SKIN CARE PRODUCT

The present invention concerns a skin. More specific it concerns a skin care composition for reduction of or prevention of ageing of skin, and for treatment of aged or damaged skin.

Prior art

It is described a number of agents and compositions containing emu oil in a combination with other compounds, like for instance aloe vera, optionally together with other additives:

US 6.949.262 describes a composition for treatment of dry skin or mucosa, comprising from 35 to 80 weight % Aloe vera in addition to other ingredients. The use of minor amounts of Emu oil and vitamin A in the composition is also mentioned.

US 5 958 384 describes the use of emu oil for the treatment of wrinkled skin and for the stimulation of hair growth.

US 2005/0196450 relates to a method for treatment of burns using composition comprising etyl and /or isopropyl alcohol. Aloe vera and vitamin A are suggested amongst numerous additives.

US 6.528.040 describes the use of a composition comprising emu oil for treating wounds.

US 6 579 543 describes a composition with several components for topical application on the skin. The composition has analgesic effect, inflammatory effect and effect on circulation of the blood.

US 6 951 658 states a process for the treatment of Alzheimer's disease, dementia and depression with an agent containing emu oil, amino acids and vitamins.

US 20020094343 is directed to a liquid composition for topical application on the skin. The composition contains inter alia emu oil and aloe vera and is sprayed or applied on the skin to relieve pain.

US 6 416 772 describes a liquid dermal agent containing an alcohol, glycerin, and emu oil for application on the skin to alleviate pain.

Vitamin A and its active derivatives are known to be effective in improving skin parameters such as skin thickness, skin elasticity and skin hydration, parameters that are important in the evaluation of skin damage and skin ageing. Retinyl palmitate conjugated with beta cyclodextrin has been shown to be to be significantly more effective than unconjugated retinyl palmitate with respect to improvement in skin thickness and skin elasticity, having an effect being comparable to retinoic acid (Thorn E. "Skin treatment with two different galenical formulations of retinyl palmitate in humans ^' ". J Appl Cosmetol, 1993, 11, 71-76, Thorn. "Long-term effects after topical application of active retinyl palmitate" . J Appl Cosmetol, 1994, 12, 25-30, and Thorn E. "A comparative double-blind within subject of the efficacy and toler -ability of two different derivatives of Vitamin A on skin thickness and elasticity: Retinoic acid and conjugated retinyl palmitate". J Appl Cosmetol, 1997, 15, 133-138.).

Retinyl palmitate conjugated with beta cyclodextrin has also been shown to have better skin penetration properties and be more stable against oxidation on the skin surface than most vitamin A derivatives (Fu PP ₅ Xia Q, Yin JJ et al. "Photodecomposition of vitamin A and photobiological implications for the skin". Photochem Photobiol 2007;83:409-24)

Vitamin A and its derivatives, such as retinyl palmitate conjugated with beta cyclodextrin, do, however, cause local irritation to the skin when applied topically, resulting in low acceptance for the preparations containing them.

There is, however, still a need for a composition for reduction of or prevention of ageing of skin, and for treatment of aged or damaged skin that is gentle for the skin and contains no agents or compounds that cause allergic reactions or local irritation of the skin.

Summary of the invention

Acording to a first aspect, the invention relates to a composition for application on the skin for the treatment of skin conditions like wrinkles, psoriasis, pigmentation, burn, sun burn, ageing, tired and stressed skin, comprising an effective amount of a mixture of emu

oil, aloe vera and retinyl palmitate conjugated with beta cyclodextrin, in addition to water, and, optionally, one or more additives chosen among the group of preserving agents, buffers, pigments, fragrances, stabilizing agents, gel forming agents, preservatives, oils, antibiotic agents, vitamins, water, thickening agents and neutralizing agents. The combination of retinyl palmitate conjugated with beta cyclodextrin, emu oil and aloe vera results in an effective antiageing treatment of skin at the same time as unwanted irritation of the skin is eliminated or at least greatly reduced. .

