WO2008036054A2

WO2008036054A2 - Anti-hair loss and hair growth enhancer product

Info

Publication number: WO2008036054A2
Application number: PCT/TN2007/000003
Authority: WO
Inventors: Ala Eddine El Amri
Original assignee: Ala Eddine El Amri
Priority date: 2006-09-21
Filing date: 2007-06-28
Publication date: 2008-03-27
Also published as: WO2008036054A3

Abstract

The present invention provides a composition to treat androgenetic alopecia in men and female pattern hair loss in women, thinning disorders, alopecia areata, alopecia totalis and promotes hair growth even in peeled regions. The present invention relates to preparation based on a vegetal extract of coniferous trees mixed with a keratin derivatives compounds, and a process for preparing the same. The preparations of the product object of the invention are in suitable formulation (gel, lotion, cream...) for local use in an effective quantity, directly in the affected body region to be treated.

Description

DESCRIPTION

ANTI-HAIR LOSS AND HAIR GROWTH ENHANCER PRODUCT

Technical Field

The present invention provides a composition to treat androgenetic alopecia in men and female pattern hair loss in women, thinning disorders, alopecia areata, alopecia totalis and promotes hair growth even in peeled regions. The present invention relates to preparation based on a vegetal extract of coniferous trees mixed with keratin derivatives compounds.

Background Art

Hair is composed of the keratin protein; each hair grows from a hair follicle. At the base of the hair follicle is dermal tissue containing a dermal papilla. The dermal papilla contains a network of capillary blood vessels to remove waste and supply oxygen, energy and the amino acids needed for hair growth. The dermal papilla is sensitive to hormones which can affect hair growth.

Hair growth involves three stages: anagen, the period of active growth which lasts for 2 to 4 years; catagen, the period of breakdown and change, and telogen the resting stage before resumption of growth which lasts for 2 to 4 months. On average, daily hair loss is between sixty and one hundred hairs, all of which are normally replaced by new hairs. If the hair loss is over one hundred hairs per day, then the hair loss will exceed replacement, as a result baldness and thinning may occur. Alopecia, colloquially known as baldness, strictly speaking cannot be considered as a disease but rather a biological dysfunction which produces a feeling of discomfort and/or uneasiness in the affected individual, which may even lead to serious psychological disorders. Pattern hair loss (androgenetic alopecia in men and female pattern hair loss in women) is the most common type of hair loss.

Familial tendency to androgenetic alopecia is well recognized as racial variation in the prevalence of balding. 95 percent of all hair loss cases are due to androgenetic alopecia (AGA). In the male AGA, the genetically affected hair follicles are susceptible to a by-product of Di- hydro-testosterone or DHT, this hormone binds to androgenic receptors in the hair follicle and the specific bond triggers cellular processes which force the hair follicle to shed the normal hair and produce thinner, shorter, and colorless hair. The DHT obligates the hair root and follicle to miniaturize, the miniaturization of the hair root and follicle shortens the growth phase and causes the next hair to grow in finer. Sooner or later the miniaturized hair follicles atrophy and die causing permanent hair loss in men.

The present invention relates to a natural hair lotion for use in a pharmaceutical compound, with properties that prevent hair loss and stimulate hair growth. The peculiarity of the hair lotion object of the invention lies in the synergic effect arising from the interaction of its active ingredients, consisting of a mixture of plant extracts and Keratin derivatives compounds to promote hair growth in any part of the body even in peeled regions. This topical solution is a universal hair growth enhancer with potent hypertrichotic effects indicated as treatment against male and female hair loss and alopecia including Alopecia areata and Alopecia totalis (scalp and eyebrow), It works for balding at the top and back of the head as well as for the front area of the scalp.

