WO2006061627A2

WO2006061627A2 - Antiaging composition

Info

Publication number: WO2006061627A2
Application number: PCT/GB2005/004727
Authority: WO
Inventors: Jonathan Stott
Original assignee: Oxonica Ltd
Priority date: 2004-12-07
Filing date: 2005-12-07
Publication date: 2006-06-15
Also published as: WO2006061627A3; GB0426820D0

Abstract

A composition suitable for cosmetic or topical pharmaceutical use which comprises: (1) an antiaging agent; and (2) an amount of a metal oxide that is capable of scavenging free radicals and /or a metal oxide which has been doped with one or more other elements and/or reduced zinc oxide; the antiaging agent comprising at least one component which is photosensitive and/or which is susceptible to free radical attack and/or in which degradation is induced by another ingredient of the composition, for example one or more cytokinins and/or one or more extracts from Boswellia Serrata.

Description

ANTIAGING COMPOSITION

The present invention relates to antiaging compositions suitable for cosmetic and topical pharmaceutical use.

It is desirable to produce antiaging compositions that provide the desired antiaging properties over a useful period of time and under ordinary conditions. Aging in this context is a well understood term, and it relates to damage or other undesirable changes to the skin or underlying tissues usually resulting in lines or wrinkles, such as crow's feet, or sagging, or in surface changes such as dryness or visual blemishes. A usual contributory, or sole, cause is the radiation from the sun. Antiaging compositions have been proposed to prevent or at least to reduce the formation of lines or wrinkles and also to hydrate the skin and to limit any oxidative or other reactions that can occur at the skin's surface. The present invention is concerned with stabilisation of the active ingredients of antiaging compositions, particularly so that direct or indirect photo-damage is limited.

In PCT/GB 2003/005658 it was disclosed that the degradation of organic sunscreen agents, and other components which are susceptible to degradation, can be retarded if the compositions also have present zinc oxide or titanium dioxide which has been doped with another element and/or reduced zinc oxide. In other words by using, in a cosmetic or topical pharmaceutical composition, these doped or reduced materials rather than ordinary titanium dioxide or zinc oxide it is, for example, possible either to provide a composition which gives better protection against UV light for the same quantity of organic sunscreen agent or a composition having the same screening effect against UV light but containing a smaller quantity of organic sunscreen agent. Indeed it was stated that it is possible to provide all day protection sunscreens by incorporating the doped and/or reduced materials.

The disclosure of PCT/GB2003/005658 is incorporated herein by reference.

In PCT/GB2003/005658 it is stated that its compositions maybe, among many things, antiaging compositions. However, no examples are given of specific antiaging active agents, nor is any suggestion made that the TiO₂ZZnO or reduced ZnO interacts in any way, directly or indirectly, with any antiaging agent; rather any antiaging properties were additional and incidental to the sunscreen activity and were incidental to the techniques for preventing degradation.

We have now found that each of various free radical-scavenging metal oxides and also surface and/or bulk doped metal oxides, particularly TiO₂/ZnO, and also reduced ZnO has specific benefits in connection with antiaging agents; and that specific and unexpected benefits are realised in connection with certain antiaging agents, particularly naturally occurring organic based products and derivatives and synthetic analogues thereof.

Since it may be desirable to apply and to wear an antiaging composition indoors, or under other conditions where there is no. significant risk of UVA/UVB skin damage, the present composition need not have any significant sunscreen activity or may be otherwise unsuitable for use as a sunscreen. For example it may be insufficiently transparent to visible light, referred to herein as substantially opaque, and/or it may be coloured. Nonetheless, it will often be desirable to be able to wear an antiaging composition during the daytime, rather than in substantial darkness, and thus problems can arise with traditional antiaging agents that degrade in the presence of radiation even if that radiation would not itself cause skin damage.

Thus, the present invention provides a composition suitable for cosmetic or topical pharmaceutical use which comprises: (1) an antiaging agent; and (2) an amount of a metal oxide that is capable of scavenging free radicals and/or a metal oxide which has been doped with one or more other elements and/or reduced zinc oxide; the antiaging agent comprising at least one, preferably organic, component which is photosensitive and/or which is susceptible to free radical attack and/or in which degradation is induced by another ingredient of the composition (possibly as a direct or indirect result of the effect of UVA or UVB or other irradiation on that other ingredient).

