BE1027772A1 - COMPOSITION OF GINSENG TO IMPROVE SKIN CONDITION AND ITS USE FOR THE TREATMENT OF DERMATOLOGICAL DISEASES - Google Patents

Abstract

Disclosed is a composition, kit and preparation for improving the condition of the skin of a subject. The invention also relates to the composition for use as a medical or therapeutic substance. The composition includes a rare ginsenoside, a ginsan and a gintonin. Preferably, the ratio of ginsan to gintonine is at least 500: 1 and at most 1: 100. Preferably, the ratio of rare ginsenosides to ginsan and gintonine is at least 250: 1 and at most 1:40.

Description

COMPOSI TION OF GINSENG FOR AMELI ORERING THE CONDITION OF THE SKIN AND ITS USE FOR THE TREATMENT OF A DERMATOLOGICAL DISEASE THAT FIELD OF THE INVENTION The invention relates to a composition comprising a rare ginsenoside, a ginsan and a gintonine, a kit thereof, their use as a medical or therapeutic substance and their preparation.

BACKGROUND The chemical constituents of Panax ginseng and other genera can be classified as saponins, polysaccharides, flavonoids and volatile oils. Most of the biological activities of ginseng have been attributed to the constituents of saponin (i.e. ginsenoside) and their metabolites. In the cosmetic industry, the chemical constituents of Panax ginseng and other genera are used for various applications. For example, Panax notoginseng extract is claimed for activating skin elasticity to improve wrinkles and prevent chronological and UV-induced aging (eg JP 2006 028 150). In addition, Rb1 ginsenoside have been described to stimulate the synthesis of elastin (for example WO 1999 007 338), to treat the hair (FR 9 300 899 or US 5 663 160), to stimulate the regeneration of wounds (JP 2002 255 826), for the reconstruction of tissues suffering from aging of the skin (WO 2002 072 599) and for treating wounds in the event of burns (JP 2004 077 456). Ginsenoside Rb1 is also used in combination with ginsenosides Rc and Rd (JP 2003 070 496) to activate the endonuclease for the repair of DNA damaged by UV. The ginsenosides Rh2 and Rg3 are mixed in a cosmetic composition which blocks UV rays because of their UV absorption properties (KR 2004 0 098 177). One of the objectives of the present invention is to provide novel compounds and compositions which are highly active and easy to obtain for improving the condition of the skin of a subject. A particular object of the invention is to provide compounds and compositions intended for use in medical treatment, preferably medical treatment for the treatment and / or prevention of a skin and / or dermatological disease in a subject. . It is also an object of the present invention to provide a method for preparing such compositions and for administering such compositions to a subject.

SUMMARY OF THE INVENTION The present invention provides a solution to at least one of the aforementioned problems by providing compositions comprising a rare ginsenoside, a ginsan and a gintonine, for improving the condition of the skin of a subject, their use as substances. medical or therapeutic and more particularly their use as a medicament for the treatment or prevention of a skin and / or dermatological disease.

Firstly, the invention relates to a composition comprising a rare ginsenoside, a ginsan and a gintonine in the report detailed in claim 1. The inventors have surprisingly found that such compositions exhibit an improvement in the state of the body. skin in a subject, in particular compared to traditional compositions based on Panax ginseng.

In a second aspect, the invention relates to a composition according to the first aspect of the invention for use as a medicament according to claim

8. The composition being provided in a pharmaceutically and / or cosmetically acceptable carrier, for use in the treatment and / or prevention of skin and / or dermatological disease.

In a third aspect, the invention relates to a method for improving the condition of the skin of a subject according to claim 9. The method comprises the step of administering to the subject a composition according to a first aspect of the invention and / or a composition according to a second aspect of the invention.

In a fourth aspect, the invention relates to a method of preparing a composition according to claim 13. The composition comprising a rare ginsenoside, a ginsan and a gintonin. The method comprising the steps of extracting each of said rare ginsenoside, ginsan and gintonin separately from a cultivated ginseng root.

In a fifth aspect, the invention relates to a method for the preparation of a composition according to claim 14. A composition according to the first and / or the second aspect of the invention is prepared according to the fourth aspect of the invention.

In a sixth aspect, the invention relates to a kit of the invention according to claim 15. DETAILED DESCRIPTION OF THE INVENTION The invention relates to a composition for improving the condition of the skin of a subject as well. than on its use and preparation. The invention further relates to a kit according to the invention. The composition of the invention essentially comprises a rare ginsenoside, a ginsan and a gintonin. In the following, the invention will be described in detail, aspects and preferred embodiments will be examined and the invention will be illustrated by way of non-limiting examples. The preferred aspects and embodiments as presented herein are not intended to limit the scope of the present invention.

Unless defined otherwise, all terms used in the disclosure of the invention, including technical and scientific terms, have the meanings commonly given to them by ordinary skill in the art to which this invention belongs. Definitions of terms are included for guidance to better appreciate the teaching of the present invention.

The following terms, as used in this document, have the following meanings: "A" and "the", as used in this document, mean both singular and plural, unless the context clearly indicates otherwise. By way of example, "a rare ginsenoside" refers to one or more rare ginsenosides, "a ginsan" refers to one or more ginsan and "a gintonin" refers to one or more gintonin.

The term "about" as used herein to denote a measurable value such as a parameter, quantity, time duration, etc., is intended to encompass variations of +/- 20% or less, preferably +/- 10% or less, more preferably +/- 5% or less, and still more preferably +/- 0.1% or less of the specified value, as long as these variations are appropriate for the execution of the disclosed invention. However, it should be understood that the value to which the modifier "about" refers is itself also specifically disclosed. The terms "comprising", "comprising", and "includes" and "composed of", as used herein, are synonymous with "including", "including", "includes" or "containing" , "containing", "contains", and are inclusive or non-limiting terms which specify the presence of the following, for example a component, and do not exclude the presence of components, characteristics, elements, members or additional steps not mentioned, known in or disclosed in the art.

Further, the terms first, second, third and the like in the description and in the claims, are used to distinguish like elements and not necessarily to describe a sequential or chronological order, unless otherwise indicated. It should be understood that the terms thus used are interchangeable in appropriate circumstances and that the elements of the invention described herein are likely to operate in sequences other than those described or illustrated herein.

The recitation of the number ranges by the end points includes all numbers and fractions subsumed within that range, as well as the recited end points. All percentages are to be understood as percentages by weight, unless they are defined otherwise or a different meaning is apparent to those skilled in the art from their use and the context in which they are used. The term "wt%", "wt%", "wt%" or "wt.%", Herein and throughout the specification, unless otherwise indicated, refers to the relative weight of the respective component based on the weight. overall weight of the formulation.

While the terms "one or more" or "at least one", such as one or more or at least one member (s) of a group of members, are clear in themselves, the term - encompasses, for example, a reference to any of said members, or to two or more of said members, such as, for example, any 23,> 4, 25, 26 or 27 etc. of said members, and up to all said members.

Unless defined otherwise, all terms used in the disclosure of the invention, including technical and scientific terms, have the meanings commonly given to them by one of the ordinary skill in the art to which this invention pertains. Definitions of the terms used in the description are included for guidance in order to better appreciate the teaching of the present invention. The terms or definitions used in this document are provided only to assist in understanding the invention.

Reference to "an embodiment" throughout this specification means that a particular feature, structure, or trait described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the phrase "in one embodiment" which appears at various places in this specification does not necessarily all refer to the same embodiment, but can do so. In addition, particular traits, structures or characteristics can. be combined in any suitable manner, as would be apparent to those skilled in the art from the present disclosure, in one or more embodiments. Furthermore, while certain embodiments described herein include certain features included in others Embodiments but not others, the combinations of features of different embodiments are intended to fall within the scope of the invention and form different embodiments, as would be understood by those of the art. in the following claims any of the claimed embodiments can be used in any… - combi naison.

The present invention provides a solution to at least one of the aforementioned problems by providing a composition comprising essentially a rare ginsenoside, a ginsan and a gintonin.

1. Composition of the invention Firstly, the invention relates to a composition intended to improve the condition of the skin of a subject. This composition preferably comprises a rare ginsenoside. Said composition preferably comprising a ginsan. Said composition preferably comprising a gintonin.

The term "subject" as used herein is to be understood as a human or animal body.

In the present document, the term “animal” preferably designates vertebrates, more preferably birds and mammals, and more preferably still mammals.

The term "subject in need" as used herein is to be understood as a patient, animal or human, who will benefit from the treatment of this disclosure. "Composition" as used herein should be understood to optionally include additional ingredients, additives, carriers, nutraceuticals, pharmaceutical compositions and physiologically acceptable compositions, and the like.

It will be understood that when, for example, a rare ginsenoside, ginsan or gintonin in a "composition" is also found in a natural source, the term "composition" does not include the natural source of the component, but may, in some embodiments, encompass a physically or chemically modified or processed form of the natural source, such as an extract from the natural source.

According to a particularly preferred embodiment of the invention, the “composition”, as used herein, should be understood as a composition intended for oral administration.

According to a particularly preferred variant of the invention, the “composition”, as used in the present document, should be understood as a dermatological and / or cosmetic preparation.

"Ginseng" as used herein is to be understood as a species belonging to the genus Panax of the family Araliaceae.

Ginseng can be available in different forms which are divided into fresh ginseng, white ginseng, and red ginseng, depending on the method of processing.

Ginseng can also be classified into artificially grown ginseng, artificially sown ginseng but cultivated in the wild, and wild ginseng depending on the growing conditions.

In particular, the term "ginseng" as used herein is intended to include all kinds of ginseng, so American ginseng and Chinese ginseng as well as Korean ginseng are within the scope of this communication. .

The term "rare ginsenoside", as used herein, should be understood as synonymous with the terms "prototype ginsenoside" or "ginsenosides - noble" and refers to a class of tetracyclic triterpenoids and their derivatives.

Examples include, but are not limited to, Rg3, Rh1, C-K, Rh2, Rg5, Rk1, Rh3, Rk2,

Rh4, Rk3, aPPT and aPPD. Preferably, the rare ginsenosides are selected from the group comprising: C-K, Rg6, Rh4, Rg3, PPT, Rk1, Rg5, Rh2, Rh3 and PPD. "Ginsan" as used herein is to be understood as an acidic polysaccharide isolated from a species of the genus Panax. In particular, ginsan has a molecular weight of around 150 kDa and is composed of 3.7% protein, 47.1% hexoses (glucose and galactose) and 43.1% uronic acid (galacturonic acid) . "Gintonine" as used herein is to be understood as a glycolipoprotein moiety isolated from a species of the genus Panax. In particular, gintonine is a pentameric entity with a molecular weight of about 67 kDa and an apparent molecular weight of about 13 kDa. More particularly, gintonine has an amino acid composition comprising cysteine and cystine, asparagine and aspartic acid, glutamine and glutamic acid, serine, glycine, arginine, threonine, alanine, proline, valine, isoleucine, leucine, phenylalanine, tryptophan and lysine, a carbohydrate composition comprising rhamnose, arabinose, glucose, mannose, xylose and glucosamine, and a composition lipids comprising linoleic acid, palmitic acid, oleic acid and stearic acid.

The inventors have surprisingly observed that the compositions according to the invention improve the condition of the skin of a subject or of a subject who needs it, especially compared to traditional compositions based on Panax ginseng. This is of particular interest, since these compositions include natural herbal components. Such compositions are also easy to obtain, as shown in the illustration below. The term "skin condition" as used herein should be understood as synonymous with the terms "skin health" or "skin quality". In a particularly preferred embodiment, "skin condition" as used herein is to be understood to refer to a plurality of phenotypic attributes of the skin. The phenotypic attributes of the skin can include one or more nutritional states of the skin and / or one or more health characteristics of the skin. The term "improvement in skin condition" as used herein should be understood to mean improvement in the "reduced skin condition" of a subject, i.e. - say a less favorable condition than an "improved skin condition".

The term "improved" as used herein is to be understood as the ability of a compound, composition, agent or method to ameliorate a described symptom or condition. , depending on the context in which the term "improve" is used. Preferably the improvement is at least 10%, more preferably at least 25%, still more preferably at least 50%, and most preferably the symptom or condition is improved by at least 75%. The term "reduced" as used herein is to be understood as the ability of a compound, composition, agent or method to reduce or interfere with a described symptom or condition. , depending on the context in which the term "reduce" is used. Preferably the reduction is at least 10%, more preferably at least 25%, still more preferably at least 50%, and most preferably the symptom or condition is reduced by at least 75%. %.

