WO2024042274A1 - Composition promoting keratinocyte growth and angiogenesis, and therapeutic and cosmetic applications thereof - Google Patents
Composition promoting keratinocyte growth and angiogenesis, and therapeutic and cosmetic applications thereof Download PDFInfo
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- WO2024042274A1 WO2024042274A1 PCT/FR2022/051629 FR2022051629W WO2024042274A1 WO 2024042274 A1 WO2024042274 A1 WO 2024042274A1 FR 2022051629 W FR2022051629 W FR 2022051629W WO 2024042274 A1 WO2024042274 A1 WO 2024042274A1
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
- A61K8/987—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of species other than mammals or birds
- A61K8/988—Honey; Royal jelly, Propolis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/007—Preparations for dry skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
Definitions
- the invention relates to a natural composition comprising citric acid, iodized salt, fresh onion juice, honey, ethyl alcohol or perfumed alcoholate, orange blossom, rose water and lemon juice.
- the invention also relates to the cosmetic use of said composition, and to this composition for use in pathologies that can benefit from angiogenesis and the growth of keratinocytes.
- the present invention relates to a composition promoting angiogenesis and the growth of keratinocytes, and its therapeutic and cosmetic applications.
- Angiogenesis is a biological process of neovascularization allowing the creation of new blood vessels from the outgrowth or budding of pre-existing vessels. This process is fundamental for the development of tissues because blood vessels, in addition to transporting blood, ensure the supply of nutrients and eliminate waste from cell metabolism.
- angiogenesis is essential during physiological phenomena such as embryonic development, the formation of the placenta, but especially during tissue reconstruction, healing or during ischemia.
- a composition which promotes angiogenesis is therefore entirely useful in the medical field for therapeutic treatments such as wound healing, inflammation but also for the regeneration of tissues in situ in the event of trauma, for the treatment of alopecia or for the endothelialization of prostheses for example.
- composition is also useful in cosmetic skin care, in order to limit itching, and to promote hair renewal.
- Blood vessels are made up of endothelial cells. These cells are normally stable, meaning they renew very slowly. Angiogenesis activates these cells which then renew themselves much more quickly. Following their activation, endothelial cells develop, migrate towards the site of creation of new vessels then proliferate to form a new vascular network.
- Angiogenesis and activation of endothelial cells occur following stimulation by angiogenic factors.
- the basic growth factor of Fibroblast FGF-P and the vascular endothelial growth factor VEGF have been identified as playing central roles in angiogenesis.
- the numerous researches carried out in this field have shown that angiogenesis is not only controlled by these two factors but by a set of inducing and inhibitory factors, which is not yet perfectly determined.
- keratinocytes make it possible to renew the epidermis and skin appendages. Indeed, keratinocytes from the deep layer of the epidermis gradually migrate towards the surface by undergoing different mutations. These cells finally lose their nucleus to reach the comeocyte stage and constitute the stratum corneum. Dead cells are naturally evacuated by sweat and sebum. The epidermis renews itself naturally in 21 to 28 days, or more quickly in the case of pathology such as psoriasis.
- compositions for therapeutic and cosmetic purposes making it possible to promote the processes of angiogenesis and the growth of keratinocytes, and to provide a benefit to the patient or the user.
- the invention relates to a composition
- a composition comprising: a. Citric acid; b. Iodized salt; vs. Fresh onion juice; d. Of honey ; e. Ethyl alcohol or perfumed alcohol; f. Orange blossom; g. Rose water; h. Lemon juice.
- said composition comprises between 0.1 and 1% citric acid.
- said composition comprises between 5 and 10% iodized salt.
- said composition comprises between 30% and 40% fresh onion juice, even more preferably 35%.
- said composition comprises between 1 and 5% honey.
- said composition comprises between 25 and 35% alcohol. ethyl or perfumed alcoholate, even more preferably 30%.
- said composition comprises between 15 and 20% orange blossom.
- said composition comprises between 0.5 and 10% rose water.
- said composition comprises between 5 and 10% lemon juice.
- said composition comprises: a. Between 0.1 and 1% citric acid; b. Between 5 and 10% iodized salt; vs. Between 30% and 40% fresh onion juice, preferably 35%; d. Between 1 and 5% honey; e. Between 25 and 35% ethyl alcohol or perfumed alcoholate, preferably 30%; f. Between 15 and 20% orange blossom; g. Between 0.5 and 10% rose water; h. Between 5 and 10% lemon juice.
- said composition also comprises between 0.03% and 1% of distilled water, preferably 0.3%.
- compositions which is the subject of the invention are natural and are easily found without it being necessary to resort to any synthesis process.
- the invention relates to the composition according to the invention for use as a medicament in the treatment of pathologies which may benefit from angiogenesis or the growth of keratinocytes.
- composition could be used in combination with other active ingredients when angiogenesis only constitutes an adjunctive therapy to a main therapy where an amplification of angiogenesis could accelerate healing.
- the composition for use is used in the treatment of inflammation.
- the composition for use is used in the treatment of psoriasis or eczema.
- the composition for use is used in the treatment of alopecia.
- the route of administration is chosen from the routes: oral, intravenous, subcutaneous, nasal or other, in the form of tablets, injectable solutions, syrups or gels.
- the invention relates to the non-therapeutic cosmetic use of the composition according to the invention.
- said non-therapeutic cosmetic use is a use as an anti-itch composition.
- said non-therapeutic cosmetic use is a use as a composition promoting hair renewal.
- the composition according to the invention contains 100% natural elements.
- composition according to the invention in addition to the elements indicated in the composition according to the invention, and a cosmetically acceptable medium, it can also comprise surfactants, complexing agents, preservatives, stabilizing agents, emulsifiers, thickeners, gelling agents, humectants, emollients, trace elements, essential oils, perfumes, dyes, matting agents, chemical or mineral filters, moisturizing agents, waters thermal baths, etc.
- the cosmetic compositions according to the invention are for topical application.
- compositions according to the invention may thus be presented in the forms which are usually known for topical administration, that is to say in particular lotions, milks, emulsions, serums, balms, masks, creams, dispersions, gels, foams or sprays.
- the cosmetic composition according to the invention is applied once or twice a day, preferably twice a day, for at least 7 days, preferably at least 15 days, more preferably at least one months, and particularly preferably at least 2 months.
- the cosmetic composition is applied in the process according to the invention 2 times a day for at least 1 month, preferably 2 months.
- FIG 1 is a photograph illustrating the results obtained in Example 1, for the control, corresponding to the cells incubated in the absence of test product or reference product.
- FIG 2 is a photograph illustrating the results obtained in Example 1, in the presence of VEGF 2 ng/ml, used as a reference activator, diluted in the culture medium.
- FIG 3 is a photograph illustrating the results obtained in Example 1, in the presence of 20 pM SURAMINE, used as a reference inhibitor, diluted in the culture medium
- FIG 4 is a photograph illustrating the results obtained in Example 1, in the presence of a 0.1% ethanol control diluted in the culture medium.
- FIG 5 is a photograph illustrating the results obtained in Example 1, in the presence of a 0.3% ethanol control diluted in the culture medium.
- FIG 6 is a photograph illustrating the results obtained in Example 1, in the presence of the composition according to the invention at 0.03%.
- FIG 7 is a photograph illustrating the results obtained in Example 1, in the presence of the composition according to the invention at 0.3%.
- FIG 8 is a photograph illustrating the results obtained in Example 1, in the presence of the composition according to the invention at 1%.
- FIG. 9 is a photograph illustrating the results obtained in the example
- Photo A was taken before treatment, and photo B after treatment, where hair regrowth is visible.
- FIG. 10 is a photograph illustrating the results obtained in the example
- FIG 11 is a photograph illustrating the results obtained in the example
- Photo A was taken before treatment, and photo B after treatment, where the reduction in psoriasis is visible.
- FIG. 12 is a photograph illustrating the results obtained in the example
- Photo A was taken before treatment, and photo B after treatment, where the reduction in psoriasis is visible.
- FIG. 13 is a photograph illustrating the results obtained in the example
- citric acid is meant an a-hydroxylated tricarboxylic acid present in abundance in lemon, of formula C ⁇ HSO?.
- iodized salt is meant salt enriched with iodine.
- fresh onion juice is meant juice obtained from the bulb of the well-known plant of the Amaryllidaceae family. This fresh onion juice can be obtained by pressing, crushing, or for example using a juice extractor, from freshly picked and peeled onions, shortly after picking them.
- honey is meant the sweet substance produced by honey bees from nectar or honeydew.
- ethyl alcohol or ethanol is meant according to the invention the alcohol of semi-structural formula CH 3 -CH 2 -OH.
- perfumed alcoholate is meant a product obtained after distillation of a natural raw material, for example vegetable, in the presence of ethanol.
- a Example of such a fragrant alcoholate is eau de Cologne.
- bitter orange blossom is meant an extract obtained from the bitter orange blossom.
- rose water or “rose hydrosol” is meant the aqueous phase obtained from the distillation of rose petals for the manufacture of rose essential oil.
- lemon juice is meant the liquid obtained by the pressing (or other alternative method) of lemons.
- distilled water is meant purified water prepared by distillation of drinking water.
- treatment or “treat” is meant the alleviation of symptoms associated with a specific disorder or condition and/or the elimination of said symptoms.
- Angiogenesis is a biological process of neovascularization allowing the creation of new blood vessels from outgrowth or budding of pre-existing vessels.
