WO2007003915A1

WO2007003915A1 - Composition for dermatological treatment

Info

Publication number: WO2007003915A1
Application number: PCT/GB2006/002438
Authority: WO
Inventors: Tulani Motsi
Original assignee: Individual
Current assignee: Individual
Priority date: 2005-07-02
Filing date: 2006-06-30
Publication date: 2007-01-11
Anticipated expiration: 2008-01-02
Also published as: EP1940520A1; AU2006264701A1; GB0513641D0

Abstract

The present invention relates to the treatment of dermatological conditions. Particularly, although not exclusively, the present invention relates to a composition containing a number of active agents and a method of using Said combination to reduce the appearance of spots and skin roughness. Compositions, methods and medicaments are described for treating ageing, eczema, dermatitis, rosacea, acne, psoriasis, light damage, sunburn, photoageing, sub-optimal wound healing, scarring, alopecia, tendon injury, thermal injury.

Description

COMPOSITION FOR DERMATOLOGICAL TREATMENT

Field of the Invention

The present invention relates to the treatment of dermatological conditions. Particularly, although not exclusively, the present invention relates to a composition containing a number of active agents and a method of using said combination to reduce the appearance of spots and skin roughness .

Background

The Epidermis, the outermost layer of the skin is made up of multilayered cells composed largely of keratinocytes . These cells change their appearance from one layer to the next. The innermost layer of the epidermis is the basal layer and it is usually only these cells that divide. The skin cells formed in the basal layer are pushed upwards by younger cells until they are shed from the surface of the skin. These outermost cells are reduced to flattened scales filled with densely packed keratin (protein) .

The period from the time a cell is born in the basal layer of the human skin to the time it is shed from the surface is around 28 to 30 days .

The Dermis lies beneath the epidermis . It is mainly composed of amorphous intercellular substance that supports the framework (collagen and elastin) of the extra cellular matrix mainly secreted by fibrolasts - basic cell of the dermis. Collagen and elastin fibres provide the dermis with its strength and elasticity. If these fibres are damaged (for example, due to ageing, UV radiation) the skin becomes loose and does not return to its original state when stretched, and looks thin and wrinkled.

Within the dermis, blood vessels bring nutrients and oxygen and remove waste products and carbon dioxide. These vessels also provide access routes for cells of the immune system to provide defences against infections.

Nerve fibres are present too, to convey sensory information from the tissue to the central nervous system and to deliver signals for glandular secretion and smooth muscle contraction (Molecular Biology of The Cells, Garland (4th ed.), 2002, Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter) .

The epidermis suffers more direct, frequent and damaging encounters with the external environment than any other tissue. Its need for renewal and repair is central to its organisation .

External factors such as sun, smoking, pollution and diet along with internal factors such as age and genetics have a bearing on the health and appearance of skin.

Photoageing caused by frequent and cumulatively prolonged sun exposure (UV radiation) results in DNA damage to skin cells, while intrinsically aged skin is atrophic, which may result in prominence of vascular, transparent quality and loss of elasticity. The epidermis thins, with a flattening of the dermoepidermal junction that is reflected by an increased fragility of the skin, along with a reduction in the number and biosynthetic capacity of fibroblasts, resulting in delayed wound healing. Fine dermal elastic fibres coarsen with age and then disappear.

Senescent fibroblasts and keratinocytes lose their proliferative capacity, and collagen synthesis decreases. Ageing fibrolasts show decreased synthesis of mRNA for type I collagen, which is the major collagen in the skin. Also, in skin cell cultures, aging fibroblasts proliferate at a slower rate than fetal fibroblasts. Thus natural ageing is at least partly the result of the limited replicative capacity of dermal fibroblasts, as well as the over expression of proteolytic activity of matrix metalloproteinase 1 (MMP-I, interstitial collagenase) . Additionally, both photoaged and naturally aged human skin have lower procollagen type 1 mRNA and protein compared to younger skin. (Procedures in Cosmetic Dermatology - Cosmeceuticals, Peptides and Proteins, Mary P Lupo, chpt. 17) .

Both intrinsic aging and photoageing result in the degeneration of the skin barrier.

Total skin tissue is lost at a speed of about 7% of total skin thickness every 10 years (Oxidative and premature skin ageing: Biesalski H. K. et al . Experimental Dermatology 2003:12 (suppl.3): 3-15).