The term "symptom" as used herein is to be understood as being interchangeable with the term "sign". Therefore, the term "symptom" as used herein refers to a physical and / or mental condition which indicates a particular disease or disorder (eg, Longman Dictionary of Contemporary English (1995). Third Edition) detectable by the subject suffering from a particular disease or disorder or detectable by a person other than the subject without verbal information from the latter. Preferably in a composition according to a first aspect, the ratio between ginsan and gintonine is at least 500: 1. The applicant points out that such a ginsan / gintonine ratio is at least necessary for the composition to improve the condition of the skin of a subject, in particular compared to traditional compositions based on Panax ginseng, the ginsan / gintonine ratio is preferably at least 490: 1, even more preferably at least 490: 1, still more preferably at least 450: 1, still more preferably at least 400: 1, still more preferably at least 350: 1, still more more preferably at least 300: 1, still more preferably at least 250: 1, still more preferably the ratio of ginsan to gintonine is at least 250: 1, still more preferably at least 200: 1, still more preferably at least 150: 1, still more preferably at least 100: 1, still more preferably at least 150: 1, still more preferably at least 100: 1, still more preferably at least 50: 1, still more preferably at least 45: 1, still more preferably at least

40: 1, still more preferably at least 35: 1, still more preferably at least 30: 1, still more preferably at least 25: 1, still more preferably at least 20: 1, still more preferably at least 17: 1, again more preferably at least 15: 1, still more preferably at least 12: 1, still more preferably at least 10: 1, still more preferably at least 9: 1, still more preferably at least 8: 1, still more preferably at least 7 : 1, still more preferably at least 6: 1 and still more preferably at least 5: 1.

Preferably in a composition according to a first aspect, the ratio between ginsan and gintonine is at most 1: 100. The applicant notes that this ginsan / gintonine ratio is at most required in such a composition for it to improve the condition of the skin of a subject, in particular compared to traditional compositions based on Panax ginseng, the ratio ginsan / gintonine is preferably at most 1:90, still more preferably at most 1:80, still more preferably at most 1:70, still more preferably at most 1:60, still more preferably at most 1:70. maximum 1:50, still more preferably maximum 1:40, still more preferably maximum 1:30, still more preferably maximum 1:20, still more preferably maximum 1:10, still more preferably maximum 1: 5, still more preferably at most 1: 4, still more preferably at most 1: 2, still more preferably at most 1: 1, still more preferably at most 2: 1 and still more preferably at most 3: 1.

More preferably, the ratio of ginsan to gintonine is about 1: 4. Applicant notes the best improvement in skin condition in a subject at ginsan / gintonine ratios of about 1: 4.

Preferably in a composition according to a first aspect, the ratio of rare ginsenosides to ginsan and gintonine is at least 250: 1. The applicant observes that such a ratio between rare ginsenosides and a total amount of ginsan and gintonine is at least necessary for the composition to improve the condition of the skin of a subject, in particular compared to traditional compositions with Panax ginseng base, and that preferably the ratio of rare ginsenosides to ginsan and gintonine is at least 200: 1, or even at least 150: 1, and preferably at least 100 : 1. Applicant notes that a ratio of rare ginsenosides to a combination of ginsan and gintonine of at least 80: 1 causes additional performance enhancing skin condition in a subject, more preferably the ratio of rare ginsenosides to ginsan and gintonine is at least 60: 1, still more preferably at least 40: 1, still more preferably at least 20: 1, still more preferably at least 10: 1.

The applicant notes that a ratio of rare ginsenosides to a combination of ginsan and gintonine of at least 8: 1 causes an even greater skin condition improving the performance of a subject, more preferably the ratio of rare ginsenosides and ginsan and gintonine is at least 6: 1, still more preferably at least 4: 1 and still more preferably at least 3: 1.

Preferably in a composition according to a first aspect, the ratio of rare ginsenosides to ginsan and gintonine is at most 1:40. The applicant observes that such a ratio between rare ginsenosides and the total amount of ginsan and gintonine is at most necessary for the composition to improve the condition of the skin of a subject, in particular compared to traditional compositions. based on Panax ginseng, the ratio between rare ginsenosides and ginsan and gintonine is preferably at most 1:30, more preferably at most 1:20 and more preferably still at most 1:10. Applicant notes that a ratio of rare ginsenosides to a combination of ginsan and gintonine of at most 1: 5 causes additional performance enhancing skin condition in a subject, preferably at most 1: 4, d '' at most 1: 3, at most 1: 2, at most 1: 1. Preferably, the ratio of rare ginsenosides to ginsan and gintonine is about 2: 1. Applicant notes that a subject's skin condition improved the most with a ratio of rare ginsenosides to ginsan and gintonine of about 1: 4. In a preferred embodiment, the present invention provides a composition comprising a ratio of rare ginsenosides to ginsan of at least 300: 1. The applicant observes that such a ratio is at least necessary for the composition to improve the condition of the skin of a subject, in particular compared to traditional compositions based on Panax ginseng, and that it is more preferable than the composition comprises a rare ginsenoside / ginsan ratio of at least 300: 1 and at most 1:30, and more preferably at least 250: 1 and at most 1:20, and more preferably still d 'at least 200: 1 and at most 1:15, more preferably still at least 150: 1 and at most 1:10, more preferably still at least 100: 1 and at most 1: 7, more preferably still at least 50: 1 and at most 1: 5, more preferably still at least 40: 1 and at most 1: 4, more preferably still at least 30: 1 and at most 1: 3, more preferably still at least 20: 1 and at maximum 1: 2, more preferably still at least 10: 1 and at most 1: 1, more preferably still at least 5: 1 and at most 1: 1.

More preferably, the ratio of rare ginsenosides to ginsan is about 2.5: 1. Applicant notes the most improved skin conditions in a subject at such ratios of rare ginsenosides relative to ginsan. The present invention provides a composition comprising a ratio of rare ginsenoside to gintonine of at least 1000: 1. The applicant points out that such a ratio is at least necessary for the composition to improve the condition of the skin of a subject, in particular compared to traditional compositions based on Panax ginseng, and that, preferably, the composition comprises a rare ginsenoside / ginsan ratio of at least 1000: 1 and at most 1:10, more preferably at least 900: 1 and at most 1: 9, more preferably at least 80: 1 and at most 1 : 8, more preferably still at least 700: 1 and at most 1: 7, more preferably still at least 600: 1 and at most 1: 6, more preferably still at least 500: 1 and at most 1: 5, more preferably still at least 400: 1 and at most 1: 4, more preferably still at least 300: 1 and at most 1: 3, more preferably still at least 200: 1 and at most 1: 2, more preferably still at least 100: 1 and at most 1: 1, more preferably still at least 90: 1 and at most 1: 1, more preferably still at least 80: 1 and at m aximum 1: 1, more preferably still at least 70: 1 and at most 1: 1, still more preferably at least 60: 1 and at most 1: 1, still more preferably at least 50: 1 and at most 1: 1, still more preferably at least 40: 1 and at most 1: 1, still more preferably at least 30: 1 and at most 1: 1 and still more preferably at least 20: 1 and at most 5: 1. Preferably, the ratio of rare ginsenosides to gintonine is about 10: 1. Applicant notes the most improved skin conditions in a subject at such ratios of rare ginsenosides relative to ginsan.

The present invention provides a composition comprising one or more rare ginsenosides selected from the group: Rg6, Rh4, Rg3, PPT, Rk1, Rg5, Rh2, Rh3 and PPD. Preferably, at least 40% by weight of the rare ginsenosides of said group are attributed to one or more ginsenosides chosen from the group comprising: Rg6, Rh4, Rg3, Rk1 and Rg5, preferably at least 42% by weight, more preferably at least. at least 45% by weight, more preferably at least 50% by weight, more preferably at least 55% by weight, more preferably at least 60% by weight, more preferably at least 65% by weight and more preferably at least less 70% by weight.

In a preferred embodiment, the present invention provides a composition further comprising a ginsenoside. The term "ginsenoside" as used in the present invention should be understood as synonymous with the term "panaxoside" and refers to a class of naturally occurring steroid glycosides and triterpene saponins found in ginseng. It should be clear that when reference is made to "ginsenoside" in this document, "rare ginsenosides" are excluded, unless otherwise specified. Thus, when "ginsenoside" is referred to in this document, it should be is referred to as "classical ginsenosides", unless otherwise specified. In particular, ginsenosides have a basic structure composed of a gonan steroid nucleus having 17 carbon atoms arranged in a tetracyclic configuration. Ginsenoside compounds, including protopanaxadiol-type ginsenosides such as the ginsenosides Rb1, Rb2, Rc and Rd, are known to those skilled in the art (see, e.g., Yu et al., Chem. Pharm. Bull. . 2007, 55 (2), 231-235; Court, "The Principal Active Chemicals in Panax species" in Ginseng: The Genus Panax (Court, ed., Harwood Academic Publishers, Amsterdam, The Netherlands, 2000). , the ginsenoside is chosen from the group comprising: Rg1, Re, Rf, Rh1, Rg2, Rb1, Rc, Rb2 and Rd. Preferably, the - ginsenoside is chosen from the group comprising: Rg2, Rb1, Rc, Rb2 and Rd The present invention provides, in a preferred form, a composition comprising one or more ginsenosides selected from the group: Rg1, Re, Rf, Rh1, Rg2, Rb1, Rc, Rb2 and Rd. Preferably, at least 40% by weight ginsenosides of said group are assigned to one or more ginsenosides chosen from the group comprising: Rg2, Rb1, Rc, Rb2 and Rd, preferably at least 45 % by weight, preferably at least 50% by weight, preferably at least 55% by weight, preferably at least 60% by weight, preferably at least 65% by weight and preferably at least 70% by weight.

In a preferred embodiment, the present invention provides a composition comprising a rare ginsenoside / ginsenoside ratio of at least 200: 1, more preferably at least 200: 1 and at most 1: 5, still more preferably d 'at least 150: 1 and at most 1: 5, still more preferably at least 100: 1 and at most 1: 5, still more preferably at least 50: 1 and at most 1: 5 , more preferably still at least 40: 1 and at most 1: 4, more preferably still at least 30: 1 and at most 1: 3, more preferably still at least 20: 1 and at most 1: 2, more preferably still at minus 10: 1 and at most 1: 1 and more preferably at least 6: 1 and at most 2: 1 and more preferably about 4: 1.

In a preferred embodiment, the present invention provides a composition comprising Rg5 and Rh2 and optionally one or more rare ginsenosides selected from the group comprising: C-K, Rg6, Rh4, Rg3, PPT, Rk1, Rh3 and PPD. Preferably, the ratio between Rg5 and Rh2 and a total amount of rare ginsenosides is at least 1: 1, more preferably at least 1: 1 and at most 1: 4. The applicant notes a higher efficiency for such reports. More preferably, the ratio of Rg5 to Rh2 and a total amount of rare ginsenoside is at least 1: 1.5 and at most 1: 2.5. Preferably, the ratio of Rg5 to Rh2 and a total amount of rare ginsenoside is about 1: 2. The applicant notes the best results at ratios of approximately 1: 2.

In a preferred embodiment, the present invention provides a composition comprising a ginsenoside selected from the group consisting of: Rg1, Re, Rf, Rh1, Rg2, Rb1, Re, Rb2 and Rd and wherein the ratio of Rc to a total amount rare ginsenoside and ginsenoside is at least 1: 1, more preferably at least 1: 1 and at most 1: 3. The applicant notes better results at such ratios. It is preferable that the ratio between Rc and the total amount of rare ginsenoside and ginsenoside is at least 1: 1.5 and at most 2.5. Preferably, the ratio of Rc to a total amount of rare ginsenoside and ginsenoside is about 1: 2. The applicant notes the best results at ratios of approximately 1: 2.

In a preferred embodiment, the present invention provides a composition comprising a ginsenoside, the ratio of one or more compounds selected from the group consisting of: CK, Rk1, Rh2, Rh3, Rh4, Rg2, Rg3 and Rg6 to a total amount of rare ginsenosides and ginsenosides in the composition is at least 1: 4. Compounds of the group: C-K, Rk1, Rh2, Rh3, Rh4, Rg2, Rg3 and Rg6 have a high bioavailability compared to other rare ginsenosides or ginsenosides.

In addition, the applicant notes a considerable improvement in the results with a ratio of at least 1: 4. More preferably, the ratio of one or more compounds selected from the group consisting of: CK, Rk1, Rh2, Rh3, Rh4, Rg2, Rg3 and Rg6 to a total amount of ginsenosides and rare ginsenosides in the composition is at least 1: 4 and at most 1: 1, more preferably at least 1: 3 and at most 1: 1.5 and more preferably about 1: 2. The applicant notes the best results at ratios of approximately 1: 2. Additional Ingredient The composition as presented herein may include an additional ingredient.

