SE1950416A1 - Cream for treatment of skin injured by the sun - Google Patents

Abstract

The invention opertains to a cream, comprising as active ingredients: 0.5 - 7 % by weight of D,L-α-lipoic acid, 0.05-0.5 % by weight of coenzyme Q-10, 0.01-3 % by weight of acetyl-L-camitine hydrochloride, 0.01 - 2% by weight of allantoin, and 0.1 -10 % by weight of Aquaxyl and a method for preparing said cream.

Description

190404 CREAM FOR TREATMENT OF SKIN INJURED BY THE SUN Field of the InventionThis invention pertains to a cream for topical treatment of visibly photodamaged skin caused by processes involving the influence of free radicals.

Background of the Invention It is known that the first visible sign of the skin aging process is complexion°sdryness followed by decrease in elasticity. Gradually the skin becomes rough, dull andflaky. The appearing of deeper Wrinkles can be observed. The further aging processleads to development of cherry hemangioma, seborrheic keratosis, actinic keratosis orpigmentary changes.

Changes observed With aging Within epiderrna consist of: thinning of epiderrniscaused by reduced proliferation of keratinocytes; thickening of stratum comeum due toproteinases dysfunction and disturbed desquamation process; reduction of the numberof melanocytes resulting in Weaker protection against UV light; decreasing the numberof Langerhans cells leading to changed immunological response in aged skin; decreasedsebum production resulting in dry skin, development of comedones and cysts as Well aschanged composition of hydrolipid barrier that becomes more sensitive to extrinsicfactors (sunlight, temperature, mechanical trauma, pathogens).

The delamination of lamina densa and changes in structure of keratinocytes instratum basale are the major causes of observed flattening of derrnal-epiderrnal junction.The adherence of epiderrnis and derrnis decreases in time.

Symptoms of aging process in derrnis include: reduced size and number offibroblast; decreased oxygen consumption and ATP concentration in extracellularmatrix; the reduction in number of macrophages results in lack of collagenases andproteinases to cleave cross-linked collagen; less hyaluronic acid and derrnatan sulphatein proteoglycan gel, making it less effective in Water binding; structural changes incollagen lead to lose of elasticity; alterations of elastin fibers resulting in actinicelastoidosis.

The skin ageing process occurs through chronological aging (natural aging)and photoaging (premature ageing). The intrinsic/chronological aging results inthinning, loss of elasticity and general degradation of the skin. The extrinsic prematureaging, photoaging, occurs in areas of habitual exposure to sunlight in form of elastosis, atrophy, Wrinkling, vascular changes (erythema, telangiectasias), pigmentation changes 190404 (hyper- and hypo-pigmentation) or the development of seborrheic keratosis, actinickeratosis, comedones and cysts.

There are skin care products for prevention and treatrnent of skin aging,addressing different aspects of the aging process. The products designed for photoagedskin usually contain vitamin A, providing improved skin appearance and function,vitamins With Well-known antioxidant potential, as vitamin E and C, and various activesubstances and peptides, targeting specific biochemical processes in the skin. Theantioxidants should be considered as the most universal ingredients for prevention andtreatrnent of photoaging: the negative impact of UV radiation and reactive oxygenspecies (ROS) is observed in various skin aging mechanisms, like glycation, DNAdamage and mitochondrial deletions, ECM degradation, chronic inflammation,pigmentation changes, increased tumover time and disrupted barrier function, oraccumulation of damaged proteins. The use of potential antioxidant as alpha lipoic acid(ALA) and/or Dihydrolipoic acid (DHLA) seems to be smart strategy regarding theirfunctionality as free radical scavengers, regenerators for other antioxidants as vitamineC and E in skin, chelators for metals, and their role in repairing oxidized proteins.Coenzyme Q-10, showing antioxidant efficacy, is found in epiderrnis in higherconcentration than other antioxidants, suggesting its important role in protectingoutrnost layers of the skin from oxidative stress. Acetyl-L-camitine supports lipidoxidation in mitochondria, a process being less efficient With age. It has beendemonstrated that topical application of a cream containing 5% ALA, 0,3% coenzymeQ10 (Q10) and 0,03% acetyl-L-camitine (AC) Was effective in reducing photo-inducedchanges in the skin (EP 1411889) The existing solutions for prevention and treatment of skin aging caused bysunlight are affected by several problems: - Vitamin A, in its most active form, tretinoin (all-trans retinoic acid), isprohibited in cosmetics due to its teratogenic properties and strong side effects. Thepure retinol is extremely sensitive to oxidation, making it difficult to keep the topicalproduct active under shelf life. Undesirable side effects observed under retinol treatmentare redness, dryness, skin flaking and sun-sensitivity. The retinol esters are more stablein time, but not as efficient as pure retinol in anti-aging treatments. Further, the use ofvitamin A in products is restricted in several markets due to regulations (allowedconcentrations at 0,3%), making it even more difficult to develop highly efficient product for prevention and treatment of photoageing. 190404 - The active ingredients targeting defined aging mechanisms in the skin infor example peptides, are efficient, but cannot be considered as a universal solution forskin ageing due to their narrow specification.

