EP4734933A1 - Cosmetic composition - Google Patents

Abstract

A cosmetic composition is disclosed comprising i) hinokitiol; and ii) a hydroxamic acid; wherein the weight ratio of the amount of said hydroxamic acid to that of hinokitiol is from 2:1 to 15:1; wherein the hydroxamic acid is caprylhydroxamic acid, benzohydroxamic acid or a mixture thereof.

Description

COSMETIC COMPOSITION

Field of the Invention

This invention relates to cosmetic compositions, preferably rinse off compositions, more preferably hair care compositions. More particularly the invention relates to cosmetic compositions that comprise hinokitiol and a hydroxamic acid.

Background of the Invention

Hinokitiol is a tropolone originally isolated from the heart wood of T. plicata that has diverse biological activities, including antifungal, antibacterial, and antiproliferative properties. Hinokitiol has been used in oral, hair and skin care products. Generally, hinokitiol is dissolved in the base composition of a product which includes surfactants, water, polymers and colouring and fragrance ingredients. When a user applies the compositions to hair, oral or skin, compound of hinokitiol get deposited thereon.

Hydroxamic acids, represented by the general formula RC (O)NR’OH, exhibit a wide spectrum of biological activity, and can be used as antifungal agents, antimicrobials.

Dandruff control is an important aspect of hair cleansing and care. Anti-dandruff benefit has been provided through hair care compositions including shampoos and hair conditioners. Dandruff is an issue that affects many people globally. The condition is manifested by the shedding of clumps of dead skin cells from the scalp. These are white in colour and provide an aesthetically displeasing appearance. A factor that contributes to dandruff is certain members of the Malassezia yeasts. To combat these, anti-dandruff products have included certain antidandruff agents which have anti-fungal activity, for example, piroctone compound such as piroctone olamine. These anti-dandruff agents remove (or at least reduce the level of) the Malassezia from the scalp and provide moderately effective treatment of the dandruff condition. Such a product performs as a hair cleansing shampoo or as a hair conditioner while mitigating the causes of dandruff.

There remains a need to provide an improved antimicrobial efficacy onto the surface of skin/scalp, upon applying the products. The present inventors have now found unexpectedly that the combination of hinokitiol and a hydroxamic acid with certain ratio can provide synergistic antimicrobial efficacy onto a topical surface of a human or animal body, preferably on skin/scalp.

Summary of the Invention

In a first aspect, the present invention is directed to a cosmetic composition comprising: i) hinokitiol; and ii) a hydroxamic acid; wherein the weight ratio of the amount of said hydroxamic acid to that of hinokitiol is from 2:1 to 15:1 ; wherein the hydroxamic acid is caprylhydroxamic acid, benzohydroxamic acid or a mixture thereof.

In a second aspect, the present invention is directed to a cosmetic composition of the first aspect for use in the treatment of dandruff by providing synergistic antimicrobial benefit against Malassezia spp on a topical surface of a human or animal body.

In a third aspect, the present invention is directed to a cosmetic composition of the first aspect for use in the treatment of against at least some Malassezia spp on a topical surface of a human or animal body.

In a fourth aspect, the present invention is directed to a cosmetic composition of the first aspect for use in the treatment of preventing or alleviating the symptoms of dandruff on the scalp or hair.

In a fifth aspect, the present invention is directed to a non-therapeutic method of providing synergistic antimicrobial benefit against Malassezia spp on a topical surface of a human or animal body comprising a step of applying a safe and effective amount of a cosmetic composition of the first aspect.

All other aspects of the present invention will more readily become apparent upon considering the detailed description and examples which follow. Detailed of the Invention

Cosmetic

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.

Hair Care Composition

“Hair care composition”, as used herein, is meant to include a composition for topical application to hair and/or scalp of mammals, especially humans. Such a composition may be generally classified as leave-on or rinse off, and includes any product applied to a human body for also improving appearance, cleansing, odor control or general aesthetics. The composition of the present invention can be in the form of a liquid, lotion, cream, foam, scrub, gel, or bar. Non-limiting examples of such compositions include leave-on hair lotions, creams, and rinse-off shampoos, conditioners, shower gels, or toilet bar. The composition of the present invention is preferably a rinse-off composition, especially preferred being a shampoo or a conditioner and most preferably a shampoo.