Its hair growth properties can be rapidly approved, a daily appliance of this solution reduces completely the shedding of hairs in only one week; afterwards it stimulates hair regrowth in both men with androgenetic alopecia and women with female pattern hair loss. The response to this remedy occurs rapidly, within few days of starting treatment, suggesting that it acts, at least in part, by triggering resting follicles into anagen. Consequently, the regrowth of new hair requires around tow weeks, however, the first signs of cosmetic hair growth improvement can already appear after one to tow months of starting treatment depending on the importance of alopecia (for a restrained hair loss problem occurred in less than a year, the hair completely grows back in not as much of tow months of treatment). Gradually, over succeeding cycles, vellus hair converts into longer and thickens terminal hair growing more quickly; these results in reversion of miniaturization occur even if miniaturization is too advanced. New hairs will be slender, uncoloured and delicate; overtime they become thick and turn darker like original hairs. This topical medication has been shown to normalize hair follicle morphology and stimulates the conversion of miniaturized follicles into anagen follicles, thereby producing terminal anagen fibres, but it is still unclear just how this drug works in inducing hair growth. There are many ways in which this preparation may stimulates hair growth; it increases the- growth rate of hair, increases the diameter of the hair fibre, alter the hair cycle, either shortening telogen or prolonging anagen. These effects of the therapy are permanent, after withdrawal treatment, the hair status remain invariable and growing hair doesn't falls out again.

Beside its regrowth action, the product arrest and prevent further progression of hair loss in the treated region, usually all the damaged follicles existing there are stimulated in maximum period of six months. The "Hair growth promoting" effect of this product don't affect hair on other regions of the body, applied to the scalp skin will promotes hair growth only in that region; no sign of abnormal hypertrichosis was observed in any other part of the body skin.

In case of peeled regions, like beard area for example, the growth of new hairs can be detected in only one week after starting use, but new hair requires almost tow months to look like normal hair, as a result we can obtain a beginning of satisfying beard growth after four to six weeks. This special capability to force "vellus hair follicles" to produce terminal hairs into region originally unoccupied makes the distinction between this cocktail and the others hair loss remedies which stimulate only miniaturized follicles previously active. This ability represents a key factor to understand the exact mode of action of the "biologically active molecules"

It is certain that this product remarkably influencing the sebaceous gland by reducing the sebum secretion, as a result, irritation and redness of the scalp disappear few days after starting treatment; these actions persist even after stopping treatment.

This remedy may includes a potential local hormonal effect like a anti-DHT aspect (such as Finasteride or Dutasteride) but this hypothesis seems to be irrelevant because if we admit that this product have an anti-DHT activity by disallowing the 5 a-reductase to convert testosterone into DHT, we will observe a temporary regrowth action which disappear few months after stopping treatment, when the new hair slowly fall out again. However, these results can be seen if this topical preparation destroys definitively androgen receptors in the hair follicles; therefore even if we accept the previous hypothesis, we will never observe stimulation of vellus hair follicles in beard region. In opposite with scalp hair follicle, beard dermal papilla cells are known to secrete growth-inducing autocrine growth factor in response to testosterone, leading to an increase in dermal papilla size and enlargement of the hair follicle and hair cortex, then the damage of androgen receptors will affects negatively the hair growth in beard region. - A -

As the dermal papilla is central in the maintenance and control of hair growth, it is likely to be the target of an unknown pharmacological activity event leading to the proliferation of dermal papilla cell of human hair follicle and reversion of miniaturization. The exact mode of action remains unknown may be it involves further unidentified pathway in other targets.

AGA: Androgenic alopecia; FPHL: Female pattern hair loss; AA: Alopecia areata; AT: Alopecia totalis, (a): Between clinical response and the commencement of therapy, (b): After withdrawal treatment.

