COSMETIC DERMATOLOGY IN ACNEIC AND COMEDOGENIC SKIN

FIELD OF THE INVENTION

The invention refers to pigments coated with anti-acne substances which afford the sustained release of said substances. The present invention also refers to a method to treat acneic and comedogenic skin through the use of a makeup comprising said pigments, wherein such use provides the immediate aesthetic relief (cover) the acneic imperfection underneath.

The invention also refers to cosmetic compositions comprising said pigments. BACKGROUND OF THE INVENTION Surface-modified pigments and fillers for cosmetic applications were introduced to formulators in USA and Europe from Japan by Shoji Murata and Ryota Myoshi in 1981.

Afterwards, filler pigments and colored pigments have been surface-treated with a variety of compounds to tailor-made their physico-chemical properties. Indeed, different performances are attained by each surface-modifier: silicones, metallic soaps, acyl amino acids, hydrogenated lecithin, collagen soaps, fluoro-carbons, fuoro-silicones, and so on. Surface-modified pigments have revolutionized the formulation of pressed powders, anhydrous foundations, blushers, and water-in-oil

(or -silicone) foundations by providing enhanced skin feel, formula stability, texture, dispersibility, and wear properties.

One unique approach is the mixed surface coatings. The "mixed" surface coating mentioned here utilizes an initial layer of coating on the pigment as a base on which an additional layer of coating is reacted. Though mixed coating consists of two different layers of chemical compounds, these two layers are synthesized (reacted) to be basically one compound that surrounds the base material.

Different from hybrid surface coatings, multiple layered surface coatings are recently beginning to gain attention, also provides similar potentials and benefits.

However, many commercially available makeup compositions contain saturated lipid and other ingredients which can be occlusive on skin pores, i.e. acting as comedogenic and/or favouring the formation of acne, particularly in oily skin of predisposed subjects.

The term "comedogenic" describes the tendency of a topical preparation or material to induce the formation of sebum plugs (comedones) in the openings of sebaceous glands. The comedones undergo to inflammatory and infective processes which end up in the visible form of acne. This occurs when an increased sebum production accompanies a simultaneous blockage of the sebaceous gland openings. Then, the closed sebaceous glands become infected by anaerobic microorganisms such as Propionibacteria.

The makeup industry is paying little if any attention to acneic and comedogenic skin, a condition prone to the acne degeneration by the infection of Propionibacteria - acnes or Corynebacterium acnes.

Instead, there is a need for pigments and topical compositions comprising thereof to treat acneic skin while providing an attractive makeup presentation, i.e. to improve the skin appearance with a concomitant effect of exfoliating/disinfecting action. SUMMARY OF THE INVENTION It has been discovered that a pigment coated with substances capable to promote skin exfoliation and/or to disinfect skin by the sustained release of said substances.

Hence, the use of pigments in the manufacturing cosmetic/dermatologic composition comprising thereof can combat acneic skin on regular use, while immediately improving the skin appearance from the application of a cosmetic/dermatologic makeup.

The above aim is reached by means of the present invention, that relates to a pigment according to claim 1.

The invention also relates a method of manufacturing such pigment according to claims 27-29 and to a cosmetic/dermatologic product incorporating said pigment. The present invention also provide a method of prevention or treatment of acneic skin while improving the skin appearance, since the acneic imperfections are hidden. DETAILED DESCRIPTION OF THE INVENTION

The pigments of invention comprise a pigment coated with anti-acne substances to promote their sustained release to afford the skin exfoliation and/or to disinfect skin and thus treat acneic skin. hi detail, the pigments of the present invention have the following structure (I):

wherein:

C is a core pigment linked by a polyvalent cation M _a the anion of a substance A capable to promote skin exfoliation and/or to disinfect skin, with the optional presence of bonded anionic surfactant B linked by a polyvalent cation M _b .

According to a preferred embodiment, the b/a ratio ranges from 0 to about 10 w/w. According to another preferred embodiment, the b/a ratio ranges from about 0.1 to about 16 w/w, more preferably from about 1 to about 2 w/w.

According to a preferred embodiment, A ranges from 0.1% to 20% w/w on C, preferably 1 % to 4% w/w on C.

