BE1027552B1 - COMPOSITION OF GINSENG AND ITS USE AS A MEDICINAL PRODUCT FOR THE TREATMENT OR PREVENTION OF STRESS - Google Patents

Abstract

The invention relates to a composition, a kit and its preparation for the treatment or prevention of stress in a subject. The composition includes a rare ginsenoside, a ginsan and a gintonine. Preferably, the ginsan / gintonine ratio 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

COMPOSITION OF GINSENG AND ITS USE AS A MEDICINAL PRODUCT

FOR THE TREATMENT OR PREVENTION OF STRESS FIELD OF THE INVENTION The invention relates to a composition comprising rare ginsenosides, ginsan and gintonine, and to its use as a medical or therapeutic substance and to its production.

INTRODUCTION The chemical constituents of Panax ginseng and other Panax can be classified into saponins, polysaccharides, flavonoids and volatile oils. Most of the biological activity of ginseng has been attributed to saponins (i.e. ginsenosides) and their metabolites. The proposed clinical applications of the constituents of ginseng include, but are not limited to, anti-hyperglycemic, anti-oxidant, anti-inflammatory, immunostimulant and anti-apoptotic effects. The biological activity of these constituents is proposed as being adaptogenic. Adaptogens improve survival by promoting the ability to adapt to stress. In particular, adaptogens modify the stress response in nonspecific ways to maintain homeostasis. An adaptogen acts as a mimetic of mild stress and can be thought of as a stress preparer. The repeated administration of an adaptogenic substance makes it possible to obtain a certain resistance to stress. The effectiveness of the components of ginseng has been extensively studied. Most of the results are insignificant or difficult to interpret. Shergis et al. (2012) reviewed 475 clinical studies. Significant results have shown an improvement in glucose metabolism and a moderation of the immune system. Other areas of interest have shown no significant results (for example: psychomotor performance, physical performance, circulatory metabolism, respiratory metabolism, erectile dysfunction, quality of life, antioxidant, cancer, symptoms of menopause and dry mouth. ).

These poor results are explained by the inadequate bioavailability of the various constituents of ginseng.

In particular, bioavailability was found to be limited for doses administered orally.

Absorption rates as low as 0.1% of an orally administered Rg1 dose and 1.9% of an orally administered Rg2 dose have been observed (Herbs, Botanicals and Teas, CRC Press , 1998, p. 28 G.

Mazza BD Oomah). The limited recovery of ginsenosides from tissue, faeces and urine is probably caused by extensive pre-systemic metabolism of ginsenosides (Masami, Takino, Yoshio, 1991). Studies have shown that for most ginsenosides the levels achieved in brain tissue are very low.

These levels in the brain are unlikely to reach the concentrations necessary for therapeutic effects.

Document EP 1 198 995 relates to an anti-stress composition.

The composition comprises a ratio of linoleic acid to linolenic acid, a compound having calming properties and a ginsenoside.

EP 995 further indicates that the effect of the composition is the result of better brain bioavailability of the active ingredients.

The ratio is able to cross the blood-brain barrier and increase membrane fluidity (essential for the functioning of the nervous system). In this regard, the Applicant notes that an improvement in bioavailability does not necessarily correspond to an improved therapeutic effect.

One of the objectives of the invention is to provide novel compounds and compositions which are highly active and easy to obtain for the treatment or prevention of stress in a subject, preferably the treatment or prevention of stress in a subject in whom the cognitive performance. are improved.

It is also an object of the invention to provide a process for the preparation of such compositions and the administration of such compositions to a subject.

SUMMARY OF THE INVENTION The invention provides a solution to at least one of the aforementioned problems by providing compositions comprising a rare ginsenoside, a ginsan and a gintonine, their use as medical or therapeutic substances in a prevention treatment. stress and / or relief and more specifically their use in a stress prevention and / or relief treatment by which the subject's cognition is improved.

In a first aspect, the invention relates to a composition comprising a rare ginsenoside, a ginsan and a gintonine in reports detailed in claim 1. The inventors have surprisingly found that such compositions can be used for treatment or prevention. stress in a subject. Such compositions are particularly advantageous unlike traditional compositions based on Panax ginseng.

In a second aspect, the invention relates to a composition described in the first aspect of the invention in a pharmaceutically or cosmetically acceptable carrier and optionally one or more pharmaceutically acceptable excipients according to claim 8. The composition can be used in the treatment or prevention of stress in a subject. In a third aspect, the invention relates to a method of treating or preventing stress in a subject according to claim 9. The method comprises a step of administering a composition described in the first aspect of the invention and / or a composition described in the second aspect of the invention. In a fourth aspect, the invention relates to a method of preparing a medicament described in claim 13. The medicament comprises daily effective doses of rare ginsenosides, ginsan and gintonine. The method - includes the step of growing ginseng under hydroponic conditions. In a fifth aspect, the invention relates to a method of preparing a medicament described in claim 14. A medicament described in the first and / or 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 described in claim 15.

DETAILED DESCRIPTION OF THE INVENTION

The invention relates to a composition, its use and its preparation for the treatment or prevention of stress in a subject. The invention also relates to a kit described in the invention. The composition essentially comprises a rare ginsenoside, a ginsan and a gintonine. In the following, the invention will be described in detail, the preferred aspects and embodiments are discussed and the invention will be illustrated by way of non-limiting examples. Preferred aspects as described herein are in no way 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 meaning as commonly understood by those skilled in the art to which this invention belongs. By way of further guidance, term definitions are included to better understand the teaching of the present invention.

As used herein, the following terms have the following meanings: "a / a" and "the", as used herein, refer to singular and plural referents, unless the context clearly indicates otherwise. . By way of example, “a rare ginsenoside” designates one or more rare ginsenosides, a “ginsan” designates one or more ginsans and “a gintonine” designates one or more gintonins.

The term "about", as used herein, referring to a measurable value such as a parameter, quantity, time duration, etc., is intended to encompass variations of +/- 20% or less, of preferably +/- 10% or less, more preferably +/- 5% or less, still more preferably +/- 1% or less, and still more preferably +/- 0.1% or less of and from the specified value, insofar as such variations are appropriate to occur in the invention disclosure. However, it should be understood that the value referred to by the modifier "about" is also specifically disclosed. "Includes", "including" and "included", as used herein, are synonymous with "includes", "including", "included" or "contains", "containing", "content" and are inclusive or open which specify the presence of the following, e.g. component and do not exclude or prevent the addition of components, characteristics, elements,

steps not known, not cited above, known in the art or described therein.

Further, the terms first, second, third and the like in the description and claims are used to distinguish like elements and not necessarily to describe sequential or chronological order, unless otherwise indicated. It should be understood that the terms so used are interchangeable in appropriate circumstances and that the embodiments of the invention described herein are capable of functioning in sequences other than those described or illustrated herein. A numeric range defined by these endpoints includes all the numbers and fractions within that range, as well as the mentioned endpoints. All percentages should be understood as percent by weight unless otherwise indicated or if a different meaning is evident to those skilled in the art from its use and in the context in which it is used. The term "wt%" or "wt%" throughout the specification, unless otherwise indicated, refers to the relative weight of the component in question relative to the total 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, by means of further examples, the term includes inter alia a reference to one of said members, or to at least two of these members, such as, for example, all> 3, 24, 25, 26 or 27, etc., and up to all members.

Unless defined otherwise, all terms used in the disclosure of the invention, including technical and scientific terms, have the meaning as commonly understood by those skilled in the art to which this invention belongs. By way of further guidance, definitions of terms used in the specification are included to better understand the teaching of the present invention. The terms or definitions used herein are provided only to assist in understanding the invention. Any reference to "an embodiment" in the specification means that a particular feature or structure described in connection with the embodiment is included in at least one embodiment of the invention. Thus, the phrases "in one embodiment" at various places in this specification do not necessarily all refer to the same embodiment, but can. Further, the particular features or structures may be combined in any suitable manner, as will be understood by those skilled in the art from this description, in one or more embodiments. Further, although some embodiments described herein include some features, but not others, included in other embodiments, combinations of features of different embodiments are within the scope of the invention and form different. embodiments, as will be understood by those skilled in the art. For example, in the following claims any of the claimed embodiments can be used in any combination.

... The 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 gintonine.

1. Compositions of the Invention In a first aspect, the invention relates to a composition for the treatment or prevention of stress in a subject. Said composition preferably comprising a rare ginsenoside. Said composition preferably comprising a ginsan. Said composition preferably comprising a gintonine.