The biologically active ingredients of this cocktail are remarkably better to both the potassium channel opener minoxidil and the DHT-inhibitor finasteride; firstly because it hasn't any noticeable side effects, secondly we haven't noticed any reverse hair loss after withdrawal treatment (at least 2 years after discontinuing treatment). Moreover this topical solution is nonirritating, nonsensitizing and devoid of systemic activity. Fuirthermore we noticed maximum activity in summer time which gives evidence that's the "biologically active molecules" activity is enhanced by high temperature (38<Θ<39°C in the treated region). In fact, previous study demonstrated that scalp growth has been shown to peak in spring and summer and reach a nadir in autumn; this may be influenced via the hypothalamus, responding to changes in sun exposure and ambient temperature.

Disclosure of Invention Technical problem

Accordingly, it is an object of the present invention to provide a pharmaceutical product comprising a mixture of active ingredients, including (i) coniferous trees extract, (ii) Keratin Ashes (Keratin combustion derivatives), (iii) coniferous trees resin, in a cosmetically acceptable medium, said active ingredients being present in the hair growth product in respective amounts effective for prevention or treatment of hair loss or promotion of hair growth in a user. However, for perfect results, it is recommended to use Aleppo pine (Pinus halepensis Miller) extract and resin.

Technical solution

Aleppo pine (Pinus halepensis Miller) is a coniferous trees belonging to the Pine family (Pinaceae) native to the Mediterranean region with a small to medium size tree reaching 15-25 tall. The bark is orange-red, thick and deeply fissured at the base of the trunk. Oleo-resins are present in the tissues of all species of Pine; they contain both a resin and essential oil. The Pine bark extract consist of phlobaphenes, strong acids, polar weak acids, fatty acids, neutrals and resin acids. Phlobaphene fraction contains condensed tannin and related polyphenols found in bark. Strong acids consist in part of azelaic, adipic, vanillic acids and other phenolic acids. Polar weak acids include simple phenolics, hydroxy acids and auto-oxidation products. The fatty acids consisted primarily of a homologous series of acids shown in (table 2). The neutrals were further fractionated into unesterified free sterols and esterified sterols, waxes, wax alcohols, esterified fatty acids, esterified strong acids, esterified polar weak acids, and the residual nonsaponifiables.

The accumulation of resin in the heartwood and resin ducts causes a maximum concentration in the base of the older trees. However, resin in the sapwood is less at the base of the tree and increases with height. Natural resins are water-insoluble mixtures of compounds, many of which have a hydroaromatic structure. Mixtures of isomeric carboxylic acids, such as abietic and pimaric acids, which occur in rosin in nature in solvent-free form, in the form of tree sap or wood rosin such as pine oleoresin, where they are dissolved in terpenic hydrocarbons. The resins are soluble in alcohol but are insoluble in water, when heated they soften and finally melt.

The neutral fraction of oleoresin further contains oxygenated compounds (caryophyllene oxide, bornyl acetate, 4-terpineol, myrtenal, trans-pinocarveol, trans-verbenol, 13-epimanoyl oxide, verbenone, myrtenol, longiborneol and methyl dehydroabietate...ect). The resin acids are formed when two and three carbon molecules couple with isoprene building units to form monoterpene, sesquiterpene, and diterpene structures. Resin acids have two functional groups, carboxyl group and double bonds. Nearly all have the same basic skeleton with the empirical formula Ci₉H₂₉COOH.

The most common terpenes in resin are contained in the turpentine fraction, such as δ-3- carene, α-Thujene, α-Pinene, β-pinene, α-terpinene (p-Cymene and limonene), Camphene, Sabinene, Myrcene, caryophyllene, δ-cadinene, longicyclene, longifolene ...

Turpentine also acts as the solvent for transporting the higher molecular weight diterpenoid resin acids (rosin fraction). Upon exposure to the atmosphere, the volatile turpentine evaporates, leaving a semi-crystalline mass of resin acids that oxidatively polymerize to form a translucent, viscous, semisolid substance. Coniferous trees resin acids can be classified into two types: abietanes (abietic, dehydroabietic, neoabietic and palustric acids) and pimaranes (pimaric, levopimaric, isopimaric, and sandaracopimaric acids). The most abundant resin acids are two abietanes, dehydroabietic acid and abietic acid (Fig. 1). In addition the labdane diterpenic acid, anticopalic acid, was shown to be a major resin acid of the bark.