- Lipoic acid (ALA) has low aqueous solubility, is unstable under heat,low pH and light, and has an unpleasant sulfide-smell and an irritating taste. Thephysico-chemical properties of ALA make it difficult to forrnulate functional andesthetically accepted skin care product. However, minor side effects exist, especially inthe initial phase of treatment, consisting of redness, rash and burning - yet these sideeffects are milder than any reaction to retinoids.

As such, there is a need for a skin cream for prevention and treatment of ageingskin, primarily caused by photoaging (i.e. sunlight), but with less risk of causing skin irritations, especially for persons with sensitive skin.

Summary of the Invention Accordingly, the present invention preferably seeks to mitigate, alleviate oreliminate one or more of the above-identified deficiencies in the art and disadvantagessingly or in any combination and solves at least the above mentioned problems byproviding a cream, comprising as active ingredients: 0.5 - 7 % by weight of D,L-u-lipoic acid, 0.05-0.5 % by weight of coenzyme Q-l0, 0.0l-3 % by weight of acetyl-L-camitine hydrochloride, 0.0l - 2% by weight of allantoin, and 0.l - l0 % by weight ofAquaxyl.

Further is provided a method for preparing a cream, comprising the steps of; a)preparing an emulsion by mixing a water phase containing allantoin and Aquaxyl intoan oil phase containing Ql0 at 75-80°C; b) adding a solution of acetyl-L-camitinehydrochloride to the emulsion from step a) at 70°C; c) adding a solution of D,L-ot-lipoicacid in caprylic/capric triglycerides to the emulsion from step b) at 50-65°C; d) coolingdown emulsion from step c) to 20 - 30°C.

The present invention has the advantage over the prior art that it provides a a facial cream with anti-ageing properties while being mild and non-irritant.

Brief Description of the Drawings These and other aspects, features and advantages of which the invention iscapable of will be apparent and elucidated from the following description ofembodiments of the present invention, reference being made to the accompanying drawings, in which; 190404 Fig. 1 is is a graph which shows a comparison of general efficacy for the(existing) 5% ALA reference forrnulations and the 3% ALA (prototype) forrnulations ofthe invention, showing average results, based on points gained. The test objectsevaluated several parameters while using the forrnulations by giving 1 to 5 points foreach parameter, and Fig. 2 is a graph which shows a comparison of a derrnatological patch testresults for the (existing) 5% ALA reference forrnulation and the 1.6% and 3% ALA(improved) forrnulations of the invention, showing: Average Irritation Index (xav); erythema after 48h - average results.

Description of embodiments The concept of the invention is a composition and a method for preparing thecomposition for prevention and treatment of ageing skin, containing unique forrnulationof synergistic ingredients to obtain the good derrnatological result. The currentinvention relates to lowered concentration of ALA in order to minimize potentialirritational properties. A composition according to the invention also comprisesallantoin and Aquaxyl in order to improve skin”s appearance and biomechanicalproperties. Despite the decrease of ALA content in the composition, which is makingproduct less irritating and more aesthetically appealing, the results of the treatment arecomparable to previously known compositions, due to two new components, allantoinand Aquaxyl, covering more skin aging manifestations than the previous composition.

Further, a method for treating skin is provided, comprising administering atopical composition according to the invention to the skin, containing alpha-lipoic acid,acetyl-L-camitine, coenzyme Q10, allantoin and Aquaxyl (INCI: Xylitylglucoside,Anhydroxylitol, Xylitol), or the derrnatologically acceptable salts of any of thesecomponents in an amount effective to treat the skin. Treating skin comprises treatingskin damage and the signs of aging of the skin. The skin damage can be due to intrinsicor extrinsic aging and includes, for example, wrinkles, sagging skin, decreased elasticityor dryness.