- Keratinocytes are cells constituting 90% of the epidermis and skin appendages (nails, hair). These cells synthesize keratin, a protein which provides the skin with its property of waterproofing and external protection. Thus, stimulating the growth of keratinocytes helps renew the epidermis and skin appendages.
- Inflammation or inflammatory process is a reaction of the immune system to any attack. Inflammatory pathologies are very common (appendicitis, arthritis, cystitis, meningitis, otitis, etc.), and can be chronic or acute. These latter heal or become chronic. The clinical syndromes of inflammation are pain, redness, edema, heat sensation and functional impotence.
- Psoriasis is a chronic inflammatory skin disease which manifests itself by red patches with scales. It is most often a benign disease, but there are severe forms (around 20% of cases), associated with generalized involvement and/or joint pain.
- Eczema or atopic dermatitis is a chronic inflammatory skin disease which causes chronic itching. It mainly affects infants and children but can persist into adolescence and adulthood. This pathology is not contagious.
- Alopecia is a diffuse or localized, acute or chronic, partial or total loss of hair. The onset of alopecia can be sudden or manifest as a gradual decline in hair density without apparent hair loss.
- anti-itch is meant according to the invention a composition making it possible to limit itching, heating, a tingling sensation and/or a feeling of tightness, prevention of dehydration skin and/or restoration of skin hydration.
- hair renewal is meant the prevention and/or non-therapeutic reduction of hair loss and baldness disorders and thus acting for the regeneration of hair in a natural way. This hair treatment allows you to quickly and naturally find visibly denser hair.
- topical application within the meaning of the present invention is meant an application to the skin (including the scalp) and the mucous membranes.
- cosmetically acceptable is meant within the meaning of the present invention that which is useful in the preparation of a cosmetic composition, which is generally safe, non-toxic and neither biologically nor otherwise undesirable and which is acceptable for a cosmetic use, in particular by topical application to the skin.
- cosmetic use is meant according to the invention a “non-therapeutic” use, which is therefore not intended to treat a patient.
- the cosmetic use according to the invention does not act as a medicine for the treatment of various diseases but makes it possible to improve the superficial visual appearance and the superficial sensations of itching.
- non-therapeutic within the meaning of the invention, a cosmetic application not intended to treat a patient.
- the cosmetic composition according to the invention does not act as a medicine for the treatment of diseases such as baldness or otherwise called alopecia, but makes it possible to improve the superficial visual appearance of the scalp.
- this cosmetic composition does not treat psoriasis, but only superficially reduces itching.
- the cosmetic composition according to the invention does not act like a medicine.
- scaling is meant according to the invention the skin which covers the skull on which the hair grows.
- the scalp includes the hair.
- Example 1 Evaluation of the effect of the composition according to the invention on angiogenesis
- Test product Composition according to the invention.
- the reagent is an angiogenesis kit purchased from BIOPREDIC INTERNATIONAL.
- the other reagents are: CARLO ERBA or SIGMA, of analytical quality.
- Endothelial cells in co-culture with fibroblasts (“angiogenesis” kit from BIOPREDIC INTERNATIONAL: cells, media, reference products and antibodies for tubule staining.
- VEGF used as a reference activator, diluted in the culture medium; tested at 2 ng/mL
- Suramin used as a reference inhibitor, diluted in the culture medium; tested at 20 pM.
- Ethanol control diluted in the culture medium; tested at 0.1 and 0.3% (the product according to the invention comprises 30% ethanol; the 0.3% dilution therefore contains 0.1% ethanol; the 1% dilution contains 0.3% .
- Reaction system co-cultures of fibroblasts and endothelial cells incubated in the presence of the products under test.
- Control corresponding to cells incubated in the absence of test product or reference product.
- Example 2 Induction of growth in vitro on human keratinocytes:
- the in vitro growth induction test is used to evaluate the ability of a test material to improve the growth of cells when they are exposed to environmental stress due to a depleted medium.
- the test is based on the evaluation of the cell density after an incubation period of 48 hours in a depleted medium in the presence of different concentrations of the test material, in comparison with growth in the complete medium.
- Cell density is measured by a vital dye, neutral red.
- Neutral red is a weak cationic dye that readily penetrates cell membranes by diffusion, and accumulates in intracellular lysosomes of living cells. Thus, when the cells are lysed, they release a pink color, the intensity of which is proportional to the quantity of living cells.
- Human epidermal keratinocytes were purchased from ScienCell Research Loratories. They were maintained in “Keratinocytes-SFM” medium (Gibco BRL) supplemented with bovine pituitary extract (30 ⁇ g/ml) and recombinant epidermal growth factor (rEGF, 0.2 ng/ml). Cultures were carried out in a humidified incubator at 37°C with an atmosphere of 5% CO2 and the culture medium was changed every 2 days. The internal reference of the primary culture was KHNp ref 1465 (ScienCell) and the cells were used at passage 5.
- Test protocol [0112] Human keratinocytes were seeded in 96-well tissue culture plates (0.2 ml per well), at a concentration of 1.104 cells/ml, and incubated at 37°C (5% CO2) for 24 h. . The culture medium was decanted and replaced with 200 ⁇ l of depleted medium prepared with “Keratinocytes-SFM” medium supplemented with bovine pituitary extract (30 ⁇ g/ml) and a reduced concentration of recombinant epidermal growth factor (rEGF).
- rEGF epidermal growth factor
- the cells were incubated at 37°C (5% CO2) for 48 hours. At the end of the incubation period, the culture medium was removed. Cells were washed, placed in neutral red medium (50 ⁇ g/ml neutral red in complete medium) and incubated for 3 hours at 37°C, 5% CO2. Then, the medium was removed and the cells were washed three times with 0.2 ml PB S to remove excess dye. The cells were lysed with a mixture containing 50% ethanol, 1% acetic acid, 49% distilled water (50 ⁇ l per well). The plates were shaken for 15–20 min at room temperature in the dark. Test samples and controls were run in triplicate, in independent experiments.
- the level of cell growth (that is to say the increase in neutral red absorption) was measured by an Infinite M200 Pro fluorescence-luminescence reader (TEC AN).
- TEC AN Infinite M200 Pro fluorescence-luminescence reader
- OD optical density
- results obtained for the wells treated with the test material were compared to those of the untreated control wells, cultured in the complete medium (positive control, 100% growth) or depleted (negative control, 0% growth) and converted to percentage values.
- Table 1 contains the different concentrations of the test material, the optical densities at 540 nm and the corresponding cell viabilities.
- composition according to the invention induces an increase in the growth of keratinocytes, from which an effect can be deduced in the treatment of eczema, inflammation, psoriasis, and alopecia.
- Example 3 Evaluation of the effect of the composition according to the invention on angiogenesis and the growth of keratinocytes in an in vivo model carried out in human patients.
- composition is applied twice a day (morning and evening) for 3 months to the scalp of the patients.
- a study of the scalp and a study of the hair bulb are carried out to determine the effect of the composition according to the invention.
- composition induces significant hair regrowth in 100% of patients on the temporal, parietal and frontal areas of the skull. This significant regrowth is visible in Figure 9. ii. a developed vascularization appeared around the hair bulb although this vascularization was little before the patients started the tests.
- composition according to the invention induces vascularization characteristic of angiogenesis and keratinocyte growth.
- composition according to the invention has a strong pro-angiogenic and pro-keratinocyte growth power, which is manifested in the formation and development of blood vessels.
- Example 4 Evaluation of the effect of the composition according to the invention on inflammation in an in vivo model carried out in human patients.
- composition is applied twice a day (morning and evening) for 3 months to the skin of patients with inflammation.
- composition according to the invention induces a reduction in inflammation.
- Example 5 Evaluation of the effect of the composition according to the invention on psoriasis in an in vivo model carried out in human patients.
- composition is applied twice a day (morning and evening) for 3 months on the skin of patients suffering from psoriasis.
- composition according to the invention has an effect in the treatment of psoriasis.
- Example 6 Evaluation of the effect of the composition according to the invention on eczema in an in vivo model carried out in human patients.
- composition is applied twice a day (morning and evening) for 3 months to the skin of patients suffering from psoriasis.
- composition according to the invention has an effect in the treatment of eczema.
Abstract
The invention relates to a natural composition comprising citric acid, iodised salt, fresh onion juice, honey, ethyl alcohol or perfumed alcoholate, orange blossom, rose water and lemon juice. The invention also relates to the cosmetic use of the composition, and to this composition for use in pathologies that can benefit from angiogenesis and keratinocyte growth.
Description
Description Description
Titre de l’invention : Composition favorisant la croissance des kératinocytes et l'angiogenèse et ses applications thérapeutiques et cosmétiques. Title of the invention: Composition promoting the growth of keratinocytes and angiogenesis and its therapeutic and cosmetic applications.
[0001] L’invention concerne une composition naturelle comprenant de l’acide citrique, du sel iodé, du jus d’oignon frais, du miel, de l’alcool éthylique ou de l’alcoolat parfumé, de la fleur d’oranger, de l’eau de rose et du jus de citron. L’invention concerne également l’utilisation cosmétique de ladite composition, et cette composition pour utilisation dans les pathologies pouvant bénéficier d’une angiogenèse et la croissance des kératinocytes. [0001] The invention relates to a natural composition comprising citric acid, iodized salt, fresh onion juice, honey, ethyl alcohol or perfumed alcoholate, orange blossom, rose water and lemon juice. The invention also relates to the cosmetic use of said composition, and to this composition for use in pathologies that can benefit from angiogenesis and the growth of keratinocytes.