By "additional ingredient" is meant herein one or more of the following excipients; surfactants; dispersing agents; inert diluents; granulation and disintegration agents; binding agents; lubricating agents; sweetening agents; flavoring agents; dyes; preservatives; physiologically degradable compositions such as gelatin; vehicles and aqueous solvents; oily vehicles and solvents; suspending agents; dispersing or wetting agents; emulsifying, demulsifying agents; tampons; salts; agents - thickeners; charges; emulsifying agents; antioxidants; antibiotics; antifungal agents; stabilizers; and pharmaceutically acceptable polymeric or hydrophobic materials.

Other "additional ingredients" which may be included in pharmaceutical compositions are known in the art and described, for example in Genaro, ed. (1985, Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa.). By “pharmaceutical composition” is meant a composition comprising at least one active principle, the composition being able to be studied with a view to obtaining a specific and effective result in a mammal (for example, without limitation, a human). Those of ordinary skill in the art will understand and appreciate the proper techniques for determining whether an active ingredient has a desired effective result based on the needs of the artisan.

Suitable excipients include carbohydrate or protein fillers such as sugars, especially lactose, sucrose, mannitol or sorbitol; starch from corn, wheat, rice, potato, etc. ; celluloses such as methylcellulose, hydroxypropylmethylcellulose or sodium carboxymethylcellulose; and gums, especially arabica and tragacanth; and proteins such as gelatin and collagen. Suitable disintegrating or solubilizing agents include agar, alginic acid or a salt thereof such as sodium alginate.

Other components such as preservatives, antioxidants, surfactants, absorption agents, viscosity enhancers or film-forming polymers, bulking agents, diluents, colorants, flavorings, modifiers of pH, sweeteners or flavor masking agents can also be incorporated into the composition. Suitable coloring agents include red, black, and yellow iron oxides and FD&C colorants such as FD&C Blue # 2 and FD&C Red # 40. Suitable flavoring agents include mint, raspberry, licorice, flavorings, etc. orange, lemon, grapefruit, caramel, vanilla, cherry grape and their combinations. Suitable pH modifiers include citric acid, tartaric acid, phosphoric acid, hydrochloric acid, maleic acid, and sodium hydroxide. Suitable sweeteners include aspartame, acesulfame K, and thaumatin. Suitable taste masking agents include sodium bicarbonate, vanilla, ion exchange resins, cyclodextrin inclusion compounds, and adsorbates. Carrier The composition as presented herein may include a carrier.

The composition as described herein can include a pharmaceutically acceptable carrier. The composition as described here can comprise a cosmetically acceptable carrier.

By "pharmaceutically acceptable carrier" as used herein, it is meant a chemical composition with which the composition and in particular the essential constituents of the composition (rare ginsenoside, ginsan and gintonine) can be combined and which, after the combination, can be used orally to administer the composition to a subject. Pharmaceutically acceptable carriers are known to those skilled in the art.

Examples of pharmaceutically acceptable carriers are sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Saline solutions and aqueous solutions of dextrose and glycerol can also be used as liquid carriers, in particular for injectable solutions. Examples of suitable pharmaceutical carriers are described in Remington: Science and Practice of Pharmacy, 21st Edition, Lippincott Williams & Wilkins, Philadelphia PA (2005) and Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems, 8th Edition, Lippincott Williams & Wilkins, Philadelphia PA (2004).

The term "cosmetically acceptable carrier" as used herein is to be understood as a chemical composition with which a suitable compound or derivative can be combined and which after combination can be used topically. to administer the composition to a subject. Cosmetically acceptable carriers are known to those skilled in the art. "Topical application", as used herein, should be understood as administration to a surface, such as the skin. This term is used interchangeably with "cutaneous application" in the case of the skin. A "topical application" is a "direct application".

The term "suitable carrier" as used herein is to be understood as a cosmetically acceptable liquid medium, and preferably a pharmaceutically acceptable liquid medium such as is commonly used in gels, lotions, shampoos. , liquid soaps, etc. Those skilled in the art will readily distinguish a "cosmetically acceptable liquid medium" and a "pharmaceutically acceptable liquid medium" from a "cosmetically unacceptable liquid medium" and a "pharmaceutically unacceptable liquid medium" respectively.

Additive The composition as presented here may include an additive.

In addition to the essential components described above, the present compositions may also include one or more optional components known or otherwise suitable for use on human or animal hair or skin. Non-limiting examples of these optional components include, for example, a foaming agent, plasticizers and humectants (such as glycerol, propan-1,2-diol, polypropylene glycol and other polyhydric alcohols), radical scavengers free, viscosity adjusting agents, colorants, fragrances, preservatives and the like. The present composition further comprises a foaming agent in a preferred embodiment. Foaming agents are agents which promote the formation of foam. Any agent having a surfactant character can be used. Surfactants can be cationic, nonionic or anionic. Examples of suitable foaming agents include, but are not limited to, cetrimide, lecithin, soaps and the like, and for example, anions (based on sulfate, sulfonate or carboxylate anions): sodium dodecylsulfate (SDS ), ammonium lauryl sulfate and other salts of alkylsulfate, sodium laurethsulfate, also called sodium laurylethersulfate (SLES), alkylbenzenesulfonate; soaps or salts of fatty acids (see salts of acids); cationic (based on quaternary ammonium cations): cetyltrimethylammonium bromide (CTAB) aka hexadecyltrimethylammonium bromide, and - other alkyltrimethylammonium salts, cetylpyridinium chloride (CPC), polyethoxylated tallow amine (POalkonium), benzene chloride (BAC), benzethonium chloride (BZT); zwitterionic (amphoteric): dodecylbetaine, dodecyl-dimethylamine oxide, cocamidopropylbetaine, coconut amphoglycinate; nonionic: alkyl-poly (ethylene oxide), alkyl-polyglucosides, including: octyl- - glucoside, decyl-maltoside, fatty alcohols, cetyl alcohol, oleyl alcohol. Commercially available surfactants, such as TWEEN "", are also suitable.

The compositions according to the invention are stored at room temperature, and preferably at a temperature below room temperature, such as for example at a temperature below 20 ° C, at 15 ° C, at 10 ° C or at 5 ° C. . Preferably, said compositions are stored at a temperature of about 4 ° C.

For reasons of efficient handling, it is preferable that the compositions are stored at a temperature above the melting temperature of the support. Kit of the composition In a sixth aspect, the invention relates to a kit comprising one or more aliquots of a composition comprising a rare ginsenoside, a ginsan and a gintonin. Preferably, the composition is a composition according to a first and / or a second aspect of the invention.

The kit may include an aliquot for each distinct component of the composition described herein. The kit can also include an aliquot for any combination of separate components of the composition described herein.

Optionally, the kit includes instructional material. By "educational material" is meant a publication, recording, diagram or other means of expression which can be used to communicate the utility of a compound of the composition disclosed in the kit for alleviating various diseases or disorders. mentioned in this document. Optionally or alternatively, the teaching aids may describe one or more methods of alleviating a disease or disorder of a subject. The teaching aids of the kit can, for example, be attached to a container containing the Compound Disclosure - identified or shipped with a container containing the identified compound Educational materials may also be shipped separately from the container with the intention that the educational material and the compound are used jointly by the recipient.

2. Use of a composition of the invention In a second aspect, the invention relates to the composition intended for use as a medicament. Preferably, for said use, the composition is provided in a pharmaceutical carrier. Preferably, for said use, the composition is provided in a cosmetically acceptable carrier. Preferably the medicament, for use in the treatment and / or prevention of skin and / or dermatological disease.

In a third aspect, the invention relates to a method for improving the condition of the skin of a subject.

The method comprises the step of administering, to the subject, a composition according to a first aspect and / or a composition according to a second aspect.

Preferably the method, for use in the treatment and / or prevention of skin and / or dermatological disease.

In accordance with the present invention, a composition comprising a rare ginsenoside, a ginsan and a gintonin, as described herein, is used to improve the condition of the skin of a subject.

Said composition can also be used for the treatment of a skin and / or dermatological disease.

Preferably, said skin and / or dermatological disease being linked to inflammation, an allergic reaction, a hypersensitivity or contact intolerance reaction, excessive sebaceous secretion, exfoliation or microbial dysbiosis.

Preferably, said skin and / or dermatological disease is related to the epidermis.

The use of the present composition includes prophylactic use.

Preferably, improving the condition of the skin of a subject or subject in need thereof is at least one of the following: skin hydration, skin whitening, wrinkle reduction or anti-aging. -aging.

The term "skin hydration" as used herein should be understood synonymously with the terms "skin hydration", "skin absorption" or "skin adsorption" and generally designates the methods for improving the absorption capacity and / or adsorption of water by the skin.

In the present document, the terms “absorption” or “absorption” designate in the broad sense the absorption of water by the skin, in particular by the epidermis and more particularly by the stratum corneum.

In the present document, the terms “adsorption” or “adsorption” designate in the broad sense the adsorption of water on the skin, in particular on the proteins of the epidermis and more particularly on the stratum corneum.

The term "skin whitening" as used herein should be understood as synonymous with the terms "skin lightening" or "skin whitening" and generally refers to methods of lightening, bleaching. and / or even skin tone, skin color and / or skin tone, and / or reduction of salinity, and / or lightening and / or discoloration of marks and / or hyperpigmented lesions including, but not limited to pigmented spots, melanin spots, age spots, sun spots, senile lentigines, freckles, lentigines simplex, pigmented solar keratosis, seborrheic keratosis, melasma, acne marks,

post-inflammatory hyperpigmentation, lentigins, ephelids, combinations of two or more of them and others.

The term "wrinkle reduction" as used herein should be understood as synonymous with the term "wrinkle minimization" and generally refers to methods of treatment, including prevention, reduction, improving and / or eliminating signs of dermatological aging, for example wrinkles, fine lines, folds and furrows of the skin.

More particularly, "wrinkle reduction" relates to the treatment or reduction of hyperhidrosis and / or improvement of the aesthetic appearance of a subject's skin.

The term "anti-aging", as used herein, generally refers to methods of treating changes in the skin, such as skin aging and, in particular, aging induced by oxidative or degenerative processes.

In particular, the term "anti-aging" as used herein refers to methods of treating symptoms of aging skin, including rhytides, wrinkles, jowls, sun damage, dull appearance of the skin, sagging skin, keratosis, hyperpigmentation, melasma, solar lentigo, solar keratosis, dermatophilosis or other skin discoloration disorders associated with aging.

The term "treatment" as used herein is to be understood to include the prophylaxis of a specific injury, disease, disorder or condition, or the alleviation of symptoms. symptoms associated with a specific injury, disease, disorder or condition and / or the prevention or elimination of such symptoms.

The term "treatment" is used interchangeably herein with the term "care". The term "prevent", as used in this document, should be understood as a means to prevent something from happening or to take prior action against a possible or probable situation.

In the context of medicine, "prevention" generally refers to measures taken to reduce the chances of contracting a disease or medical condition.

"Prophylactic" treatment, as used herein, is to be understood as treatment administered to a subject who shows no signs of illness or injury or who shows only early signs of illness or injury. , with the aim of reducing the risk of developing pathology associated with the disease or injury.

The term "disorder" as used herein is to be understood as a subject in a state of health in which the subject is able to maintain homeostasis, but in which the state of health of the subject is less favorable. than it would be in the absence of the disorder. If left untreated, a disease does not necessarily lead to further deterioration in the subject's state of health. In the context of the present application, a reduced skin condition can be regarded as a disorder. Improving a reduced skin condition can be viewed as a treatment for a disorder.

Without being bound by mechanistic theories, it is rationalized that the compositions present said skin condition by improving performance thanks to an improved adaptogenic effect. Without being bound by mechanistic theories, it is justified that the compositions exhibit said medical or therapeutic effect in the treatment and / or prevention of a skin and / or dermatological disease in a subject due to an improved adaptogenic effect. .

The term "adaptogen" as used herein is to be understood as an agent which increases the non-specific resistance of a subject to various physical, chemical or biological stressors (see adaptogenic effect). Adaptogens generally accomplish this task either by regulating the activity of hyperfunctional systems or by increasing a subject's resistance to various physical, chemical or biological stressors (see adaptogenic effect). Examples of adaptogens include, among others, astragalus root, cordyceps, maca root, schisandra berry, ashwagandha root, holy basil leaf, Reishi mushroom, Maitake mushroom, suma root. Other adaptogens which are both non-toxic to the subject and capable of increasing the subject's non-specific resistance to external stressors are also included by way of example.