An alpha-lipoic acid is a part of the topical forrnulation used in the presentinvention. ALA is available as a racemate, and as D and L forms and R and S forms.Unless otherwise stated, ALA refers to all of these forms. ALA as used herein alsoincludes the reduced form, dihydrolipoic acid (DHLA). Both forms of acid, reduced and oxidized, shows strong antioxidant properties: free radical scavengers, regenerators for 190404 other antioxidants as vitamin C and E in skin, chelators for metals, repairing agents foroxidized proteins.

Coenzyme Q-10, showing antioxidant eff1cacy, is found in epiderrnis in higherconcentration than other antioxidants, suggesting its important role in protectingoutrnost layers of the skin from oxidative stress.

Acetyl-L-camitine supports lipid oxidation in mitochondria, process being lessefficient with age.

Allantoin is generally concemed as a soothing, softening and protectingingredient in cosmetic forrnulations in a wide range of application, including skin care,toiletries and oral care products. The higher concentrations of allantoin (0,5 - 2%)supports natural regeneration of the skin by helping the skin to maintain its integrity:increases moisture retention by increasing comeocytes capacity to bin water; byloosening the intercellular kit or the desmosomes, that maintain the adhesion ofcomeocytes to each other, exfoliates dry and damaged cells and boosts the radiantappearance to the skin. In ageing skin, desquamation and regeneration processes areslowing down, resulting in dull, dry, flaky, rough complexion - condition that can beimproved by allantoin presence promoting healthy skin, by stimulating epithelial growthand functioning as chemical debrider.

Aquaxyl is a ready-made combination of natural sugars, comprisingXylitylglucoside, Anhydroxylitol and Xylitol. The mixture is developed and patented bySeppic France. The main function of Aquaxyl is being humectant, retaining andtrapping molecules of free water in skin. It has been proven by the manufacturer thatmajor improvement of skin condition can be observed, both visible on the surface andon tissue level due to Aquaxyl impact on water circulation and its reserves in skin.

Aquaxyl comprises 15-17% water, 3-20% Xylitol, 20-30% Anhydroxylitol,and 40-77% Xylitylglucoside (all % are wt%, ingredients are added to a total of 100%).

In order to make a composition with less irritant properties, forrnulations with alower ALA concentration (<5% ALA) were evaluated in relation to the combination ofALA, Q10 and AC of patent EP 1411889. It was found that for lower ALAconcentrations, further active ingredients are required for eff1cacy in preventing andtreating damaged skin to composition.

It was surprisingly found that allantoin and Aquaxyl, which are not generallyconsidered as typical anti-aging ingredients and which provide different support toaging skin than ALA, Q10 and AC, resulted in improvement of skin conditions and function, both visual on skin surface and on tissue level. 190404 When forrnulations of 3% ALA or less were evaluated, the forrnulations hadmilder scent, brighter emulsion colour and less irritating properties. However, it wasfound that the combination of the five components of a cream according to theinvention protected the skin by targeting different aging mechanisms, as mentionedabove, and provided even better antiaging effect compared to the 5% ALA compositionaccording to patent EP 1411889.

Further, it was found that suitable preparation for optimal antiaging effectconsist of: between 0,5 and 7% of alpha-lipoic acid (preferably 3%), between 0,05 and0,5% of coenzyme Q10 (preferably 0,3%), between 0,01 and 3% of acetyl-L camitineHC1 (preferably 0,03%), between 0,01 and 2% of allantoin (preferably 0,2%) andbetween 0,1 and 10% of Aquaxyl (preferably 3%).

In one embodiment, a cream, comprising as active ingredients: 0.5 - 7 % by weight of D,L-oL-lipoic acid, 0.05-0.5 % by weight of coenzyme Q-10 0.01-3 % by weight of acetyl-L-camitine hydrochloride, 0.01 - 2% by weight of allantoin, and 0.1 - 10 % by weight of Aquaxyl, is provided.

In one embodiment, the cream comprises 0.5-4.0 % by weight of D,L-u-lipoicacid, 0.1-0.4 % by weight of coenzyme Q-10, 0.03-1.0 % by weight of acety1-L-camitine hydrochloride, 0.1 - 1.0 % by weight of allantoin, and 0.5 - 5 % by weight ofAquaxyl.

In one fiirther embodiment, the Aquaxyl comprises 15-17% water, 3-20%Xylitol, 20-3 0% Anhydroxylitol, and 40-77% Xylitylglucoside.

The forrnulation of the invention improves the water balance in skin andimproves desquamation to provide young, healthy appearance. As such, it was foundthat the moisturizing properties of the forrnulation of the invention reduces the need foradditional moisturizing products, making daily skin care routine more convenient.