The photosensitivity may be sensitivity to, for example, UVA and/or UVB and/or to visible light particularly blue light.

Thus, the antiaging agent may itself be directly damaged or degraded by UV or other radiation, hi that case it will itself absorb such radiation, although the amount absorbed may be very small. In such an embodiment, component (2) of the composition will in general absorb UV the radiation that would otherwise reduce the efficacy of the antiaging agent. Many irradiation absorbers produce free radicals on absorption, and there is a risk that such free radicals will themselves damage the antiaging agent. In the present invention, however, component (2) may absorb radiation without generating free radicals, hi this case one might select doped metal oxides and/or reduced zinc oxide. Preferred doped oxides include titanium dioxide and zinc oxide. A preferred dopant is Mn, most preferably Mn³⁺. This is discussed further below.

Alternatively, the antiaging agent may be substantially immune to direct irradiation damage. However, a problem may still arise in preventing damage or degradation of the antiaging agent by direct free radical attack, the free radicals resulting from damage or degradation of an other component of the composition due, for example, to irradiation. In this case, component (2) of the invention may not only absorb the irradiation with minimum or zero generation of free radicals, but may also absorb the damaging free radicals produced by other materials (which may themselves be present as part of the same composition). Ln this case surface doping may be found to be particularly useful.

The amount of component (2) in the composition will depend on the degree of protection sought for the antiaging composition, on the nature of the antiaging agent, on the incident irradiation, on other components, on the nature of component (2) and on environmental factors. Nonetheless, some guidance may be given. The weight of component (2) based on the weight of component (1) will usually be at least 0.05%, preferably at least 0.08%, more preferably at least 0.1%. Preferred maxima are 25%, 10%, 5%, 2%, 1% and 0.5%.

The nature of preferred antiaging agents (1) will be now be discussed first, followed by a discussion of preferred materials for component (2) of the composition.

The antiaging agent may comprise, for example, a naturally occurring plant, marine or mammalian extract, and/or derivatives and/or synthetic analogues thereof. Examples of mammalian extract include musk-ox or other bovine growth hormones; and examples of plant extract include plant hormones such as cytokinins, gibberellins, phytosans and/or extracts from Boswellia serrata. A further class of agents is marine extracts. Alternative or additional agents include niacinamides, retinoids and coenzyme MEQ₁₀.

Various classes of antiaging agent may be used singly or in combination, including anti-oxidants like vitamins A, B, C and E, anti-wrinkle agents, and skin nourishments.

The invention also provides the use of a metal oxide that is capable of scavenging free radicals or a doped metal oxide or reduced ZnO to reduce degradation of an antiaging agent, by for example UV or free radical attack, the antiaging agent preferably comprising at least one antiaging component as referred to above.

The invention further provides a method of increasing the effectiveness for daytime (or other) use of an antiaging agent comprising at least one antiaging agent which is photosensitive and/or which is susceptible to free radical attack and/or in which degradation is induced by another ingredient of the composition, which comprises incorporating into the composition a metal oxide that is capable of scavenging free radicals and/or a doped metal oxide and/or reduced ZnO.

The invention still further provides a method of treating the skin which comprises applying thereto a composition comprising an antiaging agent comprising: at least one antiaging component which is photosensitive and/or which is susceptible to free radical attack and/or in which degradation is induced by another ingredient of the composition; and a metal oxide that is capable of scavenging free radicals and/or a doped metal oxide and/or reduced ZnO.

In a further embodiment, the invention provides an antiaging composition (such as the composition defined above) having substantially no sunscreen activity and/or being substantially opaque and/or being coloured.