Improving the condition of the skin and / or treating or preventing skin and / or dermatological disease in a subject comprises at least the step of administering the composition to a subject. The composition can be administered to a subject in an effective amount by any method known in the art. The "effective amount", as used herein, should be understood as an amount sufficient to produce a selected effect, such as alleviating the symptoms of a disease or disorder. The "effective daily dose", as used herein, should be understood as the effective amount of a composition required daily to achieve a desired effect in a subject. In the context of administering compounds as a combination, such as multiple compounds, the amount of each compound, when administered in combination with one or more other compounds, may be different from that administered. alone. Thus, an effective amount of a combination of compounds collectively refers to the combination as a whole, although the actual amount of each compound may vary. The term "more effective" means that the selected effect is mitigated to a greater extent by one treatment compared to the second treatment with which it is compared. Preferably, the composition comprising a rare ginsenoside, a ginsan and a gintonine according to the invention is provided in an effective amount to the subject and / or to the object in need thereof. More preferably still, the main constituents of said composition are provided in the proportions and / or the preferred effective daily doses. The composition as presented herein can be administered orally. Preferably, the composition is formulated for oral administration.

The composition can be administered to a subject in the form of a tablet, lozenge, cachet, capsule, hard gelatin capsule, etc. Preferably, the composition is enclosed in a capsule suitable for oral administration to a subject. An effective daily dose of the composition can be administered in 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 different doses. Preferably, an effective daily dose is administered in at most five different doses. Preferably, an effective daily dose is administered in two different doses. Preferably, one of these two different doses is administered after breakfast. Preferably, one of these two different doses is administered after dinner. Preferably, an effective daily dose is administered all at once. Preferably, one of these two different doses is administered after breakfast. An effective daily dose of ginsenoside and rare ginsenoside in the composition is preferably at least 1 mg, more preferably at least 1 mg and at most 150 mg, still more preferably at least 10 mg and d '' at most 100 mg, still more preferably at least 15 mg and at most 75 mg, still more preferably at least 20 mg and at most 55 mg, still more preferably at least 30 mg and of at most 45 mg and even more preferably about 37.5 mg.

An effective daily dose of rare ginsenoside in the composition is preferably at least 1 mg, more preferably at least 1 mg and at most 100 mg, more preferably at least 10 mg and at most 80 mg, more preferably at least 15 mg and at most 70 mg, more preferably at least 20 mg and at most 60 mg, more preferably at least mg and at most 50 mg and more preferably about 30 mg.

An effective daily dose of ginsenoside in the composition is preferably at least 1 mg, more preferably at least 1 mg and at most 100 mg, still more preferably at least 2.5 mg and at plus 75 mg, even more 25 - preferably at least 5 mg and at most 50 mg, still more preferably at least 5 mg and at most 30 mg, still more preferably at least 6 mg and of at most 15 mg and even more preferably about 7.5 mg.

An effective daily dose of ginsan and gintonine in the composition is preferably at least 1 mg, more preferably at least 1 mg and at most 35 mg, still more preferably at least 2 mg and at most 33 mg, still more preferably at least 4 mg and at most 31 mg, still more preferably at least 6 mg and at most 29 mg, still more preferably at least 8 mg and d at most 24 mg and still more preferably about 16 mg.

An effective daily dose of ginsan in the composition is preferably at least 0.3 mg, more preferably at least 0.3 mg and at most 30 mg, still more preferably at least 1 mg and d '' at most 27 mg, still more preferably at least 5 mg and at most 25 mg, still more preferably at least 7 mg and at most 20 mg, still more preferably at least 10 mg and of at most 17 mg and even more preferably about 13 mg.

An effective daily dose of gintonine in the composition is preferably at least 0.1 mg, more preferably at least 0.1 mg and at most 10 mg, still more preferably at least 0.3 mg. and at most 8 mg, still more preferably at least 0.5 mg and at most 7 mg, still more preferably at least 0.7 mg and at most 6 mg, still more preferably d at least 1 mg and at most 5 mg and even more preferably about 3 mg. Preferably, the composition further comprises a combination of compounds comprising a rare ginsenoside, ginsan and gintonine at a ratio of ginsan to rare ginsenoside of about 4: 1 and at a ratio of ginsan to gintonin of about 2 : 1, more preferably said composition further comprising a ratio of rare ginsenoside to ginsan of about 2.5: 1, even more preferably said composition further comprising a ratio of rare ginsenoside to gintonin of about 10: 1.

In a particularly preferred embodiment, the composition comprises a combination of a rare ginsenoside, ginsan and gintonine in respective effective daily doses of about 32 mg rare ginsenoside, at least 10 and at most 16. mg of ginsan and at least 1 mg and not more than 5 mg of gintonin.

Preferably, at respective effective daily doses of about 32 mg of rare ginsenoside, 13 mg of ginsan and at least 1 mg and at most 5 mg of gintonine. Preferably, in effective daily doses of about 32 mg of rare ginsenoside, at least 10 and at most 16 mg of ginsan and 3 mg of gintonine, respectively. Preferably, at respective effective daily doses of about 232 mg of rare ginsenoside, 13 mg of ginsan and 3 mg of gintonine. In a particularly preferred embodiment, the present invention provides a composition comprising one or more rare ginsenosides selected from the group: Rg6, Rh4, Rg3, PPT, Rk1, Rg5, Rh2, Rh3 and PPD, at respective effective daily doses. . The composition preferably comprises an effective daily dose of Rg6 of at least 0.1 mg and at most 35 mg. Preferably, the composition comprises a daily effective dose of Rh4 of at least 20 mg and at most 85 mg. Preferably, the composition comprises an effective daily dose of Rg3 of at least 5 mg and at most 50 mg. Preferably, the composition comprises an effective daily dose of PPT of at least 0.01 mg and at most 35 mg. Preferably, the composition comprises an effective daily dose of Rk1 of at least 10 mg and at most 50 mg. Preferably, the composition comprises an effective daily dose of Rg5 of at least 0.01 mg and at most 100 mg. Preferably, the composition comprises a daily effective dose of Rh2 of at least 0.1 mg and at most 30 mg. Preferably, the composition comprises an effective daily dose of Rh3 of at least 0.1 mg and at most 3 mg.

The composition as described herein can be administered topically. Preferably, the composition is formulated for topical administration.

In the context of a composition for topical administration, the terms “administration” and “application” are used interchangeably in this document.

The composition for topical administration comprises a ginseng agent.

The ginseng agent includes rare ginsenoside, ginsan, gintonine and optionally ginsenoside and / or other constituents of ginsenoside. Preferably, in the proportions of the constituents of the ginseng agent as defined here.

Preferably, the composition for topical administration comprises at least 0.001% by weight of ginseng agent by weight of the composition, more preferably at least 0.001% by weight, more preferably at least 0.005% by weight, more preferably at least 0, 01% by weight, more preferably at least 0.025% by weight, more preferably at least 0.05% by weight, more preferably at least 0.1% by weight. Preferably, the composition for topical administration comprises at most 10% by weight of ginseng agent by weight of the composition, more preferably at most 5% by weight, more preferably at most 4% by weight, more preferably at most 3% by weight, more preferably at most 1% by weight, more preferably at most 0.5% by weight. The lower limit of the ginseng agent is preferably 0.001% by weight or more, from the viewpoint of sufficient improvement in the condition of the skin according to the present invention. The upper limit of the ginseng agent is preferably 10% by weight or less from the viewpoint of workability.

Preferably, the ginseng agent included in the composition for topical administration comprises at least 1% by weight of rare ginsenoside, ginsan and gintonine by weight of ginseng agent, more preferably at least 2% by weight, more preferably at least 3% by weight.% by weight, more preferably at least 4% by weight, more preferably at least 5% by weight, more preferably at least 6% by weight, more preferably at least 7% by weight, more preferably at least 8% by weight, more preferably at least 9% by weight, more preferably at least 10% by weight. Preferably, the ginseng agent included in the composition for topical administration comprises at most 30% by weight of rare ginsenoside, ginsan and gintonine by weight of ginseng agent, more preferably at most 28% by weight, more preferably. at most 26% by weight, more preferably at most 24% by weight, more preferably at most 22% by weight, more preferably at most 20% by weight, more preferably at most 18% by weight, more preferably at most 16% by weight weight, more preferably at most 14% by weight. The lower limit of rare ginsenoside, ginsan and gintonine by weight of ginseng agent is 1% by weight or more from the viewpoint of sufficient improvement in the condition of the skin according to the present invention. The upper limit of the ginseng agent is preferably 30% by weight or less from the standpoint of commercial production and extraction processes. Ideally, the ginseng agent included in the composition for topical administration comprises - about 12% by weight of rare ginsenoside, ginsan and gintonine based on the weight of the ginseng agent. Such a concentration is preferable from an economic point of view. The composition for topical administration can be administered to a subject in the form of a cream, lotion, spray, ointment, gel, powder mask, patch. skin, paste, cleanser, foundation, etc. Preferably, the composition is administered in the form of a cream, lotion or spray suitable for topical administration to a subject. An effective daily dose of the composition can be applied at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 different topical doses. Preferably, an effective daily dose is applied at most in five different topical doses. Preferably, an effective daily dose is applied in two different topical doses.

Preferably, one of these two different topical doses is applied in the morning.

Preferably, one of these two different doses is applied in the evening.

Preferably, an effective daily dose is applied all at once.

This dose is preferably applied in the morning.

This dose is preferably applied in the evening.

An effective daily dose of ginseng agent in a topically administered composition is preferably applied at a concentration of at least 0.0001 mg / cm. on the skin of a subject, more preferably at least 0.0001 mg / cm? and not more than 2 mg / cm2. More preferably, the ginseng agent is applied at a concentration of at least 0.0005 mg / cm 2, still more preferably at least 0.001 mg / cm 2, still more preferably at least 0.005 mg / cm 2, even more preferably at least 0.01 mg / cm2. More preferably, the agent ginseng is applied at a concentration of at most 1.5 mg / cm 2, still more preferably at most 1.0 mg / cm 2, still more preferably at most 0.5 mg / cm 2, even more preferably at most 0.03 mg / cm 2. A ginseng agent applied at a concentration of less than 0.0001 mg / cm? must be diluted in order to exhibit properties for improving the condition of the skin according to the invention.

A ginseng agent applied at a concentration greater than 2 mg / cm 2 can irritate the skin of a subject.

An effective daily dose of ginsenoside and rare ginsenoside in a topically administered composition is preferably applied at a concentration of at least 0.001 mg / cm. on the skin of a subject, preferably at least 0.001 mg / cm? and not more than 0.1 mg / cm ?. More preferably, the ginsenoside and rare ginsenoside are applied at a concentration of at least 0.002 mg / cm2, more preferably at least 0.004 mg / cm 2, more preferably at least 0.006 mg / cm 2, more more preferably at least 0.008 mg / cm2, more preferably at least 0.01 mg / cm2, more preferably at least 0.012 mg / cm2, more preferably at least 0.014 mg / cm2 . More preferably, the rare ginsenoside is applied at a concentration of at most 0.1 mg / cm 2, still more preferably at most 0.08 mg / cm 2, still more preferably at most 0.06 mg / cm 2 cm 2, still more preferably at most 0.04 mg / cm 2, still more preferably at most 0.02 mg / cm 2, still more preferably at most 0.018 mg / cm 2.

An effective daily dose of rare ginsenoside in a topically administered composition is preferably applied at a concentration of at least 0.001 mg / cm. on the skin of a subject, more preferably at least 0.001 mg / cm? and not more than 0.1 mg / cm2. More preferably, the rare ginsenoside is applied at a concentration of at least 0.002 mg / cm 2, more preferably at least 0.004 mg / cm 2, more preferably still at least 0.006 mg / cm 2, more preferably still. at least 0.008 mg / cm 2, more preferably at least 0.01 mg / cm 2, more preferably at least 0.011 mg / cm 2. More preferably, the rare ginsenoside is applied at a concentration of at most 0.1 mg / cm2, still more preferably at most 0.08 mg / cm 2, still more preferably at most 0.06 mg / cm 2 , even more preferably at most 0.04 mg / cm2, still more preferably at most 0.02 mg / cm2, still more preferably at most 0.015 mg / cm2.