Art Antérieur Prior Art
[0002] La présente invention concerne une composition favorisant l'angiogenèse et la croissance des kératinocytes, et ses applications thérapeutiques et cosmétiques. The present invention relates to a composition promoting angiogenesis and the growth of keratinocytes, and its therapeutic and cosmetic applications.
[0003] L'angiogenèse est un processus biologique de néovascularisation permettant la création de nouveaux vaisseaux sanguins à partir de l'excroissance ou du bourgeonnement de vaisseaux préexistants. Ce processus est fondamental pour le développement des tissus car les vaisseaux sanguins, en plus du transport du sang, assurent l'apport des éléments nutritifs et éliminent les déchets du métabolisme des cellules. [0003] Angiogenesis is a biological process of neovascularization allowing the creation of new blood vessels from the outgrowth or budding of pre-existing vessels. This process is fundamental for the development of tissues because blood vessels, in addition to transporting blood, ensure the supply of nutrients and eliminate waste from cell metabolism.
[0004] Chez l'être humain l'angiogenèse est essentielle au cours de phénomènes physiologiques comme le développement embryonnaire, la formation du placenta, mais surtout lors de la reconstruction tissulaire, la cicatrisation ou lors d'ischémies. [0004] In humans, angiogenesis is essential during physiological phenomena such as embryonic development, the formation of the placenta, but especially during tissue reconstruction, healing or during ischemia.
[0005] Une composition qui favorise l'angiogenèse est donc tout à fait utile dans le milieu médical pour des traitements thérapeutiques comme la cicatrisation des plaies, les inflammations mais aussi pour la régénération des tissus in situ en cas de traumatismes, pour le traitement de l’alopécie ou pour l'endothélialisa- tion des prothèses par exemple. [0005] A composition which promotes angiogenesis is therefore entirely useful in the medical field for therapeutic treatments such as wound healing, inflammation but also for the regeneration of tissues in situ in the event of trauma, for the treatment of alopecia or for the endothelialization of prostheses for example.
[0006] Ce genre de composition est également utile dans le soin cosmétique de la peau, afin de limiter les démangeaisons, et pour favoriser le renouvellement capillaire. [0006] This type of composition is also useful in cosmetic skin care, in order to limit itching, and to promote hair renewal.
[0007] Les vaisseaux sanguins sont constitués de cellules endothéliales. Ces cellules sont normalement stables, c'est-à-dire qu'elles se renouvellent très lentement. L'angiogenèse active ces cellules qui se renouvellent alors beaucoup plus rapidement. Suite à leur activation, les cellules endothéliales se développent, migrent vers le lieu de création des nouveaux vaisseaux puis prolifèrent pour former un nouveau réseau vasculaire. [0007] Blood vessels are made up of endothelial cells. These cells are normally stable, meaning they renew very slowly. Angiogenesis activates these cells which then renew themselves much more quickly. Following their activation, endothelial cells develop, migrate towards the site of creation of new vessels then proliferate to form a new vascular network.
[0008] L'angiogenèse et l'activation des cellules endothéliales se font à la suite de stimulation par des facteurs angiogéniques. Le facteur de croissance basique des
fibroblastes FGF- P et le facteur de croissance de l'endothélium vasculaire VEGF ont été identifiés comme jouant un rôle central dans l'angiogenèse. Les nombreuses recherches effectuées dans ce domaine ont montré que l'angiogenèse n'est pas seulement contrôlée par ces deux facteurs mais par un ensemble de facteurs inducteurs et inhibiteurs, qui n'est pas encore parfaitement déterminé. [0008] Angiogenesis and activation of endothelial cells occur following stimulation by angiogenic factors. The basic growth factor of Fibroblast FGF-P and the vascular endothelial growth factor VEGF have been identified as playing central roles in angiogenesis. The numerous researches carried out in this field have shown that angiogenesis is not only controlled by these two factors but by a set of inducing and inhibitory factors, which is not yet perfectly determined.
[0009] La stimulation de la croissance des kératinocytes permet de renouveler l’épiderme et les phanères. En effet, les kératinocytes issus de la couche profonde de l’épiderme migrent progressivement vers la surface en subissant différentes mutations. Ces cellules perdent finalement leur noyau pour aboutir au stade de coméocytes et constituer la couche cornée. Les cellules mortes sont naturellement évacuées par la sueur et le sébum. L’épiderme se renouvelle ainsi naturellement en 21 à 28 jours, ou plus rapidement en cas de pathologie comme le psoriasis. [0009] Stimulating the growth of keratinocytes makes it possible to renew the epidermis and skin appendages. Indeed, keratinocytes from the deep layer of the epidermis gradually migrate towards the surface by undergoing different mutations. These cells finally lose their nucleus to reach the comeocyte stage and constitute the stratum corneum. Dead cells are naturally evacuated by sweat and sebum. The epidermis renews itself naturally in 21 to 28 days, or more quickly in the case of pathology such as psoriasis.
[0010] Ainsi, il perdure un besoin de composition à visée thérapeutique et cosmétique permettant de favoriser les processus d’angiogenèse et la croissance des kératinocytes, et d’apporter un bénéfice au patient ou à l’utilisateur. [0010] Thus, there continues to be a need for a composition for therapeutic and cosmetic purposes making it possible to promote the processes of angiogenesis and the growth of keratinocytes, and to provide a benefit to the patient or the user.
[0011] Dans cet objectif, le Demandeur a identifié de manière inattendue qu’une composition 100% naturelle permettait d’obtenir des résultats convaincants dans cette optique. [0011] With this objective, the Applicant unexpectedly identified that a 100% natural composition made it possible to obtain convincing results in this regard.
Résumé de l’invention Summary of the invention
[0012] Ainsi, selon un premier aspect, l’invention concerne une composition comprenant : a. De l’acide citrique ; b. Du sel iodé ; c. Du jus d’oignon frais ; d. Du miel ; e. De l’alcool éthylique ou de l’alcoolat parfumé ; f. De la fleur d’oranger ; g. De l’eau de rose ; h. Du jus de citron. [0012] Thus, according to a first aspect, the invention relates to a composition comprising: a. Citric acid; b. Iodized salt; vs. Fresh onion juice; d. Of honey ; e. Ethyl alcohol or perfumed alcohol; f. Orange blossom; g. Rose water; h. Lemon juice.
[0013] De manière préférée, ladite composition comprend entre 0,1 et 1 % d’acide citrique. Preferably, said composition comprises between 0.1 and 1% citric acid.
[0014] De manière préférée, ladite composition comprend entre 5 et 10 % de sel iodé. Preferably, said composition comprises between 5 and 10% iodized salt.
[0015] De manière préférée, ladite composition comprend entre 30 % et 40 % de jus d’oignon frais, de manière encore plus préférée 35%. [0015] Preferably, said composition comprises between 30% and 40% fresh onion juice, even more preferably 35%.
[0016] De manière préférée, ladite composition comprend entre 1 et 5 % de miel. Preferably, said composition comprises between 1 and 5% honey.
[0017] De manière préférée, ladite composition comprend entre 25 et 35 % d’alcool
éthylique ou d’alcoolat parfumé, de manière encore plus préférée 30%. [0017] Preferably, said composition comprises between 25 and 35% alcohol. ethyl or perfumed alcoholate, even more preferably 30%.
[0018] De manière préférée, ladite composition comprend entre 15 et 20 % de fleur d’oranger. [0018] Preferably, said composition comprises between 15 and 20% orange blossom.
[0019] De manière préférée, ladite composition comprend entre 0,5 et 10 % d’eau de rose. Preferably, said composition comprises between 0.5 and 10% rose water.
[0020] De manière préférée, ladite composition comprend entre 5 et 10 % de jus de citron. Preferably, said composition comprises between 5 and 10% lemon juice.
[0021] Selon un mode de réalisation, ladite composition comprend : a. Entre 0,1 et 1 % d’acide citrique ; b. Entre 5 et 10 % de sel iodé ; c. Entre 30 % et 40 % de jus d’oignon frais, de préférence 35% ; d. Entre 1 et 5 % de miel ; e. Entre 25 et 35 % d’alcool éthylique ou d’alcoolat parfumé, de préférence 30% ; f. Entre 15 et 20 % de fleur d’oranger ; g. Entre 0,5 et 10 % d’eau de rose ; h. Entre 5 et 10 % de jus de citron. [0021] According to one embodiment, said composition comprises: a. Between 0.1 and 1% citric acid; b. Between 5 and 10% iodized salt; vs. Between 30% and 40% fresh onion juice, preferably 35%; d. Between 1 and 5% honey; e. Between 25 and 35% ethyl alcohol or perfumed alcoholate, preferably 30%; f. Between 15 and 20% orange blossom; g. Between 0.5 and 10% rose water; h. Between 5 and 10% lemon juice.
[0022] De manière préférée, ladite composition comprend également entre 0.03 % et 1 % d’eau distillée, de préférence 0,3%. [0022] Preferably, said composition also comprises between 0.03% and 1% of distilled water, preferably 0.3%.
[0023] Les composants contenus dans la composition objet de l'invention sont naturels et se trouvent aisément sans qu'il soit nécessaire d'avoir recours à un quelconque procédé de synthèse. The components contained in the composition which is the subject of the invention are natural and are easily found without it being necessary to resort to any synthesis process.
[0024] Selon un deuxième aspect, l’invention concerne la composition selon l’invention pour utilisation comme médicament dans le traitement de pathologies pouvant bénéficier d’une angiogenèse ou de la croissance des kératinocytes. According to a second aspect, the invention relates to the composition according to the invention for use as a medicament in the treatment of pathologies which may benefit from angiogenesis or the growth of keratinocytes.
