From patent application WO 2008/1 13912 it is known that, compositions containing as active ingredient an extract of Allium species, an extract of Citrus species and

- either an extract of Paullinia species and an extract of Theobroma species

- or an extract of Salix species and zinc sulphate increase the hair growth in hair loss patients.

The common form of hair loss in both men and women, also known as Androgenetic alopecia and Female Pattern Hair Loss, is mainly due to the predominance binding of the male sex hormone testosterone and 5alpha-dihydrotestosterone / DHT (which are also present in women in trace amounts) to the androgen receptor of the matrix cells in the dermal papilla. This leads to decreased duration of the anagen hair as well as inhibition of hair follicle activities along with an early induction of the catagen and prolongation of telogen phase.

Under its physiological circumstances (absence of inflammation), the hair follicle is surrounded by healthy connective tissue and dermal papilla. However, an increase of DHT hormone will cause premature apoptosis of cells in both dermal papilla and extra matrix connective tissue. Abnormal cell apoptosis results in involution of the hair follicle, hair miniaturization, loss of the connective tissue integrity, lack of collagen and continued hair shedding. This process is accompanied and enhanced by the inflammatory conditions in the scalp that will cause further hair loss.

While testosterone/DHT is at the core of the balding process, an increased sensitivity to testosterone is also the maj or cause for Acne, a disease of the hair follicles of the face, chest, back, shoulders and upper arms, which affects both males and females especially during puberty. Such an oversensitivity to testosterone causes the sebaceous glands in the pilosebaceous unit (consisting of a hair follicle, sebaceous gland, and a hair) to secrete sebum excessively and brings sebaceous glands and hair follicles into chronic inflammatory disease conditions. Meanwhile, skin cells divide so rapidly as to block the opening of hair follicles in the skin. Behind this blockage, sebum builds up and forms blackheads and whiteheads. Due to the pH changes that provide the bacteria (Propionibacteria acnes) with favorable micro- environment, the bacteria overgrow rapidly and become trapped in the hair follicles, producing a deeper infection in the form of pustules and nodules. Propionibacteria acnes in blocked pores will further trigger inflammatory response by the immune system in order to defend the body against infection. The sustained inflammation will result pain, heat, swelling and redness, destroying healthy tissue and cause more damage and leave scattered lesions / acne scars. Acne affects people of all races and skin types and occurs mostly in teenagers but also in adults in their twenties through to their forties. In addition to the above-mentioned explanation, other reasons that may cause acne include genetic factors, stress, hormonal changes and the use of some medications (hormones, anabolic steroids, corticosteroids, anti- epileptic drugs, anti-tuberculosis drugs, lithium, cyclosporin and halogenated drugs).

There are several different types of acne, which can be categorized into six different forms: Acne Vulgaris, Acne conglobata, Acne fulminans, Gram-negative folliculitis, Acne Rosacea and Pyoderma faciale.

Acne Vulgaris: it is the most common form of acne, starting from puberty to twenties, thirties or beyond. Although that may emerge all over the body, most commonly it appears on the face, neck, chest, and back, forming different types of lesions such as Papules (red, inflamed bumps called papules), Whiteheads (resulting from a pore that is blocked

completely), Blackheads (due to partially blocked pore), Pustules (appeared as an inflamed red circle with a white or yellow center) and Nodules (hard and large bumps under the skin that may last for months).

Acne Conglobata: a very severe form of acne vulgaris commonly occurring in males between 18 and 30 years old. It may be found on the face, back, chest, back, upper arms, and thighs, presenting blackheads and interconnected large lesions which can cause permanent damage to the skin.

Acne Fulminans: in fact, it is an abrupt emergence of acne conglobata, which often becomes ulcerated and severely scarred. In some people, acne fulminans may cause aching joints and a fever.

Gram-Negative Folliculitis: characterized by cysts and pustules due to bacterial infection. Little knowledge is available concerning this condition.

Acne Rosacea: similar in appearance to vulgaris, but found as a red rash (coming with or without pimples, bumps and blemishes) restricted to the nose, cheeks, chin, and forehead.