M _a and M _b are preferably selected from: Zn ²⁺ , Cu ²⁺ , Ca ²⁺ , Ti ⁴⁺ , Si ⁴⁺ , Al ³⁺ , Sn ⁴⁺ , Mg ²⁺ , Sr ²⁺ , Ti ⁴⁺ , Zr ⁴⁺ , Ce ⁴⁺ , Fe ^2+/3+ , Cr ⁶⁺ , and Mn ²⁺ ; more preferably selected from: Zn ²⁺ , Cu ²⁺ , Ca ²⁺ , Mg ²⁺ , and Al ³⁺ , even more preferably selected from: Zn ²⁺ , Ca ²⁺ , and Al ³⁺ . M _a and M _b are present at least in the quantity necessary to perform the linkage of a substance A and of the anionic surfactant B (when present) to C according to the formula (I).

The pigments according the invention possess a core C (i.e. the pigment before being treated) consisting of pigments and pigment extenders of mean particle size from 3,000 μm to 0.001 μm, preferably from 20 μm to 0.01 μm.

C as used herein include any pigment to be blended in cosmetics, including mixture and composite forms, e.g. those included in Rona catalogue (Merck, Darmstadt, D).

Suitable Q include: titanium dioxide and oxide hydrated (TiO ₂ , rutile and anatase, Ti(OH) ₂ ), zinc oxide (ZnO), anhydrous and hydrated alumina (Al ₂ O ₃ , AlOOH), tin ^IV oxide (SnO ₂ ), cerium oxide (CeO ₄ ), and zirconium dioxide (ZrO ₂ ), in sub-micron (1 - 0.1 μm) or in ultrafme forms (pigments having mean particle size < 0.1 μm)

Suitable CU include: iron oxides and hydroxides such as FeO (yellow), Fe ₂ O ₃ and

Fe ₂ O ₃ -H ₂ O (red), Fe _x O _y (brown), Fe ₃ O ₄ (black); chromium oxides and hydroxides

(Cr ₂ O ₃ .nH ₂ O and Cr ₂ O ₃ ); tin ¹¹ oxide (SnO), manganese oxide (MnO), Prussian blue, ultramarine blue, inorganic blue pigments, low order Ti oxides, mango and cobalt violets.

Suitable Q _U include: mica (natural, synthetic, white, gold, red, black, and lithia micas), sericite, talc, kaolin, calcium and magnesium carbonate, calcium phosphate, alumina and aluminium hydroxide, magnesium oxide, barium sulfate, magnesium sulfate, silicic acid and silica, silicates (magnesium, aluminium, magnesium- aluminium silicate, calcium, and strontium silicates), silicon carbide, metal salts of tungstic acid, magnesium aluminate, magnesium metasilicate aluminate, chlorohydroxyaluminium, clay, bentonite, zeolite, smectite, hydroxyapatite, ceramic pigment, and boron nitride; specific composite extender pigments such as Excel Mica, Excel Pearl and Pigment La Vie (from Miyoshi Kasei, J), optically gloss pigments such as bismuth oxychloride, titanium mica, pearl essence, pigment prepared by coating synthetic mica with titanium dioxide, or by coating silica flake with titanium dioxide (e.g. Metashine™; Nippon Sheet Glass, J), or by coating alumina flake with tin oxide and titanium dioxide, or by coating aluminium flake with titanium dioxide, or by coating copper flake with silica, or by coating bronze flake with silica, or by coating aluminium flake with silica, or by coating coloring pigments (e.g. red iron oxide) with silica; other pigments such as luminescent pigment (e.g. Luminova™, Mitsui, J), aluminium and stainless pigment, tourmaline pigment, and amber pigment; etc.

Suitable Q _v include: tar pigment prepared into the form of lake, and naturally occurring dyes prepared into the form of lake such as Red No.s 3, 10, 106, 201, 202, 204, 205, 220, 226, 227, 228, 230, 401, 505, Yellow No.s 4, 5, Yellow 202, 203, 204, 401, Blue No.s 1, 2, 201, 404, Green No.s 3, 201, 204, 205, Orange No.s 201, 203, 204, 206, 207. Natural dyes lakes include pigments such as carmine, laccaic acid, carsamine, brazilin, and crocin. Further examples include hybrid pigments, e.g. those disclosed in our previous patents WO01/55262 and WO01/55263.

Suitable C _v include: cellulose fibres, wood dust, cotton fibres, starch, and synthetic

microspheres, e.g. polyvinylidene/acrylonitrile copolymer, crossliked hyaluronan, powdered poly-lactate, powdered polyethylene, powdered nylon, powdered silicone, powdered polypropylene, powdered polycarbonate, powdered urea-formaldehyde resin, powdered crosslinked gelatin, powdered collagen, powdered keratin, powdered polystyrene and powdered Teflon.