Miscellaneous

Except in the 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 may optionally be understood as modified by the word “about”.

All amounts are by weight of the final hair care composition, unless otherwise specified. It should be noted that in specifying any ranges of values, any particular upper value can be associated with any particular lower value.

For the avoidance of doubt, 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.

The disclosure of the invention as found herein is to be considered to cover all embodiments as found in the claims as being multiply dependent upon each other irrespective of the fact that claims may be found without multiple dependency or redundancy.

Where a feature is disclosed with respect to a particular aspect of the invention (for example a composition of the invention), such disclosure is also to be considered to apply to any other aspect of the invention (for example a method of the invention) mutatis mutandis.

Hinokitiol

Hinokitiol (beta-thujaplicin) according to the present invention is a monoterpenoid that is cyclohepta-2,4,6-trien-1-one substituted by a hydroxy group at position 2 and an isopropyl group at position 4. The CAS number is 499-44-5 and the compound has the general formula (I) as below:

Amount of the hinokitiol in the composition of the invention would depend on the type of the cosmetic composition and the precise nature of other antimicrobial agents used. It is preferred that the composition comprises from 2ppm to 5%, preferably from 2ppm to 2% of hinokitiol, preferably from 0.01 to 2%, more preferably from 0.05 to 1 %, furthermore preferably from 0.1 to 0.5 % by weight of the composition. Hydroxamic acid

A hydroxamic acid is a class of organic compounds bearing the functional group RC(O)N(OH)R', with R and R' as organic residues and CO as a carbonyl group. The hydroxamic acid of the present invention is caprylhydroxamic acid, or benzohydroxamic acid, or a mixture thereof, preferably it is caprylhydroxamic acid.

Piroctone is a cyclic hydroxamic acid that consists of 1-hydroxypyridin-2-one bearing methyl and 2,4,4-trimethylpentyl substituents at positions 4 and 6 respectively. The CAS number is 50650-76-5 and the compound has the general formula (II) as below:

Caprylhydroxamic acid is an amino acid derived from coconut oil. It is a preservative and broad spectrum anti-fungal agent. The CAS number is 7377-03-9 and the compound has the general formula (III) as below:

Benzohydroxamic acid is one of hydroxamic acids. The CAS number is 495-18-1 and the compound has the general formula (IV) as below:

It is preferred that the composition comprises from 13ppm to 10% of the hydroxamic acid, preferably from 0.1 to 10%, more preferably 0.25 to 8%, furthermore preferably 0.5 to 5% by weight of the composition. In the composition in accordance with the invention, the weight ratio of the amount of the hydroxamic acid to that of hinokitiol is from 2:1 to 15:1, preferably from 2.5: 1 to 15:1 , more preferably from 3:1 to 13.5:1, furthermore preferably from 5:1 to 13.5:1.

In the composition in accordance with the invention, it is preferred that the combination of hinokitiol and the hydroxamic acid comprise 17.9ppm or more by weight of the composition. The sum of the fractional inhibitory concentrations (£FIC) is widely used in the context of combinations of antimicrobial ingredients. It is a tool to determine whether the antimicrobial ingredients (when used in combination) have synergistic effect or antagonistic effect or neither of the two, i.e. , an additive effect. The present inventors have resorted to the FIC test to evaluate the combined effect of hinokitiol with hydroxamic acid against M. restricta.

It is believed that while the hinokitiol and hydroxamic acid according to the present invention present in the compositions of the invention, the hydroxamic acid interacts synergistically with the hinokitiol to make it even more efficacious.

Cosmetic composition

The composition of the invention preferably comprises a cosmetically acceptable carrier. The cosmetically acceptable carrier is such that the composition can be prepared, e.g., as a shampoo, conditioner, body wash, hand wash or face wash product, cream, lotion, gel, powder, ointment, deodorant, hand sanitiser or a soap bar and the rest of the ingredients would vary accordingly. It is preferred that the cosmetically acceptable carrier comprises water.