An effective daily dose of ginsenoside in a topically administered composition is preferably applied at a concentration of at least 0.0001 mg / cm. on the skin of a subject, more preferably at least 0.0001 mg / cm? and not more than 0.01 mg / cm2. More preferably, the ginsenoside is applied at a concentration of at least 0.0002 mg / cm 2, more preferably at least 0.0004 mg / cm 2, more preferably still at least 0.0006 mg / cm 2 More preferably at least 0.0008 mg / cm2, more preferably at least 0.001 mg / cm2, more preferably at least 0.002 mg / cm2. More preferably, the ginsenoside is applied at a concentration of at most 0.01 mg / cm 2, still more preferably at most 0.008 mg / cm 2, still more - preferably at most 0.006 mg / cm 2, still more preferably at most 0.005 mg / cm 2, still more preferably at most 0.004.

An effective daily dose of ginsan and gintonine in a topically administered composition is preferably applied at a concentration of at least 0.0001 mg / cm. on the skin of a subject, more preferably at least 0.0001 mg / cm? and not more than 0.01 mg / cm2. More preferably, the ginsan and gintonine are applied at a concentration of at least 0.0002 mg / cm 2, more preferably at least 0.0004 mg / cm 2, more preferably still at least 0.0006 mg / cm2, more preferably at least 0.0008 mg / cm2, more preferably at least 0.001 mg / cm2, more preferably at least 0.002 mg / cm2, more preferably still at least 0.002 mg / cm2, more preferably at least 0.002 mg / cm2 less 0.004 mg / cm 2, more preferably at least 0.006 mg / cm 2. More preferably, ginsan and gintonine are applied at a maximum concentration of 0.01 mg / cm2, still more preferably 0.009 mg / cm 2, still more preferably 0.008 mg / cm 2, still more preferably 0.007 mg / cm 2 ? to the maximum.

An effective daily dose of ginsan in a topically administered composition is preferably applied at a concentration of at least 0.0001 mg / cm2 to the skin of a subject, more preferably at least 0.0001 mg / cm2. ? and not more than 0.01 mg / cm ?. More preferably, the ginsan is applied at a concentration of at least 0.0002 mg / cm 2, more preferably at least 0.0004 mg / cm 2, more preferably still at least 0.0006 mg / cm 2 , more preferably at least 0.0008 mg / cm, more preferably at least 0.001 mg / cm, more preferably at least 0.002 mg / cm, more preferably at least at least 0.004 mg / cm 2, more preferably at least 0.005 mg / cm 2. Preferably, the ginsan is applied at a maximum concentration of 0.01 mg / cm 2, still more preferably 0.009 mg / cm 2, still more preferably 0.008 mg / cm 2, still more preferably 0.007 mg / cm 2, even more preferably 0.006 mg / cm? to the maximum.

An effective daily dose of gintonine in a topically administered composition is preferably applied at a concentration of at least 0.0001 mg / cm. on the skin of a subject, preferably at least 0.0001 mg / cm? and at most 0.01 mg / cm2. More preferably, the gintonine is applied at a concentration of at least 0.0002 mg / cm 2, more preferably at least 0.0004 mg / cm 2, more preferably at least 0.0006 mg / cm 2, more preferably at least 0.0004 mg / cm 2. more preferably at least 0.0007 mg / cm 2, more preferably at least 0.0008 mg / cm 2, more preferably at least 0.0009 mg / cm 2, more preferably still at least 0.0009 mg / cm 2 at least 0.001 mg / cm2, more preferably at least 0.0011 mg / cm2. More preferably, the gintonine is applied at a concentration of at most 0.01 mg / cm 2, still more preferably at most 0.008 mg / cm 2, still more - preferably at most 0.006 mg / cm 2, still more preferably at most 0.004 mg / cm2, still more preferably at most 0.002 mg / cm2.

Preferably, the composition for topical administration further comprises a combination of compounds comprising a rare ginsenoside, ginsan and gintonine at a ratio of ginsan to rare ginsenoside of about 4: 1 and at a ratio of ginsan to gintonine d. about 2: 1, more preferably still said composition further comprising a ratio of rare ginsenoside to ginsan of about

2.5: 1, even more preferably said composition further comprising a ratio of rare ginsenoside to gintonine of about 10: 1. An effective daily dose of ginseng in a topically administered composition is preferably applied for at least 1 minute to the skin of a subject. More preferably, an effective daily dose of ginseng in a topically administered composition is preferably applied for at least 1 minute and at most 10 hours to the skin of a subject. A ginseng-based agent applied topically to the skin of a subject requires at least a minute to improve the condition of the skin. A ginseng agent applied topically for more than 10 hours is no longer effective and may irritate a subject's skin. It is preferable that an effective daily dose of ginseng in a topically administered composition is applied for at least 5 minutes, more preferably for at least 10 minutes, more - more preferably for at least 15 minutes, more preferably for at least 15 minutes. less than 20 minutes, more preferably still for at least 25 minutes and more preferably still for at least 30 minutes. Preferably, an effective daily dose of ginseng in a topically administered composition is applied preferably for a maximum of 9 hours, still more preferably for a maximum of 9 hours, still more preferably for a maximum of 8 hours, still more preferably for a maximum of 9 hours. 7 hours and even more preferably for a maximum of 6 hours. According to the exemplary representations, an active combination according to the invention can be administered to a patient or to a subject alone, or in combination with other agents, drugs or hormones or in pharmaceutical compositions mixed with one or more excipients or d other pharmaceutically or cosmetically acceptable carriers. In only one embodiment, the pharmaceutically acceptable carrier is pharmaceutically inert.

The composition can be administered daily at an effective dose as many times as desired to obtain the desired effects. According to the preferred form of presentation, said composition is administered at an effective daily dose for a period of at least two days, preferably at least five days. The applicant notes that an optimal effect is obtained for a treatment of at least 5 days.

2. Preparation of a composition of the invention In a fourth aspect, the invention relates to a method of preparing a composition intended to improve the condition of the skin of a subject. The composition - includes a rare ginsenoside, ginsan and gintonine. The method comprising the steps of extracting said rare ginsenoside, said ginsan and said gintonine from a cultivated ginseng root. Preferably, said root has been cultivated in a hydroponic environment.

In a fifth aspect, the invention relates to a method according to a fourth aspect for the preparation of a composition according to a first aspect and / or a composition according to a second aspect.

The hydroponic environment is a well-known technique for growing plants using solutions of mineral nutrients, in water, without soil. In general, plants can be grown on the surface of the earth with their roots in the mineral nutrient solution only or in an inert medium, such as perlite, gravel, mineral wool, expanded clay pebbles or hull. of coconut. Under natural conditions, the soil acts as a reservoir of mineral nutrients, but the soil itself is not essential for plant growth. When the mineral elements in the soil dissolve in water, the roots of plants are able to absorb them. When the necessary mineral nutrients are artificially introduced into a plant's water supply, the soil is no longer needed for the plant to grow.

An advantage of hydroponics over traditional soil-based techniques is that the growing environment can be greatly controlled, especially the level of nutrients supplied to the root environment. Another advantage is that the water supplied to the plants can be easily retained in the system, which results in significant water savings. A hydroponic environment is particularly advantageous in view of the present invention, because the final concentrations of the constituents in the root system of ginseng can be controlled by meticulously adjusting the level of nutrients delivered to the ginseng plant. The applicant notes that to his knowledge, no other cultivation technique allows cultivating a ginseng root with the ratios and concentrations of constituents necessary to obtain a composition in accordance with the present invention, without it being necessary to proceed to additional purification steps. Further, due to the advantages described above, the applicant notes that hydroponics of ginseng takes much less time than growing in soil.

In a particularly preferred variation, the method comprises the step of cultivating a ginseng in a controlled hydroponic environment. A controlled hydroponic environment is a technique of growing plants in nutrient solutions which are fertilizers containing water with or without the use of an artificial medium such as sand, gravel, vermiculite, wool rock, perlite or sawdust to provide mechanical support in a technically controlled environment. In these systems, there is no other support for the roots of the plants. Controlled hydroponic environments are advantageous because they allow even more controlled delivery of nutrients to the growing ginseng plant.

In a particularly preferred variation, the method comprises the step of cultivating the ginseng in an aseptic hydroponic environment. An aseptic hydroponic environment is a hydroponic technique carried out under conditions of sufficient cleanliness to avoid the presence of microbes such as bacteria, yeasts, fungi and molds, but also insects and other parasites. By using an aseptic hydroponic environment, the use of pesticides can be completely avoided.

It should be clear to a person skilled in the art that the composition according to the current invention can be obtained according to any method known in the art. For example, according to one embodiment, the composition can be prepared by mixing aliquots each comprising one or more constituents of the composition.

According to a particularly preferred embodiment, the composition can be obtained by extracting the various constituents of the composition from a ginseng.

Preferably, before an extraction step, the root of a ginseng is dried. Preferably, before an extraction step, the root of a ginseng is crushed. Preferably, before an extraction step, the root of a ginseng is cooked. Preferably, before an extraction step, the root of a ginseng is dried, then crushed and finally cooked. It should however be clear that the drying and / or the grinding and / or the cooking of the ginseng are not an absolute condition for the extraction as described in this document. Grinding and / or drying ginseng increases the efficiency of subsequent extraction steps. Cooking ginseng increases the bioavailability of ginseng constituents. According to a preferred mode of expression, said rare ginsenoside, ginsenoside and gintonine are extracted from a ginseng by hydroalcoholic extraction. Preferably, using two or more subsequent hydro-alcoholic extractions. Between each of these hydroalcoholic extractions, a filtration step is provided. After this filtration step, a filtrate and a hydroalcoholic solution are obtained. The filtrate is rich in ginsan. The hydroalcoholic solution is rich in rare ginsenosides, ginsenosides and gintonine. The filtrate obtained by this filtration step is subjected to the subsequent hydroalcoholic extraction. The hydroalcoholic solution obtained by this filtration step is preferably collected. Each of these subsequent hydroalcoholic extractions preferably comprises a mixing step. Each of said subsequent hydro-alcoholic extractions preferably comprising a recirculation step. Preferably each mixing and / or recirculation step for at least 30 minutes and at most 10 hours, preferably at least 60 minutes and at most 8 hours, preferably at least 90 minutes and at most 6 hours, preferably at least 60 minutes and at most 8 hours. at least 2 hours and at most 4 hours, preferably about 2 hours 30 minutes.

The collected hydroalcoholic solution (i.e. the hydroalcoholic solution collected from said two or more subsequent hydroalcoholic extractions) can be subjected to fractionation. The term "fractionation" as used herein refers to substantial separation and recovery of a first fraction rich in rare ginsenoside and ginsenoside and a second fraction rich in gintonin. Preferably, said collected hydroalcoholic solution is subjected to fractionation using an aqueous solution. After this fractionation, a water-soluble fraction, a water-insoluble fraction and a water-insoluble precipitate fraction are obtained. The precipitated fraction insoluble in water is the fraction enriched in gintonin. The water-insoluble fraction is rich in ginsenosides and rare ginsenosides.

The collected hydro-alcoholic solution (i.e. the hydro-alcoholic solution collected from said two or more subsequent hydro-alcoholic extractions) can be subjected to a concentration treatment. Preferably, said collected hydroalcoholic solution is subjected to a treatment under partial vacuum. Preferably, said vacuum treatment at a pressure of at least 50 mbar, more preferably still at a pressure of at least 50 mbar and at most 500 mbar, more preferably still at least 75 mbar and at plus 250 mbar and more preferably at least 100 mbar and at most 200 mbar. Preferably, said vacuum treatment at a temperature of at least 10 ° C, more preferably at least 20 ° C, still more preferably at least 30 ° C, still more preferably at least 40 ° C and more preferably about 50 ° C.

It should be clear that any hydroalcohol can be used for the hydroalcoholic extraction of said rare ginsenosides, ginsenosides and gintonins. It is preferable to use ethanol because of its great availability. Preferably, said hydroalcoholic extraction is carried out at a temperature of at least 10 ° C and at most 75 ° C. Cycle times increase dramatically at temperatures below 10 ° C. Most hydroalcohols boil at temperatures above 75 ° C. Preferably, said hydroalcoholic extraction is carried out at a temperature of at least 20 ° C and at most 70 ° C, more preferably at least 30 ° C and at most 65 ° C, more preferably still d at least 40 ° C and at most 60 ° C, more preferably at least 45 ° C and at most 55 ° C, more preferably still about 55 ° C.

According to a specific embodiment, the hydro-alcoholic extraction for the extraction of said rare ginsenosides, ginsenosides and gintonines comprises two subsequent hydro-alcoholic extractions. A first hydroalcoholic extraction can be carried out with mixing and recirculation for 2 hours and 30 minutes using 35 | 70% EtOH / 30% H2O at 50 ° C. The extracted solution is filtered. The filtrate is subjected to a second hydroalcoholic extraction, which may be identical to the first. Other specific embodiments are shown in the examples. According to the preferred embodiment, said rare ginsenosides, ginsenosides and gintonine are extracted by a hydro-alcoholic extraction to obtain a filtrate.