In one embodiment, the cream is for topical administration.

In one fiirther embodiment, the cream is for derrnal anti-aging treatment.

In one embodiment, the cream is for derrnal treatment of visible sun injuries.Such sun injuries can be caused by processes involving the action of free radicals.

The cream of the invention is suitable for topical administration on areasexposed to the sun. Also, due to its non-irritant properties, it is very suitable for use onsensitive skin, such as in the face.

In one embodiment, the cream is a facial cream. 190404 It was found that a 3% ALA composition had surprisingly good efficacy. Thiscan be seen in figure 1, where in fact the 3% ALA solution of the invention preforrnsbetter than the 5% reference solution. Also, a 1,6% DLA composition for younger andmore sensitive skin also showed very good properties.

In one embodiment, the cream comprises: 1.6-3.0 % by weight of D,L-u-lipoicacid, 0.1-0.3 % by weight of coenzyme Q-10, 0.03 % by weight of acetyl-L-camitinehydrochloride, 0.2 % by weight of allantoin, and 3.0 % by weight of Aquaxyl.

In one embodiment, the cream comprises: 1.6 or 3.0 % by weight of D,L-u-lipoic acid, 0.1 or 0.3 % by weight of coenzyme Q-10, 0.03 % by weight of acetyl-L-camitine hydrochloride, 0.2 % by weight of allantoin, and 3.0 % by weight of Aquaxyl.

The cream of the invention is an oil-in-water emulsion, designed for efficientstabilization and delivery of active ingredients to the skin. The emulsion consists of rawmaterials providing proper consistency and pleasant application, emolliency, physico-chemical and microbial stability. Care has been taken to ensure optimal occlusiveproperties of emulsion: too occlusive topical product increase risk of irritation, notenough occlusion decrease invention efficacy. Suitable supporting emulsions wereevaluated, and two examples of supporting emulsions are shown below.

In one embodiment, the cream is a oil-in-water elmulsion.

To improve stability and eff1cacy of ALA, which is known to be sensitive tooxidation when exposed to light and air, it is important to incorporate it into theforrnulation in a specific way. The preferred step while making the emulsion isdissolving ALA in a suitable amount of caprylic/capric triglyceride, under heating up to50 to 65 degrees, preferrably, 55 - 58°C. This step allows to keep ALA in an intemal,dispersed phase of emulsion, protected from oxidizing factors and to preventrecrystallization of ALA in the emulsion, which would reduce its efficacy. The solutionof ALA in caprylic/capric triglyceride, due to the triglyceride properties, can penetratestratum comeum and deliver ALA more efficient to skin.

In one embodiment, a method for preparing a cream, comprising the steps of; a) preparing an emulsion by mixing a water phase containingallantoin and Aquaxyl into an oil phase containing Q10 at 75-80°C;b) adding a solution of acetyl-L-camitine hydrochloride to theemulsion from step a) at 70°C; c) adding a solution of D,L-ot-lipoic acid in caprylic/caprictriglycerides to the emulsion from step b) at 50-60°C; d) cooling down emulsion from step c) to 20 - 30°C. 190404 In one embodiment, the solution of D,L-ot-lipoic acid in caprylic/caprictriglycerides is prepared by adding D,L-ot-lipoic acid to a caprylic/capric triglyceridesolution at 50 to 60 °C, such as 55-60 °C preferably 55 - 58°C.

The cream may include a supporting emulsion With other stabilizing andpreserving ingredients.