Absent in fresh resin, Retene: methyl isopropyl phenanthrene (CigHig), is a polycyclic aromatic hydrocarbon detected only in aged coniferous trees resin. Retene is derived by degradation of specific diterpenoids biologically produced by conifer trees.

.

' The shorthand designations are analogous to those used by Burchfield and Storrs for fatty acids. Keratins, the main constituent of structures that grow from the skin are a family of fibrous structural proteins; tough and insoluble, they form the hard but non-mineralized structures found in reptiles, birds, amphibians and mammals.

• The α-keratins in the hair (including wool), horns, nails, claws and hooves of mammals.

• The harder β-keratins in the scales and claws of reptiles, their shells (chelonians, such as tortoise, turtle, terrapin), and in the feathers, beaks, and claws of birds.

The properties which make structural proteins like keratins useful depend on their super- molecular aggregation. These depend on the properties of the individual polypeptide strands, which depend in turn on their amino acid composition and sequence. The α-helix and β-sheet motifs, and disulfide bridges, are crucial to the conformations of globular, functional proteins like enzymes, many of which operate semi-independently, but they take on a completely dominant role in the architecture and aggregation of keratins.

Keratin does not dissolve in cold or hot water and does not easy undergo proteolysis. A quarter of the amino acids in keratin are cysteine, whose ability to form strong bridging (disulfide) bonds with other cysteine units accounts for keratin's great stability. The pungent smells of burning hair are due to the sulfur compounds formed, extensive disulfide bonding contributes to the insolubility of keratins, except in dissociating or reducing agents such as urea. Keratins contain a high proportion of the smallest of the 20 amino-acids, glycine, whose "side group" is a single hydrogen atom; also the next smallest, alanine, with a small and uncharged methyl group. The rest of their amino acid composition may include serine, phenylalanine, leucine, glutamine, metionine, lysine and possibly other amino acids.

It is an object of the present invention to provide a use of coniferous trees extract mixed with keratin ashes for the manufacture of therapeutic agent for the prevention of baldness disorder and stimulation of hair growth in men and women.

The term "the extract" disclosed herein includes polar solvent soluble extract, for example, the extract soluble in water, propylene glycol, butylenes glycol, ethyl acetic acid, lower alkyl alcohol such as methanol, ethanol, butanol... ect; and non-polar solvent soluble extract, for example, the extract soluble in diethyl ether, chloroform, hexane... ect. Preferably, the above described extract herein comprises the extract obtained by the step consisting of: extracting coniferous wood with water, lower alcohol such as methanol, ethanol and the mixture thereof, preferably, organic solvent mixture mixed with water and ethanol; filtrating and concentrating the filtrate.

Hereinafter, the present invention is described in detail. An inventive extract of the present invention can be prepared in detail by following procedures.

The inventive extract of coniferous trees bark can be prepared by follows; dried bark of coniferous trunk older than 50 years mixed with 1 to 10 fold, preferably, approximately 1 to 5 fold volume of distilled water; the solution was heated at the temperature ranging from 100 to 150 °C, preferably from 120 to 150 ⁰C, for the period ranging from 3 to 10 hours, preferably 6 to 8 hours; the residue is filtered to obtain the supernatant.

Additionally, lower alcohols soluble extract of the present invention can be prepared by following procedure; dried bark of coniferous trunk older than 50 years mixed with 1 to 10 fold, preferably, approximately 1 to 5 fold volume of lower alcohols such as methanol, ethanol, butanol and the like, or the mixtures thereof, preferably ethanol. The solution was extracted for the period ranging from 5 to 20 hours, preferably 10 to 15 hours with reflux extraction and the residue was filtered with filter paper (Whatman). The filtrate was concentrated with rotary evaporator to obtain ethanol soluble extract of the present invention.