Said filtrate is rich in ginsan. Preferably, said filtrate is then subjected to an aqueous extraction, more preferably to two or more subsequent aqueous extractions. Between each of these subsequent aqueous extractions, a centrifugation step is provided. After this centrifugation step, a solid fraction and a liquid fraction are obtained. The solid fraction obtained by said centrifugation step is subjected to the subsequent aqueous extraction. The liquid fraction obtained by said centrifugation step is preferably collected.

Aqueous extraction, as described herein, is effective for the further extraction of the ginsan polysaccharide. Preferably, the ginsan is extracted using two or more aqueous extractions. However, it should be noted that ginsan can be obtained directly from ginseng, preferably using aqueous extraction, preferably after drying and / or grinding and / or cooking said ginseng.

Each aqueous extraction preferably includes a mixing step. Preferably, said mixing step for at least 10 minutes and at most 6 hours, preferably at least 30 minutes and at most 5 hours, preferably at least 1 hour and at most 4 hours 30 minutes, preferably at least 1 hour 30 minutes and at most 4 hours, preferably at least 2 hours and at most 3 hours 30 minutes, preferably about 2 hours 30 minutes.

It should be clear that any aqueous solution can be used for this extraction. Preferably, said aqueous extraction is carried out at a temperature of at least 60 ° C and at most 100 ° C. Cycle time increases dramatically at temperatures below 60 ° C. At temperatures above 100 ° C, aqueous solutions boil. Preferably, said hydroalcoholic extraction is carried out at a temperature of at least 65 ° C and at most 95 ° C, more preferably still at least 70 ° C and at most 90 ° C, more preferably still d at least 75 ° C and at most 85 ° C, more preferably still about 80 ° C.

Preferably, after said mixing step, the mixture is heated to a temperature of at least 60 ° C and at most 100 ° C for at least 5 hours and at most 20 hours, preferably for about 16 hours. Cycle time increases dramatically at temperatures below 60 ° C. At temperatures above 100 ° C, aqueous solutions boil. More preferably, said hydroalcoholic extraction is carried out at a temperature of at least 65 ° C and at most 95 ° C, more preferably at least 70 ° C and at most 90 ° C, more preferably still. at least 75 ° C and at most 85 ° C, preferably at about 80 ° C.

The aqueous extract obtained, rich in ginsan, can be treated by dialysis. Preferably, before dialysis, the aqueous extract is concentrated by means of vacuum evaporation. Preferably, said concentrate is dialyzed for at least one day and at most 15 days against water. Preferably, said dialysis cleaves molecules with a molecular weight of at most 5 kDa, preferably at most 10 kDa and preferably at most 15 kDa. To obtain a ginsan precipitate, a hydroalcoholic solution can be added. The aqueous extract obtained, rich in ginsan, can be filtered. Preferably, said filtration comprises a step of filtering with a mesh size of at least 1 µm and at most 30 µm, more preferably at least 5 µm and at most 25 µm, more preferably at least. at least 10 µm and at most 20 µm and more preferably about 15 µm. Preferably, said filtration step using a filtration centrifuge. Preferably, said filtration comprising a step of filtering with a mesh size of at least 0.1 µm and at most 1 µm, more preferably at least 0.10 µm and at most 0.90 µm. , more preferably at least 0.25 µm and at most 0.75 µm, and more preferably about 0.45 µm. Preferably, said filtration comprises a step of filtering with a mesh size of at least 15 kDa and at most 25 kDa, more preferably at least 17 kDa and at most 23 kDa and more preferably about 20 kDa. Preferably, each of said filtration steps, described above, comprising 1, 2, 3, 4, 5, 6 or 7 successive cycles.

According to a specific embodiment, the aqueous extraction of said ginsan comprises two subsequent aqueous extractions. A first aqueous extraction can be carried out with mixing for 2 hours 30 min at 80 ° C using 30 | hot water. Then the mixing can be stopped and the resulting mixture can be heated at 80 ° C for a further 16 hours. The water and the resulting solid fraction are separated by centrifugation. The solid fraction can then be subjected to a second aqueous extraction, which can be identical to the first. Other specific embodiments are discussed in the examples. Ginsenosides according to any of the methods and compositions described herein can be isolated and / or purified from a ginseng, a ginseng extract or other plant source, or the ginsenoside can be a synthetic ginsenoside which is made.

In other examples, the ginsenoside of the methods and compositions described herein is isolated and / or purified from a species of ginseng belonging to the genus Panax, or an extract of ginseng of this species. In other examples, the ginsenoside of the methods and compositions described herein is formulated as a ginseng extract or is part of a ginseng extract. Ginseng extracts can be obtained from plant materials. Plant materials can be extracted with water or an aqueous solution, an alcoholic solution or a combination of water and alcohol. Plant materials can also be extracted by supercritical means alone or in combination with extraction steps using water or alcohol or combined solutions. Ginsenosides can be isolated and / or purified from ginseng or other plant source using methods known in the art, which are disclosed, for example, in the section "Chemistry and Pharmacology of Natural Products": Saponins, by K. Hostettmann, A. Marston, Cambridge University Press 1995, which is incorporated herein by reference. In other illustrations, procedures for obtaining the ginsenosides Rb1, Rb2, Rc and / or Rd generally include aqueous extraction or of one or more suitable Panax species, evaporation of the extracted solution to dryness, followed by column chromatography, thin layer chromatography and / or high performance chromatography to obtain a fraction of purified ginsenosides The techniques for extracting and purifying plant extracts are known to the skilled artisan and can be adapted for the preparation of each of Rb1, Rb2, Rc or Rd or of a mixture of the latter. iers, using techniques such as those described in the following documents: US 6,156,291, US 6,083,932, US 4,157,894, US 5,137,878 and US 5,230,889. Isolation and purification procedures for Rb1, Rb2, Rc and Rd are also described, for example, in Shibata et al, Economic and Medicinal Plant Research, World Scientific, Philadelphia pp. 217-284, 1985; US 7,235,267, Kawashima et al, J. Med. Pharmacol. Soc. Wakan-Yaku 1986, 3, 235-236 and Oura et al., Journal of Biochemistry (Tokyo) 1975, 77 (5), 1057-65. In other examples, the ginsenoside of the compositions or methods described here is a member of the dammaran family or of the oleanane family. In other examples, the ginsenoside of the compositions or methods described here is a member of a group selected from protopanaxadiols, protopanaxatriols and pseudoginsenoside FI 1.

Traditionally, ginsenosides (including ginsenosides and rare ginsenosides as used herein) have low bioavailability. However, ginsenosides are readily metabolized or hydrolyzed by intestinal bacteria to more bioavailable and more active ginsenosides. The terms "ginsenoside" and "rare ginsenoside", as used herein, should also include any rare ginsenoside or ginsenoside metabolite which is a product of the metabolism of ginsenoside or rare ginsenoside by the intestinal bacteria of mammals. Non-limiting examples of ginsenoside metabolites are 20-b-O-glucopyranosyl-20 (S) -protopanaxadiol and 20 (S) - protopanaxadiol.

The bioavailability of rare ginsenosides, ginsenosides, ginsan and gintonine as well as other constituents of ginseng, preferably ginsenosides, can be increased by cooking a harvested ginseng root. Preferably, said harvested root is cooked. Preferably, said harvested root is cooked after drying and / or crushing said harvested root. It should be clear to a person skilled in the art that any cooking method known in this field can be used. The applicant notes the better retention of the various essential constituents of ginseng during the steaming of the harvested roots. Preferably, the harvested root is steamed. Preferably, said harvested root is steamed after drying and / or crushing said harvested root. Preferably, said harvested root is steamed at a temperature of at least 100 ° C and at most 150 ° C, more preferably at most 140 ° C, more preferably at most 130 ° C. C and more preferably not more than 121 ° C. More preferably, said harvested root is steamed for at least 30 minutes, still more preferably for at least 30 minutes and at most 10 hours and even more preferably for at least 1 hour and at most 6 hours.

In another variation, the ginsenoside can also be a synthetic ginsenoside which is manufactured. Methods of making synthetic ginsenoside are known in the art and are disclosed, for example, in Organic Synthesis with Enzymes in Non-Aqueous Media, edited by Giacomo Carrea, Sergio Riva, Willey VCH 2008, which is incorporated herein by reference.

Ginsan can be isolated from any species of the genus Panax using any method known in the art. For example, as revealed by Kim et al. (1997), ginsan can be isolated from an ethanol-insoluble fraction of an aqueous extract of ginseng (Panax ginseng C.A. Meyer, Araliaceae).

Gintonine can be obtained from any species of the genus Panax using any method known in the art. For example, as disclosed in EP 2,502,933, gintonine can be obtained by subsequent partitioning, fractionation and dialysis of a methanol extract obtained from any ginseng.

PREFERENTIAL EXAMPLES

1. Firstly, the invention relates to a composition intended to improve the condition of the skin of a subject, said composition comprising a rare ginsenoside, a ginsan and a gintonine.

2. A composition according to the first aspect, wherein the ratio of ginsan to gintonine is at least 500: 1 and at most 1: 100.

3. A composition according to the first aspect, wherein the ratio of rare ginsenosides to ginsan and gintonine is at least 250: 1 and at most 1:40.

4. A composition according to the first aspect, wherein the ratio of rare ginsenosides to ginsan is at least 300: 1 and at most 1:30.

5. A composition according to the first aspect, wherein the ratio of rare ginsenoside to gintonine is at least 1000: 1 and at most 1:10.

6. Composition according to the first aspect, in which said rare ginsenoside comprises Rg5 and Rh2 and optionally one or more rare ginsenosides chosen from the group comprising: C-K, Rg6, Rh4, Rg3, PPT, Rk1, Rh3 and PPD.

7. Composition according to the first aspect, in which said rare ginsenoside comprises Rg5 and Rh2 and optionally one or more rare ginsenosides chosen from the group comprising: CK, Rg6, Rh4, Rg3, PPT, Rk1, Rh3 and PPD and in which the ratio between Rg5 and Rh2 and a total amount of rare ginsenoside is at least 1: 1 and at most 1: 4.

8. Composition according to the first aspect, in which said composition further comprises a ginsenoside, preferably said ginsenoside being chosen from the group comprising: Rg1, Re, Rf, Rh1, Rg2, Rb1, Rec, Rb2 and Rd.

9. Composition according to the first aspect, in which said composition further comprises a ginsenoside chosen from the group comprising: Rgl,

Re, Rf, Rh1, Rg2, Rb1, Rc, Rb2 and Rd and wherein the ratio of Rc to a total amount of rare ginsenoside and ginsenoside is at least 1: 1 and at most 1: 3.

10.Composition according to the first aspect, wherein the ratio of rare ginsenoside to ginsenoside is at least 200: 1 and at most 1: 5.

11. A composition according to the first aspect, wherein said composition further comprises a ginsenoside and wherein the ratio of one or more compounds selected from the group consisting of: CK, Rk1, Rh2, Rh3, Rh4, Rg2, Rg3 and Rg6 to a total amount of rare ginsenosides and ginsenosides in the composition is at least 1: 4 and at most 1: 1.

12. Composition according to the first aspect, said composition being formulated for topical administration.

13. A composition according to the first aspect, said composition being formulated for oral administration.

14. A composition according to the first aspect, said composition being enclosed in a capsule for oral administration.

15. A composition according to the first aspect, wherein said improvement in skin condition is at least skin hydration, skin whitening, wrinkle reduction or anti-aging.

16. In a second aspect, the invention relates to a composition according to the first aspect, in which said composition is provided in a pharmaceutically and / or cosmetically acceptable carrier.

17. A composition according to the second aspect, wherein the composition is provided in one or more pharmaceutically acceptable excipients.

18. Composition according to the second aspect, for use in the treatment and / or prevention of a skin and / or dermatological disease.

19.Composition according to the second aspect, for use in the treatment and / or prevention of a skin and / or dermatological disease, said skin and / or dermatological disease being linked to inflammation, an allergic reaction , hypersensitivity or contact intolerance reaction, excessive sebaceous secretion, exfoliation or microbial dysbiosis, preferably of the epidermis.

20. In a third aspect, the invention relates to a method for improving the condition of the skin of a subject, the method comprising the step of administering to the subject a composition according to a first aspect and / or a second. aspect.

21. Method according to the third aspect, for the treatment and / or prevention of a skin and / or dermatological disease.