The pigments according to the invention are basically formed of a core pigment C linked via one or more cation M _a and M _b to the anion of a substance A capable to promote skin exfoliation and/or to disinfect skin, thus treat acneic skin by the sustained release of said substance. Suitable A; include: fumaric acid and monoester thereof, i.e. optionally esterified at a end-group by a Q.s-alkyl, e.g. mono-ethyl-fumarate, or an Aj _ϋ -ester, e.g. mono- salicyl-azelate.

Preferred Ai are fumaric acid, and mono-ethyl fumarate.

Suitable AU include: cysteine and derivatives include: L-cysteine itself and its derivatives, such as N-acetyl-cysteine, S-palmitoyl-cysteine, S-carboxymethyl- cysteine, methyl-S-carbamoyl-cysteine, S-acetamidomethyl-cysteine.

Suitable AU also include: cysteine prodrugs, e.g. condensed cysteines having a 1,3- thiazolidine-4-carboxylate structure such as L-2-oxo-l,3-thiazolidine-4-carboxylic acid ("procysteine"), 2-(2-hydroxyphenyl)-l,3-thiazolidine-4-carboxylic acid, and the like.

Preferred A _U are L-cysteine, N-acetyl-cysteine, S-carboxymethyl-cysteine, S- palmitoyl-cysteine, and procysteine.

Suitable A;U include: benzoic acid; salicylic acid (2-hydroxybenzoic acid) and O- acyl- and O-aroyl-salicylates, e.g. acetyl salicylic acid ("ASA", or aspirin), salicyl salicylate, phenyl salicylate; and 5 -hydroxy-salicylates such as gentisic acid and ester thereof, e.g. 5-n-octanoylsalicylic acid.

Preferred A _v are benzoic acid, salicylic acid, acetyl salicylic acid, benzyl salicylate, and gentisic acid.

Suitable Aj _V include: pyrithione (2-pyridinethiol 1 -oxide) and analogs thereof, e.g. those described by Doose C, in Green Chemistry, 2004, 259-266; and J. Chrom. A, 2004, 1052(1-2), 103-110.

Preferred Aj _V is pyrithione.

Suitable A _v include: include octopirox (l-hydroxy-4-methyl-6-(2,4,4- trimethylpentyl)-2(7H _/ )-pyridinone), ciclopirox (1 -hydroxy-4-methyl-6-cyclohexyl- 2(7H)-pyridmone) and analogs thereof, e.g. described in U.S. Pat. No. 6,455,551. Preferred A _v are octopirox and ciclopirox.

Suitable A _v j include: tretinoin, (retinoic acid, ATRA, RA) and its isomers and equivalent, e.g. alitretinoin (9-cis-RA), isotretinoin (13-cis-RA), adapalene, bexarotene, fenretinide, acitretin, as well as free-carboxylic or free-phenolic containing arotinoids (e.g. TTNPB). The substances Aj- A _v , beside their capacity to promote skin exfoliation and/or to disinfect skin, have at least a carboxylic, phenolic or thiophenolic group which can be converted in anionic form. The anionic salt are soluble and/or dispersable in aqueous media, and this feature is of particularly use in the manufacturing steps carried out by ionic exchange either in wet-method (i.e. precipitation), or in semi-dry and dry-methods by ultra-mixing the solid powders, as further illustrated below. hi the pigments according to the invention, substances A;-A _v , may be present alone or in combination, or their intrinsic properties (e.g. texture, water repellency, dispersability, wear properties) can be further enhanced by the presence of hydrophobic and/or lipophilic substances. Accordingly, pigments of the invention may have a mixed layer comprising both A and B, the latter selected among an anionic surfactant capable of chelating M _3/ ),.

Anionic surfactants suitable for the purpose of the invention are the commercially available anionic surfactants, sold either as salt or in non-ionized form.

Suitable B; include: carboxylate of formula ⁰ OOC-R; dicarboxylate of formula ^(" toOC-R'-COO"; α-hydroxycarboxylate of formula ⁰ OOC-CHR' -O-CO-R; alkylsuccinamate of formula ⁹ OOC-CH ₂ CH ₂ -O-CO-R ; N-alkanoyl-sarcosinate or - glycinate of formula ⁰ OOC-CH ₂ -NR' -CO-R; N-acylglutamate or N-acylaspartate of formula ^(") OOC-CH ₂ (CH ₂ ) _0> i CH(NH-CO-R)-COO ⁰ ; and Nε-acyl-lysinate of formula ^θ OOC-CH(NH ₂ )-(CH ₂ ) ₄ -NH-CO-R. Suitable Bj ₁ include: alkyl- or dialkyl-phosphate of formula: ^(") O _a P(O)-(OR) _b ; wherein a=l or 2; and b=3-a.