The term "powder" disclosed herein after includes all residues derived from Keratin denaturation using harsh processes, especially thermally destruction process of the keratin which broke the disulphide bonds, and at the same time the native keratin is significantly structurally modified.

According to one embodiment, keratin and/or all containing-keratin animal tissus was heated at the temperature ranging from 500 to 1000 °C, preferably from 500 to 700 ⁰C, for the period ranging from 2 to 5 hours, preferably 2 to 3 hours; the residue was pulverized until getting a soft powder used as solid compound for the product of the present invention.

The product object of the present invention is obtained by mixing the keratin ashes (solid compound) with a suitable quantity of coniferous trees extract. The cosmetic composition of the present invention may combine with other ingredients combined with conventional cosmetic composition, if necessary, together with above described essential ingredients.

Cosmetic formulations containing the above-described composition may be prepared in any form such as skin lotion, cream, essence, shampoo, gel, spray solution and the like.

Brief Description of the drawings

The effect of the product object of the present invention on promoting hair growth in both scalp and peeled region will more clearly understood from the following detailed description taken in conjunction with the accompanying photographs, in which;

Fig.2A. represents the photography of patient n°4 hair status before the treatment with the inventive cocktail.

Fig.2B. represents the photography of patient n°4 hair status after 2 month's treatment with the inventive cocktail.

Fig.3A. represents the photography of randomized peeled area in beard region before the treatment with the inventive cocktail.

Fig.3B. represents the photography of randomized peeled area in beard region after 2 month's treatment with the inventive cocktail.

Best Mode for Carrying Out the Invention

According to one embodiment the coniferous trees extract component is preferably an Aleppo pine (Pinus halepensis Miller) extract. The Aleppo pine extract is preferably taken from Aleppo pine bark. In one form, the Aleppo pine bark extract is preferably approximately a 2:1 ratio wherein 2 kg of dried Aleppo pine bark yields 1 kg of water or alcohol soluble powdered Aleppo pine barks extract.

Hereinafter, the preparation of the present invention will be described in further details with reference to examples. It is to be understood, however, that these examples are intended for illustrative purpose and the scope of the present invention is not limited thereto. Hereinafter, the following formulation methods and excipients are merely exemplary and in no way limit the invention. To prepare 100 ml of the inventive cocktail, we have to provide the following ingredients:

• 200 g dried bark of Aleppo pine trunk older than 50 years (with age, trunk become open and irregular).

• 3Og of pure Keratin.

• 2000 ml of distilled water or 400 ml of 70% ethanol solution.

• 2g Aleppo pine resin.

• 2.5g NaCl.

Solvent preparation

The outer surface layer of the bark smooth and gray preferably removed, we recuperate the interior layers of the bark reddish brown and furrowed with rounded scaly ridges. The extraction methods described herein after are intended for illustrative purpose and the scope of the present invention is not limited thereto.

Example 1: for illustrative purpose, the composition of the invention in liquid form is prepared by dissolving the hydrosoluble vegetal extracted fraction in water.

• The dried pieces of bark are pulverized until getting a soft powder.

• Into a container, 20Og of Aleppo pine wood powder and 2g of Aleppo pine resin are mixed.

• 2 liters of distilled water was added thereto.

• The solution was heated to boiling point during 6 hours.

• The mixture was filtered with filter paper (Whatman No.2) to obtain approximately 100 ml of Aleppo pine extract used as solvent to prepare the hair growth lotion of the present invention.

Example 2: for illustrative purpose, the composition of the invention in liquid form is prepared by dissolving the vegetal extracted fraction in lower alcohol such as ethanol.

• The dried pieces of bark are pulverized until getting a soft powder.

• Into a container 20Og of Aleppo pine wood powder and 2g of Aleppo pine resin are mixed. • 400 ml of 70% ethanol solution was added thereto.

• The solution was extracted for 10 hours with reflux extraction.