[0025] En outre, la composition pourra être utilisée en combinaison avec d'autres principes actifs lorsque l'angiogénèse ne constituera qu'une thérapie d'appoint à une thérapie principale où une amplification de l'angiogénèse pourra accélérer la guérison. [0025] Furthermore, the composition could be used in combination with other active ingredients when angiogenesis only constitutes an adjunctive therapy to a main therapy where an amplification of angiogenesis could accelerate healing.
[0026] De manière préférée, la composition pour utilisation est utilisée dans le traitement de l’inflammation. Preferably, the composition for use is used in the treatment of inflammation.
[0027] De manière préférée, la composition pour utilisation est utilisée dans le traitement du psoriasis ou de l’eczéma. Preferably, the composition for use is used in the treatment of psoriasis or eczema.
[0028] De manière préférée, la composition pour utilisation est utilisée dans le traitement de l’alopécie. Preferably, the composition for use is used in the treatment of alopecia.
[0029] De manière préférée, pour ladite composition pour utilisation, la voie d'administration est choisie parmi les voies : orales, intraveineuses, sous-cutanées, nasales ou autres, sous forme de comprimés, de solutions injectables, de sirops ou
de gels. [0029] Preferably, for said composition for use, the route of administration is chosen from the routes: oral, intravenous, subcutaneous, nasal or other, in the form of tablets, injectable solutions, syrups or gels.
[0030] Selon un troisième aspect, l’invention concerne l’utilisation cosmétique non- thérapeutique de la composition selon l’invention. [0030] According to a third aspect, the invention relates to the non-therapeutic cosmetic use of the composition according to the invention.
[0031] Selon un mode de réalisation de l’invention, ladite utilisation cosmétique non- thérapeutique est une utilisation en tant que composition anti-démangeaison. [0031] According to one embodiment of the invention, said non-therapeutic cosmetic use is a use as an anti-itch composition.
[0032] Selon un mode de réalisation de l’invention, ladite utilisation cosmétique non- thérapeutique est une utilisation en tant que composition favorisant le renouvellement capillaire. [0032] According to one embodiment of the invention, said non-therapeutic cosmetic use is a use as a composition promoting hair renewal.
[0033] Selon un mode de réalisation, la composition selon l’invention contient 100% d’éléments naturels. [0033] According to one embodiment, the composition according to the invention contains 100% natural elements.
[0034] Selon un autre mode de réalisation de l’invention, en complément des éléments indiqués dans la composition selon l’invention, et un milieu cosmétiquement acceptable, celle-ci peut également comprendre des agents tensioactifs, des agents complexants, des conservateurs, des agents stabilisants, des émulsifiants, des épaississants, des gélifiants, des humectants, des émollients, des oligoéléments, des huiles essentielles, des parfums, des colorants, des agents ma- tifïants, des filtres chimiques ou minéraux, des agents hydratants, des eaux thermales, etc. [0034] According to another embodiment of the invention, in addition to the elements indicated in the composition according to the invention, and a cosmetically acceptable medium, it can also comprise surfactants, complexing agents, preservatives, stabilizing agents, emulsifiers, thickeners, gelling agents, humectants, emollients, trace elements, essential oils, perfumes, dyes, matting agents, chemical or mineral filters, moisturizing agents, waters thermal baths, etc.
[0035] De manière préférée, les compositions cosmétiques selon l’invention sont pour application topique. [0035] Preferably, the cosmetic compositions according to the invention are for topical application.
[0036] Les compositions cosmétiques selon l’invention pourront ainsi se présenter sous les formes qui sont habituellement connues pour une administration topique, c’est-à-dire notamment les lotions, les laits, les émulsions, les sérums, les baumes, les masques, les crèmes, les dispersions, les gels, les mousses ou les sprays. [0036] The cosmetic compositions according to the invention may thus be presented in the forms which are usually known for topical administration, that is to say in particular lotions, milks, emulsions, serums, balms, masks, creams, dispersions, gels, foams or sprays.
[0037] De manière préférée, la composition cosmétique selon l’invention est appliquée une à deux fois par jour, de préférence 2 fois par jour, pendant au moins 7 jours, de préférence au moins 15 jours, de manière encore préférée au moins un mois, et de manière particulièrement préférée au moins 2 mois. [0037] Preferably, the cosmetic composition according to the invention is applied once or twice a day, preferably twice a day, for at least 7 days, preferably at least 15 days, more preferably at least one months, and particularly preferably at least 2 months.
[0038] De manière tout particulièrement préférée, la composition cosmétique est appliquée dans le procédé selon l’invention 2 fois par jour pendant au moins 1 mois, de préférence 2 mois. [0038] Very particularly preferably, the cosmetic composition is applied in the process according to the invention 2 times a day for at least 1 month, preferably 2 months.
Figures Figures
[0039] La [Fig 1] est une photographie illustrant les résultats obtenus dans l’exemple 1, pour le témoin, correspondant aux cellules incubées en absence de produit à l’essai ou de produit de référence. [0039] [Fig 1] is a photograph illustrating the results obtained in Example 1, for the control, corresponding to the cells incubated in the absence of test product or reference product.
[0040] La [Fig 2] est une photographie illustrant les résultats obtenus dans l’exemple 1 , en présence de VEGF 2 ng/ml, utilisé comme activateur de référence, dilué dans le milieu de culture. [0040] [Fig 2] is a photograph illustrating the results obtained in Example 1, in the presence of VEGF 2 ng/ml, used as a reference activator, diluted in the culture medium.
[0041] La [Fig 3] est une photographie illustrant les résultats obtenus dans l’exemple 1 , en présence de SURAMINE 20 pM, utilisée comme inhibiteur de référence,
diluée dans le milieu de culture [0041] [Fig 3] is a photograph illustrating the results obtained in Example 1, in the presence of 20 pM SURAMINE, used as a reference inhibitor, diluted in the culture medium
[0042] La [Fig 4] est une photographie illustrant les résultats obtenus dans l’exemple 1, en présence d’un témoin à l’éthanol à 0,1% dilué dans le milieu de culture. [0042] [Fig 4] is a photograph illustrating the results obtained in Example 1, in the presence of a 0.1% ethanol control diluted in the culture medium.
[0043] La [Fig 5] est une photographie illustrant les résultats obtenus dans l’exemple 1, en présence d’un témoin à l’éthanol à 0,3% dilué dans le milieu de culture. [0043] [Fig 5] is a photograph illustrating the results obtained in Example 1, in the presence of a 0.3% ethanol control diluted in the culture medium.
[0044] La [Fig 6] est une photographie illustrant les résultats obtenus dans l’exemple 1, en présence la composition selon l’invention à 0,03%. [0044] [Fig 6] is a photograph illustrating the results obtained in Example 1, in the presence of the composition according to the invention at 0.03%.
[0045] La [Fig 7] est une photographie illustrant les résultats obtenus dans l’exemple 1, en présence la composition selon l’invention à 0,3%. [0045] [Fig 7] is a photograph illustrating the results obtained in Example 1, in the presence of the composition according to the invention at 0.3%.
[0046] La [Fig 8] est une photographie illustrant les résultats obtenus dans l’exemple 1, en présence la composition selon l’invention à 1%. [0046] [Fig 8] is a photograph illustrating the results obtained in Example 1, in the presence of the composition according to the invention at 1%.
[0047] La [Fig 9] est une photographie illustrant les résultats obtenus dans l’exemple[0047] [Fig 9] is a photograph illustrating the results obtained in the example
3. La photo A a été prise avant traitement, et la photo B après traitement, où la repousse des cheveux est visible. 3. Photo A was taken before treatment, and photo B after treatment, where hair regrowth is visible.
[0048] La [Fig 10] est une photographie illustrant les résultats obtenus dans l’exemple[0048] [Fig 10] is a photograph illustrating the results obtained in the example
4. La photo A a été prise avant traitement, et la photo B après traitement, où la réduction de l’inflammation est visible. 4. Photo A was taken before treatment, and photo B after treatment, where the reduction in inflammation is visible.
[0049] La [Fig 11] est une photographie illustrant les résultats obtenus dans l’exemple[0049] [Fig 11] is a photograph illustrating the results obtained in the example
5. La photo A a été prise avant traitement, et la photo B après traitement, où la réduction du psoriasis est visible. 5. Photo A was taken before treatment, and photo B after treatment, where the reduction in psoriasis is visible.
[0050] La [Fig 12] est une photographie illustrant les résultats obtenus dans l’exemple[0050] [Fig 12] is a photograph illustrating the results obtained in the example
5. La photo A a été prise avant traitement, et la photo B après traitement, où la réduction du psoriasis est visible. 5. Photo A was taken before treatment, and photo B after treatment, where the reduction in psoriasis is visible.
[0051] La [Fig 13] est une photographie illustrant les résultats obtenus dans l’exemple[0051] [Fig 13] is a photograph illustrating the results obtained in the example
6. La photo A a été prise avant traitement, et la photo B après traitement, où la réduction de l’eczéma est visible. 6. Photo A was taken before treatment, and photo B after treatment, where the reduction in eczema is visible.
Définitions Definitions
[0052] Par « l’acide citrique » est entendu un acide tricarboxylique a-hydroxylé présent en abondance dans le citron, de formule CÊHSO?. [0052] By “citric acid” is meant an a-hydroxylated tricarboxylic acid present in abundance in lemon, of formula CÊHSO?.
[0053] Par « sel iodé » est entendu du sel enrichi en iode. [0053] By “iodized salt” is meant salt enriched with iodine.