"Subject" as used in this document, should be understood as a human or animal body. As used herein, the term "animal" preferably refers to vertebrates, preferably birds and mammals, and still more mammals. "Subject in need" as used herein, should be understood as a patient, animal or human, who will benefit from the treatment of this publication.

The "composition" as used herein should be understood to include additional ingredients, additives, carriers, nutraceuticals, pharmaceutical compositions and physiologically acceptable compositions, etc. It will be understood that when, for example, a rare ginsenoside, ginsan or gintonine in a "composition" also occurs in a natural source, the term "composition" does not include the natural source of the component, but may, in some ways. realization, encompass a physically or chemically modified or transformed form of the natural source,

as an extract from the natural source.

The "ginseng" used in this document should be understood as a species belonging to the genus Panax of the Araliaceae family.

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

In addition, ginseng can be classified into artificial breed ginseng, artificially planted but wild ginseng, and wild ginseng depending on the growing conditions.

In particular, the term "ginseng" used in this document is intended to include all kinds of ginseng, so American ginseng and Chinese ginseng as well as Korean ginseng are covered by this publication.

"Ginsan" used in this document 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) . Ginsan enhances the production of cytokines and reactive oxygen (ROS) by macrophages (Shin et al., 2002) and stimulates the phagocytic activity of macrophages (Song et al., 2002). Since its initial purification, ginsan has been shown to have significant effects on immune cells (Lee et al., 1997). As an immunomodulator, ginsan plays a radioprotective role in hematopoietic and immune cells (Song et al., 2003). It increases the number of bone marrow (MO) cells, splenocytes and certain hematopoietic stem cells and improves the production of cytokines involved in hematopoietic recovery (Kim et al., 2007). Therefore, ginsan appears to protect the host from ionizing radiation through its immunomodulatory activities.

The term "gintonine" 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 having 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 lipid composition comprising linoleic acid, palmitic acid, oleic acid and stearic acid. The protein composition of gintonin leads to the hypothesis that the carbohydrate portion of gintonin could be derived from the N-glycosylations of the major latex-like protein of ginseng.

The term "rare ginsenoside" used herein should be understood as synonymous with the terms "prototype ginsenoside" or "noble ginsenosides" 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. The inventors have surprisingly found that the compositions according to the invention can lower the stress level of a subject or a subject who needs it. The inventors have also surprisingly discovered that the compositions according to the invention can prevent stress in a subject or a subject who needs it. The composition according to the current publication is particularly advantageous over traditional compositions based on Panax ginseng. The inventors have also found it surprising that the compositions according to the invention exhibit improved cognitive performance in a subject, in particular in contrast to traditional compositions based on Panax ginseng. These observations are of particular interest since these compounds are natural plant-based components. Such compounds are also easy to obtain, as will be illustrated below.

Without being bound by any mechanistic theory, it is rationalized that such compositions can lower a subject's stress level or can prevent stress in a subject due to an enhanced adaptagen effect. Further, without being bound by any mechanistic theory, it is rationalized that improved cognitive performance of a subject relates to a reduced level of stress in said subject.

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

The term "symptom" as used herein should be understood as being interchangeable with the term "sign". Therefore, as used herein "symptom" refers to a physical condition which indicates a particular disease or disorder (eg Longman Dictionary of Contemporary English (1995). Third Edition) detectable by the subject with dementia. a disease or disorder particular or detectable by a person other than the subject without verbal information of the subject.

Preferably in a composition according to a first aspect, the ratio between ginsan and gintonine is at least 500: 1. The applicant notes that such a ratio of ginsan to gintonine is at least necessary for the composition to induce improved cognitive performance and a reduced level of stress in a subject, unlike traditional compositions based on Panax ginseng, preferably the ratio between ginsan and gintonine is at least 490: 1, and more preferably at least 490: 1, and still more preferably at least - 450: 1, preferably at least 400: 1, and even more preferably at least 350: 1, still more preferably at least 300: 1, still more preferably at least 250: 1. The applicant notes that the ratio of ginsan to gintonine, which is at least 200: 1, further induces cognitive performance and reduces stress level in a subject, and that, preferably, the ratio of - ginsan and 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, again more preferably at least 150: 1, still more preferably at least 100: 1. The applicant notes that a ginsan-gintonine ratio of at least 50: 1 induces even more improved cognitive performance in a subject, and that preferably the ginsan-gintonine ratio is at least 45: 1, or even more, 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, still more preferably at least 15: 1, still more preferably at least 12: 1. The applicant notes that a ginsan-gintonine ratio of at least 10: 1 results in an even greater improvement in a subject's cognitive performance, and that preferably the ginsan-gintonine ratio is at least 9: 1, even 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 such a ratio between ginsan and gintonine is required as much as possible in such a composition for the composition to induce improved cognitive performance and a reduced level of stress in a subject, unlike traditional compositions based on Panax ginseng. , more preferably the ratio of ginsan to gintonine is 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, even more preferably at most 1:50. The applicant notes that a ginsan-gintonine ratio of at most 1:40 induces improved cognitive performance and a reduced stress level in a subject, preferably at most 1:30, and even more preferably at plus 1:20, even more preferably at most 1:10. The applicant notes that a ginsan-gintonine ratio of at most 1: 5 induces improved cognitive performance and a reduced stress level in a subject, preferably at most 1: 4, or even more ideally 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.

Preferably, the ratio of ginsan to gintonine is about 1: 4. The applicant notes that the most improved cognitive performance in a subject at ginsan to gintonine ratios of about 1: 4. These observations are supported by Examples 1 to 21.

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 notes that such a ratio of rare ginsenosides to the total amount of ginsan and gintonine is at least necessary for the composition to exhibit improved cognitive performance and reduced stress level in a subject, unlike compositions based on it. traditional Panax ginseng, more preferably the ratio of rare ginsenosides to ginsan and gintonine is a minimum of 200: 1, still more preferably a minimum of 150: 1, more preferably a minimum of 100, a minimum of 100: 1 . The applicant notes that a ratio of rare ginsenosides to a combination of ginsan and gintonine of at least 80: 1 induces a further improvement in cognitive performance and a reduction in stress level in a subject, preferably the ratio between rare ginsenosides and ginsan and gintonine is at least 60: 1, and even preferably at least 40: 1, and even preferably at least 20: 1, and even 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 induces even better cognitive performance in a subject, preferably the ratio of rare ginsenosides to ginsan and gintonine is at least 6: 1, and even preferably at least 4: 1 and even more preferably at least 3: 1. Preferably in a composition according to a first aspect, the ratio of rare ginsenosides to ginsan and to gintonine is at most 1:40. The applicant points out that this ratio of rare ginsenosides to a total amount of - ginsan and gintonine is maximally necessary for the composition to induce improved cognitive performance and reduced stress level in a subject, unlike traditional compositions based on Panax ginseng, more preferably the ratio of rare ginsenosides to ginsan and gintonine is at most 1:30, still more preferably at most 1:20, still more preferably at most 1:10. The applicant points out that a ratio of rare ginsenosides to a combination of ginsan and gintonine of at most 1: 5 induces a further improvement in cognitive performance in a subject, even more preferably at most 1: 4, even more preferably at 1: 3, still more preferably at 1: 2 maximum.

The applicant notes that a ratio of rare ginsenosides to ginsan and gintonine of no more than 1: 1 results in more improved cognitive performance and reduced stress level in a subject.

Preferably, the ratio of rare ginsenosides to ginsan and gintonine is about 2: 1. The applicant notes that cognitive performance [is] the most improved in a subject at ratios of rare ginsenosides to ginsan and gintonine of about 1: 4. These observations are supported by Examples 1 to 21.

In a preferred embodiment, the present invention provides a composition comprising a ratio of rare ginsenoside to ginsan of at least 300: 1. The applicant notes that this ratio is at least necessary to obtain an improved cognitive performance and a reduced level of stress compared to compositions traditionally based on Panax ginseng, preferably the composition comprises a ratio of rare ginsenoside to ginsan of at least 300 : 1 and at most 1:30, still more preferably at least 250: 1 and at most 1:20, still more preferably at least 200: 1 and at most 1:15, still more preferably at least 150: 1 and at most 1:10, still more preferably at least 100: 1 and at most 1: 7. The applicant points out that a ratio of rare ginsenosides to ginsan of at least 50: 1 and at most 1: 5 results in further improvement in cognitive performance and reduction in stress level in a subject, preferably at least 40: 1 and at most 1: 4, still more preferably at least 30: 1 and at most 1: 3, preferably at least 20: 1 and at most 1: 2 and still more preferably at least 10: 1 and at most 1: 1. The applicant points out that a ratio of rare ginsenosides to ginsan of at least 5: 1 and at most 1: 1 results in an even greater improvement in cognitive performance and a reduction in stress level in a subject.