It is preferred that the composition is a rinse-off or leave-on product, more preferably a hair care composition. Preferably the composition is a rinse-off product. Alternatively, the composition is preferably a leave-on composition. It is preferred that the composition comprises a cleansing surfactant.

The composition of this invention preferably comprises a cleansing surfactant comprising an anionic surfactant.

Non-limiting examples of suitable anionic surfactants are alkyl sulphates, alkyl ether sulphates, alkaryl sulphonates, alkanoyl isethionates, alkyl succinates, alkyl sulphosuccinates, alkyl ether sulphosuccinates, N-alkyl sarcosinates, alkyl phosphates, alkyl ether phosphates, and alkyl ether carboxylic acids and salts thereof, especially their sodium, magnesium, ammonium and mono-, di- and triethanolamine salts. The alkyl and acyl groups generally contain from 8 to 18, preferably from 10 to 16 carbon atoms and may be unsaturated. The alkyl ether sulphates, alkyl ether sulphosuccinates, alkyl ether phosphates and alkyl ether carboxylic acids and salts thereof may contain from 1 to 20 ethylene oxide or propylene oxide units per molecule. Typical anionic surfactants for use in compositions of the invention include, but not limited to, sodium oleyl succinate, ammonium lauryl sulphosuccinate, sodium lauryl sulphate, sodium lauryl ether sulphate, sodium lauryl ether sulphosuccinate, ammonium lauryl sulphate, sodium dodecylbenzene sulphonate, triethanolamine dodecylbenzene sulphonate, sodium cocoyl isethionate, sodium lauryl isethionate, lauryl ether carboxylic acid, sodium N-lauryl sarcosinate or mixtures thereof.

Preferred anionic surfactants are the alkyl sulphates and alkyl ether sulphates. Preferred alkyl sulphates are C8-18 alky sulphates, more preferably C12-18 alkyl sulphates, preferably in the form of a salt with a solubilising cation such as sodium, potassium, ammonium or substituted ammonium. Examples are sodium lauryl sulphate (SLS) or sodium dodecyl sulphate (SDS). It is particularly preferred that the anionic surfactant is alkyl ether sulphate. Preferred alkyl ether sulphates are those having the formula: RO(CH2CH2O)_nSO3M; wherein R is an alkyl or alkenyl having from 8 to 18 (preferably 12 to 18) carbon atoms; n is a number having an average value of greater than at least 0.5, preferably between 1 and 3, more preferably between 1 and 2; and M is a solubilising cation such as sodium, potassium, ammonium or substituted ammonium. An example is sodium lauryl ether sulphate (SLES). Preferred alkyl ether sulphate is sodium lauryl ether sulphate having an average degree of ethoxylation of from 0.5 to 3, preferably from 1 to 3, more preferably from 1 to 2.

It is preferred that the anionic surfactant is an ethoxylated alkyl sulphate a degree of ethoxylation of less than 3, preferably an ethoxylated alkyl sulphate a degree of ethoxylation of less than 2, more preferably sodium laureth sulphate (1 EO).

The anionic surfactants are typically present in the composition of the present invention at a level of from 0.5 to 20%, more preferably from 2 to 16% and most preferably from 3 to 16%, by weight of the composition.

Suitable amphoteric surfactant examples include alkyl amine oxides, alkyl betaines, alkyl amidopropyl betaines, alkyl sulphobetaines (sultaines), alkyl amphoacetates, alkyl amphopropionates, alkyl amidopropyl hydroxysultaines, wherein the alkyl group has from 8 to 19 carbon atoms.

Preferably, the amphoteric surfactant is a betaine surfactant. It is preferred that the betaine surfactant is one of alkyl amidopropyl betaines. Cocamidopropyl betaine (CAPB) is particularly preferred.

In a preferred embodiment, the composition comprises from 0.1 to 10 wt.%, preferably from 0.5 to 8 wt.%, more preferably from 1 to 5 wt.% of an amphoteric surfactant by weight of the composition.