[0054] Par « jus d’oignon frais » est entendu du jus obtenu à partir du bulbe de la plante bien connue de la famille des Amaryllidaceae. Ce jus d’oignon frais peut être obtenu par pressage, par broyage, ou par exemple grâce à un extracteur de jus, de l’oignon fraîchement cueilli et épluché, peu de temps après l’avoir cueilli. [0054] By “fresh onion juice” is meant juice obtained from the bulb of the well-known plant of the Amaryllidaceae family. This fresh onion juice can be obtained by pressing, crushing, or for example using a juice extractor, from freshly picked and peeled onions, shortly after picking them.
[0055] Par « miel » est entendu la substance sucrée élaborée par les abeilles à miel à partir de nectar ou de miellat. [0055] By “honey” is meant the sweet substance produced by honey bees from nectar or honeydew.
[0056] Par « l’alcool éthylique » ou éthanol est entendu selon l’invention l’alcool de formule semi-développée CH3-CH2-OH. [0056] By “ethyl alcohol” or ethanol is meant according to the invention the alcohol of semi-structural formula CH 3 -CH 2 -OH.
[0057] Par « l’alcoolat parfumé » est entendu un produit obtenu près distillation d’une matière première naturelle, par exemple végétale, en présence d’éthanol. Un
exemple de tel alcoolat parfumé est l’eau de Cologne. [0057] By “perfumed alcoholate” is meant a product obtained after distillation of a natural raw material, for example vegetable, in the presence of ethanol. A Example of such a fragrant alcoholate is eau de Cologne.
[0058] Par de la « fleur d’oranger » est entendu un extrait obtenu à partir de la fleur du bigaradier. [0058] By “orange blossom” is meant an extract obtained from the bitter orange blossom.
[0059] Par « eau de rose » ou « hydrolat de rose » est entendu la phase aqueuse obtenue de la distillation de pétales de roses pour la fabrication d’huile essentielle de rose. [0059] By “rose water” or “rose hydrosol” is meant the aqueous phase obtained from the distillation of rose petals for the manufacture of rose essential oil.
[0060] Par « jus de citron » est entendu le liquide obtenu par le pressage (ou autre méthode alternative) de citrons. [0060] By “lemon juice” is meant the liquid obtained by the pressing (or other alternative method) of lemons.
[0061] Par « eau distillée » est entendu de l’eau purifiée préparée par distillation d'eau potable. [0061] By “distilled water” is meant purified water prepared by distillation of drinking water.
[0062] Par « traitement » ou « traiter » est entendu l'atténuation des symptômes associés à un trouble ou un état spécifique et/ou l'élimination desdits symptômes. [0062] By “treatment” or “treat” is meant the alleviation of symptoms associated with a specific disorder or condition and/or the elimination of said symptoms.
[0063] L’ « Angiogenèse » est un processus biologique de néovascularisation permettant la création de nouveaux vaisseaux sanguins à partir d'excroissance ou du bourgeonnement de vaisseaux préexistants. [0063] “Angiogenesis” is a biological process of neovascularization allowing the creation of new blood vessels from outgrowth or budding of pre-existing vessels.
[0064] Les « kératinocytes » sont des cellules constituants 90% de l’épiderme et des phanères (ongles, cheveux, poils). Ces cellules synthétisent la kératine, une protéine qui assure à la peau sa propriété d’imperméabilité et de protection extérieure. Ainsi, stimuler la croissance des kératinocytes permet de renouveler l’épiderme et les phanères. [0064] “Keratinocytes” are cells constituting 90% of the epidermis and skin appendages (nails, hair). These cells synthesize keratin, a protein which provides the skin with its property of waterproofing and external protection. Thus, stimulating the growth of keratinocytes helps renew the epidermis and skin appendages.
[0065] L’« inflammation » ou processus inflammatoire est une réaction du système immunitaire vis-à-vis d’une agression quelconque. Les pathologies inflammatoires sont très fréquentes (appendicite, arthrite, cystite, méningite, otite.. .), et peuvent être chroniques ou aigues. Ces dernières guérissent ou passent à la chronicité. Les syndromes cliniques de l’inflammation sont la douleur, la rougeur, l’œdème, la sensation de chaleur et l’impotence fonctionnelle. [0065] “Inflammation” or inflammatory process is a reaction of the immune system to any attack. Inflammatory pathologies are very common (appendicitis, arthritis, cystitis, meningitis, otitis, etc.), and can be chronic or acute. These latter heal or become chronic. The clinical syndromes of inflammation are pain, redness, edema, heat sensation and functional impotence.
[0066] Le « psoriasis » est une maladie inflammatoire chronique de la peau qui se manifeste par des plaques rouges présentant des squames. Il s’agit le plus souvent d’une maladie bénigne, mais il existe des formes sévères (environ 20% des cas), associées à une atteinte généralisée et/ou à des douleurs articulaires. [0066] “Psoriasis” is a chronic inflammatory skin disease which manifests itself by red patches with scales. It is most often a benign disease, but there are severe forms (around 20% of cases), associated with generalized involvement and/or joint pain.
[0067] L’ « eczéma » ou dermatite atopique est une maladie inflammatoire chronique de la peau qui provoque des démangeaisons chronique. Il touche principalement les nourrissons et les enfants mais peut persister à l'adolescence et à l'âge adulte. Cette pathologie n’est pas contagieuse. [0067] “Eczema” or atopic dermatitis is a chronic inflammatory skin disease which causes chronic itching. It mainly affects infants and children but can persist into adolescence and adulthood. This pathology is not contagious.
[0068] L’« alopécie » est une chute diffuse ou localisée, aigüe ou chronique, partielle ou totale des cheveux ou des poils. L'installation d'une alopécie peut être brutale ou se manifester par une baisse de la densité capillaire progressive sans chute apparente des cheveux. [0068] “Alopecia” is a diffuse or localized, acute or chronic, partial or total loss of hair. The onset of alopecia can be sudden or manifest as a gradual decline in hair density without apparent hair loss.
[0069] Par « anti-démangeaison » est entendu selon l’invention une composition permettant de limiter une démangeaison, un échauffement, une sensation de picotement et/ou une sensation de tiraillement, la prévention de la déshydratation
cutanée et/ou la restauration de l’hydratation cutanée. [0069] By “anti-itch” is meant according to the invention a composition making it possible to limit itching, heating, a tingling sensation and/or a feeling of tightness, prevention of dehydration skin and/or restoration of skin hydration.
[0070] Par « renouvellement capillaire » est entendu la prévention et/ou la réduction non thérapeutique de la chute des cheveux et des troubles de la calvitie et ainsi agir pour la régénération des cheveux de manière naturelle. Ce soin capillaire permet de retrouver rapidement et naturellement une chevelure visiblement plus dense. [0070] By “hair renewal” is meant the prevention and/or non-therapeutic reduction of hair loss and baldness disorders and thus acting for the regeneration of hair in a natural way. This hair treatment allows you to quickly and naturally find visibly denser hair.
[0071] Par « application topique », on entend au sens de la présente invention une application sur la peau (dont le cuir chevelu), et les muqueuses. [0071] By “topical application”, within the meaning of the present invention is meant an application to the skin (including the scalp) and the mucous membranes.
[0072] Par « cosmétiquement acceptable », on entend au sens de la présente invention ce qui est utile dans la préparation d’une composition cosmétique, qui est généralement sûr, non toxique et ni biologiquement ni autrement non souhaitable et qui est acceptable pour une utilisation cosmétique, notamment par application topique au niveau de la peau. [0072] By “cosmetically acceptable” is meant within the meaning of the present invention that which is useful in the preparation of a cosmetic composition, which is generally safe, non-toxic and neither biologically nor otherwise undesirable and which is acceptable for a cosmetic use, in particular by topical application to the skin.
[0073] Par « utilisation cosmétique » est entendu selon l’invention une utilisation « non-thérapeutique », qui n’a donc pas vocation à traiter un patient. De fait, l’utilisation cosmétique selon l’invention n’agit pas comme un médicament pour le traitement de diverses maladies mais permet d’améliorer l’aspect visuel superficiel et les sensations superficielles de démangeaison. [0073] By “cosmetic use” is meant according to the invention a “non-therapeutic” use, which is therefore not intended to treat a patient. In fact, the cosmetic use according to the invention does not act as a medicine for the treatment of various diseases but makes it possible to improve the superficial visual appearance and the superficial sensations of itching.
[0074] Par « non-thérapeutique » est entendu au sens de l’invention, une application cosmétique n’ayant pas vocation à traiter un patient. De fait, la composition cosmétique selon l’invention n’agit pas comme un médicament pour le traitement de maladies comme la calvitie ou autrement dénommée l’alopécie, mais permet d’améliorer l’aspect visuel superficiel du cuir chevelu. Idem, cette composition cosmétique ne permet pas de de traiter le psoriasis, mais permet seulement de réduire de manière superficielle les démangeaisons. De fait, la composition cosmétique selon l’invention n’agit pas comme un médicament. [0074] By “non-therapeutic” is meant within the meaning of the invention, a cosmetic application not intended to treat a patient. In fact, the cosmetic composition according to the invention does not act as a medicine for the treatment of diseases such as baldness or otherwise called alopecia, but makes it possible to improve the superficial visual appearance of the scalp. Likewise, this cosmetic composition does not treat psoriasis, but only superficially reduces itching. In fact, the cosmetic composition according to the invention does not act like a medicine.