Preferably, the ratio of rare ginsenosides to ginsan is about 2.5: 1. The applicant notes the most improved cognitive performance in a subject at such ratios of rare ginsenosides to ginsan. These observations are supported by Examples 1 to 21.

In a preferred embodiment, the present invention provides a composition comprising a rare ginsenoside to gintonine ratio of at least 1000: 1. The applicant notes that such a ratio is at least required to obtain an improved effect over traditional compositions based on Panax ginseng, preferably the composition comprises a ratio of rare ginsenoside to ginsan of at least 1000: 1 and at most. 1:10, even more preferably a minimum of 900: 1 and a maximum of 1: 9, even more preferably a minimum of 80: 1 and a maximum of 1: 8, even more preferably a minimum of 700: 1 and a maximum of 1: 7, still more preferably at least 600: 1 and at most 1: 6, still more preferably at least 500: 1 and at most 1: 5, still more preferably at least 400: 1 and at most 1: 4, still more preferably at least 300: 1 and at most 1: 3, still more preferably at least 200: 1 and at most 1: 2. The applicant notes that a ratio of rare ginsenosides to gintonine of at least 100: 1 and at most 1: 1 induces further improvement in cognitive performance in a subject, preferably at least 90: 1 and at most 1 : 1, still more preferably at least 80: 1 and at most 1: 1, at least 70: 1 and at most 1: 1, still more preferably at least 60: 1 and at most 1: 1. The applicant notes that a ratio of rare ginsenosides to gintonine of at least 50: 1 and at most 1: 1 induces further improvement in cognitive performance in a subject, preferably at least 40: 1 and at most 1 : 1, still more preferably at least 30: 1 and at most 1: 1 and at least 20: 1 and at most 5: 1.

Preferably, the ratio of rare ginsenosides to gintonine is about 10: 1. The applicant notes the most improved cognitive performance in a subject at such ratios of rare ginsenosides to ginsan. These observations are supported by Examples 1 to 21.

In a 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. Preferably, at least 40% by weight of the rare ginsenosides in said group are attributed to one or more - ginsenosides selected from the group consisting of: Rg6, Rh4, Rg3, Rk1 and Rg5, more preferably at least 45 wt% by weight, plus 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 further comprising a ginsenoside. "Ginsenoside" as used herein, should be understood as synonymous with the term "panaxoside" and refers to a class of naturally occurring steroid glycosides and triterpene saponins present in ginseng. It should be clear that for "ginsenoside", "rare ginsenosides" are excluded, unless otherwise specified. Therefore, when we speak of "ginsenoside", we are referring to "classical ginsenosides", unless otherwise indicated. In particular, ginsenosides have a basic structure composed of a steroid gonan nucleus having 17 carbon atoms arranged in a tetracyclic configuration. Ginsenoside compounds, including the protopanaxadiol type of ginsenosides such as ginsenosides Rb1, Rb2, Rc and Rd, are known to those skilled in the art (see, for example, 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). Ginsenoside is selected from the group comprising: Rg1, Re, Rf, Rh1, Rg2, Rb1, Rc, Rb2 and Rd. Even more preferably, the ginsenoside is selected from the group comprising: Rg2, Rb1, Re, Rb2 and Rd.

In a preferred embodiment, the present invention provides 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 selected from the group comprising: Rg2, Rb1, Rc, Rb2 and Rd, more preferably 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 70% by weight.

In a preferred embodiment, the present invention provides a composition comprising a ratio of rare ginsenoside to ginsenoside of at least 200: 1, preferably at least 200: 1 and at most 1: 5, still greater than preferably 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, still more than preferably at least 40: 1 and at most 1: 4, still more preferably at least 30: 1 and at most 1: 3, still more preferably at least 20: 1 and at most 1: 2, still more preferably at minus 10: 1 and at most 1: 1 and most preferable at least 6: 1 and at most 2: 1 and most preferable 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 of Rg5 to Rh2 and a total amount of rare ginsenoside is at least 1: 1, more preferably at least 1: 1 and at most 1: 4. The complainant notes that such reports are more effective. Preferably, the ratio between Rg5 and Rh2 and a total amount of rare ginsenoside is at least 1: 1.5 and at most 1: 2.5. Even more preferably, the ratio of Rg5 to Rh2 and a total amount of rare ginsenoside is about 1: 2. The applicant notices the highest efficiency 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 of rare ginsenoside and ginsenoside is at least 1: 1, more preferably at least 1: 1 and at most 1: 3. The complainant notes that these reports are more effective. Preferably, the ratio of Rc to a total amount of rare ginsenoside and ginsenoside is at least 1: 1.5 and at most 2.5. Most preferably, the ratio of Rc to a total amount of rare ginsenoside and ginsenoside is about 1: 2. The applicant notes the highest efficiency at ratios of approximately 1: 2.

In a preferred embodiment, the present invention provides a composition comprising a ginsenoside, 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. Compounds of the group C-K, Rk1, Rh2, Rh3, Rh4, Rg2, Rg3 and Rg6 have high bioavailability compared to other rare ginsenosides or ginsenosides. In addition, the applicant points out that the effectiveness of the composition increases drastically at a ratio of at least 1: 4. Preferably, the ratio between one or more compounds selected from the group comprising: CK, Rk1, Rh2, Rh3, Rh4, Rg2, Rg3 and Rg6 and the total amount of rare ginsenosides and ginsenosides in the composition is at least 1 : 4 and at most 1: 1, still more preferably at least 1: 3 and at most 1: 1.5 and most preferably, about 1: 2. The applicant notes the highest effectiveness of the composition at ratios of about 1: 2.

According to one embodiment, the present invention can provide a composition comprising a phospholipid. Phospholipids are lipids containing residues of phosphoric acid in general, including soya lecithin, egg yolk lecithin, choline phosphatidyl, choline phosphatidyl, ethanolamine phosphatidyl and ethanolamine phosphatidyl. serine, which are widely present in nature, including in animals and plants. Phospholipids are found in brain cells and nervous system of mammals and are commonly used in pharmaceutical preparations. Phospholipid molecules have a hydrophilic head and two long hydrophobic chains and have been used as pharmaceutical excipients. Complexing the constituents of ginseng in a phospholipid matrix has been shown to increase the oral bioavailability of individual ginsenosides compared to aqueous solutions in animal models. Preferably, the phospholipid is formulated in the form of a nanoparticle.

Additional Ingredients The composition as described herein may include an additional ingredient.

- “Additional ingredient” as used in this document, should be understood to include one or more of the following: excipients; surfactants; dispersing agents; inert diluents; granulating and disintegrating agents; binding agents; lubricating agents; sweetening agents; flavoring agents; coloring agents; preservatives; physiologically degradable compositions such as gelatin; aqueous vehicles and solvents; oily vehicles and solvents; suspending agents; dispersing or wetting agents; emulsifying agents, emollients; tampons; salts; thickening agents; filling agents; 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 Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa.).

The "pharmaceutical composition" as used herein should be understood as a composition comprising at least one active ingredient, wherein the composition is operable for a specified result and effective in a mammal (eg: without limitation, a human). Those skilled in the art will understand and appreciate the appropriate techniques for determining whether an active ingredient has a desired effective result depending on the needs of the artisan.

Suitable excipients include carbohydrate or protein fillers such as sugars, including lactose, sucrose, mannitol or sorbitol; Starch from corn, wheat, rice, potatoes, etc .; celluloses such as methylcellulose, hydroxypropylmethylcellulose, or sodium carboxymethylcellulose; and gums, including arabic 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 enhancers, viscosity agents or film polymers, bulking agents, thinners, colorants, flavoring agents, pH modifiers, sweeteners or taste masking agents can also be incorporated. in the composition. Suitable colorants include red, black and yellow iron oxides and FD&C colorants such as FD&C Blue No. 2 and FD&C Red No. 40. Suitable flavors are mint, raspberry, licorice, 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. Sodium bicarbonate, vanilla, ion exchange resins, cyclodextrin inclusion compounds, and adsorbates are suitable taste masking agents.

= Carrier The composition as described herein may include a carrier. The composition as described herein may include a nutritionally acceptable carrier. The composition as described herein can comprise a pharmaceutically acceptable carrier. The composition as disclosed herein can comprise a cosmetically acceptable carrier.