Suitable Bui include: alkyl sulfonate of formula ^- ¹ O ₃ S-R ; alkylsulfate of formula ^O ₃ S-O-R ; alkyl ester sulfonate of formula: ^O ₃ S-CHR-COOR'; alkyl amide sulfate of formula ^OsSO-NHR'-CO-R ; alkyl-isethionate of formula: ^(2'} O ₃ S- CH ₂ CH ₂ -CO-R ; N-acyl-N-alkyltaurate of formula ^(2") O ₃ S-GH2CH ₂ -NR'-CO-R; C ₉ - C ₂₀ -alkylbenzen-sulfonate; alkylsulfosuccinate of formula ^OsS-CHtCOORO-CH^ R sulfosuccinate monoesters or diesters; alkylglycosides sulphate, and the like. hi Bj-Bjjj, each -OR or -0-COR radical is a saturated or unsaturated, linear or branched, alkyl or acyl C ₂ -C ₂₂ , preferably C ₈ -C ₁₈ ; said R optionally comprising a polyalkoxy chain of formula -(OCH ₂ CHR') _Z -O- with z comprised between 1 and 100, preferably between 1 and 10; and each R' is H or C ₁ -C ₃ alkyl, preferably C ₁ .

Preferred -OR or -0OR radicals include those derived from caprylic, capric, lauric, myristic, palmitic, stearic, isostearic, palmitoleic, oleic, 12-hydroxystearic, 10- undecylenic, and ricinoleic acids and alcohols, alone or in combination, e.g. from vegetal sources. In Bj the dicarboxylate of formula ^H OOC-R'-COO ^H is a straight C _4-14 chains end- terminated with two carboxylic groups, e.g. saturated C _8-12 -dicarboxylic acid such as adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, and dodecandioic acid unsaturated α,τσ-dicarboxylic acids such as straight C _4-14 chains end-terminated with two carboxylic groups, e.g. saturated C _8-12 -dicarboxylic acid such as adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, and dodecandioic acid.

Each B offers distinctive performances, e.g. increases holding moisture capacity; reduce stickiness, increase spreading; enhances smooth feel and skin adhesion; increases refreshment and smoothness to cosmetic/dermatologic makeup.

Preferably the substances A and the optional surfactants B are employed as alkaline salts (e.g. sodium and potassium salts) or ammonium salts (e.g. ammonium and DEA salts) to facilitate water dispersion and the ionic exchange with polyvalent cations.

Suitable polyvalent cations are selected among water soluble salts, e.g. sulfates, nitrates, chlorides and acetates of polyvalent cations including Zn ²⁺ , Cu ²⁺ , Ca ²⁺ , Ti ⁴⁺ ,

Si ⁴⁺ , Al ³⁺ , Sn ⁴⁺ , Mg ²⁺ , Sr ²⁺ , Ti ⁴⁺ , Zr ⁴⁺ , Ce ⁴⁺ , Fe ^2+/3+ , Cr ⁶⁺ , Mn ²⁺ , and mixture thereof; or amphoteric salts of Zn ²⁺ , Ti ⁴⁺ , Al ³⁺ , Si ⁴⁺ such as Na or K zincate, titanate, aluminate, and silicate.

According to another preferred embodiment, B is comprised up to 8% w/w on C.

As for the process of manufacturing the pigments of invention, it can either be carried out in wet/slurried form, wherein core pigment C is suspended in water and treated until the desired coating is attained; or in dry or semi-dry conditions, e.g. by high-intensity agitation, high-impact mixing, or a combination of these methods.

A general wet method is attained by ion-exchange in water of one or more A, or by the simultaneous or the sequential coating of A and B via ion-exchange.

A preferred wet method is the reaction onto the core pigments C suspended in water with one or more water-soluble multivalent cation(s), then with the slurry is reacted with an alkaline solution of A, optionally in the presence of B, as described in the Example.

Another preferred method is the direct precipitation. In this case the core pigments C are suspended in a solution of the alkaline salts of the substances A (and B if desired), then precipitation is carried out by the addition of a solution of the water- soluble salt of the polyvalent cation(s).