The external appearance changes through atrophy and the development of wrinkles as a result of the decrease in epidermal cell layers, as dermal components, from a reduction in protein and collagen synthesis. Reduced protein synthesis is reflected in Keratin, Filaggrin and Involucrin. Keratin deficiency has an effect on the epidermal cell structure and its water-binding capacity. Filaggrin is an antecedent of natural moisturizing factor (NMF) . Involucrin is seen as significant for the cell envelope and structure of the stratum corneum. The effects of reduced protein synthesis are poorer structure and reduced skin elasticity, as well as a decrease in the efficiency of the epidermal barrier function with a reduction in horny layer moisture (Gehring W, Nicotinic acid/ niacinamide and the skin; Journal of Cosmetic Dermatology, 2004; 3, 33-93) .

Numerous products are currently sold to minimise the effects of ageing skin:

* Vitamin C (L-ascorbic acid) administered topically is effective against wrinkles and fine lines. The disadvantages of topically administered vitamin C are that it is relatively unstable and when exposed to air it oxidises making it ineffective and also potentially harmful. Also, vitamin C products are irritating for many people . Topical vitamin C products need a concentration of 10% or more to increase collagen synthesis, which is highly acidic and can cause irritation.

* Retinoids are able to rejuvenate ageing skin as well as treating acne. They too have a tendency to cause skin damaging irritation and dryness, leaving the skin in a worse state than before the treatment. * Moisturizers provide moisture to the skin, preventing moisture loss but with no effect on the underlying biochemical processes involved in ageing skin.

Presently known methods for treating dermatological conditions include the use of vitamin A derivatives such as roacutane (isotretinoin) and for use of α-hydroxy and β- hydroxy acids often from plants, coenzyme Q containing solutions and some cobalt containing proteins. Many of these art known compositions can result in tenderness of the skin and other unwanted side effects, for example, liver damage and/or migration through the placental barrier to a developing foetus causing abnormalities . Many of the more useful treatment regimes, for example, isotretinoin treatment, are available only by prescription and costs in various jurisdictions can be quite high to the end user who is often of limited income due to age and/or work status. It would be useful if a therapeutic agent and method were available to obviate the above-mentioned disadvantages associated with the art.

It is therefore an object of the present invention to provide an agent for the treatment of dermatological problems .

One aspect of the present invention is to sidestep the above-mentioned problems in the art by providing an anti- aging composition that can be administered orally, and by methods other than, but not excluding, topical administration. Summary of the Invention

In accordance with a first aspect the invention provides a composition comprising:

a) a source of carotenoids;

b) a source of flavonoids; and

c) a source of epithelial cells.

The source of carotenoids may contain any naturally occurring, semi-synthetic or synthetic carotenoid or any prodrug or mixture thereof .

Preferably the source of carotenoids contains one or more carotenoids selected from the group actinioerythrol, astaxanthin, bixin, canthaxanthin, capsanthin, capsorubin, beta-8 ' -apo-carotenal (apo-carotenal) , beta-12 ' -apo- carotenal, alpha-carotene, beta-carotene, "carotene" (a mixture of alpha- and beta-carotenes) , gamma-carotene, alpha-cryptoxanthin, beta-cryptoxanthin, lutein, lycopene, violerythrin, zeaxanthin, and esters of hydroxyl- or carboxyl-containing members thereof.

Preferably the source of carotenoids is selected from carrots, sweet potatoes, spinach, kale, collard greens, tomatoes, carrot oil, marine oils and the algae dunaliella salina or any other vegetable, algal or bacterial source of carotenoids.

Most preferably the source of carotenoids is tomato. In preferred embodiments the source of carotenoids is a source of lycopene.

In particularly preferred embodiments the source of carotenoids contains more than about one milligram per kilogram of lycopene.

The source of flavonoids may be any one or a mixture of naturally occurring, semi-synthetic or synthetic flavonoids or any prodrug or mixture thereof.

Preferably the source of flavonoids contains one or more flavonoids selected from the group catechin, epicatechin, gallocatechin, epigallocatechin, flavan-3-ols, flavan-3,4- diols optionally esterified, or any other vegetable, algal, or bacterial source of flavonoids .

Preferably the source of flavonoids contains guercertin or kaempferol .