A suitable supporting emulsion comprises: 20 - 80% of purified Water(preferably 59,46%), 1-20% caprylic/capric triglyceride (preferably 10%), 1 - 10%C15-19 alkane from renewable sources (preferably 5,315%), 1 - 5% of shea butter ethylesters (preferably 3%), 1 - 5% of cetearyl alcohol (preferably 2,6%), 1 - 5% of glycerin(preferably 2,6%), 1 - 5% of jojoba oil (preferably 2%), 1 - 5% of arachidyl alcohol(preferably 1,51%), 1 - 5% of glyceryl stearate (preferably 1,5%), 0,05 - 5% of sheabutter (preferably 1,0%), 0,05 - 5% of octyldodecyl myristate (preferably 1,0%), 0,01 -1% of behenyl alcohol (preferably 0,825%), 0,01 - 1% of sodium acrylate/sodiumacryloyldimethyltaurate copolymer (preferably 0,525%), 0,01 - 1% of arachidylglucoside (preferably 0,413%), 0,01 - 1% of cetearyl glucoside (preferably 0,4%), 0,01- 1% of sodium hydroxide (preferably 0,372%), 0,01 - 1% of parfum (preferably0,34%), 0,01 - 1% of lactic acid (preferably 0,324%), 0,01 - 1% of retinyl palmitate(preferably 0,25%), 0,01 - 1% of tocopherol (preferably 0,2%), 0,01 - 1% of ascorbylpalmitate (preferably 0,1%), 0,01 - 1% of xanthan gum (preferably 0,1%), 0,01 - 1% ofpropanediol (preferable 0,08%), 0,01 - 1% of sunflower oil (preferably 0,06%), 0,01 -1% of citric acid (preferably 0,04%), 0,01 - 1% of polyglycerin-6 (preferable 0,028%),0,01 - 1% of tartaric acid (preferable 0,016%), 0,001 - 0,1% of gluconic acid(preferable 0,008%). All % are Wt%, and ingredients are added to a total of 100%.

In one embodiment, the cream of the inVention comprises a supportingemulsion (cream base) Which comprises one or several components selected from: 20 -80% of purif1ed Water, 1-20% caprylic/capric triglyceride, 1 - 10% C15-19 alkane, 1 -5% of shea butter ethyl esters, 1 - 5% of cetearyl alcohol, 1 - 5% of glycerin, 1 - 5% ofjojoba oil, 1 - 5% of arachidyl alcohol, 1 - 5% of glyceryl stearate, 0,05 - 5% of sheabutter, 0,05 - 5% of octyldodecyl myristate, 0,01 - 1% of behenyl alcohol, 0,01 - 1% ofsodium acrylate/sodium acryloyldimethyltaurate copolymer, 0,01 - 1% of arachidylglucoside, 0,01 - 1% of cetearyl glucoside, 0,01 - 1% of sodium hydroxide, 0,01 - 1%ofparfum, 0,01 - 1% oflactic acid, 0,01 - 1% ofretinyl palmitate, 0,01 - 1% oftocopherol, 0,01 - 1% of ascorbyl palmitate, 0,01 - 1% of xanthan gum, 0,01 - 1% ofpropanediol, 0,01 - 1% of sunflower oil, 0,01 - 1% of citric acid, 0,01 - 1% of 190404 polyglycerin-6, 0,01 - 1% of tartaric acid, 0,001 - 0,1% of gluconic acid. All % areWt%, and ingredients are added to a total of 100%.

Another suitable supporting en1ulsion con1prises: 20 - 80% of purified Water(preferably 59,30%), 1-20% caprylic/capric triglyceride (preferably 11%), 1 - 10%C15-19 alkane from renewable sources (preferably 3,315%), 1 - 5% of shea butter ethylesters (preferably 4%), 1 - 5% of ethylhexyl stearate (preferably 4%), 1 - 5% ofcetearyl alcohol (preferably 1,5%), 1 - 5% of glycerin (preferably 3,46%), 1 - 5% ofarachidyl alcohol (preferably 2,2%), 1 - 5% of glyceryl stearate (preferably 1,5%), 0,05- 5% of shea butter (preferably 1,5%), 1 - 5% of behenyl alcohol (preferably 1,2%),0,01 - 1% of sodiun1 acrylate/sodiuni acryloyldiniethyltaurate copolynier (preferably0,525%), 0,01 - 1% of arachidyl glucoside (preferably 0,60%), 0,01 - 1% of sodiunihydroxide (preferably 0,245%), 0,01 - 1% of parfun1 (preferably 0,34%), 0,01 - 1% oflactic acid (preferably 0,324%), 0,01 - 1% of retinyl paln1itate (preferably 0,12%), 0,01- 1% of tocopherol (preferably 0,2%), 0,01 - 1% of ascorbyl palniitate (preferably0,1%), 0,01 - 1% of propanediol (preferable 0,08%), 0,01 - 1% of sunflower oil(preferably 0,06%), 0,01 - 1% of citric acid (preferably 0,04%), 0,01 - 1% ofpolyglycerin-6 (preferable 0,028%), 0,01 - 1% of tartaric acid (preferable 0,016%),0,001 - 0,1% of gluconic acid (preferable 0,008%). All % are Wt%, and ingredients areadded to a total of 100%.