According to an embodiment, the composition comprises emu oil in an amount from 5 to 25 % by weight, aloe vera in an amount from 1 to 10 % by weight, and retinyl palmitate conjugated with beta cyclodextrin in an amount from 500 to 10 000 IU per 100 g of the composition.

According to a second aspect, the invention relates to the use of emu oil, aloe vera and retinyl palmitate conjugated with beta cyclodextrine for the preparation of a skin care agent for the application on the skin for the treatment of skin conditions like wrinkles, pigmentation, psoriasis, burns, sun burns, ageing, tired and stressed skin.

According to a third aspect, the invention relates to a method for treatment of aged or damaged skin comprising the step of adding to the skin to be treated a composition as described above.

Detailed description of the invention

Emu oil Emu oil is an oil with very favorable effect on the human skin. Its advantageous penetration capability makes the skin smooth and flexible, and counteracts the formation of wrinkles. The oil may be applied on the body and feet as it is applied directly on the skin in one or several thin layers, or it can be used in the bath water.

Emu oil may also treat sunburn and burns from other heat sources, abrasion of the skin, mosquito bite, other insect bites or similar irritations. The oil diminishes the symptoms and helps the skin to a quicker normalizing. In addition the emu oil has a mild disinfection effect. The emu oil retains the skin smooth, in such a way that dry skin with wounds and wrinkles are avoided.

The oral history of the Australian Aborigine indicates their use of Emu oil for over forty thousand years. They used Emu oil to gain relief from minor aches and pains, to help heal wounds quicker, and protect their skin from the harsh elements of wind and sun. Emu oil, a food by-product, is obtained from the fat of the Emu. When the Emu is processed for its healthy red meat, the fat is then refined into oil. It is an all natural substance. When processed, the fat is taken through a series of steps to refine, sterilize and deodorize it. Not all emu oil on the market is "refined". Some forms of emu oil are simply "rendered"; this means the oil has only been filtered, and may contain contaminants. In the refining process, it is important that the oil be brought up to a high enough temperature to eliminate all bacteria. A safe oil is one which has been heated high enough to kill all bacteria and does not diminish the integrity of the oil. The Emu oil to be used in the present invention is preferably meeting the highest quality criteria.

Recent research and examinations have shown that the Emu oil may increase the growth of skin cells with more than 20 %.

The fat of the Emu provides protection against the extreme temperatures prevailing in the nature. Dermatological examinations have shown that nearly 70 % of the fatty acids from the emu are unsaturated, and nearly half thereof are monosaturated. Oleic acid is the most abundant fatty acid, together with other fatty acids essential for the human health.

The emu oil has a wide range of favorable properties:

- An important quality is the capability to penetrate (permeate) the human skin. - The oil combats inflammation in muscles and joints, and diminishes pain, swelling and stiffness in joints.

- It is an emulsifying agent, and has favourable mixing ability with other oils and e.g. water.

- Emu oil inhibits growth of bacteria, and therefore has long storage life. Due to the low contents of polyunsaturated fat, which normally is exposed to oxidation, the emu oil does not turn rancid fast.

- Emu oil does not irritate the skin upon application and has in addition generally few side effects.

- During application it does not clog the pores of the skin, and does not cause

impure skin or formation of acne.

Emu oil is an effective moisturizer and brings the protecting properties into the skin, which further provide an anti-ageing effect to the skin. It is assumed that the unique combination of saturated and unsaturated fatty acids may be the explanation of its ability to improve the properties of the skin by retaining water and prevent dehydration. This will increase the thickness of the skin and thus reduce the tendency to wrinkles and formation of wrinkles in the skin. Experiments have shown that the thickness of the skin may be increased by more than 10 % by using emu oil.

Emu oil has in addition advantageous properties regarding ageing of the skin, tired and injured skin and skin damaged by fire. Animal experiments have shown that emu oil has favourable effect on DNA synthesis. Emu oil has positive impact on hair growth, as the sack of hair in dormant condition, is being wakened and production of new hair is stimulated.