"Nutritionally acceptable carrier" as used in this document, should be understood as any nutritional supplement, nutritional product, food product and / or food article with which the composition and in particular the essential constituents of the composition (rare ginsenoside , ginsan and gintonine) can be combined and which, after combination, can be used orally to administer the composition to a subject. Nutritionally acceptable carriers are known to those skilled in the art. Examples of acceptable nutritional carriers are flour, bread dough, breakfast cereals, snack bars, prepared meals and beverages (eg, carbonated drinks, soy milk, etc.). By combining the composition and in particular the essential constituents of the composition in a nutritionally acceptable carrier, a nutritionally improved food is formed which can then be processed or packaged. "Pharmaceutically acceptable carrier" as used herein, should be understood as 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 combining, can be used orally to administer the composition to a subject. Pharmaceutically acceptable carriers are known to those skilled in the art. Examples of acceptable pharmaceutical carriers are sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, etc. mineral oil, sesame oil, etc. Saline solutions and aqueous solutions of dextrose and glycerol can also be used as liquid carriers, particularly for injectable solutions. Examples of suitable pharmaceutical vectors are described in Remington: Science and Practice of Pharmacy, 21st ed., Lippincott Williams & Wilkins, Philadelphia PA (2005) and Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems, 8th ed., Lippincott Williams & Wilkins, Philadelphia PA (2004).

"Cosmetic 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 deliver the composition to the body. a subject.

Cosmetically acceptable carriers are known to those skilled in the art.

"Topical application" as used herein is to 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 "suitable carrier" as used herein is to be understood as an acceptable cosmetic liquid medium, and preferably as a pharmaceutically acceptable liquid medium as it is commonly used in gels, lotions, shampoos, liquid soaps, and the like.

Those skilled in the art will easily distinguish a "cosmetically acceptable liquid medium" and a "pharmaceutically acceptable liquid medium" from a "non-cosmetically acceptable liquid medium" and a "non-pharmaceutically acceptable liquid medium" respectively.

Additives The composition as described in this document can comprise an additive.

In addition to the essential components described above, current compositions may also include one or more optional components which are known or otherwise suitable for use on human / 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 correcting agents, dyes and - dyes, fragrances, preservatives, etc.

In a preferred embodiment, the current composition also comprises a foaming agent.

Foaming agents are agents which promote the formation of foam. Any agent having a surfactant character can be used. The surfactants can be cationic, nonionic or anionic. Examples of suitable foaming agents included, but are not limited to cetrimide, lecithin, soaps etc. And for example anionic (based on sulfate, sulfonate or carboxylate anions): sodium dodecyl sulfate (SDS), ammonium lauryl sulfate, and other alkyl sulfate salts, sodium lauryl sulfate, also known as the name of sodium lauryl sulfate (SLES), alkyl benzene sulfonate; soaps or salts of fatty acids (see acid salts); cationic (based on quaternary ammonium cations): cetylpyridinium trimethylammonium bromide (CTAB) also known as hexadecyl trimethylammonium bromide, and other alkyltrimethylammonium salts, cetylpyridinium chloride (CPC), polyoxyethylene amine (POEA) ), benzalkonium chloride (BAC), benzethonium chloride (BZT); zwiterrions (amphoteric): dodecyl-betaine, dodecyldioxymethylamine, cocamidopropyl betaine, cocoampho glycinate; nonionic: polyethylene glycol, akylpolyglucosides, including: octylglucosides, decyl maltoside, fatty alcohols, cetyl alcohol, oleic alcohol. Commercially available surfactants such as TWEEN "" are also suitable.

In a preferred embodiment, the compositions according to the invention are stored at room temperature, and preferably at a temperature below room temperature, for example at a temperature below 20 ° C, below 15 ° C, below 10 ° C or less than 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 carrier. 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 gintonine. 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 separate component of the composition set forth herein. The kit can also include an aliquot for any combination of distinct constituents of the composition set forth herein.

"Teaching material" as used herein, should be understood to include a publication, recording, diagram, or other means of expression which can be used to communicate the utility of a compound of the publication in the kit in order to alleviate the various diseases or disorders mentioned in this document. Optionally, or alternatively, the teaching materials may describe one or more methods for alleviating diseases or disorders in a subject. For example, the training material in the kit may be affixed to a container that contains the indicated compound or be shipped with a container that contains the indicated compound. Alternatively, the course material may be shipped separately from the container with the intention that the course material and the compound will be used jointly by the recipient.

Use of a Composition of the Invention In a second aspect, the invention relates to a composition for use as a medicament. Preferably a medicament for the treatment or prevention of stress in a subject. Preferably a medicament for the treatment or prevention of stress in a subject whose cognitive performance of said subject is improved. Preferably, for this purpose, the composition is provided in a pharmaceutically or cosmetically acceptable carrier. Preferably, for this purpose, the composition is provided in one or more pharmaceutically acceptable excipients.

In a third aspect, the invention relates to a method of treating or preventing stress in a subject. The method comprising a step of administration to the subject, a composition according to a first aspect and / or a composition according to a second aspect.

In accordance with the present invention, a composition comprising a rare ginsenoside, a ginsan and a gintonine as described herein is used for the treatment of stress in a subject in need thereof. Use of the current composition for the treatment of stress includes prophylactic use.

"Treatment" as used herein, should be understood to include the prophylaxis of the particular injury, disease, disorder or condition, or alleviation of symptoms associated with an injury, disease or condition. disease, a particular disorder, or the condition and / or prevention or elimination of said symptoms. The term "treated" is used interchangeably with the term "treatment". "Prevent" as used here, should be understood as a way to prevent something from happening, or to take early action against something possible or probable to happen. In the context of medicine, the term "prevention" generally refers to measures taken to reduce the risk of contracting a disease or condition.

"Prophylactic" treatment as used herein, should be understood as treatment given to a subject who does not show signs of illness or injury or who shows only early signs of illness or injury. injury in order to reduce the risk of developing pathology associated with the disease or injury.

Stress is a condition of the body which is characterized by a specific syndrome (increased sympathetic activity, increased secretion of catecholamines, high blood pressure, etc.) and can be triggered by a variety of non-specific stimuli (infections, injuries, burns , radiation effects and also anger, joy, pressure to perform and other factors). Stress can also be understood as external influences to which the body is not adequately adapted, eg operations, poisoning, pregnancy (anon., Pschyrembel- "Klinisches Wôrterbuch, 1990, Walter de Gruyter, Berlin-New York (1990)).

Stress can generally be described as environmental processes that trigger processes in the body through perceptual impulses where eustress is understood as excitatory influences having a positive effect and distress is understood as destructive influences having a negative effect. One effect of stress in a subject is cognitive impairment of the subject.

Humans respond to distress with headaches, insomnia, heart problems, stomach upset, diarrhea, skin irritation, allergies, tension and / or cramps. Typical psychic stress reactions are nervous restlessness, virritability, lack of concentration and sleep disturbances. The stress hormones cortisone and ACTH (adrenocorticotrophic hormone) are primarily responsible for these reactions. Studies have shown that the constituents of ginseng regulate the levels of cortisol and corticosteroids. Other studies have shown the immunostimulatory action of certain constituents of ginseng. Thus, the constituents of ginseng have a calming effect, control stress hormones and control the activity of the immune stimulator.

"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 not be in the absence of the disorder. Without treatment, a disorder does not necessarily cause a further decline in the subject's health. In the context of the present application, stress can be considered as a disorder.

Without being bound by mechanistic theories, it is rationalized that such compositions exhibit said stress treatment and / or performance prevention due to enhanced adaptogenic effect.

The term "adaptogen" used herein is to be understood as an agent which elevates a subject's non-specific resistance to various physical, chemical or biological stressors (see Adaptogenic effect). Adaptogens generally do this by regulating the activity of hyperfunctional systems. The… - examples of adaptogens included, but not limited to these: Astragalus root, Cordyceps, Maca root, Schisandra berry, Ashwagandha root, Holy basil leaf, Reishi mushroom, Maitake mushroom , suma root. Other adaptogens which are non-toxic to the subject and which are capable of elevating the subject's non-specific resistance to external stressors are also included as an example.

Without being bound by any mechanistic theory, it is rationalized that such compositions exhibit said stress treatment and / or performance prevention due to better regulation of cortisol and corticosteroid concentrations and / or improved immunostimulatory action.

In a particularly preferred embodiment, the invention relates to a composition for use as a medicament for the treatment or prevention of stress in a subject. Preferably, a medicament for the treatment or prevention of stress in a subject whose cognitive performance of said subject is improved. Without being bound by any mechanistic theory, it is rationalized that by improving a subject's stress level, that subject's cognitive performance is improved and vice versa. It is mostly rationalized that these effects are caused by an enhanced adaptagen effect.