More preferably the source of flavonoids contains both quercertin and kaempferol.

In preferred embodiments the source of flavonoids is selected from the group cocoa, apples, grapes, green tea, onions or any other source of flavonoids.

In particularly preferred embodiments the source of flavonoids is onion. The carotenoids and flavonoids for use in the composition according to the present invention may be synthetic or semisynthetic or isolated from a source not traditionally considered a food, for example, bark, leaves, or algae.

The most preferred embodiments of the present invention contain naturally occurring sources of carotenoids and flavonoids.

The source of epithelial cell may be derived from an animal, preferably a mammal .

In preferred embodiments the epithelial cells are porcine, bovine or ovine. In particularly preferred embodiments the source of epithelial cells is bovine.

The source of epithelial cells may be derived from one or more organs selected from the group lungs, intestines, liver, kidneys, pancreas or any other organ or tissue containing epithelial cells.

Where a mixture of different sources of epithelial cells is utilised the sources may be from the same or different animals .

In particularly preferred embodiments the source of epithelial cells is intestine, for example, cooked bovine tripe .

In accordance with a second aspect there is provided a method of treating a dermatological condition in a subject - B -

in need thereof comprising administering thereto a composition according to the present invention.

In preferred embodiments the dermatological condition may be selected from the group consisting of ageing, eczema, dermatitis, rosacea, acne, psoriasis, light damage, sunburn, photoageing, sub-optimal wound healing, scarring, alopecia, tendon injury, thermal injury and any other condition where insufficient regeneration of the epidermis is implicated including any inflammatory condition.

In an alternative embodiment, the present invention provides a method of preventing and/or reducing and/or reversing the dermatological aging in a subject comprising administering thereto a composition according to the present invention.

In preferred embodiments the condition to be treated is selected from ageing, dry patches, acne and uneven skin surface .

Preferably the source of carotenoids provides between 0.01 and 100 milligrams per 100 grams of carotenoids. More preferably the source of carotenoids provides between 0.1 and 10 milligrams per 100 grams of carotenoids. In particularly preferred embodiments the source of carotenoids provides between 0.5 and 5 milligrams per 100 grams of carotenoids .

Preferably the source of flavonoids provides between 0.01 and 100 milligrams per 100 grams of flavonoids. More preferably the source of flavonoids provides between 0.1 and 10 milligrams per 100 grams of flavonoids. In particularly preferred embodiments the source of flavonoids provides between 0.5 and 5 milligrams per 100 grams of flavonoids.

Some embodiments of the composition according to the present invention may have up to 10% by weight of carotenoids and flavonoids .

In preferred embodiments the composition is formulated so that 10 to 1000 grams of the source of epithelial cells or extracts equivalent thereto may be administered every two weeks .

In some embodiments the composition may take the form of tablets, etc. formulated for administration on a daily basis.

Preferably the method of the present invention is carried out every two weeks . In other embodiments of the invention the method may be carried out on a daily basis.

Some skin conditions appear on a regular basis in response to hormone levels in the body. In some embodiments the administration step of the method of the invention is carried out in response to or in anticipation of hormone level fluctuations. The hormone levels may be associated with menstruation, puberty or menopause and thyroid problems .

In a further embodiment the present invention also provides the use of a composition in accordance with the present invention in therapy for ageing, eczema, dermatitis, rosacea, acne, psoriasis, light damage, sunburn, photoageing, sub-optimal wound healing, scarring, alopecia, tendon injury, thermal injury and conditions where insufficient regeneration of the epidermis is implicated including inflammatory conditions.

The therapy may also include a method of preventing and/or reducing and/or reversing the dermatological aging in a subject.

The use of a composition according to the present invention in the manufacture of a medicament for treating a dermatological condition, ageing or inflammatory conditions.

In a further aspect the present invention also provides a method for manufacturing a medicament comprising a composition according to the present invention including the step of combining a source of flavonoids, a source of carotenoids, and a source of epithelial cells.

Preferably the method of the invention includes a step which sterilizes the medicament.

The step of sterilizing the medicament may involve heating for a time sufficient to effect sterilization.

In the method of the invention the ingredients may be combined with the water and/or oil prior to heating.

In particularly preferred embodiments the method of making the composition according to the invention involves the steps of extracting active ingredients from a source of flavonoids, a source of carotenoids, and a source of epithelial cells and combining same.