Further preferred wet methods is based on co-precipitation. An illustrative example of this procedure comprises the formation of an alkaline solution of substances A (and B if desired), and Na or K aluminate or zincate. The core pigment C is then suspended into the alkaline solution and brought to a pH between 9.5-10.5 by adding a mineral acid. The system is then neutralized with acidic polyvalent cation(s) and/or mineral acid.

A further example of co-precipitation comprises the pre-coating with Zn ²⁺ , Cu ²⁺ or alkaline-earthy oxide-hydroxides, formed by suspending the core pigment C into water, heating at 40-90°C, followed adding an acidic salt of a polyvalent cation. Simultaneously, a mineral alkali or acid is added to keep pH 5-to-9 until precipitation takes place, then substance A (and B if desired) is precipitated by an acidic salt of the polyvalent cation(s).

Another example is the reaction on C of amphoteric salts of multivalent cation(s) or alkaline-earthy hydroxides (e.g. Ca(OH) ₂ ) and a alkaline solution of substances A (and B if desired), followed by neutralization acidic polyvalent cation(s) and/or mineral acid.

Other examples of wet precipitation may be carried out by suspending substances A (and B if desired) in neutral or slightly acidic water under heating, e.g. 70°-95°C. This suspension is added with the core pigment C and stirred until at least part of substances A (and B if desired) are absorbed onto C. The water-soluble salts of multivalent cation(s) are then admixed under stirring, the slurry is heated and stirred, eventually neutralized.

Another preferred method is the dry or semi-dry coating of the core pigment C, which is carried out under high-intensity agitation or high-impact mixing of the powdered C with the substances A (and B if desired) in dry or "semi-dry" manner. The latter means that A (and B if desired) are sprayed onto C as concentrated (e.g. alkaline or solvent) solutions.

This method applies to core pigments C comprising, or at least are surface-treated with, a metal oxide and hydroxide, since the cationic bridge C-M _a -A (and C-M _b -B) is formed at high temperature in situ by ion exchange of A (and B) in acidic form or as alkaline salt.

The pigments of invention can be produced by further well-known coating techniques which with only minor modifications to the overall features of the present invention.

Noteworthy, the aqueous slurry obtained by a wet method can be dried up by several drying methods, e.g. filtration and grinding, spray drying, jet-milling or fluidized bed drying. Alternatively, the slurry may be washed up from the salts and the pigments can be used directly to manufacture the cosmetic/dermatologic compositions as suspensions, optionally with 0.1-10% added dispersant(s) to stabilize them on storage (before use). According to another aspect, the present invention refers to a method of treatment of acneic skin by the use of said pigments in cosmetic/dermatologic compositions.

Acneic skin types have more oil-producing sebaceous follicles with little, if any, hair in them. This means the oily waste inside the follicle builds up because there's nothing to act as a transport system out of the skin. The sebum produced also is thicker and stickier in acneic skin types. Acneic skin produces 4-to-5 times more skin cells inside of the follicle than normal skin, so that the follicle tends to occlude

because the skin does not exfoliate at sufficient high rate. When follicles fill with excess oil from the sebaceous glands and an accumulation of dead cells, a favourable environment for bacteria is created. Blackheads form and create a blockage at the mouth of the follicle. The follicles swell and rupture, causing the debris to escape into skin, irritating it and producing an inflamed red bump.

The method of the invention afford the prevention or treatment of acneic skin with the regular use of a makeup composition comprising the pigment of invention, while these also beautify the skin and hidden the acneic imperfection underneath.

According to another aspect, the invention refers to cosmetic/dermatological compositions comprising the pigments described above.

The compositions according to the invention may also comprise any cosmetically acceptable ingredients, and can be associated with other components with auxiliary action in the treatment and prevention of acne or providing skin benefits.

Examples of said additional components are, for instance, other ingredients active against proliferation of Propionibacterium acnes, e. g. antibiotics such as erythromycin, clindamycin and tetracyclines; antimicrobials such as chlorexidine and benzoylperoxide, synthetic or natural substances described as possessing inhibitory activity against P. acnes such as 1-pentadecanol and derivatives thereof, cedrene, caryophyllene, and longifolene; retinoids other-than-tretinoin such as adapalene, tazarotene, etc.; NSAID antinflammatory agents such as ibuprofen, naproxen, sulfacetamide; steroidal antinflammatory agents (e. g. hydrocortisone); vitamins; skin healing agents; and skin conditioners.