The method of treating or preventing stress in a subject includes at least the step of administering the composition to a subject. The composition can be administered to a subject in an effective amount according to any method known in the art. Preferably, the composition is formulated for oral administration. The composition can be administered to a subject in the form of a tablet, lozenge, pill, capsule, hard gelatin, etc. Preferably, the composition is included in a capsule which can be administered orally 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, a daily effective dose is at most administered in five different doses. More preferably, a daily effective dose is administered in two different doses. Preferably, one of these two different doses is given after breakfast. Preferably, one of these two different doses is given after dinner. Preferably, a daily effective dose is administered in one dose. Said dose is preferably administered after breakfast. A daily effective 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 at most 100 mg, again more preferably at least 15 mg and at most 75 mg, even more preferably at least 20 mg and at most 55 mg, still more preferably at least 30 mg and at most 45 mg and, most preferably about 37, 5 mg. A daily effective dose of rare ginsenoside in the composition is preferably at least 1 mg, still more preferably at least 1 mg and at most

100 mg, even more preferably at least 10 mg and at most 80 mg, still more preferably at least 15 mg and at most 70 mg, still more preferably at least 20 mg and at most 60 mg, still more preferably at minus 25 mg and at most 50 mg and most ideally about 30 mg.

A daily effective 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 most 75 mg, still more than 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 at most 15 mg and most preferably about 7.5 mg.

A daily effective dose of ginsan and gintonine in the composition is preferably at least 1 mg, 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 at most 24 mg and most preferably about 16 mg.

A daily effective 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 at most 27 mg, still more than 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 at most 17 mg and most preferably about 13 mg.

A daily effective 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, even more preferably at least 0.7 mg and at most 6 mg, still more preferably at least 1 mg and at most 5 mg and most preferably about 3 mg.

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 of rare ginsenoside, at least 10 and at most 16 mg of ginsan and at least. less 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, at respective 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. Most preferably, at respective effective daily doses of about 32 mg of rare ginsenoside, 13 mg of ginsan and 3 mg of gintonine. The applicant notes the most improved cognitive performance in a subject at such effective daily doses. This is for example corroborated in Examples 1-21.

Preferably, the composition also comprises a combination of compounds comprising a rare ginsenoside, ginsan and gintonine at a ginsan to rare ginsenoside ratio of about 4: 1 and a ginsan to gintonine ratio of about 2: 1, plus preferably that 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. As illustrated in Examples 1 to 21, the applicant notes the most improved cognitive performance in a subject on such reports, especially when these reports are provided at preferred daily effective doses, as noted above. 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 the respective effective daily doses. Preferably, the composition comprises a daily effective 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 a daily effective dose of PPT of at least 0.01 mg and at most 35 mg. Preferably, the composition comprises a daily effective dose of Rk1 of at least 10 mg and at most 50 mg. Preferably, the composition comprises a daily effective 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 a daily effective dose of Rh3 of at least 0.1 mg and at most 3 mg.

The "effective amount" used in this document should be understood as an amount sufficient to produce a selected effect, such as alleviating symptoms of a disease or disorder. The "daily effective dose" used herein is to be understood as the effective amount required daily by 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 when that compound is. 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. Even more preferably, the main constituents of this composition are provided in preferred ratios and / or effective daily doses.

According to illustrative embodiments, 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 an excipient (s) ( s) or other pharmaceutically or cosmetically acceptable carriers. In 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 a preferred embodiment, said composition is administered for a period of at least two days, preferably at least five days. As shown in Figure 1, an optimum effect for the composition is obtained for a treatment of at least 5 days.

Preparation of a Composition of the Invention In a fourth aspect, the invention relates to a method of preparing a medicament. Preferably a medicament for the treatment or prevention of stress in a subject. The composition preferably comprising a daily effective dose of rare ginsenoside of at least 1 mg and at most 100 mg. The composition preferably comprising a daily effective dose of ginsan of at least 0.3 mg and at most 30 mg. The composition preferably comprising a daily effective dose of gintonin of at least 0.1 mg and at most 10 mg. The method preferably includes the step of growing a ginseng in a hydroponic environment. The method preferably comprises the step of harvesting a root from said cultivated ginseng. The method preferably comprising the step of crushing said harvested root to obtain said medicament. The method also optionally includes a step of drying the harvested ginseng before grinding. The method also optionally includes a step of cooking the crushed ginseng.

In a fifth aspect, the invention relates to a method according to a fourth aspect of the current invention for the production of a composition according to a first aspect for use as a medicament and / or a composition for use as a medicament. according to a second aspect of the invention.

A hydroponic environment is a well-known technique for growing plants using mineral nutrient solutions, in water, without soil. In general, plants outside the ground 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 coconut shell. Under natural conditions, the soil acts as a reservoir of mineral nutrients, but the soil itself is not essential for plant growth. When soil nutrients dissolve in water, plant roots can 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 thrive. An advantage of hydroponics over conventional soil-based techniques is that the growing environment can be tightly controlled, especially the level of nutrients supplied to the root environment. Another advantage is that the water supplied to factories can be easily stored in the system, resulting in significant water savings. A hydroponic environment is particularly advantageous in view of the current invention, as the final concentrations of constituents in the ginseng root system can be controlled by carefully adjusting the nutrient content administered to the ginseng plant. The applicant notes that to his knowledge, no other cultivation technique makes it possible to cultivate a ginseng root with the constituents necessary to obtain a composition according to the current invention. In addition, due to the advantages described above, Applicant points out that hydroponics of ginseng takes much less time than growing in soil. In a particularly preferred embodiment, the method comprises the step of growing a ginseng in a controlled hydroponic environment. A controlled hydroponic environment is a technique of growing plants in nutrient solutions which are water containing fertilizers with or without the use of an artificial medium such as sand, gravel, vermiculite, rock wool, perlite, or sawdust to provide mechanical support in a technically controlled environment. Under 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 cultivated ginseng plant. In a particularly preferred embodiment, the method comprises the step of cultivating a ginseng in an aseptic hydroponic environment. An aseptic hydroponic environment is a hydroponic technique performed under conditions of sufficient cleanliness to avoid the presence of microbes such as bacteria, yeasts, fungi and molds, but also insects and other harmful organisms. By using an aseptic hydroponic environment, the use of pesticides can be completely avoided.

However, it should be clear to those skilled in the art that the composition according to the current invention can be produced according to any method known in the art. For example, according to an alternative embodiment, the composition can be prepared by mixing aliquots each comprising one or more constituents of the composition.

The ginsenosides according to one of the methods and compositions described in the present document can be isolated and / or purified from a ginseng, from a ginseng extract or from another plant source, or the ginsenoside can be a ginsenoside synthetic that is manufactured.

In other illustrative embodiments, 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 a ginseng extract thereof. In other illustrative embodiments, the ginsenoside of the methods and compositions described herein is formulated as or is part of a ginseng extract. Ginsen extracts can be obtained from plant materials. Plant materials can be extracted with water or an aqueous solution, an alcohol solution or a combination of water and alcohol. Ginsenosides can be isolated and / or purified from ginseng or other plant source using methods known in the art, which are reported, for example, in Chemistry and Pharmacology of Natural Products: Saponins, Par K. Hostettmann, A. Marston, Cambridge University Press 1995, which is incorporated herein by reference. In other illustrative embodiments, the procedures for obtaining ginsenosides Rb1, Rb2, Rc and / or Rd generally comprise the aqueous or organic extraction of one or more suitable Panax species, evaporating the extracted solution to dryness. , followed by column chromatography, thin layer chromatography and / or high performance chromatography to obtain a purified fraction of ginsenoside. The techniques for extracting and purifying plant extracts are known to those skilled in the art and can be adapted for the preparation of each or a mixture of one or more Rb1, Rb2, Rc or Rd, from techniques such as those listed 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. The isolation and purification procedures for Rb1, Rb2, Rc and Rd are also described in, for example, 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 illustrative embodiments, the ginsenoside of the compositions or methods described herein is a member of the dammaran or oleanan family. In other illustrative embodiments, the ginsenoside of the compositions or methods described herein is a member of a group selected from protopanaxadiols, protopanaxatriols, and pseudoginsenoside FI 1.

