and acyl glucamides such as cocoyl methyl glucamide. Representive amphoteric surfactant includes cocamidopropyl betaine.

It is more preferred that the shampoo composition for use in the invention comprises sodium laureth sulfate and co-surfactant which is cocamidopropyl betaine.

Mixtures of any of the above-described materials may also be used.

Shampoo compositions for use in the invention may also include one or more cationic polymers, which can be included in an amount ranging from 0.01 to 5%, preferably from 0.05 to 2% by weight based on the total weight of the composition. Representative cationic polymers include cationic polysaccharide polymers such as cationic cellulose derivatives and cationic guar gum derivatives such as guar hydroxypropyltrimethylammonium chloride.

Shampoo compositions for use in the invention may also include one or more suspending agents, which can be included in an amount ranging from 0.05 to 5%, preferably from 0.1 to 3% (by weight based on the total weight of the composition). Representative suspending agents include polyacrylic acids, cross-linked polymers of acrylic acid, copolymers of acrylic acid with a hydrophobic monomer, copolymers of carboxylic acid-containing monomers and acrylic esters, cross-linked copolymers of acrylic acid and acrylate esters, heteropolysaccharide gums and crystalline long chain acyl derivatives such as ethylene glycol distearate.

The shampoo composition further preferably comprises a suspending agent. Suitable suspending agents are polyacrylic acids, cross-linked polymers of acrylic acid, copolymers of acrylic acid with a hydrophobic monomer, copolymers of carboxylic acid- containing monomers and acrylic esters, cross-linked copolymers of acrylic acid and acrylate esters, heteropolysaccharide gums and crystalline long chain acyl derivatives. The long chain acyl derivative is desirably selected from ethylene glycol stearate, alkanolamides of fatty acids having from 16 to 22 carbon atoms and mixtures thereof. Ethylene glycol distearate and polyethylene glycol distearate are preferred long chain acyl derivatives, since these impart pearlescence to the composition. Polyacrylic acid is available commercially as Carbopol® 420, Carbopol® 488 or Carbopol® 493. Polymers of acrylic acid cross-linked with a polyfunctional agent may also be used; they are available commercially as Carbopol® 910, Carbopol® 934, Carbopol® 941 and Carbopol® 980.

Suitable cross-linked polymers of acrylic acid and acrylate esters are Pemulen® TR1 and Pemulen® TR2. A suitable hetero polysaccharide gum is xanthan gum, for example that available as Kelzan.

Alternatively, the use of the cosmetic composition is in a skin care e.g. body or face wash composition. The topical composition for use in the invention may further comprise a surfactant. The preferred surfactants are nonionic surfactants.

Thus, in a highly preferred aspect, the topical compositions include the surfactant selected from the group of anionic surfactants.

When the surfactants are present, the topical composition for use in the invention preferably comprises 1 to 90% surfactant by weight of the composition.

When surfactant is used, a particularly preferred surfactant is soap. Soap is a suitable surfactant for personal washing applications of the topical composition for use in the invention.

When present, the soap, of the present is preferably present in an amount of 1 to 90%, preferably from 10 to 85%, more preferably 25 to 75% by weight of the composition. Preferred compositions for use in the invention may include other known ingredients such as perfumes, pigments, preservatives, emollients, sunscreens, emulsifiers, gelling agents and thickening agents. Choice of these ingredients will largely depend on the format of the composition. Water is a preferred carrier. When water is present, it is preferably present in at least 1%, more preferably at least 2%, furthermore preferably at least 5% by weight of the composition. When water is the carrier, a preferred liquid composition comprises 10 to 99.8% by weight water. The liquid topical composition is useful as a skin antiseptic liquid, for skin cleansing, in particular for hand wash or a face wash. When water is the carrier, a preferred solid composition comprises 5 to 30% by weight water.

The solid topical composition for use in the invention is preferably in form of a shaped solid, more preferably a bar. The solid topical composition for use in the invention is particularly useful for skin cleansing in particular for hand wash or a face wash.

According to another aspect, inorganic particulate material is also a suitable carrier. When inorganic particulate material is the carrier, the topical composition for use in the invention is in a solid form. Preferably the inorganic particulate material is talc. When the inorganic particulate material is talc, the solid antimicrobial composition is particularly useful as a talcum powder for application on face or body.

The present invention now will be demonstrated by way of following non-limiting examples.

Examples

Example 1

These examples are to explore the effect of a prototype shampoo with Octopirox^® on scalp microbiome versus a placebo shampoo (without anti-dandruff actives), through investigation of both scalp fungal and bacterial communities.

The shampoo formulations are prepared as below in Table 1. Table 1

a. Commercial guar hydroxypropyltrimonium chloride has a DS of 0.16 to 0.20 and a weight average molecular weight from 1.0 to 1.5 million g/mol under the trade name

BB-18 from Lamberti.

A clinical study was conducted on a group of subjects who were classified as suffering with dandruff were treated for 4 weeks with a shampoo 1 containing Octopirox^® comparing with a placebo shampoo A without Octopirox^®.

Microbial quantification: Malassezia restricta, Malassezia globosa, C. acnes, S. capitis were quantified (copies/mL buffer) respectively by quantitative polymerase chain reaction (qPCR) method following the procedures as reported by Sally G. Gramshaw et al. from pellet of scalp buffer scrub samples.