In one en1bodin1ent, the crean1 of the invention con1prises a supportingeniulsion (creani base) Which coniprises one or several con1ponents selected from: 20 -80% of purif1ed Water, 1-20% caprylic/capric triglyceride, 1 - 10% C15-19 alkane fronirenewable sources, 1 - 5% of shea butter ethyl esters, 1 - 5% of ethylhexyl stearate, 1 -5% of cetearyl alcohol, 1 - 5% of glycerin, 1 - 5% of arachidyl alcohol, 1 - 5% ofglyceryl stearate, 0,05 - 5% of shea butter, 1 - 5% of behenyl alcohol, 0,01 - 1% ofsodiuni acrylate/sodiun1 acryloyldiniethyltaurate copolynier, 0,01 - 1% of arachidylglucoside, 0,01 - 1% of sodiuni hydroxide, 0,01 - 1% ofparfun1, 0,01 - 1% of lacticacid, 0,01 - 1% of retinyl paln1itate, 0,01 - 1% of tocopherol, 0,01 - 1% of ascorbylpaln1itate, 0,01 - 1% of propanediol, 0,01 - 1% of sunflower oil, 0,01 - 1% of citricacid, 0,01 - 1% of polyglycerin-6, 0,01 - 1% of tartaric acid, 0,001 - 0,1% of gluconicacid. All % are Wt%, and ingredients are added to a total of 100%.

A crean1 according to the the invention coniprises of ingredients of naturalorigin, is free fron1 conventional preservatives and silicones. Cosnietic forrnulations considered as “natural” are generally n1ore difficult to develop and stabilize, especially 190404 when they are rich in active components (increased risk of incompatibility, oxidation and deterioration).

Example I - 3 % DLA preparation A prototype 3 % sample composition comprises: 3 % of a1pha-1ipoic acid,0,3% of coenzyme Q10, 0,03% of acetyl-L camitine HC1 0,2 % of a11antoin and 3 % ofAquaxyl.

The supporting emu1sion comprises: 59,46 % of purified water, 10%caprylic/capric triglyceride, 5,315% C15-19 alkane from renewab1e sources, 3% of sheabutter ethy1 esters, 2,6% of cetearyl a1coho1, 2,6% of glycerin, 2% of jojoba oi1, 1,51%of arachidy1 a1coho1, 1,5% of glyceryl stearate, 1,0% of shea butter, 1,0% ofocty1dodecy1 myristate, 0,825% of beheny1 a1coho1, 0,525% of sodium acrylate/sodiumacry1oy1dimethy1taurate copolymer, 0,413% of arachidy1 glucoside, 0,4% of cetearylglucoside, 0,372% of sodium hydroxide, 0,34% of parfum, 0,324% of 1actic acid, 0,25%of retinyl pa1mitate, 0,2% of tocophero1, 0,1% of ascorby1 pa1mitate, 0,1% of xanthangum, 0,08% of propanedio1, 0,06% of sunflower oi1, 0,04% of citric acid, 0,028% ofpo1yg1ycerin-6, 0,016% of tartaric acid, 0,008% of gluconic acid. A11 % are wt%, andingredients are added to a total of 100%. A11 % are wt%, and ingredients are added to atota1 of 100%.

Example 2 - 1,6 % DLA preparation A 1,6% sample composition for extra sensitive skin comprises: between 1,6 %ofa1pha-1ipoic acid, between 0,1% of coenzyme Q10, between 0,03% of acetyl-Lcamitine HC1, between 0,2% of a11antoin and between 3% of Aquaxyl.

A supporting emu1sion comprises: 59,30% of purified water, 11%caprylic/capric triglyceride, 3,315% C15-19 alkane from renewab1e sources, 4% of sheabutter ethy1 esters, 4% of ethylhexyl stearate, 1,5% of cetearyl a1coho1, 3,46% ofglycerin, 2,2% of arachidy1 a1coho1, 1,5% of glyceryl stearate, 1,5% of shea butter,1,2% of behenyl a1coho1, 0,525% of sodium acrylate/sodium acry1oy1dimethy1tauratecopolymer, 0,60% of arachidy1 glucoside, 0,245% of sodium hydroxide, 0,34% ofparfum, 0,324% of 1actic acid, 0,12% of retinyl pa1mitate, 0,2% of tocophero1, 0,1% ofascorby1pa1mitate, 0,08% of propanedio1, 0,06% of sunflower oi1, 0,04% of citric acid,0,028% of po1yg1ycerin-6, 0,016% of tartaric acid, 0,008% of gluconic acid. A11 % arewt%, and ingredients are added to a tota1 of 100%. 190404 ll Efiicacy Trials Comparative study:The efficacy of two prototype forrnulations was tested and compared to eff1cacy of a forrnulation according to EP 1411889 (5 % ALA). The eff1cacy wasevaluated in non-controlled user test: 25 Caucasian woman, age 40+, users of, applyingtest product twice a day on face under period of 6 weeks. After the test period objectswere asked to evaluate the product within five categories: observed effect, scent,consistency, afterfeel, moisturising properties, and rating each category with 1 to 5points, where 1 was the lowest, the least satisfying result and 5 was the best, the mostsatisfying result. Subjects were not trained within topical product evaluation.