Traditionally, ginsenosides (including the rare ginsenosides and ginsenosides as used herein) have low bioavailability. Ginsenosides are, however, readily metabolized or hydrolyzed by intestinal bacteria in addition to the bioavailable and active ginsenosides. The "ginsenoside" and "rare ginsenoside" used herein should also include any metabolite of rare ginsenosides or ginsenosides which is a product of the metabolism of rare ginsenoside or ginsenoside by a mammalian intestinal bacteria. Non-exhaustive examples of a ginsenoside metabolite, include 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. More ideally, 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 the art can be used. The applicant notes the better retention of the various essential constituents of ginseng during steaming of the harvested roots. Preferably, said harvested root is steamed. More preferably, said harvested root is steamed after drying and / or crushing said harvested root. Preferably, the harvested root is steamed at a temperature of at least 100 ° C and at most 150 ° C, still more preferably at 140 ° C at most, still more preferably at 130 ° C at most and even more preferably at 121 ° C maximum. Preferably, said harvested root is steamed for at least 30 minutes, even more preferably at least 30 minutes and at most 10 hours and even more preferably at least 1 hour and at most 6 hours.

In another embodiment, the ginsenoside can also be a synthetic ginsenoside which is made. Methods of making ginsenoside synthetically are known in the art and are published, 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 all 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 insoluble ethanol fraction of a deginseng water extract (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 indicated in publication EP 2 502 933, gintonine can be obtained by fractionation and dialysis of a methanol extract obtained from any ginseng.

PREFERRED EMBODIMENTS OF THE INVENTION

1. First, the invention relates to a composition comprising a rare ginsenoside, ginsan and gintonine, for use in the treatment or prevention of stress in a subject.

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

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

4. The composition according to the first aspect, where the ratio of rare ginsenoside to ginsan is at least 300: 1 and at most 1:30.

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

6. The composition according to the first aspect, wherein said rare ginsenoside is selected from the group comprising: C-K, Rg6, Rh4, Rg3, PPT, Rk1, Rg5, Rh2, Rh3 and PPD.

7. The composition according to the first aspect, where said rare ginsenoside comprises 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.

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

9. The composition according to the first aspect, wherein said composition further comprises a ginsenoside, preferably said ginsenoside is selected from the group comprising: Rg1, Re, Rf, Rh1, Rg2, Rb1, Rec, Rb2 and Rd.

10.The composition according to the first aspect, wherein said composition further comprising a ginsenoside selected from the group comprising: Rg1, 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.

11.The composition according to the first aspect, where the ratio of rare ginsenoside to ginsenoside is at least 200: 1 and at most 1: 5.

12.The 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, Rki, 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.

13.The composition according to the first aspect, wherein said composition is formulated for oral administration.

14.The composition according to the first aspect, wherein said composition is enclosed in a capsule for oral administration.

15. In a second aspect, the invention relates to a composition according to the first aspect, where the composition is provided in a pharmaceutically or cosmetically acceptable carrier.

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

17. In a third aspect, the invention relates to a method of treating or preventing stress in a subject, the method comprising the step of administering, to the subject, a composition according to a first aspect and / or a composition according to a first aspect. composition according to a second aspect.

18. The method according to the third aspect, wherein said composition comprises a daily effective dose of rare ginsenoside of at least 1 mg and at most 100 mg.

19. The method according to the third aspect, according to which this composition comprises a daily effective dose of ginsan of at least 0.3 mg and at most 30 mg.

20. The method according to the third aspect, wherein said composition comprises a daily effective dose of gintonine of at least 0.1 mg and at most 10 mg.

21. In a fourth aspect, the invention relates to a method of preparing a medicament, preferably a medicament for the treatment or prevention of stress in a subject, the medicament comprising: an effective daily dose of rare ginsenoside of at less 1 mg and not more than 100 mg; a daily effective dose of ginsan of at least 0.3 mg and at most 30 mg; and a daily effective dose of gintonine of at least 0.1 mg and at most 10 mg, the method comprising the following steps: growing ginseng in a hydroponic environment; harvesting a root from said cultivated ginseng; and crushing said harvested root to obtain said medicament.

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

23. 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.

24. The kit according to the sixth aspect, wherein said composition is a composition according to the first aspect and / or a composition according to the second aspect.

EXAMPLES The following examples are intended to further clarify the present invention and are in no way intended to limit its scope.

EXAMPLES 1-21 A simple composition according to the current invention comprises a rare ginsenoside, a ginsan and a gintonin. Table 1 gives an overview of the simple compositions according to the invention. Table 2 gives an overview of the compositions according to the invention comprising the ginsenosides. Table 3 gives an overview of the compositions according to the invention also comprising an additional ingredient, an additive, a vector and / or an excipient. Throughout the examples, these components will be considered as additional ingredients, unless otherwise indicated.

Table 1 simple compositions Example Jinsenoside rare ginsan …… Jintonine… _…

OS MO ZM MO MO FIMO rs MO MO PME create LP 30 Mg MG rs B 90 Mg MG ME Table 2 compositions comprising ginsenosides Example rare ginsenoside _ginsan gintonine ginsenoside Bo mg MO 10 mg Mg 2 100 Mg Mg Mg MG 10 20mg 29 Mg Mg Mg 11 80mg mg 05 mg 60mg 12 32mg 3 Mg Mg Mg 13 37mg mg 2 Mg Mg 14 37mg Mg 4Mmg Mg

Table 3 compositions comprising an additional ingredient Example ginsenoside ginsan gintonine ginsenoside ingredient formulation Me Additional 32 mg 13 mg 3 mg 5 mg 32.4 mg 2 capsules 16 40 mg 15 mg 5 mg 10 mg 200 ml Powdered saline composition of 106 mg for daily intake of preferably dissolved in Saline 17 31 mg 12mg 4mg 6 mg 500 mg 1 capsule Acid for daily alginic intake preferably after 18 1 mg 30mg 10 mg 9 mg 350 mg 5 Gum arabic tablets of 100 mg for one intake Dr AUOtidienne 19 99 mg 0.4mg 0.1mg 0.5mg 100mg 2 capsules 100mg rice flour for one intake Daily 20mg 25mg 9mg 15mg 5mg Composition Dextrose powder below for one in 30cl daily water intake .

Preferably dissolved in a solution of 21 80 mg 45 mg 0.5 mg 65 mg 450 mg Agar based dessert for a daily intake.

Close-up Table 4 shows the results of analysis of the compositions for cognitive enhancement in a patient after five days of absorption. A detailed experimental setup for performing the compositions is provided in Example

31. Examples 1-14 were administered daily in two capsules as shown in Example 31. Maintenance of cognitive improvement was assessed by repeating a d2 test of attention 24 hours after ingestion of the last dose compared to the baseline for the first day of treatment. The performance of the different compositions is the strength classified according to a positive and negative control. The positive control and the negative control were prepared as shown in Example 31. Table 4 Examples of performances 1-21. “Example cognitive improvement maintenance of cognitive improvement 24 hours after the Lee Treatment A ee a B rene Flour de En +4 ee nn 18 * + a

+++ Performance significantly better compared to the negative control (p <0.0001) and performance significantly better compared to the positive control (p <0.0001). ++ Performance significantly better compared to the negative control (p <0.0001) and performance significantly better compared to the positive control (p <0.05). + Significantly better performance compared to the negative control (p <0.05) + Higher performance observable compared to the negative and positive controls (not significant) xx Higher performance observable compared to the other performance groups (not significant) EXAMPLE 22 A composition according to current invention comprises a rare ginsenoside. A composition according to the current invention can also comprise a ginsenoside. Table 5 gives an overview of the average ginsenoside profile of a composition according to the invention. Table 6 gives an overview of the average rare ginsenoside profile of a composition according to the invention. A duplicate sample (n = 2) was taken in Examples 1 to 21. All other ingredients were removed from the samples. 42 samples were prepared and analyzed according to the methodology described in Example 28. Table 5 mean profile in ginsenoside “ginsenosides Average (mg / g of Min (mg / g of Max (mg / g of Dry matter)… Dry matter) dry) Re OO rs 063 Re OR re 23 EB | <JE: RDD OO ee Ge IDL ROZ De Ge ZIT

RD ZZ Re AL re Or DOS ROZ rer AO re ZIN RO 438 D rc 10.81 Table 6 average profile in rare ginsenoside “ginsenosides Average (mg / g of Min (mg / g of - Max (mo / gde - ares Dry matter ) dry matter) Dry matter)…… Rg6 221692

EdT 41.55 PPT PE 774 Ed 40.98 RB E27 009 13.91 EXAMPLES 23-27 A composition according to the current invention comprises a rare ginsenoside. A composition according to the current invention can also comprise a ginsenoside.