Aloe vera

Aloe vera is a widely-used product within the cosmetic and skin care field, especially for application on and treatment of the human skin. The plant, from which the aloe vera is extracted, has from ancient times been known as a beauty preparation and a medicine plant with relieving properties.

Further it is known that aloe vera can relieve and diminish inflammations, and has positive action on eczema, dry, cracked and tired skin. Aloe vera has therefore also wide use in a number of cosmetic products like body lotion, cleansing cream, soap, sun cream, shampoo and ointment. It has also been used for the treatment of fungus infection.

Many of the advantageous properties of aloe vera are a result of the content of muco polysaccharides.

Vitamin A

Vitamin A is essential and therefore must be supplied to the human body. Vitamin A exists in many different types like for instance alcohol (retinol), aldehyde (retinal) or acid (retinoic acid). The precursors of vitamin A are found in the food of plant origin

containing retinoids. Vitamin A is fat soluble and has shown favorable effect on ageing of the skin. In the present invention the vitamin A is in the form of retinyl palmitate that is conjugated with beta cyclodextrine. The conjugated retinyl palmitate is metabolized into retinylic acid in the cell.

The skin

The skin is one of the most important organs in the body, and has a thickness of 2 - 3 mm. On an adult person the skin may cover a total of 1,5 to 2 m ² , and may amount to about 15 % of the weight of the body. The skin is a complex organ consisting of a plurality of different components and cells with different and important functions. An average square cm (cm ² ) of the skin may inter alia contain about 300 sweat glands, 10 blood vessels, 30 000 melanocytes and 1000 nerve endings. The skin is rich in lipids, DNA and proteins.

It is customary to divide the skin into three main layers, namely epidermis which is the outermost, then follows the dermis, and innermost is the hypodermis. The skin has many important functions, and the most important is to protect the body against the environment, of pathogens and infections. The skin also protects the underlying cells and tissue, muscles and internal organs.

The skin also provide for insulation and regulation of the temperature, body feeling and synthesis of vitamin B and D. Further the skin contains pigmentation and melanocytes that absorb the potential dangerous ultra violet rays of the sun light. The skin contains enzymes that aid, repair and reverse injuries caused by the ultra violet rays on the skin. The injuries may by time develop into skin cancer, if they are not repaired in due time. Injured skin will try to heal by formation of tissue, and the injury may give rise to a visible scar with discoloration of the skin area.

The present invention in contrast to the above referenced patents, is directed to a product wherein the most important components are emu oil, aloe vera and retinyl palmitate that is conjugated with beta cyclodextrine. The combination of said components has proven surprising good impact on human skin.

As mentioned above both emu oil and aloe vera have proven positive properties on the

skin. It is, however, surprising to find that the combination of the compounds according to the invention, eliminates or reduces substantially the side effect of local irritation of vitamin A and its derivatives, as retinyl palmitate that is conjugated with beta cyclodextrine. Additonally, the specific combination has a significantly better effect than the retinyl palmitate that is conjugated with beta cyclodextrine, itself.

The product or compositions according to the invention are in form of a cream, ointment or oil for application on the skin for the treatment of skin conditions like wrinkles, psoriasis, burns, sun burns, ageing, tired and stressed skin, being characterized by containing a mixture of emu oil, aloe vera and retinyl palmitate that is conjugated with beta cyclodextrine, and optional may contain other conventional additives.

Emu oil is used in an amount of at least 5 % by weight of the composition, more preferably at least 7 % by weight, such as 10 % by weight or more, such as up to 25 % by weight. The preferred amount of emu oil may depend on the content of retinyl palmitate that is conjugated with beta cyclodextrine. The emu oil reduces or eliminates the local irritation resulting from the application of retinyl palmitate that is conjugated with beta cyclodextrine to the skin. This effect is dependent on the concentration of the retinyl palmitate that is conjugated with beta cyclodextrine.

The main effect of aloevera is humidifying of the skin. It has been found to be preferably to use from 1 to 10 % by weight of aloevera, such as from 2 to 5 % by weight.