By antiaging composition is meant any cosmetic or topical pharmaceutical or other composition that has antiaging properties or that includes an active ingredient to which are attributed antiaging properties, even if its principal function may not be antiaging. Thus, the principal function may be, for example, sunscreening activity. If sunscreening activity is in itself important, it will be appreciated that the doped TiO₂/ZnO or other metal oxide or reduced ZnO may but need not be the only ingredient of the composition having UV sunscreening activity i.e. the composition may contain also an organic UV sunscreen agent. It is to be understood that the composition can also contain TiO₂ and/or ZnO, or other metal oxide, which has not been doped or reduced.

A preferred antiaging agent comprises one or more cytokinins, particularly kinetin (6-Furfurylarninopurine). In general, therefore, the agent may comprise:

wherein each of R and R¹, which may be the same or different, is a substituted or unsubstituted Cl -6 group, preferably Cl, C2, C3 or C4.

As an alternative to a cytokinin, or in addition to it, one or more extracts from Boswellia Serrata may be used. The active agent may be extracted from the gum resin which contains:

• Monoterpenes (a-thujene)

• Diterpenes (macrocyclic diterpenoids such as incensole, incensole oxide, iso- incensole oxide, a diterpene alcohol (serratol))

• Triterpenes (such as a-and b-amyrins)

• Pentacyclic triterpenic acids (boswellic acids)

• Tetracyclic triterpenic acids (tirucall-8,24-dien-21-oic acids)

The four major pentacyclic triterpenic acids present in the acidic extract of Boswellia Serrata gum resin (Boswellin, trade mark) are:

• b-Boswellic Acid (I)

• Acetyl-b-Boswellic Acid (II)

• 11 -keto-b-Boswellic Acid (III)

• Acetyl- 11 -keto-b-Boswellic Acid (IV)

Two other pentacyclic triterpenic acids have also been isolated: a-Boswellic Acid (V) g-Boswellic Acid (VI)

(5) (6) In addition to the above six pentacyclic triterpenic acids, four tetracyclic triterpenic acids have also been identified. These are: 3 a-tirucall-8,24-dien-21-oic acid (VII); 3-ketotirucall-8,24-dien-21-oic acid (VIII); 3 a-hydroxytirucall-8,24-dien-21-oic acid (IX); 3 b-hydroxy tirucall-8,24-dien-21 -oic acid (X)

Component (2) of the composition will now be discussed.

In general the free radical-scavenging oxides are of rare earth or transition metals, preferably the latter. A "transition metal" as used herein is a member of group VA to VIII of the periodic table (see Chemistry of the Elements, Greenwood & Earnshaw, Pergamon 1984). The metals should possess adjacent oxidation states e.g. Mn²⁺ and Mn³⁺. Furthermore, it is generally necessary that these adjacent energy states differ by not more than 2 eV, preferably by not more than 1 eV. Rare earth metals which can be used include terbium, europium, and cerium which is preferred. As mentioned above, preferred transition metals that can be used include manganese, which is preferred, chromium, iron and vanadium as well as ruthenium. Thus, the preferred oxide is currently manganese oxide.

Although it will be more usual to employ a simple oxide, it is also possible to use mixed oxides. These mixed oxides will generally be of two or more transition/rare earth metals but the use of other metals such as aluminium and titanium is not excluded.

Preferred doped metal oxides will now be discussed.

The dopant for the titanium or zinc or other metal oxide is preferably manganese, which is especially preferred, e.g. Mn²⁺ but especially Mn³⁺ or Mn⁴⁺, vanadium, for example V³⁺ or V⁵⁺, chromium and iron but other metals which can be used include nickel, copper, tin, aluminium, lead, silver, zirconium, zinc, cobalt, gallium, niobium, for example Nb⁵⁺, antimony, for example Sb³⁺, tantalum, for example Ta⁵⁺, strontium, calcium, magnesium, barium, molybdenum, for example Mo³⁺, Mo⁵⁺ or Mo⁶⁺ as well as silicon. Manganese is preferably present as Mn³⁺, cobalt as Co²⁺, tin as Sn⁴⁺ as well as Sn²⁺. These metals can be incorporated singly or in combination of 2 or 3 or more. Thus, the present use of doped titanium oxide and/or zinc oxide and/or reduced zinc oxide may allow undoped metal oxides to be used without overcoming the disadvantages that such materials can give rise to.