• The mixture was filtered with filter paper (Whatman No.2).

• The filtrate was concentrated with rotary evaporator to obtain 100 ml of ethanol soluble Aleppo pine extract used as solvent to prepare the hair growth lotion of the present invention.

Following the same process, Aleppo pine (extract and/or resin) can be substituted by any members of coniferous trees, particularly those of the genus Pinus.

Powder preparation

Keratin -must be denatured using harsh processes. We used a thermally destruction process of the keratin which broke the disulphide bonds, and at the same time the native keratin is significantly structurally modified.

Example 1:

• Put 30Og of keratin in a kiln at the temperature of 600 ⁰C during 2 hours.

• When the keratin turn darker and the sulfurous odor disappear, switch off the kiln.

• Pulverize the keratin ashes until getting a soft powder.

• Keratin remains will be used as solid compound for the lotion.

Following the same process, pure keratin may be replaced by all animal tissues containing keratin such as horn, hoof of mammals; shells, scales of reptiles...ect

Example 2:

Moreover, keratin may be replaced by one of its amino acids constituent: cysteine, to prepare the powder of this cocktail with the following process:

• Put 75g of L-cysteine in a kiln at the temperature of 400 ⁰C during 30 mn.

• When the cysteine turn darker and the sulfurous odor disappear, switch off the kiln.

• Pulverize the cysteine ashes until getting a soft powder.

• Cysteine remains will be used as solid compound for the lotion. Lotion preparation

The composition for topic application of the invention can be in liquid form such as lotions, solutions, and also in solid form, such as gel, creams, pomades, masks... The composition for local application of the invention can conveniently comprise additive commonly used in cosmetic or pharmaceutical preparation for local use, such as preservatives, bacterial agent, stabilizers and other excipients commonly used in cosmetic or pharmaceutical preparation techniques.

Using the following method, 100 ml of the hair growth lotion object of the invention is prepared with the following composition:

keratin Ashes 5g

NaCI ....;.: 2.5g

Aleppo pine extract solvent s.q.f 100 ml

We proceed with the following methods:

Example 1:

• Into graduate container, put down 5g Keratin ashes and 2.5g NaCI.

• Pour 50 ml of Aleppo pine water extract solvent.

• Heat up the solution to boiling point during 10 mn.

• Pour a sufficient quantity of solvent for 100 ml of solution.

• Shake the solution.

• Once ready, the therapeutic agent could be packaged in suitable container such as small bottles or phials.

Example 2:

• Into graduate container, put down 5g Keratin ashes.

• Pour 100 ml of Aleppo pine ethanol extract solvent.

• Mix up the solution.

• Once ready, the therapeutic agent could be packaged in suitable container such as small bottles or phials. Treatment method

The medicine for local use of the invention is used for application, in an effective quantity, directly in the affected body region to be treated. In the treatment of hair loss, for example, a lotion based on the active principals of the invention is applied directly on the scalp, once a day, conveniently for cycles lasting 2-3 months alternating with rest periods of 2 months. The solution should be applied once daily, one hour before bed.

• Wash the hair with warm water and adequate shampoo.

• Rinse, the scalp must be dry before applying to allow high penetration of the substance into the hair follicle.

• Shake the bottle during 1 minute to homogenize the solution

• Take immediately 3 ml; draw it to be applied in the affected regions of the skin by circular movement of a dropper applicator over the scalp for optimal drug delivery to the skin.

• Follow by delicate massage for five minute.

• Cover up your head with a cap during the night, warmth help to expand the hair follicle pore and allow maximum action for the product.

• In the morning, take off the cap and wash the hair and wait until the night to do the next application.