It is permitted to use up to 10 000 IU (International Units) of Vitamin A,or its derivatives, per 100 g in cosmetic products. The effect on the skin caused by retinyl palmitate that is conjugated with beta cyclodextrine is dependent on the amount present in the composition. It is assumed that the lower limit for the composition to have any valuable effect is 500 IU per 100 g, such as more than 1000 IU per 100 g. Presently, an amount of retinyl palmitate that is conjugated with beta cyclodextrine from 2000 IU to 3000 IU per 100 g has been found adequate for most purposes. Any amount up to 10 000 IU, such as up to 8000, or up to 5000, may also be applicable in compositions according to the present invention to obtain sufficient tolerability of the skin, and to avoid that persons with particularly sensitive skin experience any reactions.

The skin care agent according to the invention is being produced by mixing the components in correct quantities and mixed until a homogeneous mixture is obtained. The agent is preferably in the form of a cream or ointment for application on the entire body. The usual parts of the body for application of the cream are the face, hands and feet, but the cream is suitable for the entire body.

The composition according to the invention may in addition contain one or more of the additives chosen among the group of preservatives, buffers, pigments, fragrances, stabilizing agents, pH-controlling agents, gel forming agents, preservatives, oils, antibiotic agents, other vitamins like E and C, water, thickening agents and neutralizing agents.

The thickening agents that may be used according to the invention are for instance polyacrylat based compositions. Neutralizing agents that may be used are for instance Methanol amin, and propylparaben may be used as anti microbiological preservative. The additives mentioned here are only examples, and the present invention is not restricted to these. Compounds known in the art may be used.

An important prerequisite to use the additives in the composition, is that they do not provoke allergic or irritating reactions.

Tests

Test l

Two test creams were prepared. Both creams comprise about 2500 IU retinyl palmitate that is conjugated with beta cyclodextrine and about 2.5 % by weight of aloe vera in addition to a base of water and conventional additives. The first test cream, formulation I, comprised about 7 % by weight of emu oil, and the second test cream, formulation II, comprised about 10 % by weight of emu oil.

The creams were tested on test persons that were asked to report any side effects. The formulation I cream (7 % emu oil) was tested by about 100 test persons. 20 % of the test persons reported side effects as rash or skin eruption. The formulation II cream has been tested by about 1000 test persons without any report on side effects. Accordingly, the emu oil seems to be effective to avoid or reduce side effects caused by retinyl palmitate

that is conjugated with beta cyclodextrine.

Test 2

Material and Methods The study was carried out as a randomized double-blind within-subject study in 20 females who applied the formula II cream on the volar part (protected part) of either the right or left arm. The other arm was treated with the cream vehicle (placebo). The total treatment period was 3 months and administration was bid (in the morning and in the evening) during the study period. The study was carried out in accordance with the Helsinki declaration. All subjects received information about the aim of the study before inclusion and participated voluntarily in the study and signed an informed consent before being included.

The Investigational Formulation The two preparations studied in this trial were the second test cream of Test 1 , formula II, and an vehicle (placebo).

The formula II cream and the vehicle were packed in identical jars with a unique subject number from 1 to 20. The jars were identified to be used on either the right arm or the left arm according to the randomization schedule. The other arm should be treated with placebo. Three identical sets of jars will be prepared for each subject. In total did each of the participating subjects receive 3 jars of the formula II test composition and 3 jars of the vehicle.

The active preparation was delivered by the applicant.

Measurements of Skin Thickness. Sldn Elasticity and Skin Hydration The measurements of skin thickness, skin elasticity and skin hydration were carried out with equipment from Cortex Inc; Arhus; Denmark) as outlined and described in the enclosed study protocol. Measurement was carried out at baseline, after 1 month and after 3 months, by the same person (ET) on all occasions. Measurements were performed on the mid-region of the volar part of the forearm. AU measurements were in triplicate and average values were used for statistical evaluations.