Further examples of said additional components are the Aj-A _v substances itself, in the sense that, one or more of Aj- A _v can be present both in form of C-bonded and dispersed (unbonded) form, i.e. admixed into the composition by physical means, hi this way the composition according to the invention afford both immediate and sustained release of As.

The pigments of the invention can be employed alone or in combination with others other non-coated or differently coated pigment, as well as nacres and/or fillers in makeup and sun protection compositions in any amounts between 0.1 and 80 % by weight or more.

The cosmetic/dermatologic comprising the pigment of the invention includes, for example, makeup cosmetics such as powder foundation, liquid foundation, cream foundation, oily foundation, stick foundation, pressed powder, face powder; lipstick, rouge; eye shadow, pencil, and liner; mascara; fundamental cosmetics such as emollient cream, emollient lotion, milky lotion, massage lotion, cold cream, whitening cream, emulsion, lotion, aesthetic lotion, carmine lotion; cleansing cosmetic/dermatologic for makeup, cleansing jell, liquid wash, washing foam, washing cream, washing powder; and others including cream and emulsions for sun screening and sun tanning. Preferred cosme-dermatologic compositions are the foundations in different form, and the fundamental cosmetics as listed herein.

Finally, the scope of the composition comprising the pigments of invention and of the curative method of invention are:

1. sustain release of substances promoting skin exfoliation and/or to disinfect skin; 2. carry out bactericidal or bacteriostatic action on causative organism Propionibacteria acnes ("P. acnes");

3. prevent comedonal secondary infection with any other organisms like gram+ bacteria, gram- bacteria and pathogenic fungi;

4. promote the exfoliation of high proliferating layers that accompany the inflammatory nodules and lead to comedone formation;

6. restore the skin complexion by covering acne disorders or acne disfiguring sings;

7. provide a beautifying cosmetic makeup to give aesthetic comfort;

8. normalize sebum secretion to avoid follicular plugging;

9. avoid an immediate, high gradient of anti-acne substances to come into contact with skin and thus to provoke skin irritation;

10. finally, supply a synergistic combination of components in treatment of acneic skin.

Accordingly, the composition of invention may appropriately be compounded, e.g. with pigment dispersants, oils, surfactants, UV absorbents, preservatives, anti- oxidants, film forming agents, emollient agents, thickeners, dyes, and fragrance within a broad range with further advantages of the inventive purposes.

EXAMPLES

PIGMENT PREPARATION - MATERIALS AND METHODS The materials used in the preparation of the pigments are listed in Table I TABLE I

Type Compound Brand/Type Supplier; Origin

Ci Titanium dioxide TiO ₂ Tioxide RHD2™ Tioxide Europe; Follonica (IT)

Cj Zinc oxide ZnO Alfa Aesar J. M.; Karlsruhe (D)

Cj Alumina Al ₂ O ₃ Sigma- Aldrich; Milan (IT)

C _U Iron oxide black Fe ₃ O ₄ Diploxide™ 88P Rockwood Specialties; Turin (IT)

Qi Iron oxide red Fe ₂ O ₃ Diploxide™ 226P Rockwood Specialties; Turin (IT)

Qi Iron oxide yellow FeOOH Diploxide™ 51OP Rockwood Specialties; Turin (IT)

Ci _H Mica Mica M Merck; Darmstadt (D)

Q _ϋ Bismuth oxychloride BiOCl Biron Fines Merck; Darmstadt (D)

Aj Mono-ethyl fumarate Shanghai Huawan Chem. (China) Au N- Acetyl cysteine Zambon; Bresso (IT)

A _U S-palmitoyl cysteine obtained according to Biochem. J., 1999 343 pag. 558.

Au Procysteine Sigma- Aldrich; Milan (IT)

Ai _U Salicylic acid ACEF; Fiorenzuola d'Arda (IT)

Ai _U Gentisic acid Baslini. Darfo (IT) Ai _v Pyrithione ACEF; Fiorenzuola d'Arda (IT)

A _v Octopirox Sigma- Aldrich; Milan (IT)

Ayi Tretinoin (retinoic acid) - Sigma- Aldrich; Milan (IT)

M ZnCl ₂ .6H ₂ O; CaCl ₂ .2H ₂ O - Sigma- Aldrich; Milan (IT)

M CuCl ₂ .2H ₂ O; A1C1 ₃ .6H ₂ O - Sigma-Aldrich; Milan (IT) Bj Ricinoleic acid DrJ. Pharmachem (Bombay; Ind)

Bi Undecylenic acid Sigma-Aldrich; Milan (IT)