The ratio of ethoxylated anionic surfactant to amphoteric surfactant in which the ratio of anionic surfactant to amphoteric surfactant is less than 10:1, preferably from 2:1 to 10:1, more preferably from 3:1 to 9:1.

The total amount of cleansing surfactant in the composition for use in the invention is generally from 3 to 35 wt%, preferably from 5 to 25 wt%, most preferably from 7 to 16 wt% of the total composition.

Hair care composition

Preferably the composition is a shampoo, hair conditioner, hair cream, hair gel, hair serum, mousse or hair oil.

In a preferred embodiment, the hair care composition is rinse-off composition, particularly a shampoo. Shampoo compositions for use in the invention are generally aqueous, i.e. they have water or an aqueous solution or a lyotropic liquid crystalline phase as their major component. Suitably, the shampoo composition will comprise from 50 to 98%, preferably from 60 to 92% water by weight based on the total weight of the composition. Such compositions are referred to as having an aqueous base.

The hair care composition may additionally comprise a conditioning agent to provide conditioning benefit. Preferably, the hair care composition comprises discrete dispersed droplets of a water-insoluble conditioning agent, which has a mean droplet diameter (D3,2) of less than 15 microns, preferably less than 10 microns, more preferably less than 5 microns, most preferably less than 3 microns. The mean droplet diameter (D3,2) of a water-insoluble conditioning agent may be measured by means of a laser light scattering technique, for example using a 2600D Particle Sizer from Malvern Instruments.

The water-insoluble conditioning agent may include non-silicone conditioning agent comprising non-silicone oily or fatty materials such as hydrocarbon oils, fatty esters and mixtures thereof. Preferably, the water-insoluble conditioning agent is emulsified silicone oil.

Suitable silicones include polydiorganosiloxanes, in particular polydimethylsiloxanes which have the CTFA designation dimethicone. Also suitable for use in compositions of this invention (particularly shampoos and conditioners) are polydimethyl siloxanes having hydroxyl end groups, which have the CTFA designation dimethiconol. Also suitable for use in compositions of this invention are silicone gums having a slight degree of cross-linking, as are described for example in WO 96/31188. Preferably, the silicone oil comprises dimethicone, dimethiconol or a mixture thereof.

Suitable emulsified silicones for use in the hair care compositions of this invention are available as pre-formed silicone emulsions from suppliers of silicones such as Dow Corning and GE silicones. The use of such pre-formed silicone emulsion is preferred for ease of processing and control of silicone particle size. Such pre-formed silicone emulsions will typically additionally comprise a suitable emulsifier, and may be prepared by a chemical emulsification process such as emulsion polymerisation, or by mechanical emulsification using a high shear mixer.

Examples of suitable pre-formed silicone emulsions include DC1785, DC1788, DC7128, all available from Dow Corning. These are emulsions of dimethiconol/dimethicone.

Another class of silicones which may be used are functionalized silicones such as amino functional silicones, meaning a silicone containing at least one primary, secondary or tertiary amine group, or a quaternary ammonium group. Examples of suitable amino functional silicones include polysiloxanes having the CTFA designation “amodimethicone.”

The water-insoluble conditioning agent is generally present in hair care composition of this invention in an amount from 0.05 to 15%, preferably from 0.1 to 10%, more preferably from 0.5 to 8%, most preferably from 1 to 5%, based on total weight of the hair care composition. Preferably the composition of the invention further comprises a suspending agent. Suitable suspending agents are selected from polyacrylic acids, cross-linked polymers of acrylic acid, copolymers of acrylic acid with a hydrophobic monomer, copolymers of carboxylic acidcontaining 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 3 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. An example of a suitable copolymer of a carboxylic acid containing monomer and acrylic acid esters is Carbopol 1342. All Carbopol (trademark) materials are available from Goodrich.

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

Mixtures of any of the above suspending agents may be used. Preferred is a mixture of crosslinked polymer of acrylic acid and crystalline long chain acyl derivative.