In particularly preferred embodiments the use and method of the invention may also involve the steps of adding at least one pharmaceutically acceptable excipient.

The compositions and medicaments of the invention may take the form of a tablet, capsule, indictable solution, implantable slow release matrix or device or any other form known in the art .

The compositions and medicaments according to the invention may also take the form of a powder for direct inhalation, a suppository, or a solution which may be suitable for transdermal application. For example, one medicament according to the invention may simple comprise a solution of the active agents in dimethyl sulphoxide .

The compositions and medicaments according to the invention may be manufactured using any methods known in the art. For example, the compositions may be dry milled and mixed prior to tableting and the composition may therefore necessarily contain other pharmaceutically expectable excipients such as a lubricant selected from the group consisting of calcium stearate, magnesium stearate, zinc stearate, stearic acid, talc and combinations thereof, a binding agent selected from the group consisting of hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose and a polyvinyl pyrrolidone (PVP) . Compositions and medicaments according to the invention may- contain any pharmaceutically acceptable excipients such as binders, fillers, pigments, disintegrating agents, lubricants, wetting agents, buffers and other excipients conventionally used in the pharmaceutical and chemical fields. Some examples of excipients for use in the compositions and medicaments of the present invention are microcrystalline cellulose, lactose, starch, colloidal silica, talc, glycerol esters, sodium stearyl fumarate, and titanium dioxide.

For oral administration compositions or medicaments of the invention may be administered with any inert diluent or with an edible carrier. They may be incorporated directly into food or beverages making up part of the patient ' s diet . The compositions or medicaments of the invention may be formulated with excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspension syrups, wafers, and the like.

The tablets, troches, pills, capsules and the like may contain those excipients already mentioned and in some cases may also contain sweetening agents, such as sucrose, glucose, aspartame or saccharin, flavouring agents such as essential oils of mint, peppermint, spearmint or any other suitable flavouring. When the dosage unit is a capsule it may additionally contain a liquid carrier such as an oil or buffered aqueous solution.

Medicaments and compositions of the invention may also be formulated with phospholipids or fatty acids or other synthetic nanoparticles as carriers . Medicaments and compositions of the invention may take the form of formulations for parenteral administration and may include sterile aqueous solutions or dispersions, and sterile powders for the preparation of sterile, injectable solutions or dispersions. The solutions or dispersions may also contain buffers, diluents, and other suitable additives that may be designed to promote the cellular uptake of the active agents in the composition, for example, liposomes.

Pharmaceutical formulations for topical administration may be especially useful for localized treatment. Formulations for topical treatment included ointments, sprays, gels, suspensions, lotions, creams, and the like. Formulations for topical administration may include known carrier materials such as isopropanol, glycerol, paraffin, stearyl alcohol, polyethylene glycol, and the like.

Medicaments and compositions of the invention may also include a known chemical absorption promoter. Absorption promoters include, for example, trichloroethanol, trifluoroethanol, and certain alcohols and mixtures thereof according to GB 1,001, 949 to Meyer and GB 1,464, 975 to AstraLakemedel) .

Medicaments and compositions of the invention suitable for rectal or vaginal administration may be presented as a suppository, which may include one or more suitable nonirritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, and which is solid at room temperature, but liquid at body temperature and, therefore, will melt in the rectum or vaginal cavity and release the active compound.

Formulations of the present invention which are suitable for vaginal administration also include pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are known in the art to be appropriate .

Disclosed herein are medicaments, compositions and methods for treating dermatological conditions in a human, preferably a human in need of such treatment . As used herein, a human in need of treatment may be a patient diagnosed with a dermatological condition, or a patient wanting to prevent or delay the onset of a dermatological condition, for example, someone with a family history of acne or early ageing. However, the medicament compositions may be simply taken as a prophylactic.

The terms "treating" and "treatment" as used herein refer to reduction in severity and/or frequency of symptoms, elimination of symptoms and/or underlying cause, prevention of the occurrence of symptoms and/or their underlying cause, and improvement or remediaton of damage. Thus, for example, the present method of "treating" a dermatological condition, as the term is used herein, encompasses both prevention of the disorder and treatment of the disorder in a clinically symptomatic individual .