Bj Azelaic acid Cognis; Dusseldorf (D)

Bi Palmitic acid Kortacid™ 1698 Akzo Nobel; Arese (IT)

Bi DiNa stearoyl glutamate Plantapon™ ACG 35 Cognis; Dusseldorf (D) Bj Nε-lauroyl-L-lysine Amihope™ LL Ajinomoto; Tokyo (JP)

Bu Stearoyl phosphoric acid Knapsack™ MDST Clariant; Frankfurt (D)

Example A - Wet method

Into a 1 -litre beaker fitted with a mechanical stirrer are suspended 200 g of zinc oxide in 500 ml of water, then 50 ml of ZnCl ₂ IM are added. A pH from 3 to 5 is attained and the slurry is kept under stirring at 60°C for 25 min. In another 200-ml beaker 8 g of azelaic acid and 4 g of pyrithione are dissolved in 100 ml of NaOH IN under stirring. The solution is slowly poured under stirring into 1-1 beaker containing the slurry and the system is stirred at 60°C for other 25 min.

The slurry is finally filtered, the filtrate is washed with warm deionized water until the soluble salts are removed, and the resulting cake is dried at 8O ⁰ C and grinded. Example B - Semi-dry method

10 kg of zinc oxide are carried into a vacuum blender, then a hot solution of 250 g of salycilic acind and 800 g of undecylenic acid in 4 litres of ethanol is sprayed onto the pigment surface. The blender temperature is set at 80°C and the powdered system is rolled and dried for 1 hour. After a 10 minute post-process blend and cooling, the powder is discharged from the blender. Examples C - AA

Pigments prepared according by Example A or B are listed in Table II.

Noteworthy, in the wet-methods the amount of the water-soluble multivalent cation salt and the caustic soda can be adjusted according to the amount of A (and B) used. Whenever A (and B) in the form of alkaline salts are soluble and/or dispersible at room temperature, then the coating is carried out without warming; whilst the temperature is brought to 75-80°C when at least one of A and/or B not dissolves in water but as melted form (e.g. sodium palmitate).

TABLE II - Pigment according to the invention

Ex. M • ₁ a/b A B B%

S-palmitoyl-Cysteine + Retinoic ZnO Zn acid 8:2 4 ^'

D ZnO Zn L-cysteine 5 Palmitate 3

E ZnO Zn Procysteine + Pyrithione 2 : 1 3 Ricinoleate 3

F ZnO Zn N-acetyl-cysteine + Pyrithione 2 : 1 3 Ricinoleate 3

G ZnO Zn Mono-ethyl fumarate 2 Undecylenic acid 4

H TiO ₂ Ca N-acetyl-cysteine 3 Stearoyl glutamate 3

I TiO ₂ Zn Pyrithione + Salicylic acid 3:1 2 Ricinoleate 4

J TiO ₂ Ti Pyrithione 2 Undecylenate 4

K TiO ₂ Al Benzoic acid 2 Undecylenate 6

L TiO ₂ Al Salicylic acid 2 Azelate 4

M TiO ₂ Ca Octopirox 3 Azelate 3

N Al ₂ O ₃ Al Salycilic acid 2 Undecylenate 3

O Al ₂ O ₃ Al Benzoic acid 4 Stearoyl glutamate 4

P Al ₂ O ₃ Al Gentisic acid + L-cysteine 2:1 3 Stearyl phosphate 3

Q FeOOH Al Octopirox 3 Ricinoleate 3

R FeOOH Al Octopirox 1 Azelate 5

S Fe ₃ O ₄ Zn Retinoic acid 0,5 Ricinoleate 3,5

T Fe ₃ O ₄ Al Retinoic acid 0,5 Azelate 15,5

U Fe ₂ O ₃ Zn Procysteine 3 Ricinoleate 3

V Fe ₂ O ₃ Cu Mono-ethyl fumarate 6 Palmitate 2

W BiOCl Ca Octopirox 3 Stearyl phosphate 3

Y BiOCl Ca Pyrithione 2 Azelate 6

Nε-Lauroyl-L-

Z Mica Al Retinoic acid 4

0,4 lysinate

Nε-Lauroyl-L-

AA Mica Al 4

Benzoic acid 4 lysinate

Noteworthy, the combination of two A or two M are expressed as w/w ratio; whilst the content of A, and the optional B, are expressed as % on weight on C.