[0075] Par « cuir chevelu » est entendu selon l’invention la peau qui recouvre le crâne sur laquelle pousse les cheveux. Dans le cadre de l’invention, le cuir chevelu comprend les cheveux. [0075] By “scalp” is meant according to the invention the skin which covers the skull on which the hair grows. In the context of the invention, the scalp includes the hair.
Exemples Examples
[0076] Exemple 1 : Évaluation de l’effet de la composition selon l’invention sur l’angiogenèse [0076] Example 1: Evaluation of the effect of the composition according to the invention on angiogenesis
[0077] I - Matériel et méthodes : [0077] I - Material and methods:
[0078] Produit à l’essai : Composition selon l’invention. [0078] Test product: Composition according to the invention.
[0079] Réactif-. [0079] Reagent-.
[0080] Le réactif est un Kit angiogénèse acheté chez BIOPREDIC INTERNATIONAL. [0080] The reagent is an angiogenesis kit purchased from BIOPREDIC INTERNATIONAL.
[0081] Les autres réactifs sont : CARLO ERBA ou SIGMA, de qualité analytique. [0081] The other reagents are: CARLO ERBA or SIGMA, of analytical quality.
[0082] Système d’essai : [0082] Test system:
[0083] Cellules endothéliales en co-culture avec des fibroblastes (kit « angiogénèse » de BIOPREDIC INTERNATIONAL : cellules, milieux, produits de référence
et anticorps pour la coloration des tubules. [0083] Endothelial cells in co-culture with fibroblasts (“angiogenesis” kit from BIOPREDIC INTERNATIONAL: cells, media, reference products and antibodies for tubule staining.
[0084] Préparation des produits de référence et des produits à l’essai : [0084] Preparation of reference products and test products:
[0085] VEGF, utilisé comme activateur de référence, dilué dans le milieu de culture ; testé à 2 ng/mL VEGF, used as a reference activator, diluted in the culture medium; tested at 2 ng/mL
[0086] Suramine, utilisée comme inhibiteur de référence, diluée dans le milieu de culture ; testée à 20 pM. Suramin, used as a reference inhibitor, diluted in the culture medium; tested at 20 pM.
[0087] Produit selon l’invention dilué dans le milieu de culture : testé à 0,03, 0,3 et 1%. [0087] Product according to the invention diluted in the culture medium: tested at 0.03, 0.3 and 1%.
[0088] Témoin éthanol dilué dans le milieu de culture ; testé à 0,1 et 0,3% (le produit selon l’invention comprend 30% d’éthanol ; la dilution 0,3% contient donc 0,1% d’éthanol ; la dilution 1% en contient 0,3%. [0088] Ethanol control diluted in the culture medium; tested at 0.1 and 0.3% (the product according to the invention comprises 30% ethanol; the 0.3% dilution therefore contains 0.1% ethanol; the 1% dilution contains 0.3% .
[0089] Protocole d’incubation : [0089] Incubation protocol:
[0090] Système réactionnel : co-cultures de fibroblastes et de cellules endothéliales incubées en présence des produits à l’essai. [0090] Reaction system: co-cultures of fibroblasts and endothelial cells incubated in the presence of the products under test.
[0091] Temps d’incubation : 9 jours [0091] Incubation time: 9 days
[0092] Les produits à l’essai sont incubés et les milieux sont renouvelés à J0, J2, J5, J7, et les résultats sont observés à J9. The products under test are incubated and the media are renewed on D0, D2, D5, D7, and the results are observed on D9.
[0093] Température d’incubation : 37°C [0093] Incubation temperature: 37°C
[0094] Autres conditions : atmosphère humide contenant 5% de CO2 [0094] Other conditions: humid atmosphere containing 5% CO2
[0095] Témoin : correspondant aux cellules incubées en absence de produit à l’essai ou de produit de référence. [0095] Control: corresponding to cells incubated in the absence of test product or reference product.
[0096] Pour les témoins, les milieux sont renouvelés à J0, J2, J5, J7, et les résultats sont observés à J9. [0096] For the controls, the media are renewed on D0, D2, D5, D7, and the results are observed on D9.
[0097] Evaluation des effets : [0097] Evaluation of the effects:
[0098] Images prises 9 jours d’incubation à des positions prédéterminées dans chaque puits. Mesure des longueurs de tubules par un système d’analyse d’images (Foster Findlay Associates). [0098] Images taken 9 days of incubation at predetermined positions in each well. Measurement of tubule lengths using an image analysis system (Foster Findlay Associates).
[0099] Traitement des données : [0099] Data processing:
[0100] Valeurs exprimées en unités arbitraires (pixels) de longueur de tubules par champ microscopique et en pourcentage du groupe témoin. [0100] Values expressed in arbitrary units (pixels) of tubule length per microscopic field and as a percentage of the control group.
[0101] II — Résultats : [0101] II — Results:
[Table 1] Effet des produits de référence sur la formation de tubules :
[Table 1] Effect of reference products on tubule formation:
[Table 2] : Effet des produits à l’essai sur la formation de tubules :
[Table 2]: Effect of test products on tubule formation:
[0102] Les figures 1 à 8 montrent les résultats obtenus. [0102] Figures 1 to 8 show the results obtained.
[0103] Exemple 2 : Induction de la croissance in vitro sur kératinocytes humains : [0103] Example 2: Induction of growth in vitro on human keratinocytes:
[0104 ] I. But de l ’étude [0104] I. Purpose of the study
[0105] Le test d'induction de croissance in vitro est utilisé pour évaluer la capacité d'un matériel d'essai à améliorer la croissance des cellules lorsqu'elles sont exposées à un stress environnemental dû à un milieu appauvri. [0105] The in vitro growth induction test is used to evaluate the ability of a test material to improve the growth of cells when they are exposed to environmental stress due to a depleted medium.
[0106] IL Matériels et méthodes [0106] IL Materials and methods
[0107] Le test est basé sur l'évaluation de la densité cellulaire après une période d'incubation de 48 heures dans un milieu appauvri en présence de différentes concentrations du matériel d'essai, en comparaison avec la croissance dans le milieu complet. La densité cellulaire est mesurée par un colorant vital, le rouge neutre. Le rouge neutre est un colorant cationique faible qui pénètre facilement les membranes cellulaires par diffusion, et s'accumule dans les lysosomes intracellulaires des cellules vivantes. Ainsi, lorsque les cellules sont lysées, elles relarguent une coloration rose, dont l’intensité est proportionnelle à la quantité de cellules vivantes. [0107] The test is based on the evaluation of the cell density after an incubation period of 48 hours in a depleted medium in the presence of different concentrations of the test material, in comparison with growth in the complete medium. Cell density is measured by a vital dye, neutral red. Neutral red is a weak cationic dye that readily penetrates cell membranes by diffusion, and accumulates in intracellular lysosomes of living cells. Thus, when the cells are lysed, they release a pink color, the intensity of which is proportional to the quantity of living cells.
[0108] Produits chimiques et milieux de culture [0108] Chemical products and culture media
[0109] Tous les réactifs de culture cellulaires ont été obtenus chez Dutscher (Brumath, France), excepté l’extrait pituitaire de bœuf, le facteur de croissance épidermique (rEGF) et le milieu de culture pour kératinocytes (K-SFM) qui proviennent de GIBCO-BRL (Cergy Pontoise, France). [0109] All the cell culture reagents were obtained from Dutscher (Brumath, France), except the beef pituitary extract, the epidermal growth factor (rEGF) and the culture medium for keratinocytes (K-SFM) which came from from GIBCO-BRL (Cergy Pontoise, France).
[0110] Kératinocytes humains [0110] Human keratinocytes
[0111] Les kératinocytes épidermiques humains ont été achetés auprès de ScienCell Research Loratories. Ils ont été maintenus dans du milieu « Keratinocytes-SFM » (Gibco BRL) supplémenté d'extrait pituitaire bovin (30 pg / ml) et de facteur de croissance épidermique recombinant (rEGF, 0,2 ng / ml). Les cultures ont été réalisées dans un incubateur humidifié à 37 °C avec une atmosphère à 5% de CO2 et le milieu de culture a été changé tous les 2 jours. La référence interne de la culture primaire était KHNp réf 1465 (ScienCell) et les cellules ont été utilisées au passage 5. [0111] Human epidermal keratinocytes were purchased from ScienCell Research Loratories. They were maintained in “Keratinocytes-SFM” medium (Gibco BRL) supplemented with bovine pituitary extract (30 µg/ml) and recombinant epidermal growth factor (rEGF, 0.2 ng/ml). Cultures were carried out in a humidified incubator at 37°C with an atmosphere of 5% CO2 and the culture medium was changed every 2 days. The internal reference of the primary culture was KHNp ref 1465 (ScienCell) and the cells were used at passage 5.