The doped metal oxide can be obtained by any one of the standard processes for preparing doped oxides and salts, in particular any of the standard processes suitable for preparing oxide particles. Further details of these doped oxides can be found in WO 99/60994 as well as WO 01/440114. Other routes which may be used to prepare the doped materials include a precipitation process of the type described in J. Mat. Sci. (1997) 36, 6001-6008. Further details of preparation can be found in the aforesaid patent specifications.

Doped TiO₂/ ZnO or other doped oxides can also be obtained by flame pyrolysis or by plasma routes where mixed metal containing precursors at the appropriate level are exposed to a flame or plasma to obtain the desired product.

The doping may be surface doping, i.e. doping may be limited to the surface of the particles of titanium or zinc oxide. This may be contrasted with bulk doping. In surface doping there will be a concentration gradient, for example such that the ratio of dopant atoms to titanium or zinc atoms at the surface or outermost skin of the particles is greater than the ratio in the core or centre where it may be zero.

The rutile form of titania is known to be more photostable than the anatase form and is therefore preferred. Reduced zinc oxide particles (i.e. particles which possess an excess of zinc ions relative to the oxygen ions) may be readily obtained by heating zinc oxide particles in a reducing atmosphere to obtain reduced zinc oxide particles which absorb UV light, especially UV light having a wavelength below 390 nm, and re-emit in the green, preferably at about 500 nm. It will be understood that the reduced zinc oxide particles will contain reduced zinc oxide consistent with minimising migration to the surface of the particles of electrons and/or positively charged holes such that when said particles are exposed to UV light in an aqueous environment the production of hydroxyl radicals is substantially reduced as discussed above.

It is believed that the reduced zinc oxide particles possess an excess of Zn²⁺ ions within the absorbing core. These are localised states and as such may exist within the band gap. A further discussion of this can be found in WO 99/60994.

The average primary particle size of the particles may be generally from about 1 to 200 nm, for example about 1 to 150 nm, preferably from about 1 to 100 nm, more preferably from about 20 to 80 nm. The particle size may be chosen to avoid colouration and to achieve transparency to visible light of the final product where that is desirable, as indeed it is in the case of sunscreens. Thus, nanoparticles maybe used. However, in one embodiment slightly larger particles for example from 100 to 500 nm, typically 100 to 400 or 450 nm especially from 150 to 300 nm and particularly 200 to 250 nm, can be employed. These provide good coverage of, for example, skin imperfections without unacceptable skin whitening. Still larger particles, up to say 20000 nm, may be used where transparency to visible light is not required. In that case it may be desirable for the size of the particles to be at least 500, preferably at least 1000, often at least 5000 nm.

Where particles are substantially spherical then particle size will be taken to represent the diameter. However, the invention also encompasses particles which are non-spherical and in such cases the particle size refers to the largest dimension.

The oxide particles used in the present invention may have an inorganic or organic coating. For example, the particles maybe coated with oxides of elements such as aluminium, zirconium or silicon, especially silica. The particles of metal oxide may also be coated with one or more organic materials such as polyols, amines, alkanolamines, polymeric organic silicon compounds, for example,

RSi[{OSi(Me)₂}xOR^I]₃ where R is Ci-Ci₀ alkyl, R¹ is methyl or ethyl and x is an integer of from 4 to 12, hydrophilic polymers such as polyacrylamide, polyacrylic acid, carboxymethyl cellulose and xanthan gum or surfactants such as, for example, TOPO. Such coatings can have the effect of masking, at least to some extent, any colour which the doped particles may have, and may diminish the free radical scavenging capability of the particles, In the other hand, the coatings may be desirable to aid dispersion.

The compositions of the present invention are generally for cosmetics use and may be in the form of, for example, creams, including anti-wrinkle formulations, exfoliating preparations including scrubs, creams and lotions, skin lightening compositions in the form of, for example, face powders and creams, preparations for the hands including creams and lotions, moisturising preparations, gels, skin cleansing compositions including wipes, sprays, lotions and gels, eye shadow and blushers, lipsticks, skin toners and serums as well as washing products such as shower gels, bath products including bubble baths, bath oils, and sunscreens. The compositions may also be pharmaceutical compositions suitable for topical application. Such compositions are useful, in particular, for patients suffering from disorders of the skin such as those that are adversely affected by UV light such as those giving rise to polymorphous light eruptions. The compositions may incorporate perfumes or fragrances.