Pyoderma Faciale: a severe acne form (nodules) only found on the face of females. It may be painful, uncomfortable and severely scarring if untreated.

Because 95% of acne patients will develop scarring to some degree, the earlier an appropriate treatment is initiated, the better the scar formation will be mild. Delaying or improper treatment of acne may raise one's risk to have more significant acne and permanent scarring or disfiguring. However, the currently available products for acne are ineffective in terms of treatment. Although not considered to be an extremely serious medical condition, the psychological implications may be much more serious than the physical manifestations (undermined self-esteem, reduced self-confidence and increased anxiety). Additional social difficulties include isolation, depression and diminished potential to gain employment.

The root cause and issues of acne are related to hormones, inflammatory conditions, infection, hyper-pigmentation and collagen modelling (acne scars). The efficacious product for acne management should address such causes and issues. This would mean that the actions of an ideal treatment (like this invention) should have the following characteristics: reducing androgen-effect, dampening inflammation, disabling bacterial infection, remodelling collagen and reducing skin hyper pigmentation / acne scars.

Inflammation can be induced by apoptotic cells that release inflammatory cytokines such as Fas ligand (Brown SB et al. J Immunol, 1999 162:2110-9; Stuart LM et al. J Immunol 2003 171 :2610-5). Hence, by normalizing the intracellular level of anti-apoptotic protein Bcl-2, the abnormal cell apoptosis process can be inhibited and consequently the inflammation be attenuated. On the other hand, JL Niu et al. previously showed that Bcl-2 expression attenuated inflammation in the context of monocyte chemoattractant protein- 1(MCP-1)- induced cardiomyopathy (Cardiovascular Research 71 , 2006 1 9 - 148).

It has also been shown that Langerhans cells emigrate in response to inflammatory stimuli (Silberberg-Sinakin et al, 1976; Patrizia Stoitzner et al, 2002). The migratory phenomenon and increased number of Langerhans cells after application of the anti-apoptotic and anti-inflammatory product were also observed in our own study (see "Observation 2").

Epidermal Langerhans cells are distinct tissue dendritic cells (antigen-presenting immune cells) located in the skin epidermis and mucosa. They are thought to play a key role to initiate adaptive immune responses. Daniel H. Kaplan et al. (Immunity, Dec. 2005 Vol. 23, 611-620,) further revealed an unappreciated function of Langerhans cells to dampen the skin's reaction to inflammation and infection. Thus, Langerhans cells may play an important role in preventing excessive immune and inflammatory responses in the skin.

This explicitly suggests that a local increase of Langerhans cells may improve inflammatory skin conditions and autoimmune diseases such as lupus (especially skin lupus), psoriasis, skin transplantation, keratosis, contact hypersensitivity (CHS), sunburn, dandruff, scar treatment and wound healing, as well as dermatitis or eczema, of which at least seven types have been identified: Contact eczema, Allergic contact eczema, Seborrheic eczema, Nummular eczema, Neurodermatitis, Stasis dermatitis and Dyshidrotic eczema.

Take the example of psoriasis, which is a common autoimmune inflammatory skin disorder affecting about 2% of the population. It occurs when the immune system mistakes the skin cells as a pathogen, sends out wrong signals so that the psoriasis plaques exhibits abnormal proliferation and differentiation of epidermal keratinocytes. Such skin inflammation process leads to five types of psoriasis: plaque, guttate, inverse, pustular and erythrodermic psoriasis. The most common is chronic plaque psoriasis, consisting of red, heavily scaled, well-demarcated plaques on elbows, knees, scalp, lower back and any other skin surface.

As mentioned above, the migration ability of Langerhans cells from epidermis to regional lymph nodes is essential to regulate skin immune and inflammatory responses. This process is orchestrated by cutaneous cytokines and chemokines. Previoius analyses of psoriasis plaques showed a predominance and an increased activity of TNF-a, as well as Thl cytokines, (such as IL-2 and IFN-γ). Following the clinical discovery that the Langerhans cells are functionally impaired in psoriasis patients, Marie Cumberbatch et al. (JEM Vol. 203, No. 4, April 2006 953-960) have further confirmed that psoriasis is associated with a considerable impairment of epidermal Langerhans cells' mobilization capacity.