The term "pharmaceutically acceptable carrier" includes a material which is not biologically or otherwise undesirable. Such a material may be administered to an individual along with the selected active agent without causing any undesirable biological effects or interacting in a deleterious manner with any of the other components of the pharmaceutical composition in which it is contained.

Brief Description of the Drawings

The present invention will now be described in detail and with reference to the accompanying drawings in which:

Figure 1 : show a plot of subjective score verses time for treatment of an individual with a preferred composition according to the invention;

Figure 2 : shows a plot of subjective score verses time for a multiple treatment regimen according to a method according to the present invention;

Figure 3 : shows a plot of subjective score verses time for a differing, but preferred, dosage regime according to the present invention;

Figure 4 : shows the results of a comparative study in which subjective score is plotted against time for treatment with active agents isolated from tomato only; and

Figure 5 : shows a plot of subjective score verses time for a for a multiple treatment regimen comprising daily administration according to a method of the present invention.

Certain aspects of the invention will now be exemplified and discussed in detail. The experiments detailed below are given by way of example only and do not limit the scope of the invention as defined in the accompanying claims.

Examples

Preparation Example 1

Bovine intestine (600g) was boiled in distilled water (IL) for 40 minutes. Vegetable oil (200ml) was then added to the mixture and the mixture was heated for a further 20 minutes. Onions (20Og) were finely chopped and added to the mixture, cooking was continued for 15 minutes. Tomatoes (20Og) were added and the mixture was allowed to simmer for a further 30 minutes. The mixture was blended and consumed as a single dose.

The dosage constitutes one preferred embodiment of the composition according to the present invention.

Preparation Example 2

The composition produced according to preparation example 1 was freeze-dried and powdered. The powdered composition was then ground and compressed with pharmaceutically acceptably excipients to give 168 tablets. The preferred dosage for a healthy adult is 5-6 tablets a day depending on weight.

Tablets A

5.7g of the composition of preparation example 1 were mixed with lactose (5.5g), corn starch (3.Og), microcrystalline cellulose (3.5g) and polyvinylpyrrolidone (PVP) (1.5g). The mixture was screened and worked with further corn starch (6.Og) and water to form a granulate which is dried and screened. Sodium-carboxymethyl starch (2.3g) and magnesium stearate (200mg) were added and mixed in and the mixture was compressed to form tablets.

Preparation Example 3

The composition according to claim 1 was spray-dried in a counter current spray-dryer at approximately 72°C and the resultant dry powder was stored under an inert atmosphere to prevent oxidation of fats .

Alternative compositions wherein the compositions intermixed with vitamin E prior to spray-drying are more stable to atmospheric oxidation and therefore do not need to be stored under an inert gas .

Composition make-up

The composition of preparation example 1 was examined to determine the amino acid composition and the amounts of other selected constituents present . Table 1 shows the results for the amino acid determination by HPLC of an acid hydrolysed sample. Table 1: amino acid analysis

AA g/lOOg

Cysteic acid* 0.34

Hydroxypro1ine 1.32

Aspartic acid 1.76

Threonine 0.83

Serine 0.94

Glutamic acid 2.8

Proline 1.66

Glycine 2.48

Alanine 1.48

Valine 0.87

Methionine 0.46

Isoleucine 0.71

Leucine 1.35

Phenylalanine 0.75

Histidine 0.46

Tryptophan 0.18

Lysine 1.2

Arginine 1.66

♦cysteine and cystine measured as cysteic acid after performic acid oxidation. Note: Asn and GIn are completely converted to Asp and GIu during acid hydrolysis of the protein.

Other constituents of the sample are detailed in table 2.

Table 2: other constituents

Constituent mg/lOOg

Calcium 62

Copper <0.09

Iron 1.3

Magnesium 10

Potassium 161

Selenium 0.016

Zinc 2.6 Niacinamide 1.01

Nicotinic acid 0.17

Quercertin 2.2

Kaempferol 0.05

Lycopene 1.9

Efficacy Test 1

A single test subject who normally had facial skin which was dull with a rough uneven surface, visible dry patches, particularly around the cheek and eyelid area and with spots on the forehead region was examined at the beginning of the treatment period. A subjective scale was used for assessing skin condition where 0 = no improvement, 1 = slight improvement, 2 = marked improvement, 3 = almost completely clear, and 4 = completely clear. The subject was examined at time periods after consumption of the medicaments according to the invention and the skin condition was assigned a mark on the subject of scale and the comments of the Examiner were noted. The comments and the subjective score assigned are listed below next to the time in weeks from when the medicament was consumed.