Table 7 provides examples of ginsenoside profiles according to the current invention. Table 8 gives examples of profiles of rare ginsenosides according to the current invention.

Table 7 Examples of ginsenoside profile (mg / ml of extract) “Example Rgl Re Rf Rhi Rg2 Rbl Rc Rb2 Rd 2300 001 0.01 0.01 0.4 04 22.001 08 Table 8 Example of rare ginsenoside profile (mg / ml extract) 'Example Rg6 Rh4 Rg3 PPT Rkl Rg5 Rh2 Rh3 PPD 25 bern! 8,215,109 a Ge De Table 9 shows the relative results of analysis of the compositions for cognitive enhancement in a patient after five days of absorption. A detailed experimental setup for the performance of the compositions is provided in Example 31. Examples 23-27 were administered daily in two capsules, as shown in Example 31. Additionally, about 13 mg of ginsan and 3 mg of gintonine were provided in each of these capsules. The performance of the different compositions is ranked against each other.

Table 9 Relative Performance of Examples 23-27 Gemeenten gite EXAMPLE 28 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 that operates as a continuous plug system. The operating speed of such a plug-flow production plant is increased by a factor of at least three between seeding and harvesting. The effectiveness of the composition was tested in Example 31. The composition was obtained by drying, grinding and cooking ginseng roots. Tables 10 to 12 detail the composition.

Analysis of Ginsenoside Content The content of ginsenoside and rare ginsenoside, detailed in Tables 11 to 12, was analyzed using HPLC. Before analysis, the crushed ginseng roots were subjected to hydroalcoholic extraction and subsequent aqueous extraction. The initial hydroalcoholic extraction was carried out on 6 kg of crushed ginseng roots. The hydroalcoholic extraction is effective for the extraction of ginsenosides and gintonine. The hydroalcoholic 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% H20 at 50 ° C. The hydroalcoholic solution was recovered by filtration. The second cycle was applied to this filtrate. During this second cycle, another hydroalcoholic extraction was carried out with mixing and recirculation for 2 hours 30 min using 30 | 70% Etoh / 30% H20 at 50 ° C. The hydroalcoholic solution was again recovered by filtration. Said filtrate was then subjected to aqueous extraction.

The aqueous extraction is effective for the extraction of ginsan polysaccharide. The aqueous extraction was carried out in two cycles. During a first cycle, aqueous extraction was carried out on said filtrate under admixture for 2 hours 30 min at 80 ° C using 30 | hot water. After this 2 hour 30 minute period, the mixture was quenched and heated to 80 ° C for a further 16 hours. Subsequently, the water fraction 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.

The hydroalcoholic extract was concentrated by evaporation (rotavapor; T °: 50 ° C; vacuum: 100-200 mbar). 60 | of hydroalcoholic extract were divided into 4 batches of 15 |. Each batch was concentrated to 5 | and 1,875 | of glycerol was added. The aqueous extract was pre-filtered through 15 µm (by centrifugal filtration) and microfiltered through 0.45 µm. The resulting solution was then ultrafiltered (20 Kda). From about 31 kg of aqueous extract, about 9.3 kg was obtained after ultrafiltration. The concentrated hydroalcoholic extract (57%) was then pooled with the ultrafiltered aqueous extract (43%). Said mixture was analyzed by HPLC. HPLC analysis is detailed in Tables 10 to 12.

Analysis of Ginsan Content The ginsan content detailed in Table 11 was analyzed by percolating the crushed ginseng roots with 5 volumes of 85% ethanol to extract materials soluble in ethanol. The remaining residue was percolated a second time with 5 volumes of distilled water. The water soluble extracts were concentrated using a vacuum evaporator. The concentrate was dialyzed against running tap water for 7 days to completely cleave small molecules with a molecular weight below 15 kDa. Four volumes of absolute ethanol were added to precipitate the polysaccharide from the internal dialysate. The precipitate was dried in a vacuum drying oven and was finally used as the acidic red ginseng polysaccharide. Extraction and measurements were performed according to the study by Choi et al. (Red Ginseng Acidic Polysaccharide (RGAP) in combination with IFN-Y Results in Enhanced Macrophage Function through Activation of the NF-KB Pathway. Hye-Sook CHOI, Kyung-Ho KIM, Eunwha SOHN,

Jong-Dae PARK, Byung-Oh KIM, Eun-Yi MOON, Dong-Kwon RHEE and Suhkneung PYO.

Biosci.

Biotechnol.

Biochem., 72 (7), 1817-1825, 2008). Analysis of Gintonine Content The gintonine content shown in Table 10 was analyzed by extracting ginseng with fermented ethanol.

Said extract is fractionated with water to obtain a water soluble fraction and a water insoluble fraction.

The water insoluble precipitate is the gintonine enriched fraction (FEG). Extraction and measurements were performed according to the study by Choi et al. (A brief method for preparation of gintonin-enriched fraction from ginseng.

Sun-Hye Choi, Seok-Won Jung, Hyun-Sook Kim, Hyeon-Joong Kim, Byung-Hwan Lee, Joon Yong Kim, Jung- Hyun Kim, Sung Hee Hwang, Hyewon Rhim, Hyoung-Chun Kim, Seung-Yeol Nah .

J Ginseng Res., 39, 398-405, 2015). EXAMPLE 29 The current example relates to another method of preparing a composition according to the current invention.

The composition was obtained by extracting the rare ginsenosides, ginsan and gintonine separately from ginseng.

Example 17 describes in detail the constituents of the composition.

Ginsan has been extracted from ginseng by isolating ginsan from an insoluble ethanol fraction of a water extract of ginseng, as revealed by Kim et al. (1997). Gintonine has been extracted by fractionation, fractionation and dialysis of a methanol extract obtained from any ginseng disclosed in PE 2,502,933. Commercially available ginsenosides and rare ginsenosides have been purchased.

The extracts were aliquoted to obtain a simple composition according to the current invention.

EXAMPLE 30 A saline solution of 30% ginsenoside, 15% ginsan and 3% gintonine by weight was evaluated for effectiveness in improving stress levels in athletes diagnosed with burnout. .

Performance was assessed using a Recovery and Stress Questionnaire (Kellmann & Kallus, 2001), an Athlete Burnout Questionnaire (Raedeke & Smith, 2001), and a scale. mood of Stellenbosch (Terry et al., 2003). Performance was assessed before and after treatment.

The treatment comprising a five day oral administration of 100 mg of the composition. The composition has been shown to be effective in reducing stress levels in treated subjects.

EXAMPLE 31 The current example relates to an efficacy study of a herbal preparation of Panax ginseng. To better illustrate this example, reference will be made to FIG. 1. The aim of this study was to test the effectiveness of a herbal preparation of Panax ginseng according to the current invention. In particular, the effectiveness of improving cognition in a subject was tested. More specifically, the study examines the effectiveness of the herbal preparation in preventing stress-related symptoms. These symptoms include fatigue, impaired memory, impaired concentration, impaired attention deficit, nervousness, and restlessness.

Test Composition The herbal preparation used in this study was produced according to the methodology illustrated in Example 28. Tables 10-12 give an overview of the average composition of the herbal preparation (n = 3) . Table 11 gives an overview of the average profile of the ginsenosides of the herbal preparation (n = 3). Table 12 gives an overview of the average profile of rare ginsenosides of the herbal preparation (n = 3). Profiles only include tested ginsenosides and rare ginsenosides.

Positive control A Panax ginseng Arkopharma available on the market for six years was used as a positive control. A powdery composition was obtained by cryogenic grinding. Two capsules were provided for daily administration. 382 mg of the pulverulent composition were aliquoted into said two capsules.

Negative control A mixture of cane sugar and rice flour was used as a negative control. A powdery composition was enclosed in a capsule. Table 10 gives an overview of the mean composition of the negative control (n = 3).