Although it is not considered as fatal disease, psoriasis causes important morbidity and impact most negatively on patients' quality of life. Currently, there is no satisfactory cure for psoriasis. To successfully manage issues caused by psoriasis, an ideal agent (like this invention) should have the properties to normalize the immune capacity by further mobilizing epidermis Langerhans cells in the aim to attenuate the irregular inflammatory process in psoriasis.

Psoriasis, together with Seborrhoeic eczema, Cradle Cap (a form of seborrhoeic eczema mainly found in newborn babies), as well as dandruff can cause scaly scalp, which is a common problem and very often causes discomfort, scaling and itching. Moreover, when it comes with hair loss, embarrassing bald patches will tend to appear. Such a scalp problem can be found in people of any age group.

Both acne and psoriasis may leave disfiguring scars or lesions. Wound healing is a complex and dynamic process of restoring cellular structures and tissue layers, which can be divided into 3 distinct phases: the inflammatory phase, the proliferative phase and the remodeling phase. Coordinated series of biological / biochemical processes for repairing the damaged tissues include chemotaxis, apoptosis, phagocytosis, angiogenesis (producing new capillaries), production of new glycosaminoglycans, proteoglycans, neocollagenesis, collagen degradation and collagen remodeling.

Although apoptosis has been previously described in many physiological processes as exampled above in case of hair loss, recent research work has shown that apoptosis / anti- apoptosis mechanism is also actively involved in skin wound healing or scar formation. A better understanding of the regulation of apoptosis (e.g. for removal of inflammatory cells or fibroblasts during dermal reconstruction / skin graft) and anti-apoptosis (e.g. for promotion of fibroblasts, epithelial cells growth in the proliferative phase) may be extremely helpful in identifying novel faster-healing agents for wounds in order to minimize as much as possible the formation of irregular healing phenomena such as hypertrophic scar and keloid.

The research work performed in the animal model has shown that normal wound healing is an orderly process where the levels of pro-apoptotic (e.g. p53) and anti-apoptotic (e.g. Bcl-2) proteins vary during inflammatory phase of tissue repair. Upon injury, Bcl-2 expression increases (in order to allow cellular proliferation) while that of p53 decreases. As the inflammation process declines, p53 levels augment while Bcl-2 levels drop off (an inverse relationship between Bcl-2 and p53, Kane et al. Wound Rep Reg 2000; 8:45-58). This study in mice revealed the necessary balance between the anti-apoptotic protein Bcl-2 and the pro- apoptotic protein p53 during the inflammatory phase of wound healing. Besides, collagen remodeling and new capillaries production (Angiogenesis) are also crucial steps to guarantee normal wound repair. The newly generated capillaries (via Angiogenesis) are needed to assure the skin tissues to obtain enough blood and nutrition, while collagen is needed to restore anatomic structure and function. When too much collagen is deposited in the wound site, fibrosis will occur due to loss of normal anatomical structure and function.

The healing process can go wrong and bring about either insufficient healing (e.g. atrophic scar formation) or an exuberance of fibroblastic proliferation (e.g. hypertrophic scar). Further exuberance can result in keloid formation, where the body continues to produce tough, fibrous collagen after a wound has healed. Persistent inflammation, disorders in proliferation (or apoptosis), Angiogenesis and collagen modeling may end in non-healing wounds or pathologic responses leading to fibrosis or chronic ulcers. Hence, limiting irregular inflammation and keeping ordered processes of cell proliferation, Angiogenesis and collagen deposition / remodeling will be paramount to an effective wound healing such as in epidermis regeneration, scar reduction and skin implants.

In conclusion, a natural product (like this invention) for scar or wound management should be able to help the human body regulate healing processes in order to avoid

abnormalities in inflammation, proliferation, angiogenesis and collagen remodeling, even to reverse these existing irregularities in wound healing.