The suspending agent is generally present in hair care composition of this invention in an amount of from 0.1 to 10%, more preferably from 0.2 to 6%, and most preferably from 0.3 to 4%, based on total weight of the hair care composition and including all ranges subsumed therein.

Preservatives may also be incorporated into the hair care composition of this invention to protect against the growth of potentially harmful microorganisms. Suitable traditional preservatives include alkyl esters of parahydroxybenzoic acid, hydantoin derivatives, propionate salts, and a variety of quaternary ammonium compounds. Illustrative yet non-limiting examples of the types of preservatives that may be used in this invention include, for examples, phenoxyethanol, sodium salicylate, methyl paraben, butyl paraben, propyl paraben, diazolidinyl urea, sodium dehydroacetate, benzyl alcohol, sodium benzoate, iodopropynyl butylcarbamate, caprylyl glycol, disodium EDTA or mixtures thereof. In an especially preferred embodiment, the preservative is sodium benzoate, phenoxyethanol, sodium salicylate or a mixture thereof.

Preservatives are preferably employed in amounts ranging from 0.01 to 2% by weight of the hair care composition.

It is further preferred that the hair care composition of the invention comprises a cosmetic ingredient. Preferably the cosmetic ingredient is selected from the group consisting of a silicone, an antibacterial agent other than antidandruff agents, a foam booster, a perfume, encapsulates (for example encapsulated fragrance) a dye, a colouring agent, a pigment, a preservative, a thickener, a protein, a phosphate ester, a buffering agent, a pH adjusting agent, a pearlescer (for example; mica, titanium dioxide, titanium dioxide coated mica, ethylene glycol distearate (INCI glycol distearate)) and/or opacifier, a viscosity modifier, an emollient, a sunscreen, an emulsifier, a sensate active (for example menthol and menthol derivatives), vitamins, mineral oils, essential oils, lipids, natural actives, glycerin, natural hair nutrients such as botanical extracts, fruit extracts, sugar derivatives and amino acids, microcrystalline cellulose and mixtures thereof.

Preferably, the composition of the present invention includes from 0.01 to 20 wt% of the at least one cosmetic ingredient, more preferably from 0.05 to 10 wt%, still more preferably from 0.075 to 7.5 wt% and most preferably, from 0.1 to 5 wt% of the at least one cosmetic ingredient, by weight of the total composition.

As an alternative, the cosmetic composition of the invention is a hair conditioner. When conditioning benefits are to be delivered through the composition of the invention the composition is called a hair conditioner. Typically, the most popular conditioning agents used in hair care compositions are water-insoluble oily materials such as mineral oils, naturally occurring oils such as triglycerides and silicone polymers. Conditioning benefit is achieved by the oily material being deposited onto the hair resulting in the formation of a film, which makes the hair easier to comb when wet and more manageable when dry. An especially useful conditioning agent is a silicone, preferably a non-volatile silicone. Advantageously compositions herein may include one or more silicones. The silicones are conditioning agents found in dispersed or suspended particulate form. They are intended to deposit onto hair remaining behind after rinsing of the hair with water. Suitable silicone oils may include polyalkyl siloxanes, polyaryl siloxanes, polyalkylaryl siloxanes, polyether siloxane copolymers and mixtures thereof. Amino silicones are often formulated with shampoo compositions. Amino silicones are silicones containing at least one primary amine, secondary amine, tertiary amine or a quaternary ammonium group. High molecular weight silicone gums can also be utilized. Another useful type are the crosslinked silicone elastomers such as Dimethicone/Vinyl/Dimethicone Crosspolymers (e.g. Dow Corning 9040 and 9041).

It is preferred that hair conditioner composition of the invention comprises 0.1 to 10 wt%, more preferably from about 0.1 to about 8 wt% silicone. Alternatively, the hair conditioner is silicone-free, containing not more than 1 wt% silicone. It is preferred that pH of the composition is more than 4.0, more preferably 5.0 to 7.0.