Both prototype forrnulations contained same composition of active ingredients:ALA - 3%, Q10 - 0,3%, AC - 0,03%, allantoin - 0,2% and Aquaxyl - 3% and differed slightly in oil phase composition, without significance for result obtained.

Clinical studv with instrumental measurement of effects: The eff1cacy of the cream according to the invention in preventing and treatingaging skin was also evaluated in a clinical study on 20 Caucasian women, age 40+,applying the product on face under 8 weeks (56 days) period, according to the followingschedule: the first week - once every other day, the second week - once every day; thethird to eighth week -twice a day (moming and evening). To obtain independentresults, the following measurements were taken to control antiaging eff1cacy of inventedforrnulation: - Comeometer CM 825 - measurement of skin moisturization before andafter the product application - Cutometer MPA 580 - measurement of biomechanical parameters(firmness and elasticity) before and after the product application - Visioline VL 650 + 3D photo - measurement of length and depth ofwrinkles before and after the product application with 3D photo.

Another cream was provided for younger, more sensitive skin, consisting ofdecreased concentrations of ALA, Q10 and acetyl-L-camitine to minimize skinirritation risk. Even this forrnulation is an object of clinical test on 20 Caucasian woman, age 25+, using product under 8 weeks period.

Dermatological semi-open patch test: 190404 12 Creams according to the invention Were tested to assess their irritating potentialand results Were compared to analogical result obtained for all existing referenceforrnulation.

The purpose of the study Was to assess irritating and sensitizing properties(skin tolerance) of a cream according to the invention on a healthy adult skin. Patch skintests according to J adassohn-Bloch as modified by Rudzki Were perforrned under thesupervision of a derrnatologist. The semi-occlusive test is the basic kind of testconfirming contact allergy. The preparation Was applied into a filter paper discs of llmm diameter, manufactured by SmartPractice and then fixed to the arm or interscapulararea using sticking plaster. In a parallel time to obj ectify the results of the studies, tWocontrol samples Were carried out: blind and With Water. The patches Were removed byderrnatologist after 48h and the skin response Was evaluated l5 min after removal. Afterfurther 24h and 48h from last verification, the skin response is again evaluated byderrnatologist. Test subj ects: 25 healthy volunteers With negative history of allergy, age18+. None of the volunteers reported documented oversensitivity or a history of adverse reactions to individual ingredients of the tested product.

Table l. Evaluation parameters of skin reaction Evaluation parameters of skin reaction Erythema Classification pointNo erythema 0 Light erythema 0,5Erythema and/or papules lErythema and/or papules and/or vesicles 2Erythema and/or papules and/or vesicles and/or blisters 3Erythema, bullous and/or ulcerative reaction, and/or papules and/or 4 vesicles and/or blisters Edema No edema 0 Very light edema (hardly visible) Light edema Moderate edema (about lmm raised skin) .lšbJl\)>-fl Strong edema (extended sWelling even beyond the application area) Results Classification point 190404 13 Comparative study:The results obtained in the comparative study on 25 persons show that both prototype (3% ALA) forrnulations are well accepted by accustomed users and gainedhigher average results than existing forrnulation (5% ALA), which proves that changesmade in original composition, despite reduction of ALA concentration, surprisinglyimproved product eff1cacy(Fig. 1). The existing forrnulation (5% ALA) was given 4,24pts in average, while prototype A gained 4,41 pts and prototype B - 4,35 pts. Theobserved improvement of product efficacy should be considered as a result of additionof two actives: allantoin and Aquaxyl to existing forrnulation. Although the addedcomponents have moisturizing and calming properties, it was not expected that theywould enhance the anti-ageing properties of the composition to such an extent.

In Fig. 1, a comparison of general eff1cacy of the forrnulations - averageresults, based on points gained. The test objects evaluated several parameters while using the forrnulation by giving 1 to 5 points for each parameter.