The skin consists of the epidermis (superficial layer, an outermost layer of the skin) and the dermis (a deeper vascular connective tissue). The epidermis is mainly made up of keratinocytes and stratified with squamous epithelium. Older cells migrate up to the surface of the skin, wear off daily and constantly replaced by newly produced cells. The dermis consists of dense connective tissue with blood vessels, lymphatic glands, nerve receptors and hair follicles. Elastic fibers in the dermis give the skin its elasticity nature. These elastic fibers degenerate because of the age-related process (aging) and inflammation. Furthermore, the boundary between dermis and epidermis becomes undulating and dermal papilla projecting into the epidermis, which consequently make the skin wrinkled.

Blood vessels in the dermal papillae nourish all hair follicles and bring nutrients and oxygen to the lower layers of epidermal cells. Dermal papilla plays pivotal roles not only in hair formation, growth and cycling, but also in strengthening the dermal and epidermal layers by forming ridges in-between. Meanwhile, it supports the epidermis and facilitates the exchange of oxygen, nutrients, and waste products between these two layers. With age, because of cell apoptosis (either naturally programmed or premature), the papillae tend to flatten. This is another factor that contributes to the wrinkled skin.

Therefore, intervention by natural anti-apoptotic agent (like this invention) may reduce fine wrinkles in the skin. Such an agent will decelerate or prevent the skin cells, especially those in the dermal papillae, from premature cell apoptosis due to insults from surrounding environment.

Collagen disorder can also cause harms to the skin, Stretch marks (also called Striae Distensae) are common skin lesions. There exist two types: red and white stretch marks. They appear in a range of pigmentations being red, pink, purple, brown, reddish or dark brown. Up to 90% of pregnant women, 70% of pubescent girls and 40% of pubescent boys develop stretch marks. For this reason, they are believed to be hormone-related, such as during pregnancy, puberty, and advancing obesity, where the glucocorticoid levels get much higher. It could also be related to rapid weight gain and use of certain medications (e.g. adrenal hormones), exampled by the cases in serious weight-lifters and the majority of obese sufferers.

Under normal conditions, the collagen and elastin fibers deeply interlock in the skin structure so as to keep the skin tight. However, when collagen and elastin lose integrity, they can no longer accommodate stretching. Then, the colorful furrows and slits will form and stand out against normal skin. Bleeding can cause the dark pigmentation of new stretch marks that are not easily fading with time due to collagen breakdown or scarring.

It has been discovered that the administration by topical route of a composition containing as active ingredient an extract of Allium species, an extract of Citrus species, an extract of Paullinia species and an extract of Theobroma species has a novel and previously unknown effect in the treatment of inflammatory skin conditions, scaly scalp conditions and collagen remodeling.

Thus the present invention concerns a new use of compositions for the treatment of inflammatory skin conditions, scaly scalp conditions and collagen remodeling, and more particularly of all skin disorders related to inflammation, apoptosis, angiogenesis and collagen / collagen remodeling, fine lines & wrinkles, chronic wounds, acute wounds, incisional wounds, burn wounds, hypertrophic scars, keloid, skin implant, skin graft scars, acne, acne scars, psoriasis, rashes, cracked and dry skin, seborrheic and actinic keratosis, lupus, especially skin lupus / acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, chronic cutaneous lupus erythematosus) and all types of dermatitis or eczema, contact hypersensitivity (CHS), hyper-pigmentation / melasma, skin ulcers, post-surgical scars, dandruff, acne, wound healing, rosacea, management of sun burn, psoriasis, seborrheic dermatitis, atopic dermatitis and all types of eczema, scaly hair and scaly skin that can also be found in Ichthyosis, Ichthyosis Vulgaris and Acquired Ichthyosis, skin allergies, shrinking old scars, sagging skin, skin aging, age spots, depigmentation of the skin, spider veins, freckles and brown spots and cellulite / Orange peel, said new use, comprising the administration by topical route of said compositions containing as active ingredient an extract of Allium species, an extract of Citrus species, an extract of Paullinia species and an extract of Theobroma species .