Hair conditioner composition of the invention preferably may also comprise 0.5 to 10 wt% fatty alcohol. The combined use of fatty alcohols and cationic surfactants in conditioning compositions is believed to be especially advantageous, because this leads to the formation of a lamellar phase, in which the cationic surfactant is dispersed.

Representative fatty alcohols comprise from 8 to 22 carbon atoms, more preferably 16 to 22. Fatty alcohols are typically compounds containing straight chain alkyl groups. Examples of suitable fatty alcohols include cetyl alcohol, stearyl alcohol and mixtures thereof. The use of these materials is also advantageous in that they contribute to the overall conditioning properties of compositions of the invention.

Skin cleansing

The composition of the invention may be used for skin care e.g. body or face wash. The cosmetic composition 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 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 of 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 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 cosmetic composition is preferably in form of a shaped solid, more preferably a bar. The solid topical composition 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 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.

In another aspect of the present invention, the composition of the present invention is suitable for use in wipes for personal hygiene.

Method and Use

The present invention provides for a cosmetic composition of the first aspect for use in providing synergistic antimicrobial benefit on a topical surface of a human or animal body, preferably on skin/scalp.

The present invention provides for a cosmetic composition of the first aspect for use in the treatment of dandruff by providing synergistic antimicrobial benefit against Malassezia spp on a topical surface of a human or animal body. The present invention provides for a cosmetic composition of the first aspect for use in the treatment of against at least some Malassezia spp on a topical surface of a human or animal body, preferably on skin/scalp. Preferably the cosmetic composition is an antidandruff composition effective against at least some Malessezia spp on a topical surface of a human or animal body, preferably on scalp. Preferably the Malessezia spp is Malessezia restricta.

The present invention provides for a cosmetic composition of the first aspect for use in the treatment of preventing or alleviating the symptoms of dandruff on the scalp or hair.

The present invention provides for a non-therapeutic method of providing synergistic antimicrobial benefit against Malassezia spp on a topical surface of a human or animal body comprising a step of applying a safe and effective amount of a cosmetic composition of the first aspect. Preferably the topical surface is skin/scalp. Preferably it is for cosmetic purpose. The term safe an effective amount is well known to persons skilled in the art and such amounts may vary depending on the product format, for example, the said amount in the case of a leave on composition could be 1 to 2 ml for each application, while the same amount could be 5 to 10 ml for each application in the case of shampoos. The method may be utilized for preventing or treating acne, dandruff or for maintaining general hygiene.

Mode of Use

The compositions of the invention are primarily intended for topical application to scalp and/or at least a portion of the hair or skin of an individual, either in rinse-off or leave-on compositions, preferably in rinse-off compositions like shampoos or skin cleansing products.

When the composition is a shampoo, it is topically applied to the hair and then massaged into the hair and scalp. Then it is rinsed with water prior to drying the hair.

The invention will be further illustrated by the following, non-limiting Examples, in which all percentages quoted are by weight based on total weight unless otherwise stated.

The examples are intended to illustrate the invention and are not intended to limit the invention to those examples perse. The antimicrobial efficacy of exemplary compositions according to the invention was determined as against M. restricta.

The concerned procedures will now be briefly explained.

Method 1 : M. restricta.

M. restricta (CBS 7877) was maintained on Modified Leeming & Notman Agar (MLNA) agar (Solution A) plate and then cultured into 20ml of growth medium Modified Leeming & Notman broth (MLNB, Solution B).

Solution A

Modified Leeming & Notman Agar (MLNA) 10g Bacteriological Peptone

10g Glucose

2g Yeast Extract

8g Ox bile

10ml Glycerol

0.5g Glycerol Monostearate

5ml Tween 60

20ml Olive oil

15g Agar No.1

Deionized Water to 1000ml

(Ensure stirring thoroughly including after autoclaving)

Solution B

Modified Leeming & Notman Broth (MLNB)

10g Bacteriological Peptone

10g Glucose

2g Yeast Extract 8g Ox bile

10ml Glycerol

0.5g Glycerol Monostearate

5ml Tween 60

20ml Olive oil

Deionized Water to 1000ml

(Ensure stirring thoroughly including after autoclaving)

The culture was then incubated at 32 °C for 72 hrs with shaking. Then, 1ml of the first broth culture was transferred into 9ml of fresh MLNB and incubated at 32 °C for 72 hrs with shaking. The final culture should contain 2 to 6x10⁶ cells/ml.