Organic sunscreen agents which can be used in the compositions of the present invention, but which may usefully be omitted, include any conventional sunscreen agent which gives protection against UV light. There need be no photosensitive component, nor any component that is degraded by another ingredient of the composition, other than the antiaging agent.

Where organic sunscreen agent(s) are present they are typically present in the compositions at a concentration from 0.1 to 20%, preferably 1 to 10%, and especially 2 to 5%, by weight based on the weight of the composition.

In the antiaging compositions, which may be, for example, generally aqueous or may be water-in-oil or oil-in-water emulsions, the metal oxides are preferably present at a concentration of about 0.05 to 25 % by weight, preferably about 0.5 to

20% by weight, more preferably 1 to 10 % by weight, yet more preferably about 3 to 8 % by weight, and in particular about 4 to 7%, such as 4 to 6%, for example about 5%, by weight.

The antiaging compositions may be in the form of, for example, lotions, typically with a viscosity of 4000 to 10,000 mPas, e.g. thickened lotions, gels, vesicular dispersions, creams, typically a fluid cream with a viscosity of 10,000 to 20,000 mPas or a cream of viscosity 20,000 to 100,000 mPas, milks, powders, solid sticks, and may be optionally packaged as aerosols and provided in the form of foams or sprays.

The antiaging compositions may contain any of the ingredients used in such formulations including fatty substances, organic solvents, silicones, thickeners, liquid and solid emollients, demulcents, UVA, UVB or broad-band sunscreen agents, antifoaming agents, antioxidants such as butyl hydroxy toluene, buffers such as lactic acid with a base such as triethanolamine or sodium hydroxide, plant extracts such as Aloe Vera, cornflower, witch hazel, elderflower and cucumber, activity enhancers, moisturizing agents, and humectants such as glycerol, sorbitol, 2-pyrrolidone-5- carboxylate, dibutylphthalate, gelatin and polyethylene glycol, perfumes, preservatives, such as para-hydroxy benzoate esters, surface-active agents, fillers and thickeners, sequesterants, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, alkalizing or acidifying agents, colorants and powders, including metal oxide pigments with a particle size of from 100 nm to 20000 nm such as iron oxides along with conventional (undoped) TiO₂ and ZnO.

The organic solvents are typically from lower alcohols and polyols such as ethanol, isopropanol, propylene glycol, glycerin and sorbitol as well as methylene chloride, acetone, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol mono-ethyl, ether, dimethyl sulphoxide, dimethyl formamide and tetrahydrofuran.

The fatty substances may consist of an oil or wax or mixture thereof, fatty acids, fatty acid esters, fatty alcohols, vaseline, paraffin, lanolin, hydrogenated lanolin or acetylated lanolin, beeswax, ozokerite wax and paraffin wax. 42- The oils are typically from animal, vegetable, mineral or synthetic oils and especially hydrogenated palm oil, hydrogenated castor oil, vaseline oil, paraffin oil, Purcellin oil, silicone oil such as polydimethyl siloxanes and isoparaffin.

The waxes are typically animal, fossil, vegetable, mineral or synthetic waxes. Such waxes include beeswax, Carnauba, Candelilla, sugar cane or Japan waxes, ozokerites, Montan wax, macrocrystalline waxes, paraffins or silicone waxes and resins.

The fatty acid esters are, for example, isopropyl myristate, isopropyl adipate, isopropyl palmitate, octyl palmitate, Ci₂-Ci₅ fatty alcohol benzoates ("FINSOLV TN" from FINETEX), oxypropylenated myristic alcohol containing 3 moles of propylene oxide ("WITCONOL APM" from WITCO), capric and caprylic acid triglycerides ("MIGLYOL 812" from HULS).