A first study was performed in mice and two studies were performed in humans. In addition to morphological and clinical observations on the hair and scalp, tissue and scalp biopsies were also taken for histological and biochemical evaluation of various parameters. The results of the studies confirmed that the administration of a composition according to the invention had significant beneficial effects on hair growth, hair cycle, inflammatory skin conditions, scaly scalp conditions and collagen remodeling. The biochemical observations however have suggested other substantial features that may point towards additional uses of the natural mixture.

The studies were conducted to evaluate the efficacy of a topical active ingredient containing an extract of Allium species and an extract of Citrus species to accelerate the rate of hair re-growth.

Among the new uses of compositions for the treatment of inflammatory skin conditions, scaly scalp conditions and collagen remodeling, according to the invention, those which are of more particular interest are the uses in which the preferred topical composition contains an aqueous-alcoholic extract of Allium species, an aqueous-alcoholic extract of Citrus species, an aqueous alcoholic extract (atomised or not) of Paullinia species and an aqueous-alcoholic extract (atomised or not) of Theobroma species.

Among the new uses for the treatment of inflammatory skin conditions, scaly scalp conditions and collagen remodeling according to the invention, those which are of more preferred interest are the uses in which the compositions are containing from 65% to 93% of an aqueous-alcoholic extract of Allium species, from 5% to 33% of an aqueous-alcoholic extract of Citrus species, from 0.25% to 2.5% of an aqueous-alcoholic extract (atomised or not) of Paullinia species and from 0.25% to 2.5% of an aqueous-alcoholic extract (atomised or not) of Theobroma species and especially those containing from 65% to 93% of an aqueous-alcoholic extract of Allium cepa, from 5% to 33% of an aqueous-alcoholic extract of Citrus lemon, from 0.25% to 2.5% of an aqueous-alcoholic extract (atomised or not) of Paullinia species and from 0.25% to 2.5% of an aqueous-alcoholic extract (atomised or not) of Theobroma species. The term extract of Allium species or aqueous-alcoholic extract of Allium species refers particularly to aqueous-alcoholic extracts and native extracts obtained from all species of the genus Allium (family Liliaceae) and especially Allium cepa.

The term extract of Citrus species or aqueous-alcoholic extract of Citrus species refers particularly to aqueous-alcoholic extracts and native extracts obtained from all species of the genus Citrus (family Rutaceae) and especially Citrus lemon.

The term extract (atomised or not) of Paullinia species or aqueous-alcoholic extract (atomised or not) of Paullinia species refers particularly to aqueous-alcoholic extracts and native extracts obtained from all species of the genus Paullinia (family Sapindaceae) and especially Paullinia cupana.

The term extract (atomised or not) of Theobroma species or aqueous-alcoholic extract

(atomised or not) of Theobroma species refers particularly to aqueous-alcoholic extracts and native extracts obtained from all species of the genus Theobroma (family Malvaceae) and especially Theobroma cacao. The most preferred compositions used according to the invention are those containing approximately 87% of an aqueous-alcoholic extract of Allium cepa, approximately 12% of an aqueous-alcoholic extract of Citrus lemon, approximately 0.5% of an aqueous-alcoholic extract (atomised or not) of Paullinia cupana and approximately 0.5% of an aqueous- alcoholic extract (atomised or not) of Theobroma cacao. The invention concerns also a method for the treatment of inflammatory skin conditions, scaly scalp conditions and collagen remodeling, and more particularly of all skin disorders related to inflammation, apoptosis, angiogenesis and collagen / collagen remodeling, fine lines & wrinkles, chronic wounds, acute wounds, incisional wounds, burn wounds, hypertrophic scars, keloid, skin implant, skin graft scars, acne, acne scars, psoriasis, rashes, cracked and dry skin, seborrheic and actinic keratosis, lupus, especially skin lupus / acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, chronic cutaneous lupus erythematosus) and all types of dermatitis or eczema, contact hypersensitivity (CHS), hyper-pigmentation / melasma, skin ulcers, post-surgical scars, dandruff, acne, wound healing, rosacea, management of sun burn, psoriasis, seborrheic dermatitis, atopic dermatitis and all types of eczema, scaly hair and scaly skin that can also be found in Ichthyosis, Ichthyosis Vulgaris and Acquired Ichthyosis, skin allergies, shrinking old scars, sagging skin, skin aging, age spots, depigmentation of the skin, spider veins, freckles and brown spots and cellulite / Orange peel, said method for treatment, said method for treatment, comprising the administration by topical route of said compositions containing as active ingredient an extract of Allium species, an extract of Citrus species, an extract of Paullinia species and an extract of Theobroma species.