Week 1 (7 days after consuming composition)

No visible improvement to the appearance of skin. For week 1, a subjective score of 0 was assigned.

Week 2 (14 days after consumption) Visible improvement to appearance of skin.

The skin looked and felt more supple & moisturised, and visible dry patches had disappeared. Skin hydration within the stratum corneum increased significantly. As was an increase in skin thickness, increasing the stratum corneum barrier layer components, providing an increased enhanced barrier more resistant to damage.

A marked decrease in fine lines, a significant improvement in skin roughness and improved texture to the surface with less pigmentation.

Spots along the forehead disappeared due to a reduction in sebum excretion and pore size.

The overall effect was a brighter radiant appearance. A subjective score of 3 was assigned.

Week 3 (21 days after consumption)

The appearance of skin remains visibly improved without dry patches, spots or uneven surface rough surface. A subjective score of 4 was assigned.

Week 4 (28 days after consumption)

The skin reverted back to same appearance as at baseline - week 0. A subjective score of 1 was assigned.

Efficacy Example 2

The same composition was used as in efficacy example 1, that is the composition prepared according to composition example 1 was consumed on day 1 and at the beginning of week 3 (21 days after consumption of the first medicament) . Again, a subjective score was assigned and comments from the Examiner were recorded. The results are as follows: Week 1 No visible improvement to the appearance of skin. A subjective score of 0 was assigned.

Week 2 Visible improvement to appearance of skin. The skin looked and felt more supple & moisturised, and visible dry patches had disappeared. Skin hydration within the stratum corneum increased significantly. As was an increase in skin thickness, increasing the stratum corneum barrier layer components, providing an increased enhanced barrier more resistant to damage.

Week 3 As in experiment One at week 3, appearance remained bright and radiant, free from any spots, or uneven rough and dry patches whilst the suppleness and moisterization is maintained. A subjective score of 4 was assigned.

Week 4 Same as week 3.

Week 5 Same as week 4.

Week 6 Same as week 5 but a subjective score of 2 was assigned. Week 7 Same as week 6 but a subjective score of 1 was assigned.

Week 8 The appearance of the skin reverts back to same state as baseline in experiment 1.

Efficacy Example 3

The composition of preparation example 1 was halved and taken by the same subject at day 1 and the following subjective scores and Examiner's comments were noted.

Week 0 Baseline Appearance of facial skin is dull with rough uneven surface, visibly dry patches particularly around the check and eye lid area and spots on the forehead region. Composition administered orally.

Weekl No change in the appearance of skin. A subjective score of 0 was assigned.

Week 2 An improvement in the hydration of skin with the reduced appearance of dry patches .

A slight increase in the thickness of skin, along with slight reduction in the appearance of rough uneven skin. There was a reduction in the appearance of spots but not as significant as in experiment 1. A subjective score of 2 was assigned.

Week 3 Same results as in week 2 above but a subjective score of 1 was assigned.. Week 4 Skin reverted back to the same state as baseline.

Efficacy Example 4

The same subject was administered 2000mg or vitamin C and 10 mg of Lycopene at day 1 in order to provide a comparative study. The following subjective scores and Examiner's comments were recorded.

Week 0 Baseline Skin surface rough and uneven with dry patches and spots . Vitamin C and Lycopene was consumed orally.

Week 1 Appearance of skin unchanged. A subjective score of 0 was assigned.

Week 2 Slight reduction in the size of spots along with a slight decrease in skin roughness & pigmentation. Dry patches still remained without an increase in skin thickness and suppleness. A subjective score of 1 was assigned.

Week 3 Skin reverted to the same state as baseline. A subjective score of 0 was assigned.

Week 4

Same as week 3

Efficacy example 5 Tablets prepared according to preparation example 2 were administered to the patient. The patient consumed 3 tablets in the morning before eating and 3 after the evening meal . Tablets were consumed for the first 28 days of the trial and then placebo tablets were given for the remainder of the 8 week trial. The subjective score assigned by the Examiner is plotted against time in weeks in Figure 5.