Case studies

Hair growth effect in the scalp region

The aim of this study was to demonstrate hair density and possible changes in hair follicles that may occur during treatment period using image analysis of a target area in the scalp. It was conducted on 5 patients presenting with different pattern hair loss (Table III). Table III. Patients' hair status

Patient n'l Patient n"2 Patient n"3 Patient n"4 Patient n"5

Age/Sex 28/M 29/M 21/M 26/M 20/M

Stage of hair loss Advanced Advanced Mild Advanced Moderate

Baldness type Parietal + Vertex recession Diffuse parietal Vertex Parietal recession Frontoparietal recession Fronto-parietai recession

Family history Positive Positive Positive Negative Negative

Systemic illness No No No No No

Scalp irritation Yes No Yes No No

Race Oriental Oriental Caucasian Caucasian Caucasian

Total and anagen hair count were determined from colour macrophotographs of 1.75 cm² circular area of the frontoparietal scalp from five patients. The target area was firstly clipped, after 3 days a macrophotograph was taken to determine total hair count, terminal hair count (anagen+telogen), and vellus hair count at baseline (initiation of treatment). Tow weeks later, the target area was clipped, a macrophotograph was taken after 3 days for the determination of anagen hair count based on the number of resting hairs that lengthened over the intervening time period. The use of tow macrophotographs of a defined region in the scalp hair taken tow weeks apart allows differentiating hairs in anagen, which lengthen by about 0.35 mm/day, from resting, non growing hairs. During the study period (4 weeks), macrophotographs were taken 3 days after clipping the target area, at baseline and every tow weeks (0, 2, and 4).

Table IV. Patient's hair counts data

Patient n°l Patient n°2 Patient n°3 Patient n°4 Patient n°5

Baseline Week 4 Baseline Week 4 Baseline Week 4 Baseline Week 4 Baseline Week 4

Total hair count 42 77 55 83 106 135 93 100 117 139

Anagen 23 49 27 57 64 105 46 64 91 115

Telogen 19 28 28 26 42 30 47 36 26 24

Ang/Tel ratio 1.21 1.75 0.96 2.19 1.52 3.5 0.97 1.77 3.5 4.7

% Anagen 54.7 63.6 49 68.6 60.3 77.7 49.4 64 77.7 82.7 Table IV shows a mean change in anagen hair coμnt from baseline across the 4 weeks study. There was also a little decrease in the anagen to telogen compared with baseline. Moreover treatment during 4 weeks led to a net improvement in total hair count in target area compared with baseline.

Hair growth effect in peeled region

The quantification of hair growth by digital photo provides reproducible measures on the number of hair follicles in the anagen phase relative to the total hair count, providing dynamic measurements of the hair growth cycle. We used two macrophotographs of a target area of the peeled region: (A) taken at t=0 and (B) taken at t=60 days. Using this technique, terminal hairs, which lengthen by about 0.35 mm/day can be differentiated from non-growing vellus hairs.

Treatment led to a progressive increase of total and terminal hair count over 8 weeks of ^"use! The total hair count increased from 56 at baseline (A; t=0) to 81 at week 8 (B; t=60 days). The percentage of terminal hairs increased from 60.7% at baseline to 65.4% at week 8, the increase in terminal hair count from 34 at baseline to 53 at week 8, together with the increase in the terminal/vellus hair ratio from 1.54 to 1.89, is direct evidence that treatment promotes the conversion of vellus hair follicles into the anagen phase.

Table V. Baseline characteristics of randomized area

The vellus hair count would be expected eventually to decrease with treatment, due to continued conversion of hair follicles into the anagen phase. But in this study, the vellus hair count increased from 22 at baseline to 28 at week 8, this observable fact possibly due to the conversion of quiescent hair follicles (never be active) to vellus and after that to terminal phase. These positive changes in the hair cycle, associated with the progressive improvement in facial coverage observed in treated area, imply favourable consequences on clinically important aspects of hair quality (thickness, length, growth rate, growth duration and/or pigmentation). In conclusion, the results of this study confirm that in case of several patterns hair loss, this remedy, once used correctly; favourably affect the hair growth cycle by promoting hair follicles into the anagen phase even in case of severe hair loss.