These compositions are prepared as indicated in patent application

WO 2008/113912 .

These pharmaceutical compositions and /or the cosmetic compositions are prepared by conventional methods, in which pharmaceutically inert, organic or inorganic excipients are added to the compositions obtained according to the invention.

According to the invention the composition is administered daily during a period of several months with a composition containing as active ingredient an extract of Allium species, an extract of Citrus species, an extract of Paullinia species and an extract of Theobroma species.

In order to obtain an impressive effect on the hair growth and in the treatment of inflammatory skin conditions, scaly scalp conditions and collagen remodeling; it is necessary to perform the administration of the compositions during at least 1 to 3 months.

When using the compositions obtained according to the invention, doses may vary within relatively wide limits and must be set according to the person being treated and the condition concerned. Pharmaceutical compositions and /or cosmetic compositions normally contain from 0.2 to 500 mg, preferably from 1 to 200 mg, of active ingredients as defined above, in the form of dry extract.

Examples of Compositions As a drug

Hair Lotion

Active ingredient: Composition A 40 g per 100 ml

Excipients: aqueous ethanol at 55 °

Treatment : Application 1-2 times daily friction

As a cosmetics

1°) Hair Lotion

Active ingredient: Composition A 21 g per 100 ml

Ingredients: aqua, alcohol, betaine, glycerin, polysorbate 20, maltodextrin, silica. Treatment : Application 1 to 2 times daily friction.

2°) Hair Gel

Active ingredient: Composition A 21%

Excipients: 96% ethanol (10%>), betaine 2%, 5% glycerin, polyquaternium-37 (1%>), demineralized water qs 100%).

Treatment : Application 1 to 2 times daily massage.

3°) Shampoo

Active ingredient: Composition A 10 %>

Excipients: sodium dodecyl sulfate at 25% (10%), sodium chloride, 3% citric acid 0.1%, 0.5% imidazolydinyl urea, demineralized water qs 100%

Treatment : 1 shampoo every day.

4°) After Shampoo

Active ingredient: Composition A 20 %

Excipients: cetearyl alcohol (2,5%), cetearyl glucoside (2,5%), quaternium-82 (2%), 3% dimethicone, imidazolydinyl urea 0.5%, demineralized water qs 100%).

Treatment : 1 shampoo every day.

5°) Skin Gel

Active ingredient: Composition A 21%

Excipients: 96% ethanol (10%), betaine 2%, 5% glycerin, polyquaternium-37 (1,5%), demineralized water qs 100%.

Treatment : Application 1 to 2 times daily massage.

6°) Cream

Active ingredient: Composition A 21%

Excipients: 96% ethanol (10%), glyceryl stearate 2%, 5% glycerin, Carbomer (1,5%), demineralized water qs 100%.

Treatment : Application 1 to 2 times daily massage.

EXAMPLE OF TREATMENT

During a period of 4 months, the patients have received, every day on the skull a lotion containing :

- an aqueous-alcoholic extract of Allium cepa: 87.04 %

- an aqueous-alcoholic extract of Citrus lemon: 11.96 %

- an atomised aqueous-alcoholic extract of Paullinia cupana: 0.50 %

- an atomised aqueous-alcoholic extract of Theobroma cacao: 0.50 %

(hereafter composition A).

This lotion has been prepared as indicated in example 1 of patent application WO 2008/113912.

Composition A which is a mixture of four natural ingredients has been reported to beneficially affect the Anagen/Telogen ratio in men with androgenetic alopecia and women suffering from Female Pattern Hair Loss. In addition, people using the product occasionally accelerated re-growth of hair.