The ratio of Malassezia restricta / Malassezia globosa was tested after treating with different shampoo samples and is summarized in Table 2.

Table 2

The data in Table-2 indicates that for the dandruff subjects, after 4 weeks of shampoo wash, Shampoo 1 (with Octopirox^®) has significantly lower (p<0.001) ratio of

Malassezia restricta and Malassezia globosa than the Shampoo A, indicating the improvement of the Malassezia balance with the treatment of piroctone olamine.

The quantity of Staphylococcus capitis was tested after treating with different shampoo samples and is summarized in Table 3.

Table 3

The data in Table-3 indicates that for the dandruff subjects, after 4 weeks of shampoo wash, Shampoo 1 (with Octopirox^®) has significantly lower (p<0.001) Staphylococcus capitis level than the Shampoo A, indicating the improvement of the Staphylococcus capitis balance with the treatment of piroctone olamine.

Cutibacterium acnes is the most abundant bacteria species on scalp, which is a scalp commensal whose absolute level is not altered in dandruff scalp comparing with healthy scalp. The quantity of Cutibacterium acnes was tested after treating with different shampoo samples and is summarized in Table 4.

Table 4

The data in Table 4 indicates that for the dandruff subjects, after 4 weeks of shampoo wash, there’s no significant difference (p=0.25) in level between Sample 1 (with Octopirox^®) and Sample A, indicating that the piroctone olamine does not affect the scalp commensal.

Example 2 These examples are to explore the effect of a prototype shampoo with zinc pyrithione on scalp microbiome versus a placebo shampoo (without anti-dandruff actives), through investigation of both scalp fungal communities.

The shampoo formulations are prepared as below in Table 5.

Table 5

a. Commercial guar hydroxypropyltrimonium chloride has a DS of 0.16 to 0.20 and a weight average molecular weight from 1.0 to 1.5 million g/mol under the trade name BB-18 from Lamberti.

A clinical study was conducted on a group of subjects who were classified as suffering with dandruff were treated for 4 weeks with a shampoo 2 containing zinc pyrithione comparing with a placebo shampoo B without zinc pyrithione.

Microbial quantification: Malassezia restricta and Malassezia globosa were quantified (copies/mL buffer) respectively by quantitative polymerase chain reaction (qPCR) method following the procedures as reported by Sally G. Gramshaw et al. from pellet of scalp buffer scrub samples. The ratio of Malassezia restricta / Malassezia globosa was tested after treating with different shampoo samples and is summarized in Table 6.

Table 6

The data in Table 6 indicates that for the dandruff subjects, after 4-week of shampoo wash, Shampoo 2 (with zinc pyrithione) has significantly lower (p<0.001) ratio of Malassezia restricta and Malassezia globosa than the Shampoo B, indicating the improvement of the Malassezia balance with the treatment of zinc pyrithione.

Claims

1. Use of zinc pyrithione or a piroctone compound in a topical composition for balancing microbiota of skin, where balancing means reducing the ratio of level of Malassezia restricta to that of Malassezia globosa, or selectively reducing microbial count of at least one genus of microbes belong to Staphylococcus ; wherein said skin is scalp having dandruff; wherein the said genus of microbes belong to Staphylococcus is Staphylococcus capitis.

2. Use as claimed in claim 1 wherein said topical composition is a cosmetic composition.

3. Use as claimed in claim 1 or claim 2 wherein total count of microbes belonging to genus Staphylococcus is reduced to the level normally indicative of healthy skin.

4. Use as claimed in any of claims 1 to 3 wherein the microbial count of at least one genus of microbes belong to commensal of skin is maintained.

5. Use as claimed in claim 4 wherein said commensal is Cutibacterium, preferably Cutibacterium acnes.

6. Use as claimed in any of claims 1 to 5 wherein the ratio of level of Malassezia restricta to that of Malassezia globosa is reduced to the level normally indicative of healthy skin.

7. Use as claimed in any of claims 1 to 6 wherein the balancing is progressive.

8. Use as claimed in any of claims 1 to 7 wherein said composition comprises 0.01 to 5 wt% of zinc pyrithione or a piroctone compound.

9. Use as claimed in any of claims 1 to 8 wherein said piroctone compound is piroctone olamine.

10. A method of balancing microbiota of skin comprising a step of applying thereto zinc pyrithione and a piroctone compound in a topical composition, where balancing means reducing the ratio of level of Malassezia restricta to that of Malassezia globosa, or selectively reducing microbial count of at least one genus of microbes belong to Staphylococcus, wherein said skin is scalp having dandruff; wherein the said genus of microbes belong to Staphylococcus is Staphylococcus capitis.

11. A topical composition comprising zinc pyrithione or a piroctone compound for use in balancing microbiota of skin, where balancing means reducing the ratio of level of Malassezia restricta to that of Malassezia globosa, or selectively reducing microbial count of at least one genus of microbes belong to Staphylococcus, wherein said skin is scalp having dandruff; wherein the said genus of microbes belong to Staphylococcus is Staphylococcus capitis.

12. Use of zinc pyrithione or a piroctone compound for balancing microbiota of skin, where balancing means reducing the ratio of level of Malassezia restricta to that of Malassezia globosa, or selectively reducing microbial count of at least one genus of microbes belong to Staphylococcus, wherein said skin is scalp having dandruff; wherein the said genus of microbes belong to Staphylococcus is Staphylococcus capitis.