22. A method according to the third aspect, whereby the composition is administered topically.

23. Method according to the third aspect, according to which the composition is administered topically and according to which said composition comprises a concentration of ginsan and gintonine of at least 10% by weight and at most 50% by weight of said composition .

24. A method according to the third aspect, by which the composition is administered topically and wherein said composition comprises a rare ginsenoside concentration of at least 60% by weight and at most 90% by weight of said composition.

25. A method according to the third aspect, wherein the composition is administered topically and wherein said composition comprises a ginsan concentration of at least 10% by weight and at most 35% by weight of said composition.

26. Method according to the third aspect, by which the composition is administered topically and in which said composition comprises a concentration of gintonin of at least 1% by weight and at most 10% by weight of said composition.

27.A method according to the third aspect, wherein the composition is administered orally.

28. A method according to the third aspect, wherein the composition is administered orally and wherein said composition comprises an effective daily dose of rare ginsenoside of at least 1 mg and at most 100 mg.

29. Method according to the third aspect, according to which the composition is administered orally and according to which said composition comprises an effective daily dose of ginsan of at least 0.3 mg and at most 30 mg.

30. Method according to the third aspect, according to which the composition is administered orally and according to which said composition comprises a daily effective dose of gintonin of at least 0.1 mg and at most 10 mg.

31. In a fourth aspect, the invention relates to a method of preparing a composition for improving skin conditions in a subject, said composition comprising a rare ginsenoside, a ginsan and a gintonine, the method comprising the steps of extracting each of said rare ginsenoside, ginsan and gintonine from a cultivated ginseng root.

32. Method according to the fourth aspect, according to which said root is cultivated in a hydroponic environment.

33. Method according to the fourth aspect, according to which said root is cultivated in a controlled hydroponic environment.

34. Method according to the fourth aspect, according to which said root is cultivated in an aseptic hydroponic environment.

35. Method according to the fourth aspect, according to which said rare ginsenoside is extracted by a hydroalcoholic extraction.

36. Method according to the fourth aspect, according to which said ginsan is extracted by aqueous extraction.

37. Method according to the fourth aspect, according to which said gintonine is extracted by hydroalcoholic extraction.

38. Method according to the fourth aspect, according to which said rare ginsenoside and gintonine are extracted by hydroalcoholic extraction and according to which the resulting hydroalcoholic extract is filtered to obtain a filtrate.

39. A method according to the fourth aspect, whereby said gintonine is extracted from said filtrate using aqueous extraction.

40. Method according to the fourth aspect, according to which said resulting hydroalcoholic extract is subjected to fractionation to obtain said gintonine.

41. Method according to the fourth aspect, according to which extracts of rare ginsenoside, ginsan and gintonine are aliquoted to the composition.

42. In a fifth aspect, the invention relates to a method according to the fourth aspect for the preparation of a composition according to a first aspect and / or a composition according to a second aspect.

43. In a sixth aspect, the invention relates to a kit comprising one or more aliquots of a composition, said composition comprising a rare ginsenoside, a ginsan and a gintonin.

44. Method according to the sixth aspect, according to which said composition is a composition according to a first aspect and / or a composition according to a second aspect.

EXAMPLES The following examples are intended to further clarify the present invention and are not intended to limit its scope.

EXAMPLES 1-42 A simple composition according to the current invention comprises a rare ginsenoside, a ginsan and a gintonin. The composition can be a composition for oral administration. Table 1 gives an overview of the compositions which are simple to administer orally according to the invention. Table 2 gives an overview of compositions for oral administration also comprising ginsenosides. For example, other constituents of ginseng were purged from the samples examined in Examples 1-14.

Table 1. Simple compositions for oral administration. ‚Example Ginsenoside rare ginsangintonin _ ……. Table 2. Compositions for oral administration comprising ginsenosides. example __Ginsenoside rare _ginsan _gintonin ___ginsenoside Bonn tg 30 mg 10 mg Mg 2 100 mg Mg Mg OMG. 10 20 mg 25 Mg Mg Mg +14 80 mg MG MgO Mg 22 2e Mg MG MG MG 243 37 M9 MG 2 MG MG

14.237 Mg MG MG MG The composition may be a composition for topical administration. A composition for topical administration comprises a ginseng agent. A ginseng agent includes a rare ginsenoside, a ginsan, a gintonine and optionally a ginsenoside and / or another component of ginsenoside. A simple ginseng agent includes rare ginsenoside, ginsan, and gintonine.

Table 3 gives an overview of the simple ginseng agents for topical administration according to the invention.

Table 4 provides an overview of ginseng agents for topical administration also including ginsenosides.

Examples 15-28 detailed below are expressed by weight of ginseng agent.

For example, other constituents of ginseng were purged from the samples examined in Examples 15-28. Table 3. Topical Administration of Single Compositions * (wt%). Example Ginsenoside rare ginsan_… intonin _î_î… _;… î nn 16 GB re SO er Br Ed Ee Cl re BL ere D 20 PO res DD ere cs et crc P Darren FD rever AO irresrmrrer + The compositions for topical administration were prepared in providing 5% by weight of the ginseng agent (by weight of the composition) in glycerol.

Table 4 Compositions for topical administration * comprising ginsenosides (% by weight). example… Ginsenosiderare… ginsan_ gintonin__ ginsenoside 22 CB ABÉ En LH es 23 Br dr Br BB rs U dB BMD res A As. | rs Or LB rs °° LB rs 28 A A A A * The compositions for topical administration have been prepared by providing 5% by weight of the agent ginseng (by weight of the composition) in glycerol.

Table 5 provides an overview of compositions for oral administration also comprising an additional ingredient, additive, carrier and / or excipient.

In the examples, these components will be treated as additional ingredients, unless otherwise specified.

Table 5. Compositions for oral administration comprising an additional ingredient. ex. ginsenginsan gintonin ginsen- constituents ingredient formulation oside oside no additional rare identified from ginseng rs 29 32mg 13mg 3mg 5mg 390mg 57mg sugar 2 brown capsules comprising 250mg for daily intake. 40 mg 15mg 5mg 10 mg 510 mg 200 ml saline Powder composition of 580 mg for daily intake.

Preferably dissolved in 200 ml of Sine solution. 31 31mg 12mg 4mg 6 mg 315 mg 632 mg acid 1 g of alginic capsule for daily intake.

Preferably this Near dinner, 32 1mg 30mg 10mg 9mg 310 mg 640 mg 5 tablets Gum of 200 mg Erabic per day. 33 99 mg 0.4mg 0.1mg 0.5mg 400 mg 100 mg flour 2 rice capsules 300 mg for daily intake. 34 20 mg 25mg 9 mg 15 mg 580 mg 350 mg Composition dextrose powder dissolved in for one 30 cl of water daily consumption.

Preferably dissolved in a solution 80 mg 45mg 0.5mg 65mg 170mg> 1 g agar Dessert based on agar for daily consumption.

Preferably

Table 6 provides an overview of compositions for topical administration also comprising an additional ingredient.

The ginseng agents and the other constituents of the composition are expressed by weight of the composition.

The ginseng agents of Examples 36 to 42 comprise the following constituents of ginseng by weight of ginseng agent: 67% by weight of rare ginsenoside, 27% by weight of ginsan and 6% by weight of gintonine.

Table 6. Compositions for topical administration comprising an additional ingredient (% by weight). example carrier agent excipient agent other suitable foaming formulation A A. 36 7% 20% water 2% 66% 5% applied to lecithin Tween the surface of the skin at a dose of 0.3 mg / cm? for 37 0.5% 10% water 1% 84.5% 1% applied to cetrimide perfume the surface and 3% of the skin Tween at a dose of 4 mg / cm? During 1 day. 38 1% 35% water 1% SDS 62% 1% lives applied to C the surface of the skin at a dose of 2 mg / cm? for at least 30 39 2% 15% 1% 80% 2% lives applied with CTAB C solution to the saline surface of the skin at a rate of 1 mg / cm2 per day, preferably Mr JO Morning 40 5% 25% oil 5% 64% perfume applied to mineral cetrimide 1% skin surface LOA cs g / m ee SO 41 0.1% 40% 15% 53.4% 5% lives applied to glycerol BAC C the skin surface at a dose of 15 mg / cm? for 10 eee MID 6 42 10% 10% oil 1% CPC 83% 1% vit = applied sesame C on the and 5% surface of oil the skin to mineral 0.17 mg / cm? to EXAMPLE 43 A composition according to the current invention comprises a rare ginsenoside. A composition according to the present invention can also comprise a ginsenoside. Table 7 provides an overview of the average ginsenoside profile of a ginseng agent of a composition for topical administration according to the invention. Table 8 gives an overview of the average profile of rare ginsenosides of a ginseng agent of a composition for topical administration according to the invention. A duplicate sample (n = 2) was collected from Examples 15-28 and 36-42. All additional ingredients were purged from the samples. 42 samples were prepared and analyzed according to the methodology described in Example 49. Table 7. Average profile of ginsenosides. “Ginsenosides average (mg / g of min (mg / g of max (m / g of dry matter) dry matter) Dry matter) RAN Oe 003 Re ee ee 234 Rf GOE 0 8 Rh 02 re On OR LL R92 3

RD ZZ LRE eee 20 ROZ 02 28 RO 10.81

Table 8. Average profile of rare ginsenosides. Ginsenosides average (mg / g min (mg / gde - max (mg / g rare dry matter) dry matter) dry matter)… Ed 1692 LRRG 4793 007 41.955 LR HZ 2418 PPT DB ee ZA RK IZA BAE 24.02 RGD ZI A 40198 Rh2 22034 RD BZ OOI 13.91 PPD ee OT OE LOL. EXAMPLES 44-48 A composition according to the current invention comprises a rare ginsenoside. A composition according to the present invention can also comprise a ginsenoside. Table 9 gives examples of profiles of ginsenoside in a composition for topical administration. Table 10 gives examples of rare ginsenoside profiles in a composition for topical administration. Samples were prepared and analyzed according to the methodology described in Example 49. Table 9. Examples of ginsenoside profiles (mg / ml extract). example Rgl Re Rf Rhi Ro2 Rbl Re Rb2 Rd 44001 0.01 0.01 0.01 04 04 22.001 08 45 00 02 D OO On D 46 M On Or du OL LB On DOTE 4 2 005 O1 005 02 M5 1800106

48.0 ... 03.6. G ... 001 01.22 OL O5 Table 10. Examples of rare ginsenoside profiles (mg / ml of extract). example Rg6 Rh4 Rg3 PPT Rk1 Rg5 Rh2 Rh3 PPD \ 44 11832 109 AD 200 148 Ed 47 E20 LE LE Lt LS Re EL LE LA

EXAMPLE 49 The current example relates to a preferred method of preparing a composition according to the current invention. The composition was obtained by growing ginseng roots in a hydroponic environment. The hydroponic environment used in the current example is a controlled hydroponic system and operates as a continuous plug flow system. The operating speed of the plug flow production plant is increased by a factor of at least three between the sowing stage and the harvesting stage. The composition was obtained by drying, then by grinding and cooking the ginseng roots. The crushed ginseng roots were subjected to different extraction steps to obtain the different constituents of the composition. Hydroalcoholic Extraction - The initial hydroalcoholic extraction, according to this example, was carried out on 6 kg of crushed ginseng roots. The hydroalcoholic extraction is effective for the extraction of rare ginsenosides, ginsenosides and gintonine. The hydro-alcoholic extraction was carried out in two cycles.

During a first cycle, a hydroalcoholic extraction was carried out with mixing and recirculation for 2 hours 30 min using 35 | 70% EtOH / 30% H2O at 50 ° C. The hydro-alcoholic extract was recovered by filtration. The second cycle was applied to said filtrate. During this second cycle, another hydroalcoholic extraction was carried out with mixing and recirculation for 2 hours 30 minutes using 30 | 70% EtOH / 30% H2O0 at 50 ° C. The hydroalcoholic extract was again recovered by filtration. The two hydroalcoholic extracts can be combined. The hydroalcoholic extract * obtained is rich in rare ginsenosides, ginsenosides and gintonine. The filtrate is rich in ginsan.

- Said hydroalcoholic extract was fractionated with water to obtain a fraction soluble in water, a fraction insoluble in water and a precipitated fraction insoluble in water. The precipitated fraction insoluble in water is the fraction enriched in ginsan. The water-insoluble fraction is rich in ginsenosides and rare ginsenosides.

Aqueous extraction The filtrate obtained after the hydroalcoholic extraction was subjected to aqueous extraction. The aqueous extraction is effective for the extraction of ginsan polysaccharide. The aqueous extraction was carried out in two cycles.