[0112] Protocole du test
[0113] Les kératinocytes humains ont été ensemencés dans des plaques de culture tissulaire à 96 puits (0,2 ml par puits), à la concentration de 1,104 cellules/ml, et incubés à 37°C (5% CO2) pendant 24 h. Le milieu de culture a été décanté et remplacé par 200 pi de milieu appauvri préparé avec du milieu «Keratinocytes- SFM» supplémenté d'extrait d'hypophyse bovine (30 pg/ml) et une concentration réduite de facteur de croissance épidermique recombinant (rEGF, 0,02 ng/ml, dilution au 1/10 du facteur de croissance par rapport au milieu complet), contenant les concentrations appropriées du matériel d’essai (différentes concentrations de 0,005% à 10% v: v), puis les cellules ont été incubées à 37°C (5% CO2) pendant 48 heures. A la fin de la période d'incubation, le milieu de culture a été retiré. Les cellules ont été lavées, placées dans du milieu avec du rouge neutre (50 pg/ml de rouge neutre dans un milieu complet) et incubées pendant 3 heures à 37°C, 5% de CO2. Ensuite, le milieu a été éliminé et les cellules ont été lavées trois fois avec 0,2 ml de PB S pour éliminer l'excès de colorant. Les cellules ont été lysées par un mélange contenant 50% d'éthanol, 1% d'acide acétique, 49% d'eau distillée (50 pl par puits). Les plaques ont été agitées pendant 15 à 20 minutes à température ambiante dans l'obscurité. Les échantillons de test et les contrôles ont été exécutés en triplicat, dans des expériences indépendantes. [0112] Test protocol [0113] Human keratinocytes were seeded in 96-well tissue culture plates (0.2 ml per well), at a concentration of 1.104 cells/ml, and incubated at 37°C (5% CO2) for 24 h. . The culture medium was decanted and replaced with 200 μl of depleted medium prepared with “Keratinocytes-SFM” medium supplemented with bovine pituitary extract (30 μg/ml) and a reduced concentration of recombinant epidermal growth factor (rEGF). , 0.02 ng/ml, 1/10 dilution of growth factor relative to complete medium), containing the appropriate concentrations of the test material (different concentrations from 0.005% to 10% v:v), then the cells were incubated at 37°C (5% CO2) for 48 hours. At the end of the incubation period, the culture medium was removed. Cells were washed, placed in neutral red medium (50 µg/ml neutral red in complete medium) and incubated for 3 hours at 37°C, 5% CO2. Then, the medium was removed and the cells were washed three times with 0.2 ml PB S to remove excess dye. The cells were lysed with a mixture containing 50% ethanol, 1% acetic acid, 49% distilled water (50 μl per well). The plates were shaken for 15–20 min at room temperature in the dark. Test samples and controls were run in triplicate, in independent experiments.
[0114] Évaluation de la croissance cellulaire [0114] Evaluation of cell growth
[0115] Le niveau de croissance cellulaire (c'est-à-dire l'augmentation de l'absorption de rouge neutre) a été mesuré par un lecteur à fluorescence-luminescence Infinite M200 Pro (TEC AN). La densité optique (DO) de chaque puits a été lue à[0115] The level of cell growth (that is to say the increase in neutral red absorption) was measured by an Infinite M200 Pro fluorescence-luminescence reader (TEC AN). The optical density (OD) of each well was read at
540 nm. Les résultats obtenus pour les puits traités avec le matériel d'essai ont été comparés à ceux des puits témoins non traités, cultivés dans le milieu complet (témoin positif, croissance à 100%) ou appauvri (témoin négatif, croissance à 0%) et convertis en valeurs de pourcentage. 540nm. The results obtained for the wells treated with the test material were compared to those of the untreated control wells, cultured in the complete medium (positive control, 100% growth) or depleted (negative control, 0% growth) and converted to percentage values.
[0116] Calcul du pourcentage d’induction de la croissance cellulaire [0116] Calculation of the percentage of induction of cell growth
[0117] Les pourcentages d'induction de croissance cellulaire des kératinocytes par rapport aux témoins de milieu complet et appauvri ont été calculés comme suit: [0117] The percentages of cell growth induction of keratinocytes compared to the complete and depleted medium controls were calculated as follows:
[0118] [Math 1] [0118] [Math 1]
> ... , atériel d'essai-DO contrôle négatif)> ..., test equipment-DO negative control)
[0119] Pourcentage d induction (%) =
-[0119] Percentage of induction (%) = -
DO contrôle positif-DO contrôle négatifOD positive control-DO negative control
[0120] Les pourcentages d'induction de croissance cellulaire par rapport aux témoins de milieu complet et appauvri ont été calculés comme suit: [0120] The percentages of cell growth induction relative to the complete and depleted medium controls were calculated as follows:
[0121] III. Résultats [0121] III. Results
[0122] Les résultats complets obtenus pour les trois essais indépendants sont résumés dans le tableau 1. Ce tableau contient les différentes concentrations du matériel d'essai, les densités optiques à 540 nm et les viabilités cellulaires correspondantes. [0122] The complete results obtained for the three independent tests are summarized in Table 1. This table contains the different concentrations of the test material, the optical densities at 540 nm and the corresponding cell viabilities.
[Table 3] Résultats obtenu pour les trois essais indépendants
[Table 3] Results obtained for the three independent tests
[0123] IV. Discussion [0123] IV. Discussion
[0124] Une induction de croissance cellulaire intéressante a pu être observée avec le matériel d'essai, avec une augmentation de croissance maximale observée à la concentration la plus faible de 0,05% (74,78% d'induction de croissance par rapport au milieu complet). Cette induction de croissance diminue avec l'augmentation des concentrations, et une cytotoxicité peut être observée à des concentrations supérieures à 5%. [0124] An interesting cell growth induction could be observed with the test material, with a maximum growth increase observed at the lowest concentration of 0.05% (74.78% growth induction compared to in the middle complete). This growth induction diminishes with increasing concentrations, and cytotoxicity can be observed at concentrations above 5%.
[0125] Ces résultats indiquent que la composition selon l’invention induit une augmentation de la croissance des kératinocytes, dont on peut déduire un effet dans le traitement de l’eczéma, de l’inflammation, du psoriasis, et de l’alopécie. [0125] These results indicate that the composition according to the invention induces an increase in the growth of keratinocytes, from which an effect can be deduced in the treatment of eczema, inflammation, psoriasis, and alopecia.
[0126] Exemple 3 : Évaluation de l'effet de la composition selon l'invention sur l'angiogenèse et la croissance des kératinocytes dans un modèle in vivo réalisé chez des patients humains.
[0127] Les résultats d'une étude in vivo réalisée sur 10 patients humains atteints d'alopécie de type V, VI et VII selon l'échelle d'Hamilton, mettent en évidence le fort pouvoir pro-angiogénique et de croissance des kératinocytes de la composition selon l'invention. Example 3: Evaluation of the effect of the composition according to the invention on angiogenesis and the growth of keratinocytes in an in vivo model carried out in human patients. [0127] The results of an in vivo study carried out on 10 human patients suffering from type V, VI and VII alopecia according to the Hamilton scale, highlight the strong pro-angiogenic and growth power of keratinocytes of the composition according to the invention.
[0128] Dans ces expériences, la composition est appliquée 2 fois par jour (matin et soir) pendant 3 mois sur le cuir chevelu des patients. [0128] In these experiments, the composition is applied twice a day (morning and evening) for 3 months to the scalp of the patients.
[0129] Une étude du cuir chevelu et une étude du bulbe pileux sont mises en œuvre pour déterminer l'effet de la composition selon l'invention. [0129] A study of the scalp and a study of the hair bulb are carried out to determine the effect of the composition according to the invention.
[0130] Après trois mois d'application : i. la composition induit une repousse significative des cheveux chez 100% des patients sur les zones temporales, pariétales et frontales du crâne. Cette repousse significative est visible en Figure 9. ii. une vascularisation développée est apparue autour du bulbe pileux alors que cette vascularisation était peu importante avant que les patients ne commencent les tests. [0130] After three months of application: i. the composition induces significant hair regrowth in 100% of patients on the temporal, parietal and frontal areas of the skull. This significant regrowth is visible in Figure 9. ii. a developed vascularization appeared around the hair bulb although this vascularization was little before the patients started the tests.
[0131] Ces premiers prouvent que la composition selon l'invention induit une vascularisation caractéristique de l'angiogénèse et de la croissance kératinocytaire. [0131] These first prove that the composition according to the invention induces vascularization characteristic of angiogenesis and keratinocyte growth.
[0132] En conclusion, dans les conditions expérimentales retenues, la composition selon l'invention, a un fort pouvoir pro angiogénique et pro-croissance des kératinocytes, qui se manifeste sur la formation et le développement des vaisseaux sanguins. [0132] In conclusion, under the experimental conditions retained, the composition according to the invention has a strong pro-angiogenic and pro-keratinocyte growth power, which is manifested in the formation and development of blood vessels.
[0133] Exemple 4 : Évaluation de l'effet de la composition selon l'invention sur l’inflammation dans un modèle in vivo réalisé chez des patients humains. [0133] Example 4: Evaluation of the effect of the composition according to the invention on inflammation in an in vivo model carried out in human patients.
[0134] Les résultats d'une étude in vivo réalisée sur 10 patients humains atteints d’inflammation, mettent en évidence le fort pouvoir anti-inflammatoire de la composition selon l'invention. [0134] The results of an in vivo study carried out on 10 human patients suffering from inflammation demonstrate the strong anti-inflammatory power of the composition according to the invention.
[0135] Dans ces expériences, la composition est appliquée 2 fois par jour (matin et soir) pendant 3 mois sur la peau de patients ayant des inflammations. [0135] In these experiments, the composition is applied twice a day (morning and evening) for 3 months to the skin of patients with inflammation.
[0136] Une étude de la peau avant/après traitement est mise en œuvre pour déterminer l'effet de la composition selon l'invention. [0136] A study of the skin before/after treatment is carried out to determine the effect of the composition according to the invention.
[0137] Après 3 mois d'application : i. La peau a visuellement dégonflée ; ii. Les rougeurs ont diminué voire disparues. [0137] After 3 months of application: i. The skin has visually deflated; ii. The redness has diminished or even disappeared.
[0138] Ces résultats sont confirmés en Figure 10 pour l’un des patients. [0138] These results are confirmed in Figure 10 for one of the patients.