The compositions may also contain thickeners such as cross-linked or non cross-linked acrylic acid polymers, and particularly polyacrylic acids which are cross- linked using a polyfunctional agent, such as the products sold under the name "CARBOPOL" by the company GOODRICH, cellulose, derivatives such as methylcellulose, hydroxymethylcellulose, hydroxypropyl methylcellulose, sodium salts of carboxymethyl cellulose, or mixtures of cetylstearyl alcohol and oxyethylenated cetylstearyl alcohol containing 33 moles of ethylene oxide.

Desirably, the weight ratio of water-dispersible metal oxide and/or doped metal oxide and/or reduced zinc oxide to oil-dispersible metal oxide and/or doped metal oxide and/or reduced zinc oxide titanium is from 1 :4 to 4:1, preferably from 1 :2 to 2:1 and ideally about equal weight proportions.

Suitable emollients include stearyl alcohol, glyceryl monoricinoleate, mink oil, cetyl alcohol, isopropyl isostearate, stearic acid, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, eicosanyl alcohol behenyl alcohol, cetyl palmitate, silicone oils such as dimethylpolysiloxane, di-n-butyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, Methylene glycol, lanolin, cocoa butter, corn oil, cotton seed oil, olive oil, palm kernel oil, rapeseed oil, saffiower seed oil, evening primrose oil, soybean oil, sunflower seed oil, avocado oil, sesame seed oil, coconut oil, arachis oil, caster oil, acetylated lanolin alcohols, petroleum jelly, mineral oil, butyl myristate, isostearic acid, palmitic acid, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myristyl myristate.

Suitable propellants include propane, butane, isobutane, dimethyl ether, carbon dioxide, nitrous oxide.

Suitable powders include chalk, talc, fullers earth, kaolin, starch, gums, colloidal silica sodium polyacrylate, tetra alkyl and/or trialkyl aryl ammonium smectites, chemically modified magnesium aluminium silicate, organically modified montmorillonite clay, hydrated aluminium silicate, fumed silica, carboxyvinyl polymer, sodium carboxymethyl cellulose, ethylene glycol monostearate.

The compositions of the present invention may be in the form of, for example, suspensions or dispersions in solvents or fatty substances or as emulsions such as creams or milks, in the form of ointments, gels, solid sticks or aerosol foams. The emulsions, which can be oil-in-water or water-in-oil emulsions, may further contain an emulsifier including anionic, nonionic, cationic or amphoteric surface- active agents; for a water-in-oil emulsion the HLB is typically from 1 to 6 while a larger value i.e >6 is desirable for an oil-in-water emulsion. Generally water amounts to up to 80%, typically 5 to 80%, by volume. Specific emulsifiers which can be used include sorbitan trioleate, sorbitan tristearate, glycerol monooleate, glycerol monostearate, glycerol monolaurate, sorbitan sesquioleate, sorbitan monooleate, sorbitan monostearate, polyoxyethylene (2) stearyl ether, polyoxyethylene sorbitol beeswax derivative, PEG 200 dilaurate, sorbitan monopalmitate, polyoxyethylen (3.5) nonyl phenol, PEG 200 monostearate, sorbitan monostearate, sorbitan monolaurate, PEG 400 dioleate, polyoxyethylene (5) monostearate, polyoxyethyene (4) sorbitan monostearate, polyoxyethylene (4) lauryl ether, polyoxyethylene (5) sorbitan monooleate, PEG 300 monooleate, polyoxyethylene (20) sorbitan tristearate, polyoxyethylene (20) sorbitan trioleate, polyoxyethylene (8) monostearate, PEG 400 monooleate, PEG 400 monostearate, polyoxyethylene (10) monooleate, polyoxyethylene (10) stearyl ether, polyoxyethylene (10) cetyl ether, polyoxyethylene (9.3) octyl phenol, polyoxyethylene (4) sorbitan monolaurate, PEG 600 monooleate, PEG 1000 dilaurate, polyoxyethylene sorbitol lanolin derivative, polyoxyethylene (12) lauryl ether, PEG 1500 dioleate, polyoxyethylene (14) laurate, polyoxyethylene