In a first cycle, aqueous extraction was carried out on said filtrate under mixing for 2 hours 30 min at 80 ° C using 30 | hot water. After this 2 hour 30 minute period, the mixture was stopped and the mixture was heated at 80 ° C for an additional 16 hours. Then, the aqueous extract and the solid fraction were separated by centrifugation. The solid fraction was then subjected to a second cycle, in which each step detailed in the first cycle was repeated to obtain the final aqueous extract **, Said aqueous extract was concentrated using a vacuum evaporator. . The concentrate was dialyzed against running tap water for 7 days in order to completely cleave small molecules with a molecular weight of less than 15 kDa. Four volumes of absolute ethanol were added to precipitate the polysaccharide in the internal dialysate. The precipitate was dried in a vacuum drying oven and was finally used as the acid polysaccharide of -ginseng. Composition The constituents of the composition (that is to say the hydroalcoholic solution, the fraction enriched in gintonine and the acidic ginseng polysaccharide) were aliquoted to obtain a composition in accordance with the invention in the desired proportions. Analysis The contents of rare ginsenosides, ginsan and gintonine were analyzed. The hydro-alcoholic extract before the fractionation was combined with - the aqueous extract to obtain a composition in accordance with the invention. This mixture was analyzed by HPLC. The composition comprised about 7072 mg / ml of ginsan extract and about 1768 mg / ml of gintonin extract. The content of ginsenoside and rare ginsenoside is detailed in Tables 11 and 12.

Table 11. Average profile of ginsenosides. ginsenosides Average (mg / ml of extract) RL ee OD res Re creer OO crc ee cr RD ON rs

ROZ OB RBL MB T crc RL 7 ROZ ee DO crc

RL RE LA Table 12. Average profile of rare ginsenosides. Rare medium ginsenosides (mg / ml extract). RG IO rs Rh4 eee LL es RB LD re RK EE es

RZ ID

RS EEE EEE PPD rer LD rs EXAMPLE 50 The current example relates to a method for preparing an extract. The prepared extract can be used in commercial applications. These applications include orally administrable compositions and topical formulations. Before preparing said extract, the hydroalcoholic solution * and the aqueous extract **, as indicated above in Example 49, are treated. Treatment of the hydroalcoholic extract * The hydroalcoholic extract *, as indicated above in Example 49, can be concentrated. The following example illustrates a preferred method. The hydroalcoholic solution *, which is rich in rare ginsenosides, ginsenosides and gintonine, is first concentrated under partial vacuum (for example Rotavapor Büchi R 220; 100 to 200 mbar; bath temperature 50 ° C; 90 rpm ; condenser temperature 5 ° C). Glycerol is added to the concentrate as a humectant.

In a pilot plant, 60 L of hydroalcoholic solution * were divided into 4 batches of 15 L. Each of these 4 batches was concentrated to a volume of approximately 5 L. 1875 L of food grade glycerol were added to each of these 4 concentrated lots. The net yield obtained by this pilot plant, from 5.97 kg of ginseng roots, is approximately 27.5 L of glycerol concentrate1. Treatment of the aqueous extract ** The aqueous extract **, as indicated above in Example 49, can be concentrated. The following example illustrates a preferred method.

The aqueous extract **, which is rich in ginsan, is processed in three different filtration steps. In a first step, the extract is filtered in two cycles using a filtration centrifuge with a mesh size of about 15 μm (for example, the Rousselet Robatel filtration centrifuge). In a second step, the extract is microfiltered with a mesh size of approximately 0.45 µm. In a third step, the extract is ultrafiltered in three cycles with a mesh size of 20 kDa. In a pilot plant, 74.4 kg of aqueous extract ** was filtered using a filtration centrifuge with a mesh size of about 15 µm, resulting in - about 30 L of extract. These 30 L of extract (corresponding to 31.6 kg of ginseng root) were microfiltered over an area of 0.064 m? at a flow rate of 28 L / h. After 11 hours of filtration, about 30 kg of extract was recovered. These 30 kg of recovered extract were ultrafiltered with a mesh size of about 20 kDa over an area of about 0.02 m? at a flow rate of about 1.4 to about 1.6 L / h and at a pressure of about 1.3 to 1.8 bar. After three days, 9.3 kg of extract? were recovered. Preparing the extract Here is an illustration of the procedure to follow to prepare an extract.

The extract? is stored in a freezer. Before any manipulation, the extract? must be thawed. 69 g of the extract? are pipetted and aliquoted into an autoclavable 250 ml bottle. 81 g of the glycerol1 concentrate are pipetted and aliquoted in said autoclavable 250 ml flask. The solution in the bottle is homogenized by mixing. said bottle is supplied in an autoclavable vacuum bag with a control bottle comprising 250 ml of distilled water and eight dropper bottles. After autoclaving, the solution is aliquoted to the counting vials.

drops under sterile conditions under a laminar flow hood. This solution can also be processed as an extract of totum. This solution preferably comprises at least 1% by weight and at most 30% by weight of rare ginsenoside, ginsan and gintonine, most preferably about 12% by weight.

EXAMPLE 51 The current example relates to an alternative method of preparing a composition according to the current invention. The composition was obtained by extracting separately from ginseng rare ginsenosides, ginsan and gintonine. Example 15 details the constituents of the composition. Ginsan has been extracted from ginseng by isolating ginsan from an ethanol insoluble fraction of an aqueous extract of ginseng, as revealed by Kim et al. (1997). Gintonine has been extracted by partitioning, fractionation and dialysis of a methanol extract obtained from any ginseng, as disclosed in EP 2,502,933. Optionally, the methanol extract is filtered using ultrafiltration with a mesh size of about 20 kDa. Commercially available ginsenosides and rare ginsenosides have been purchased. The extracts were aliquoted to obtain a simple composition according to the current invention.

EXAMPLE 52 A composition of 7.5% by weight of rare ginsenoside, 3.75% by weight of ginsan and 0.75% by weight of gintonine by weight of ginseng agent was evaluated for its effectiveness in improving the agent. skin condition in subjects. 400 mg of the composition in combination with 100 mg of brown sugar was administered orally in a capsule. The skin conditions evaluated are skin hydration, skin whitening, reduction of wrinkles and other symptoms associated with aging. A store bought red ginseng extract was used as a positive control. Skin hydration was evaluated in subjects with dry skin. Skin hydration was assessed using a Nova "DPM 9003 dermal phasemeter, which measures impedance-based capacitance readings using varying frequencies of the applied AC current. The Nova" DPM 9003 measures the relative water content of the stratum corneum. Skin whitening was evaluated in subjects with scar-induced hyperpigmentation. Skin whitening was evaluated by the subjects themselves and by a qualified technician. Wrinkle reduction and anti-aging were evaluated in subjects aged 40 to 55. Wrinkle reduction and anti-aging were evaluated by the subjects themselves and by a qualified technician.

The performance of the composition and the positive control were evaluated based on the skin conditions tested before and after a five-day treatment. Treatment comprising oral administration for five days of 100 mg of the composition or of the positive control. The composition has been found to be effective in increasing the water content of treated subjects. The composition has also been found to be effective in visually reducing hyperpigmentation due to scarring as well as signs of skin aging such as wrinkles. The composition was also found to be more effective compared to the positive control.

EXAMPLE 53 An extract of totum comprising 7.5% by weight of rare ginsenoside, 3.75% by weight of ginsan and 0.75% by weight of gintonine was evaluated for its effectiveness in improving the condition of the skin in patients. topics. The extract was provided at 2.0% by weight of the composition and was administered topically (cream or serum). The skin conditions evaluated are skin hydration, skin whitening, reduction of wrinkles and other symptoms associated with aging. A store-bought red ginseng extract was used as a positive control.

The skin conditions were evaluated according to the methodologies described in Example 51. The performance of the composition and the positive control were evaluated according to the condition of the skin tested before and after a five day treatment. Treatment - including topical administration over five days of approximately 1 mg / cm? composition or positive control. The composition was applied to three different regions of a subject's face (i.e. the forehead, the eye region and the corners of the lips). The composition has been found to be effective in increasing the water content of treated subjects. The composition has also been found to be effective in visually reducing hyperpigmentation due to scarring as well as signs of skin aging such as wrinkles. The composition was also found to be more effective in view of the positive control.

EXAMPLE 54 An extract of totum comprising 10% by weight of rare ginsenoside, 5% by weight of ginsan and 1% by weight of gintonine was evaluated for its effectiveness in improving the condition of the skin. The extract was evaluated on cell cultures in vitro. The skin conditions evaluated are skin whitening, reduction of wrinkles and other symptoms associated with aging. A store-bought red ginseng extract was used as a positive control.

Skin whitening was evaluated in vitro by evaluating melanogenesis, in particular by measuring the expression of proteins involved in skin pigmentation. Wrinkle reduction and anti-aging have been evaluated in in vitro models. The reduction of wrinkles and anti-aging were evaluated by measuring the expression of proteins involved in the degradation of the skin matrix (MMP) and regeneration (collagen). The performances of the composition and of the positive control were evaluated according to the conditions tested before and after the treatment. The composition has been found to be effective in reducing skin pigmentation as well as signs of skin aging such as wrinkles. The composition was also found to be more effective in view of the positive control.

Claims (15)

1. A composition for improving the condition of the skin in a subject, characterized in that the composition comprises a rare ginsenoside, a ginsan and a gintonine, wherein the ratio of ginsan to gintonine is at least 500: 1. and not more than 1: 100 and in which the ratio of rare ginsenosides to ginsan and gintonine is at least 250: 1 and not more than 1:40. 2. Composition according to preceding claim 1, in which the ratio of rare ginsenosides to ginsan is at least 300: 1 and at most 1:30. 3. Composition according to any one of the preceding claims 1 or 2, in which the ratio of rare ginsenoside to gintonine is at least 1000: 1 and at most 1:10. 4. Composition according to any one of the preceding claims 1 to 3, in which said rare ginsenoside is selected from the group comprising: C-K, Rg6, Rh4, Rg3, PPT, Rk1, Rg5, Rh2, Rh3 and PPD. 5. Composition according to any one of the preceding claims 1 to 4, in which said composition further comprises a ginsenoside, preferably said ginsenoside being chosen from the group comprising: Rg1, Re, Rf, Rh1, Rg2, Rb1, Rc, Rb2 and Rd. 6. Composition according to any one of the preceding claims 1 to 5, in which said rare ginsenoside comprises Rg5 and Rh2 and optionally one or more rare ginsenosides chosen from the group comprising: CK, Rg6, Rh4, Rg3, PPT, Rk1, Rh3 and PPD and wherein the ratio of Rg5 and Rh2 to a total amount of rare ginsenoside is at least 1: 1 and at most 1: 4. 7. Composition according to preceding claims 1 to 6, said improvement in the condition of the skin being at least a hydration of the skin, a whitening of the skin, a reduction of wrinkles or an anti-aging. 8. A composition according to any one of the preceding claims 1 to 7, wherein said composition is provided in a pharmaceutically - and / or cosmetically acceptable carrier, for use in the treatment and / or prevention of a disease of the. skin and / or dermatological, preferably said skin and / or dermatological disease being linked to inflammation, allergic reaction, hypersensitivity or contact intolerance reaction, excessive sebaceous secretion, exfoliation or microbial dysbiosis , preferably the epidermis. 9. A method for improving the condition of the skin in a subject, the method comprising the step of administering to the subject a composition according to any one of preceding claims 1 to 7 and / or a composition according to preceding claim 8 . 10. A method according to claim 9 above, wherein said composition is administered orally. 11. A method according to any one of the preceding claims 9 or 10, wherein said composition is administered topically. 12. A method of preparing a composition for improving the condition of the skin in a subject, said composition comprising a rare ginsenoside, a ginsan and a gintonine, the method comprising the steps of extracting each of said - rare ginsenoside, ginsan and gintonine from a root of a cultivated ginseng, preferably said root being cultivated in a hydroponic environment. 13. A method according to preceding claim 12, wherein said rare ginsenoside is extracted using hydroalcoholic extraction, wherein said ginsan is extracted using aqueous extraction, and wherein said gintonine is extracted using hydroalcoholic extraction. 14. A method according to any one of preceding claims 12 or 13 for the preparation of a composition according to any one of preceding claims 1 to 7 and / or of a composition according to preceding claim 8. 15. A kit comprising one or more aliquots of a composition, said composition comprising a rare ginsenoside, a ginsan and a gintonine, preferably, said composition being a composition according to any one of the preceding claims 1 to 7 and / or a composition according to the preceding claim 8.