Without wishing to be bound by theory, it is believed that the particular ingredients in the composition act in a synergistic way, protecting each other from degradation during preparation of the compositions according to the present invention, thereby allowing certain factors in the epithelial cells to retain their biological functions. Once administered these factors may assist in the development of the dermis so that in a patient where autochthonous levels of these or similar factors may be contributing to dermatological conditions or ageing, relief from symptoms is given.

Claims

CLAIMS :

1. A composition comprising: a) a source of carotenoids; b) a source of flavonoids; and c) a source of epithelial cells.

2. The composition of claim 1 wherein the source of carotenoids is tomato.

3. The composition of claims 1 or 2 wherein the carotenoids comprise lycopene.

4. The composition of any one of claims 1 to 3 wherein the source of flavonoids is onion.

5. The composition of any one of claims 1 to 4 wherein the flavonoids comprise quercetin or kaempferol.

6. The composition of any one of claims 1 to 5 wherein the source of epithelial cells is derived from an animal.

7. The composition of claim 6 wherein the animal is bovine .

8. The composition of any one of claims 1 to 7 wherein the source of epithelial cells is intestine.

9. The composition of any one of claims 1 to 8 wherein the source of carotenoids provides between 0.01 and 100 milligrams per 100 grams of carotenoids.

10. The composition of any one of claims 1 to 9 wherein the source of carotenoids provides between 0.1 and 10 milligrams per 100 grams of carotenoids.

11. The composition of any one of claims 1 to 10 wherein the source of carotinoids provides between 0.5 and 5 milligrams per 100 grams of carotenoids.

12. The composition of any one of claims 1 to 11 wherein the source of flavonoids provides between 0.01 and 100 milligrams per 100 grams of flavonoids.

13. The composition of any one of claims 1 to 12 wherein the source of flavonoids provides between 0.1 and 10 milligrams per 100 grams of flavonoids.

14. The composition of any one of claims 1 to 13 wherein the source of flavoniods provides between 0.5 and 5 milligrams per 100 grams of flavonoids.

15. The composition of any one of claims 1 to 14 wherein the composition is formulated to contain 10 to 1000 grams of the source of epithelial cells or extracts equivalent thereto .

16. The composition of any one of claims 1 to 15 further comprising one or more pharmaceutically acceptable excipients.

17. The composition of any claim 16 wherein the excipient is selected from calcium stearate, magnesium stearate, zinc stearate, stearic acid, talc and combinations thereof, a binding agent selected from the group consisting of hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose and polyvinyl pyrrolidone (PVP) .

18. The composition of any of claims 1 to 17 further comprising a pharmaceutically acceptable carrier.

19. The composition of claim 18 wherein the carrier is selected from isopropanol, glycerol, paraffin, stearyl alcohol, polyethylene glycol.

20. The composition of any of claims 1 to 19 for use in therapy.

21. A method of treating a dermatological condition or ageing in a subject in need thereof comprising the step of: administering to the subject a therapeutically effective dose of the composition of any one of claims 1 to 19.

22. The method of claim 21 wherein the dermatological condition is selected from the group consisting of dry patches, acne and uneven skin.

23. A method of treating an inflammatory condition in a subject comprising the step of: administering to the subject a therapeutically effective dose of the composition of any one of claims 1 to 19.

24. A method of preventing,, reducing or reversing dermatological aging in a subject comprising the step of: administering to the subject dose of the composition of any one of claims 1 to 19. ^'

25. The method of any of claims 21 to 24 wherein the administration step is carried out in response to or in anticipation of hormone level fluctuations.

26. The method of claim 25 wherein the hormone level ^' fluctuation is associated with menstruation, puberty, menopause or thyroid problems .

27. The method of any one of claims 21 to 26 wherein the administration step carried out once every two weeks.

28. The method of any one of claims 21 to 26 wherein the administration step carried out every day.

29. A pharmaceutical composition comprising a composition according to any one of claims 1 to 19.

30. use of a composition according to any one of claims 1 to 19 in the manufacture of a medicament for treating a dermatological condition, ageing or inflammatory conditions.

31. Use according to claim 30 wherein the medicament is for treating ageing, eczema, dermatitis, rosacea, acne, psoriasis, light damage, sunburn, photoageing, sub-optimal wound healing, scarring, alopecia, tendon injury, thermal injury.

32. The use of claim 30 or claim 31 wherein the medicament is formulated for daily administration.