APPLICATIVE EXAMPLES (COMPOSITIONS) Applicative Examples 1-3 - Foundations

A fatty blend is produced by mixing waxes and oils at 80°C with stirring until a homogeneous mixture is obtained. The pigments and fillers are added always at 80°C and with stirring until a homogeneous color is obtained. The remainder of the components are added and the temperature is maintained at 80°C for 2 hours with

stirring. The resulting foundations have the following compositions:

Appl. Ex.1 Appl. Ex.2 Appl. Ex.3

Macrocrystalline wax 4.Og 4.Og 4.Og

Carnauba wax 6.Og 6.Og 6.Og

Octyl palmitate 14 g 14 g 14 g

Hydrogenated polyisobutane 17.5 g 17.5 g 17.5 g

Trilaurin 7.Og 7.Og 7.Og

Propyl paraben 0.1 g 0.1 g 0.1 g

Curative Fe ₃ O ₄ of Appl. Ex. T 0.7 g 1.0 g 0.5 g

Curative Fe ₂ O ₃ of Appl. Ex. V 1.9 g 1.7 g 2.1g

Curative FeOOH of Appl. Ex. Q 4.9 g 4.4 g 4.7 g

Curative TiO ₂ of Appl. Ex. K 16.6 g 9.Og -

Curative TiO ₂ of Appl. Ex. L - 8.Og 16.5 g

Curative ZnO of Appl. Ex. E 3.Og - 2.Og

Curative ZnO of Appl. Ex. F - 3.0g 1.3 g

Curative Mica of Appl. Ex. Z 15.Og 8.Og -

Curative Mica of Appl. Ex. AA 15.Og 7.Og 15.Og

Nylon (untreated) 8.Og 8,0g 8.0g

Benzophenone-3 0.5 g 0.5 g 0.5 g

Octyl methoxycinnamate 0.5 g 0.5 g 0.5 g

Dimethicone, 0.3 g 0.3 g 0.3 g

Applicative Example 4 - Beautifying dav cream

The emulsion contains: Glycerin 87% 3.0g

Decyl Glucoside 1.0 g

Xanthan Gum 0.3 g

D-Panthenol in Propylene Glycol 2.0 g

ZnO pigment of the Applicative Example G 5.0g Zinc undecylenate 4.0 g

Diethylamino Hydroxybenzoyl Hexyl Benzoate 2.0 g

Cycloniethicone 2.O g

Ceteareth-6, Stearyl Alcohol 5.5 g

Ceteareth-25 1.5 g

Bees Wax 0.5 g Caprylic/Capric Triglyceride 10.0 g

Tocopheryl Acetate 1.0 g

Preservatives and perfume q.s. Demineralized water q.b. to 100 g

METHOD OF USE

Efficacy and safety assessment

Ten acne-prone female subjects or undergoing acneic disorders are rated as follows: grade 0 = no comedones or papules but an history of recurring acne; grade I = a few to moderate comedones + a few papules; grade II = a few to moderate papules + a few pustules; grade III = a few to moderate pustules + nodule/cyst and scarring.

The subjects are given the Applicative Examples 1 or 2 or 3 according to their skin hues, to be applied on regular daily base as decorative foundation. The volunteers are assessed for the baseline and at the end of week 1, 2, 4, and 6. The assessment is scored according to the following scale: Irritation: 1. - = no irritation; 2. + = minimal; 3. ++ = moderate; 4. +++ = severe irritation. Efficacy score: 0. = unchanged; 1 = poor improvement; 2 = fair; 3 = high; 4 = very high improvement. Subject are asked to judge the following parameters: 1) = irritation (none, some or troublesome); 2) = dryness of skin (none, some or troublesome); 3) improvement in acne (none, satisfactory or very satisfactory); and 4) willingness to continue the product (yes or no).

Efficacy assessment at the end of 6 ^th week showed that 8/10 had good to very good effect of treatment. At the end of 2 ^nd week of treatment 4/10 showed good to very good improvement followed by 4/10 of subjects showing fair response. The profile of side effects revealed that 6/10 of subjects did not have any irritation, 3/10 had minimal irritation whereas 1 subject had moderate irritation.

Improvement of acne reported by the subjects, data showed that 7/10 subjects have

satisfactory improvement after 6 weeks, 2/10 reported very satisfactory improvement and only 1 has an unsatisfactory response. Assessment of irritation showed that 5/10 of subjects reported no irritation, 4/10 had some irritation, whereas only one subjects reported troublesome irritation. Dryness of skin reported dryness in 4/10 of subjects, only 1 reported troublesome dryness; low-to-no dryness is reported by 5/10 subjects.