Having now described the invention as above, it will be understood by those skilled in the art that the invention can be performed within a variety of conditions, formulations and other parameters as may be required on case to case basis without affecting the scope of the invention or any embodiment thereof which is claimed thereafter.

Industrial applicability

As described in the present invention, a product consisting of mixture of active ingredients, including coniferous trees extract Keratin ashes. Showed potent promoting effect on hair growth through carried out clinical experiment conducted on five persons. Accordingly, the inventive mixture can be used as pharmaceutical composition and cosmetic composition for the treatment and prevention of baldness disorder.

Claims

[I]. A hair growth enhancer product comprising a mixture of active ingredients, including (i) coniferous trees extract, (ii) Keratin Ashes (Keratin combustion derivatives), in a cosmetically acceptable medium, to treat androgenetic alopecia in men and female pattern hair loss in women, thinning disorders, alopecia areata, alopecia totalis and promote hair growth even in peeled regions.

[2]. The composition of claim 1 wherein the keratin ashes might be obtained from pure keratin and all keratin-containing animals tissues, such as horns and hooves of mammals; scales and shells of reptiles; feathers, beaks, claws of birds.

[3]. The composition of claim 1 wherein the keratin ashes comprises at least one active principle selected from keratin derivatives. Keratin derivatives may be derived in particular from oxidation, reduction and/or polymerisation of its amino acids and combination thereof.

[4]. The composition of claim 1 further comprising cysteine, alanine, glycine, serine, phenylalanine, leucine, glutamine, metionine, lysine, other amino acids, possibly amino acids derivatives and mixtures thereof.

[5J. The composition of claim 1 wherein the keratin might be substituted with cysteine- containing peptide, cysteine and/or cysteine derivatives. Cysteine derivatives may be derived in particular from oxidation, reduction and/or polymerisation of the L-cysteine.

[6]. The composition of claim 1 wherein the coniferous trees extract is preferably extracted from Pinus genus, more preferably from Aleppo pine tree (Pinus halepensis Miller).

[7]. The composition of claim 1 wherein the coniferous trees extract comprises at least one active principle selected from coniferous trees bark extract, coniferous trees resin derivatives, hydrocarbon-based resins and mixtures thereof.

[8]. The composition of claims 1, 6 and 7 further including but not limited, the following molecules and theirs derivatives and isomeric forms, derivatives may be derived in particular from the polymerisation, hydrogenation, esterification and combination thereof.

- Trace of turpentine fraction, containing monoterpene and sesquiterpene such as δ-3- carene, α-Thujene, α-Pinene, β-pinene, δ-cadinene, Camphene, caryophyllene, α- terpinene (p-Cymene and limonene), Sabinene, Myrcene, longicyclene, longifolene ...

- Rosin fraction, containing diterpenoid resin acids such as abietanes (abietic, dehydroabietic, neoabietic and palustric acids) and pimaranes (pimaric, levopimaric, isopimaric, and sandaracopimaric acids).

- Labdane diterpenic acid and anticopalic acid.

- Retene: methyl isopropyl phenanthrene (CigHis).

- Phlobaphene fraction contains condensed tannin and related polyphenols found in bark.

- Strong acids consist in part of azelaic, adipic, vanillic acids and other phenolic acids.

- Fatty acids comprise branched fatty acids, conjugated fatty acids and/or cyclic fatty acids containing from 12 to 26 carbon atoms.

- A neutral fraction comprising unesterified free sterols, esterified sterols, waxes, wax alcohols, esterified fatty acids, esterified strong acids, esterified polar weak acids, and the residual nonsaponifiables.

[9]. The composition of claim 1 wherein the product object of the present invention may comprises at least one active principle selected from coniferous trees bark extract, coniferous trees resin, keratin ashes and/or combination thereof.

[10]. The composition of claim 1 may further comprises an auxiliary ingredient or ingredients selected from the group consisting of vitamins, colorants and fragrances.