Self-Evaluation by the Participants

At the same times as the objective measurements were carried out, the participants made a self-evaluation of the skin quality using visual analogue scales of 10 cm with end points " No change" and "Very pronounced change". Subjects were asked to score the global change in skin quality by placing a mark on the line between the endpoints. The distance from the end-point (0 cm) to the mark was used as the score for the subject.

Statistical Methods

A significance level of 5% was used in the tests and two-tailed tests were applied. The one-sample test was used analyzing change over time within treatments. Two-sample t- tests were used to compare arms with regard to continuous variables.

RESULTS

20 females aged between 40 and 60 years (mean 48.6 yrs) were included in the study and all participants were compliant with the study protocol. AU the included subjects concluded the study according to the protocol.

Efficacy Parameters: Skin thickness and elasticity, and hydration The results from skin thickness measurements are shown in table 1. As can be seen from the table the cream gave an average increase in skin thickness of 49.4% on the arm treated with formula II cream while the effect on the vehicle treated arm was negligible. The change in skin thickness after treatment with the formula II cream is highly significant (p≤O.01).

Table 1, Change in skin thickness (mm) after administration of the cream or the vehicle for 3 months in 20 females (results given as mean (SD))

Initially after 1 month after 3 months

Formulation II 0.87(0.13) 1.07(0.19) 1.30(0.17)

Vehicle 0.89 (0.14) 0.90 (0.20) 0.91(0.19)

The results for the skin elasticity measurements are shown in table 2. As can be from the table the elasticity is improved by 31% in average on the arm treated with the formula II cream, while no significant changes are seen following the use of the vehicle.

Table 2, Change in skin elasticity (%) after administration of the cream or the vehicle for 3 months in 20 females (results in mean (SD)).

Initially After 1 month After 3 months

Formulation II 60.0(9.0) 71.0(8.0) 78.5(8.3)

Vehicle 59.0(8.5) 60.0(8.0) 60.5(7.9)

The formula II cream gives in addition an increase in the hydration of the skin of 50% after 3 months, while the vehicle only gives a minor increase of 7%. The difference between the two products with respect to increase in hydration is highly significant in favour of the formula II cream.

Efficacy Parameters; Self-Evaluation by use of VAS

The self-evaluations show impressing results. The results are shown in table 3. The average global score was 8.1 cm for the formula II cream treated arm. This is highly significant (p<0.001) as compared to the control arm (placebo) where only minor none • statistically changes were reported. The participants felt that they got a smoother and more elastic skin after treatment with the formula II Cream and the glow of the skin was also improved. The cosmetic properties of the cream were also highly appreciated by the participants mainly judged by good skin penetration of the cream.

Table 3, Change in VASs scores (cm) after administration of the cream or the vehicle for 3 months in 20 females (results given as mean (SD)). Initially After 1 month After 3 months

Spero Cream - 4.3(1.6) 8.1(2.5)

Vehicle - 0.2(1.5) 0.3 (1.7)

Tolerabilitv No tolerability problems were reported during the study. The tolerability was excellent. It was no difference in tolerability between the two treatment regimes.

DISCUSSION

The results from this study show very good effect in improving skin thickness, elasticity and hydration. As compared to our previous studies with conjugated Vitamin A esters he results are better showing an average improvement in skin thickness of almost 50% and in elastiticity of 31 %. This should be compared with around 32% and 19%, respectively,

for the plain conjugated creams we have tested previously using similar measuring devices. In addition the increase in hydration capacity of the skin is also impressive. The average global score on the satisfaction of the cream is also impressive with an average final score of 8.1 cm.

Introduction of the two new ingredients ,the Emu oil and Aloe Vera, in addition the β- cyclodextrin conjugated retinyl palmitate have a well founded rational and has beyond doubt given added value to the cream with respect to efficacy.

The formula II is an exciting new concept with a new dimension in skin treatment. Produced according to GMP with consistency from batch to batch it will be a valuable and attractive expansion of today's antiageing skin treatment