(20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (20) stearyl ether, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) cetyl ether, polyoxyethylene (25) oxypropylene monostearate, polyoxyethylene (20) sorbitol monolaurate, polyoxyethylene (23) lauryl ether, polyoxyethylene (50) monostearate, and PEG 4000 monostearate. Alternatively the emulsifier can be silicone surfactant, especially a dimethyl polysiloxane with polyoxyethylene and/or polyoxypropylene side chains, typically with a molecular weight of 10,000 to 50,000, especially cyclo-methicone and dimethicone copolyol. They may also be provided in the form of vesicular dispersions of ionic or nonionic amphiphilic lipids prepared according to known processes.

It can be advantageous to use both a water-dispersible and an oil-dispersible metal oxide and/or doped metal oxide and/or reduced zinc oxide. It has been found that when an emulsion is spread on the skin it has a tendency to break down into oily and non-oily areas. When the water evaporates the oil-dispersible particles will tend to be in the oily areas thus leaving areas unprotected. This can be avoided by having both hydrophilic and hydrophobic particles in the emulsion so that some are retained in hydrophilic areas and others in hydrophobic areas.

Water-dispersible particles can be uncoated or coated with a material to impart a hydrophilic surface property to the particles. Examples of such materials include aluminium oxide and aluminum silicate. Oil-dispersible particles which exhibit a hydrophobic surface property are suitably coated with metal soaps such as aluminium stearate, aluminium laurate or zinc stearate, or with organosilicone compounds.

Example

The following experiments were conducted to assess thephotostability ofkinetin combined with a Mn³⁺ -doped TiO₂ composition.

Three formulations were made up using an antiaging formulation consisting of the following active ingredients: (1) 2% Degussa T805 (trade mark)/4% kinetin (2) 2% Mn³VTiO₂, 4% kinetin

(3) 4% kinetin.

Vitro-Skin substrate for UV- visible absorption experiments was purchased from IMS Testing Group. The substrate was cut into 6 x 9 cm rectangles and placed in a hydration chamber containing glycerin [15% (w/v)] at room temperature for 16 - 24 hours. Kinetin samples were applied to the substrate at a surface density of 2 mg/cm² and rubbed into the film with a gloved finger. The film was then mounted into a 6 x 6 cm glassless slide mount and left for 15 minutes to dry. UV absorption measurements (Hitachi U-4100, equipped with an integrating sphere system to collect scattered radiation) were made immediately following the dry-down period and following illumination by a Spectral Energy xenon arc solar simulator equipped with a Schott WG320 filter. The output of the solar simulator as measured by a Bentham DM150 double spectral radiometer is shown in Figure 1. The output energy over the 290nm to 400nm range is 5 mW.cm^"2.

Kinetin samples were run in duplicate in each run under the solar simulator and the mean was taken. A further two sets of duplicate samples of new formulations were exposed in separate experiments and the total mean of the data was recorded. The total %loss of kinetin was calculated as a percentage loss of the UV absorbance at 260nm (λ max = 260nm for kinetin) and compared between all three samples.

A sample of kinetin solution was also obtained from Sigma Aldrich (lmg/ml in water). This was applied to the Vitro-Skin in the same method as stated above and irradiated in the solar simulator for two hours. Readings were taken at t=0, t=60 and t=120 minutes, and the results were plotted as a graph shown as Figure 2.

HPLC testing:

Samples contained 4% (w/w) kinetin and 2% (w/w) TiO₂ were extracted from the Vitro Skin following 2 hours solar illumination under the xenon arc solar simulator. The Vitro Skin was cut up into smaller parts and the kinetin was extracted into isopropanol (15 ml) in a Falcon tube. The samples were then sonicated and the insoluble components removed by centrifugation (1200Og, 15 minutes). The supernatant was taken and analyzed by HPLC using a LiChrospher (trade mark) 100 RP-18 (5μM) column and a mobile phase of 88% (w/w) MeOH, 0.1% (w/w) TFA (1 ml/minute). Kinetin was eluted with a retention time of 2.5-3.5 minutes at a detection wavelength of 260nm.