[0139] Ces résultats prouvent que la composition selon l'invention induit une réduction de l’inflammation. [0139] These results prove that the composition according to the invention induces a reduction in inflammation.
[0140] Exemple 5 : Évaluation de l'effet de la composition selon l'invention sur le psoriasis dans un modèle in vivo réalisé chez des patients humains. [0140] Example 5: Evaluation of the effect of the composition according to the invention on psoriasis in an in vivo model carried out in human patients.
[0141] Les résultats d'une étude in vivo réalisée sur 10 patients humains atteints de psoriasis, mettent en évidence l’effet de la composition selon l'invention. [0141] The results of an in vivo study carried out on 10 human patients suffering from psoriasis demonstrate the effect of the composition according to the invention.
[0142] Dans ces expériences, la composition est appliquée 2 fois par jour (matin et
soir) pendant 3 mois sur la peau de patients atteint de psoriasis. [0142] In these experiments, the composition is applied twice a day (morning and evening) for 3 months on the skin of patients suffering from psoriasis.
[0143] Une étude de la peau avant/après traitement est mise en œuvre pour déterminer l'effet de la composition selon l'invention. [0143] A study of the skin before/after treatment is carried out to determine the effect of the composition according to the invention.
[0144] Après 3 mois d'application : i. Les plaques sont moins visibles et moins étendues ; ii. Les démangeaisons ont diminué. [0144] After 3 months of application: i. The plaques are less visible and less extensive; ii. The itching has lessened.
[0145] Ces résultats sont confirmés en Figure 11 et 12 pour deux patients. [0145] These results are confirmed in Figure 11 and 12 for two patients.
[0146] Ces résultats prouvent que la composition selon l'invention a un effet dans le traitement du psoriasis. [0146] These results prove that the composition according to the invention has an effect in the treatment of psoriasis.
[0147] Exemple 6 : Évaluation de l'effet de la composition selon l'invention sur l’eczéma dans un modèle in vivo réalisé chez des patients humains. [0147] Example 6: Evaluation of the effect of the composition according to the invention on eczema in an in vivo model carried out in human patients.
[0148] Les résultats d'une étude in vivo réalisée sur 10 patients humains atteints d’eczéma, mettent en évidence l’effet de la composition selon l'invention. [0148] The results of an in vivo study carried out on 10 human patients suffering from eczema demonstrate the effect of the composition according to the invention.
[0149] Dans ces expériences, la composition est appliquée 2 fois par jour (matin et soir) pendant 3 mois sur la peau de patients atteint de psoriasis. [0149] In these experiments, the composition is applied twice a day (morning and evening) for 3 months to the skin of patients suffering from psoriasis.
[0150] Une étude de la peau avant/après traitement est mise en œuvre pour déterminer l'effet de la composition selon l'invention. [0150] A study of the skin before/after treatment is carried out to determine the effect of the composition according to the invention.
[0151] Après 3 mois d'application : i. Les rougeurs de la peau ont diminué ; ii. L’étendue des plaques d’eczéma a diminué iii. La zone de la peau a dégonflé. [0151] After 3 months of application: i. The redness of the skin has decreased; ii. The extent of eczema patches has decreased iii. The skin area has deflated.
[0152] Ces résultats sont confirmés en Figure 13 pour un patient. [0152] These results are confirmed in Figure 13 for a patient.
[0153] Ces résultats prouvent que la composition selon l'invention a un effet dans le traitement du eczéma.
[0153] These results prove that the composition according to the invention has an effect in the treatment of eczema.
Claims
[Revendication 1] Composition comprenant : a. De l’acide citrique ; b. Du sel iodé ; c. Du jus d’oignon frais ; d. Du miel ; e. De l’alcool éthylique ou de l’alcoolat parfumé ; f. De la fleur d’oranger ; g. De l’eau de rose ; h. Du jus de citron. [Claim 1] Composition comprising: a. Citric acid; b. Iodized salt; vs. Fresh onion juice; d. Of honey ; e. Ethyl alcohol or perfumed alcohol; f. Orange blossom; g. Rose water; h. Lemon juice.
[Revendication 2] Composition selon la revendication précédente comprenant : a. Entre 0,1 et 1 % d’acide citrique ; b. Entre 5 et 10 % de sel iodé ; c. Entre 30 % et 40 % de jus d’oignon frais, de préférence 35% ; d. Entre 1 et 5 % de miel ; e. Entre 25 et 35 % d’alcool éthylique ou d’alcoolat parfumé, de préférence 30% ; f. Entre 15 et 20 % de fleur d’oranger ; g. Entre 0,5 et 10 % d’eau de rose ; h. Entre 5 et 10 % de jus de citron. [Claim 2] Composition according to the preceding claim comprising: a. Between 0.1 and 1% citric acid; b. Between 5 and 10% iodized salt; vs. Between 30% and 40% fresh onion juice, preferably 35%; d. Between 1 and 5% honey; e. Between 25 and 35% ethyl alcohol or perfumed alcoholate, preferably 30%; f. Between 15 and 20% orange blossom; g. Between 0.5 and 10% rose water; h. Between 5 and 10% lemon juice.
[Revendication 3] Composition selon l’une quelconque des revendications précédentes, où ladite composition comprend également entre 0.03 % et 1 % d’eau distillée, de préférence 0,3%. [Claim 3] Composition according to any one of the preceding claims, where said composition also comprises between 0.03% and 1% distilled water, preferably 0.3%.
[Revendication 4] Composition selon l’une quelconque des revendications précédentes, pour utilisation comme médicament dans le traitement de pathologies pouvant bénéficier d’une angiogenèse ou de la croissance des kératinocytes. [Claim 4] Composition according to any one of the preceding claims, for use as a medicament in the treatment of pathologies which may benefit from angiogenesis or the growth of keratinocytes.
[Revendication 5] Composition pour utilisation selon la revendication 4, dans le traitement de l’inflammation. [Claim 5] Composition for use according to claim 4, in the treatment of inflammation.
[Revendication 6] Composition pour utilisation selon la revendication 4, dans le traitement du psoriasis ou de l’eczéma.
[Claim 6] Composition for use according to claim 4, in the treatment of psoriasis or eczema.
[Revendication 7] Composition pour utilisation selon la revendication 4, dans le traitement de l’alopécie. [Claim 7] Composition for use according to claim 4, in the treatment of alopecia.
[Revendication 8] Composition selon l’une quelconque des revendications 4 à 7, où la voie d'administration est choisie parmi les voies : orales, intraveineuses, sous-cutanées, nasales ou autres, sous forme de comprimés, de solutions injectables, de sirops ou de gels. [Claim 8] Composition according to any one of claims 4 to 7, where the route of administration is chosen from the routes: oral, intravenous, subcutaneous, nasal or other, in the form of tablets, injectable solutions, syrups or gels.
[Revendication 9] Utilisation cosmétique non-thérapeutique de la composition selon l’une quelconque des revendications 1 à 3, en tant que composition anti-démangeaison. [Claim 9] Non-therapeutic cosmetic use of the composition according to any one of claims 1 to 3, as an anti-itch composition.
[Revendication 10] Utilisation cosmétique non -thérapeutique de la composition selon l’une quelconque des revendications 1 à 3, en tant que composition favorisant le renouvellement capillaire.
[Claim 10] Non-therapeutic cosmetic use of the composition according to any one of claims 1 to 3, as a composition promoting hair renewal.
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| FRFR2208441 | 2022-08-22 | ||
| FR2208441 | 2022-08-22 |
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| PCT/FR2022/051629 WO2024042274A1 (en) | 2022-08-22 | 2022-08-30 | Composition promoting keratinocyte growth and angiogenesis, and therapeutic and cosmetic applications thereof |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6171604B1 (en) * | 1996-04-12 | 2001-01-09 | Mahmoud A. Mousa | Honey preparations |
| WO2003003992A2 (en) * | 2001-07-03 | 2003-01-16 | Guermi, Salim | Hair lotion stimulating hair growth |
| WO2005087288A1 (en) * | 2004-02-10 | 2005-09-22 | Ahmed Kadri | Medicinal preparation for angiogenesis |
| CN101987147B (en) * | 2010-08-27 | 2012-10-17 | 葛德钜 | Medicament for treating eczema and preparation method thereof |
| US20150374613A1 (en) * | 2014-06-30 | 2015-12-31 | Ruzanna Kirakosyan | Hair loss prevention and restoration solution |
-
2022
- 2022-08-30 WO PCT/FR2022/051629 patent/WO2024042274A1/en unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6171604B1 (en) * | 1996-04-12 | 2001-01-09 | Mahmoud A. Mousa | Honey preparations |
| WO2003003992A2 (en) * | 2001-07-03 | 2003-01-16 | Guermi, Salim | Hair lotion stimulating hair growth |
| WO2005087288A1 (en) * | 2004-02-10 | 2005-09-22 | Ahmed Kadri | Medicinal preparation for angiogenesis |
| CN101987147B (en) * | 2010-08-27 | 2012-10-17 | 葛德钜 | Medicament for treating eczema and preparation method thereof |
| US20150374613A1 (en) * | 2014-06-30 | 2015-12-31 | Ruzanna Kirakosyan | Hair loss prevention and restoration solution |
Non-Patent Citations (1)
| Title |
|---|
| RELLY W J: "PHARMACEUTICAL NECESSITIES", SCIENCE AND PRACTICE OF PHARMACY, XX, XX, vol. 2, 1 January 1995 (1995-01-01), pages 1380 - 1416, XP002939997 * |
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