Dermatological semi-open patch test results: The facial cream prototype solutions of 1.6 % and 3 % ALA of the inventionwas the subject of objective clinical test under derrnatological control to assess itsirritating and sensitizing properties, showing any skin reaction under 72h afterapplication (96h examination was skipped due to 100% negative results). Similar testswere done for existing (5% ALA) forrnulation and some cases of erythema wereobserved 24h after application. The results a cream according to the invention is lessprone to cause irritation and sensitization than the reference cream. Results in form of Average Irritation Index (xav) are shown in table 2 and presented in Fig. 2.

Table 2. Calculated values of Average Irritation Index (xav).

Existing Result 48h after Result 72h after Result 96h afterformulation application application applicationErythema 0,08 0,00 0,00Edema 0,00 0,00 0,00 xav 0,0 1 3 Improved Result 48h after Result 72h after Result 96h afterformulation 1.6% application application applicationErythema 0,00 0,00 examination skipped 190404 14 Edema 0,00 0,00 examinationskippedxav 0,000Improved Result 48h after Result 72h after Result 96h afterformulation 3.0% application application applicationErythema 0,00 0,00 examinationskippedEdema 0,00 0,00 examinationskippedxav 0,000 In Fig. 2, it is shown that the cream according to the invention is less prone tocause irritation or sensitization than a composition comprising 5 % ALA, thus minimising the risk of adverse reactions.

Although the present invention has been described above With reference to (a)specific embodiment(s), it is not intended to be limited to the specific form set forthherein. Rather, the invention is limited only by the accompanying claims and, otherembodiments than the specific above are equally possible Within the scope of theseappended claims, e.g. different than those described above.

If not otherwise stated, all %-values are % by Weight.

In the claims, the term "comprises/comprising" does not exclude the presenceof other elements or steps. Furthermore, although individually listed, a plurality ofmeans, elements or method steps may be implemented. Additionally, althoughindividual features may be included in different claims, these may possiblyadvantageously be combined, and the inclusion in different claims does not imply that acombination of features is not feasible and/or advantageous. In addition, singularreferences do not exclude a plurality. The terms "a", "an", “first”, “second” etc do not preclude a plurality.

Claims (1)

1. A cream, comprising as active ingredients: 0.5 - 7 % by Weight of D,L-ot-1ipoic acid, 0.05-0.5 % by Weight of coenzyme Q-10, 0.01-3 % by Weight of acety1-L-camitine hydroch1oride,0.01 - 2% by Weight of a11antoin, and 0.1 - 10 % by Weight of Aquaxyl. The cream according to c1aim 1, Wherein the cream is a oi1-in-Water emulsion. The cream according to any of c1aims 1 to 2, Wherein the cream is fortopical administration. The cream according to any of c1aims 1 to 3, Wherein the cream is a facia1cream. The cream according to any of c1aims 1 to 4, Wherein the cream is forderrnal anti-aging treatment. The cream according to any of c1aims 1 to 5, Wherein the cream is for treatment of Visible sun injuries on skin. The cream according to any one of c1aims 1 to 6, comprising:0.5-4.0 % by Weight of D,L-ot-1ipoic acid, 0.1-0.4 % by Weight of coenzyme Q-10, 0.03-1.0 % by Weight of acety1-L-camitine hydroch1oride,0.1 - 1.0 % by Weight of a11antoin, and 0.5 - 5 % by Weight of Aquaxyl. The cream according to any one of c1aims 1 to 6, comprising:1.6-3.0 % by Weight of D,L-ot-1ipoic acid, 0.1-0.3 % by Weight of coenzyme Q-10, 0.03 % by Weight of acety1-L-camitine hydroch1oride, 0.2 % by Weight of a11antoin, and 3.0 % by Weight of Aquaxyl. 190404 9. 10. 16 A method for preparing a cream according to any one of claims 1 to 8, comprising the steps of;a) preparing an emulsion by mixing a Water phase containingallantoin and Aquaxyl into an oil phase containing Q10 at 75-80°C;b) adding a solution of acetyl-L-camitine hydrochloride to theemulsion from step a) at 70°C;c) adding a solution of D,L-ot-lipoic acid in caprylic/caprictriglycerides to the emulsion from step b) at 50-65°C;d) cooling down emulsion from step c) to 20 - 30°C. The method according to claim 9, Wherein solution of D,L-u-lipoic acidin caprylic/capric triglycerides is prepared by adding D,L-u-lipoic acid toa caprylic/capric triglyceride solution at 50 to 60 °C, preferably 55 - 58°C.