Caprylhydroxamic acid compound (stock: 10 mg/ml in DMSO) was diluted 2 folds with DMSO to get 5mg/ml solution. Then, it was 1.5-fold serially diluted in MLNB to prepare in a range of 5000-87 ppm. 20 pL of the serially diluted solutions were added to the 96- working plate (corning- 3788).

Hinokitiol compound (stock: 10 mg/ml in DMSO) was diluted 40 folds with water to get 0.25mg/ml solution. Then, it was 1.5-fold serially diluted in MLNB to prepare in a range of 250- 22 ppm. 20 pL of the serially diluted solutions were added to the 96- working plate.

Malassezia restricta was added into the working plate to reach a final cell density at around 5*10⁴ cell/ml. Final concentrations of the test compounds in each well of the 96-well plate is shown as below:

Caprylhydroxamic acid: 500, 333.3, 222.2, 148.1 , 98.8, 65.8, 43.9, 29.3, 19.5, 13, 8.7, 0 ppm.

Hinokitiol: 25, 16.7, 11.1 , 7.4, 4.9, 3.3, 2.2, 0 ppm

Benzohydroxamic acid compound (stock: 10 mg/ml in DMSO) was diluted 2 folds with water to get 5mg/ml solution. Then, it was 1 .5-fold serially diluted in MLNB to prepare in a range of 5000- 87 ppm. 20 pL of the serially diluted solutions were added to the 96- working plate (corning- 3788). Hinokitiol compound (stock: 10 mg/ml in DMSO) was diluted 50 folds with water to get 0.2mg/ml solution. Then, it was 1.5-fold serially diluted in MLNB to prepare in a range of 200-17.6 ppm. 20 pL of the serially diluted solutions were added to the 96- working plate.

Malassezia restricta was added into the working plate to reach a final cell density at around 5*10⁴ cell/ml. Final concentrations of the test compounds in each well of the 96-well plate is shown as below:

Benzohydroxamic acid: 500, 333.3, 222.2, 148.1 , 98.8, 65.8, 43.9, 29.3, 19.5, 13, 8.7, 0 ppm.

Hinokitiol: 20, 13.3, 8.9, 5.9, 4.0, 2.6, 1.8, 0 ppm

Multi-channel pipette was used to mix the compound and strain suspension. For M. restricta, after 2-days incubation, 10 pL alamar blue was added to culture and cultured for one additional day. Color change from blue to red was recorded.

Step 3: Calculation: 7FIC test

(1) Minimum Inhibition Concentration (MIC):

The MIC is defined as the absolute lowest concentration of active that provides complete microbial growth inhibition as indicated by the blue color of alamar blue under the tested condition.

(2) Fractional Inhibition Concentration (FIC):

The differing behaviours of inhibitory antimicrobials in isolation and mixtures have been widely explored using the concept of the Fractional Concentration (FC) and Fractional Inhibitory Concentration (FIC). The parameter can be defined as follows:

FIC (component a) = MIC (component a tested in the mixture)

MIC (component a tested as a single active)

(3) Synergy and Additivity

The interactions between antimicrobials can be additive, synergistic or antagonistic depending on whether the efficacy of the combination is equivalent to, greater than or less than that obtained for the same total concentration of the individual components when tested alone.

These relationships can be expressed mathematically by summing the fractional MIC values for all the components present in the mixture to give the “fractional inhibition index”. There is no consistent approach in the academic or patent literature in defining precise limiting EFIC values that differentiate synergy from additivity or antagonism. In this study, we have adopted a liberal approach defining any binary mixture with EFIC < 0.9 as showing evidence of synergistic behaviour.