This has suggested that composition A is capable of affecting positively the hair cycle after the shedding (telogen) process, in order to provoke a quicker restart next hair growth (anagen) phase, as such shortening the resting phase. In the studies, the effects of composition A on hair-growth were evaluated. One study was performed in mice (applying non-formulated composition A) and two studies were performed in human. In addition to morphological and clinical observations on the hair, tissue and hair samples were also taken for histological and biochemical evaluation of various parameters such as:

In human epidermis

Langerhans CD1A+ cells

Ki-67+ cells

BCL2+ cells

In human dermis

HSP47+

Collagen synthesis

In murine mice (applying non-formulated composition A)

Collagen production in the dermis

The results of the studies confirmed that composition A had significant beneficial effects on hair growth and hair cycle. The biochemical observations however have suggested other substantial features that point towards additional uses of the natural mixture Observation 1: Collagen remodeling

In this study, 21 day mouse study with non-formulated composition A, the histological examination of skin samples from 15 male murine DAL/C mice and 15 paired controls showed that there was highly significant increase in deposition of collagen after 21 days treatment as compared to the controls. A subsequence Collagen synthesis human study of 13 male patients suffering from AGA was conducted not only to evaluate the effect of composition A on hair cycle but also to find confirmation of the collagen observation in mice (applying non- formulated composition A). The study participants received composition A twice a day for four months. Scalp biopsies were taken at start and at Day 120. Histological sections at day 0 showed small and thin collagen fibers with disorganized appearance. Histological sections of the scalp biopsies at day 120 showed a higher density of collagen fibers which were also better organized and thicker in appearance.

Observation 2: Reduced inflammation

In this study, 20 patients suffering from AGA were treated with composition A twice daily for 12 weeks. Scalp biopsies were taken at start and after 12 weeks of application. The histological results of the biopsies showed that after treatment, there was a 74% increase of Langerhans CD1A+ cells in the epidermis, a 42% increase in Ki-67+ cells in the epidermis, and 89%) increase of BCL2+ cells in the epidermis. These observations support a statistically significant effect on inflammatory parameters.

Conclusion

The animal data obtained in mice (applying non-formulated composition A), corroborated by the human data observed on scalp biopsies, confirm a profound effect of composition A on the formation of collagen in the dermis. The outcome of the histological examinations of the human biopsies indicates a potent effect of Composition A on a number of histological markers associated with inflammation, apoptosis and angiogenesis. The marked changes of those parameters support the beneficial activities in anti-inflammation, regulation of apoptosis, angiogenesis and collagen remodeling. It is known that often AGA is associated with increased inflammatory reactions around the hair follicle, accelerating as such the exogen of the hair. Hence observations on studies from both animal (with non-formulated composition A) and human biopsies add support at molecular and cellular levels to the clinical observations made with Composition A in various hair growth studies. In addition, they indicate that Composition A will beneficially affect a variety of inflammatory conditions in scalp and skin, as there are: dandruff, acne, wound healing, rosacea, management of sun burn, psoriasis, seborrheic dermatitis, atopic dermatitis and all types of eczema.

Furthermore, it is postulated that chronic application of composition A will result in beneficial effects in a variety of skin disorders related to inflammation, apoptosis,

angiogenesis and collagen / collagen remodeling. The examples are: fine lines & wrinkles, , chronic wounds, acute wounds, incisional wounds, burn wounds, hypertrophic scars, keloid, skin implant, skin graft scars, acne, acne scars, psoriasis, rashes, cracked and dry skin, seborrheic and actinic keratosis, lupus (especially skin lupus / acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, Chronic cutaneous lupus

erythematosus) and all types of dermatitis or eczema, Contact hypersensitivity (CHS), Hyper- pigmentation / Melasma, skin ulcers, post-surgical scars, scaly hair and scaly skin that can also be found in Ichthyosis.

It will also work on both Ichthyosis Vulgaris and Acquired Ichthyosis, skin allergies, shrinking old scars, sagging skin, skin aging, age spots, depigmentation of the skin, spider veins, freckles and brown spots and cellulite / Orange peel. In addition, enhanced deposition and remodeling of collagen will also have beneficial effect of pore size, meaning that composition A can be used to minimize the pore size.