Each formulation was sampled three times for HPLC measurements after UV illumination. The procedure was then repeated a further two times for a new set of test formulations. In total, three separate formulation sets are each sampled three times.

Figure 3 shows the percentage retention of kinetin over two hours solar irradiation. It can clearly be seen that the Mn³⁺-doped TiO₂ performs better than undoped TiO₂ and performs better than T805 by stabilizing the kinetin from free radical attack and consequent degradation.

The results are shown in Figures 1, 2 and 3. It can be seen that the presence of the Mn³⁺ -doped TiO₂ has noticeable benefits on the performance of the kinetin after irradiation.

Claims

1. A composition suitable for cosmetic or topical pharmaceutical use which comprises: (1) an antiaging agent; and (T) an amount of a metal oxide that is capable of scavenging free radicals and/or a metal oxide which has been doped with one or more other elements and/or reduced zinc oxide; the antiaging agent comprising at least one component which is photosensitive and/or which is susceptible to free radical attack and/or in which degradation is induced by another ingredient of the composition.

2. A composition according to claim 1, in which component (1) is photosensitive and/or is thus susceptible and/or in which said degradation is induced in the presence of irradiation.

3. A composition according to claim 1 or 2, in which the photosensitivity is sensitivity to UVA and/or UVB.

4. A composition according to claim 1, 2 or 3, in which component (2) comprises one or more oxide of cerium, manganese, vanadium, chromium and iron capable of scavenging free radicals.

5. A composition according to any preceding claim, in which component (2) comprises doped titanium dioxide and/or doped zinc oxide.

6. A composition according to any preceding claim, in which component (2) comprises reduced zinc oxide.

7. A composition according to any preceding claim, in which the antiaging agent comprises a naturally occurring plant, marine and/or mammalian extract, and/or a derivative and/or a synthetic analogue thereof.

8. A composition according to claim 7, in which the mammalian extract comprises musk-ox or other bovine growth hormone; and/or in which the plant extract comprises one or more cytokinins, gibberellins, phytosans and/or extracts from Boswellia s errata.

9. A composition according to any preceding claim, in which the antiaging agent comprises an anti-oxidant; and/or anti-wrinkle agent; and/or skin nourishment.

10. A composition according to claim 1 substantially as hereinbefore described.

11. Use of a metal oxide that is capable of scavenging free radicals and/or a doped metal oxide and/or reduced ZnO to reduce degradation of an antiaging agent comprising at least one organic component having photosensitivity and/or being susceptible to free radical attack and/or being susceptible to degradation induced by another ingredient of the composition.

12. Use according to claim 11 , in which the antiaging agent comprises one or more cytokinins, gibberellins, a phytosans and/or extracts from Boswellia serrata.

13. A method of increasing the effectiveness for daytime use of an antiaging agent comprising at least one organic component which is photosensitive and/or which is susceptible to free radical attack and/or in which degradation is induced by another ingredient of the composition, which comprises incorporating into the composition a metal oxide that is capable of scavenging free radicals and/or a doped metal oxide and/or reduced ZnO.

14. A method according to claim 13, in which the antiaging agent comprises one or more cytokinins, gibberellins, a phytosans and/or extracts from Boswellia serrata.

15. A method of treating the skin which comprises applying thereto a composition comprising: an antiaging agent comprising at least one organic component which is photosensitive and/or which is susceptible to free radical attack and/or in which degradation is induced by another ingredient of the composition; and a metal oxide that is capable of scavenging free radicals and/or a doped metal oxide and/or reduced ZnO.

16. A method according to claim 15, in which the antiaging agent comprises one or more cytokinins, gibberellins, phytosans and/or extracts from Boswellia serrata.

17. A method according to claim 15 or 16, in which said treatment is carried out predominantly during daytime.

18. An antiaging composition having substantially no sunscreen activity and/or being substantially opaque and/or being coloured, and comprising: a metal oxide that is capable of scavenging free radicals and/or a doped metal oxide and/or reduced zinc oxide; and an antiaging agent.

19. A composition according to any of claims 1 to 10, having substantially no sunscreen activity and/or being substantially opaque and/or being coloured.