EFIC = FIC (component 1) + FIC (component 2)

EFIC = 1 corresponds to additive microbial inhibition activity

EFIC > 1 corresponds to antagonistic microbial inhibition activity

EFIC < 0.9 corresponds to synergistic microbial inhibition activity

Results:

It was observed that there was synergistic effect of hinokitiol with hydroxamic acid with certain ratio against M. restricta (Table 1).

TABLE 1

The observations tabulated in Tables 1 clearly indicate that the hinokitiol interacts synergistically with hydroxamic acid for inhibiting the growth of M. restricts ( FIC<0.9) only when the weight ratio between hydroxamic acid and hinokitiol is from 2:1 to 15:1 (Examples 1- 4) according to the present invention. It also implies that is possible to formulate highly efficacious antimicrobial compositions comprising the two active ingredients within the weight ratio range after giving due consideration to the fact that the experiments were conducted under test conditions and the amount of the ingredients may not match or reflect the practical amounts under in-use conditions, i.e., compositions like a shampoo.

As far as the experiments were concerned, the concentrations of the ingredients were chosen to fall within the allowable limits permitted by the concerned tests and in which it was possible to record the technical effects. Therefore, the concentrations at which the tests were conducted might not appear to fall within the range in which such ingredients are generally used in cosmetic compositions (usually in wt%).

It was observed that there was synergistic effect of hinokitiol with benzohydroxamic acid within the scope of the invention against M. restricta (Table 2).

TABLE 2

The observations tabulated in Tables 2 clearly indicate that the hinokitiol interacts synergistically with benzohydroxamic acid for inhibiting the growth of M. restricts ( FIC<0.9) when the weight ratio is within the claimed scope of the invention (Example 5), while the one with weight ratio outside the claimed scope couldn’t (Example V).

Claims

1. A cosmetic composition comprising i) hinokitiol; and ii) a hydroxamic acid; wherein the weight ratio of the amount of said hydroxamic acid to that of hinokitiol is from 2:1 to 15:1 ; wherein the hydroxamic acid is caprylhydroxamic acid, benzohydroxamic acid or a mixture thereof.

2. A composition as claimed in claim 1 wherein the weight ratio of the amount of said hydroxamic acid to that of hinokitiol is from 2.5:1 to 15:1 , preferably from 3:1 to 13.5:1, more preferably from 5:1 to 13.5:1.

3. A composition as claimed in claims 1 or 2 wherein the hydroxamic acid is caprylhydroxamic acid.

4. A composition as claimed in any of claims 1 to 3 wherein the composition comprises from 2ppm to 2% of hinokitiol by weight of the composition.

5. A composition as claimed in any of claims 1 to 4 wherein the composition comprises from 13ppm to 10% of said hydroxamic acid by weight of the composition.

6. A composition as claimed in any of claims 1 to 5 wherein the composition comprises a cosmetically acceptable carrier comprising water.

7. A composition as claimed in any of claims 1 to 6 wherein the composition is a rinse-off or leave-on composition, preferably rinse-off composition.

8. A composition as claimed in any of claims 1 to 7 wherein the composition comprises a cleansing surfactant.

9. A composition as claimed in claim 8 wherein said cleansing surfactant comprising an anionic surfactant, preferably alkyl sulphates or alkyl ether sulphates, more preferably sodium lauryl ether sulphate.

10. A composition as claimed in any of claims 1 to 9 wherein said composition is a hair care composition, preferably a shampoo.

11. A composition as claimed in any of claims 1 to 10 for use in the treatment of dandruff by providing synergistic antimicrobial benefit against Malassezia spp on a topical surface of a human or animal body.

12. A composition as claimed in any of claims 1 to 10 for use in the treatment of against at least some Malassezia spp on a topical surface of a human or animal body.

13. A composition as claimed in any of claims 1 to 10 for use in the treatment of preventing or alleviating the symptoms of dandruff on the scalp or hair.

14. A non-therapeutic method of providing synergistic antimicrobial benefit against Malassezia spp on a topical surface of a human or animal body comprising a step of applying a safe and effective amount of a cosmetic composition as claimed in any of claims 1 to 10.