Table 10 average compositions tested

OO ginsenoside ginsan gintonine ginsenoside ingredient formulation - rare additional “composition 31.7 mg 12.68 3.17 mg 5.7 mg 209 mg test composition mg rice flour from test 2 (excipient capsules inactive) and daily approximately 209 mg 1356 mg of other constituents of ginseng “control Omg Omg Omg Omg = - 418 mg of 2capsules negative rice root control daily (excipient containing inactive) 209 mg * Arkopharma capsules purchased on“ NewPharma.be ”, lot nr. HO5178A Table 11 Test composition of the mean profile of ginsenosides ginsenosides Average (mg / ml of extract) RAT Oee Re OD res AU rs RML 0 res ROZ GB rs RBI ee OST rer RE 2 res KU res Rd ed rs Table 12. Composition d average profile test of rare ginsenosides. Rare ginsenosides Average (mg / ml of extract) RG rem OO res RAGE re LS es

ER A RK1 mother MIE rer U D rs RS Ed

Cognitive function and stress level The d2 test of attention was used as an estimate of cognitive performance and stress level in a subject. The d2 Attention Test is a neuropsychological measure of selective and sustained attention and visual scanning speed. This is a paper-and-pencil test that asks participants to cross out any letter "d" with two marks around, above or below, in any order. Surrounding distractors are generally similar to the target stimulus, for example a "p" with two marks or a "d" with one or three marks. The original version of the test was created by Brickenkamp (1981) as an undo task. The precision of the test d2 is expressed as an error rate (%) which is the ratio between the errors made and the total number of correct answers for 4 minutes and 40 seconds with respect to a determined baseline. In order to avoid interference from external factors, measurements were taken in the morning at 9 a.m. (reference time) and at the end of the working day at 4 p.m. The difference between these two periods indicates the potential effect of a substance on cognitive performance. The error percentage of the d2 test should normally increase between morning and afternoon due to stress and fatigue during a working day. Study A randomized, double-blind, double-blind, crossover trial was performed on 50 healthy subjects. Subjects were randomized and tested for illegibility. The subjects were forbidden to take drugs or food supplements. Subjects were prohibited from consuming more than one cup of coffee per day for the duration of the study. An overview of the different time points (t0-t30) is provided below.

tO: A baseline d2 attention test was performed at 9 a.m. The cognitive function and stress level of all subjects were measured. The methodology is detailed above. t1: The d2 test of the attention test was repeated at 4 p.m. - t2-9: The time points t0 and t1 were repeated for four consecutive days.

t10: Start of treatment. A herbal preparation, positive control or negative control (Tables 7-9) were administered daily to each subject. Each dose was consumed at 10 a.m. t10-15: Time points t0 and t1 were repeated on the first, fifth and twelfth day after the start of treatment.

t16-30: According to the crossover design, participants received opposite treatments after a two week washout period. Results Figure 1 shows the results of the efficacy study. The y-axis in Figure 1 shows the% difference in the error rate (delta (post-pre) workload) of test d2 between the first and the second test during each day. The x-axis indicates the duration of the experiment. A significant reduction in errors was observed on days 1, 5 and 12 for the herbal preparation tested compared to positive and negative controls. No significant reduction in errors was observed for the positive control compared to the negative control. In addition, the% difference in the error rate is negative for the composition tested on days 1, 5 and 12. A negative difference in the% error rate indicates an improvement in the subjects' cognitive performance as well as a reduction in performance. stress level during the day. It is rationalized that by improving the cognitive performance of the subjects, the stress level of the latter is also reduced. EXAMPLE 32… The current example relates to an efficacy study of a herbal preparation of Panax ginseng. The aim of this study was to determine whether an herbal preparation of Panax ginseng according to the current invention is an effective and safe treatment for preventing symptoms of stress, fatigue and cognitive impairment. Test composition A herbal test composition was used as described in the example

31.

Positive control

A positive control was used as set forth in Example 31. Negative Control A positive control was used as set forth in Example 31.

Cognitive function and stress level Cognitive performance and stress levels in subjects were estimated by measuring changes over time in baseline electrical activity in the brain of each subject. In particular, a quantitative-topographic EEG (qEEG) was performed in multiple psychometric tests, followed by frequency analysis of the data using a fast Fourier transform (FFT). More specifically, the responses of electrical brain activity were measured by the use of spectral power in 17 different regions of the brain in 6 specially defined frequency ranges (delta, theta, alpha1, alpha2, beta and beta2) during a cognitive performance test d2 attention (d2-test), a memory test (ME-test) and a concentration test with financial reward (CPT-test). In addition, subjects were asked to complete a mood profile questionnaire (POMS) and a stress and coping questionnaire.

Study A randomized, double-blind, double-blind, crossover trial was carried out on 30 subjects aged 60 to 75 years. The subjects were forbidden to take drugs or food supplements. Subjects were subjected to strict inclusion and exclusion criteria (eg, breathalyzer and QEEG screening).

The selected subjects consumed a daily dose of the test preparation (test composition, positive control or negative control) during three consumption periods (A-B, C-D and E-F). Each consumption period lasts four weeks. A washout period of four weeks has been planned between each consumption period. An overview of the different study days (A-F, SC (preselection) and FE (final exam)) is provided below. SC: The procedural steps performed during SC are detailed below. The procedure steps were performed in the order shown below.

- Clarification with the subject about the study with the subsequent participation of the study.

- Blood alcohol test to check the compliance of subjects. - Recording of a safety EEG - Measurement of blood pressure and pulse before recording qEEG. - gEEG-recording-screening: 10 minutes (eyes open (6 min), eyes closed (4 min)) - comparison of qEEG data with the standard database. - Determination of suitability. - Appointment for study day A.

A-B: The steps of the procedure carried out on the study days of a first consumption period (A-B) are detailed below.

The procedure steps were performed in the order shown below. - Blood alcohol test. - Standard breakfast. - Questionnaire - POMS - Questionnaire - stress and adaptation. - Measurement of blood pressure and pulse before qEEG recording. - gEEG registration - baseline with mental work.

Experimental series used: 6 min gEEG Eyes open, 4 min qEEG Eyes closed, 5 min gEEG and d2-test, 5 min qEEG and ME-test and 5 min qEEG and CPT-test. - Taking the preparation for the study. - dEEG recording - after 2 hours - with mental work.

Experimental series used: 6 min gEEG Eyes open, 4 min gEEG Eyes closed, 5 min gEEG and d2-test, 5 min qEEG and ME-test and 5 min qEEG and CPT-test. - Questionnaire - POMS C-D: The detailed procedure steps for consumption period A-B were repeated for consumption period C-D after a four week wash period.

E-F: The detailed procedure steps for drinking period A-B were repeated for drinking period E-F after a wash period of four weeks after drinking period C-D.

FE: The procedural steps performed during FE are detailed below.

The procedure steps were performed in the order shown below. - Blood alcohol test - Standard breakfast. - Measurement of blood pressure and pulse. - Safety EEG recording.

- Final clinical registration (request). - Discharge of the study Results As in Example 31, there was a significant reduction in the errors of the d2 test of attention for the composition of the test at the end of each consumption period compared to the positive and negative controls.

No significant reduction in errors was observed for the positive control compared to the negative control.

The difference in% of the error rate is also negative for the composition of the test at the end of each consumption period.

In addition, more relaxed mental stress conditions were observed for the test composition at the end of each consumption period compared to the positive and negative controls.

Claims (14)

1. A composition comprising a rare ginsenoside, a ginsan and a gintonine, wherein the ratio of ginsan to gintonine is at least 500: 1 and at most 1: 100 and wherein the ratio of rare ginsenosides to ginsan and gintonine is at least 250: 1 and at most 1:40, for use in the treatment or prevention of stress in a subject. 2. Composition according to preceding claim 1, wherein the ratio of rare ginsenoside to ginsan is at least 300: 1 and at most 1:30. 3. A composition according to any one of preceding claims 1 or 2, wherein 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 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. 5. Composition according to any one of the preceding claims 1 to 4, further comprising a ginsenoside selected from the group comprising: Rg1, Re, Rf, Rh1, Rg2, Rb1, Rc, Rb2 and Rd and in which the ratio of Rc to a total amount of rare ginsenoside and ginsenoside is at least 1: 1 and at most 1: 3. 6. A composition according to any one of the preceding claims 1 to 5, wherein said rare ginsenoside is selected from the group comprising: Rg6, Rh4, Rg3, PPT, Rk1, Rg5, Rh2, Rh3 and PPD. 7. Composition according to any one of the preceding claims 1 to 6, said composition further comprising a ginsenoside, in which the ratio of one or more compounds selected from the group comprising: Rg5, 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. 8. A composition according to any one of the preceding claims 1 to 7, in a pharmaceutically or cosmetically acceptable carrier and optionally one or more pharmaceutically acceptable excipients, intended for use as a medicament for the treatment or prevention of stress in a subject, preferably a medicament for the treatment or prevention of stress in a subject, which improves the cognitive performance of said subject. 9. A method for the treatment or prevention of stress 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. The method of claim 9, wherein said composition comprises a daily effective dose of rare ginsenoside of at least 1 mg and at most 100 mg. 11. The method of preceding claims 9 or 10, wherein said composition comprises a daily effective dose of ginsan of at least 0.3 mg and at most 30 mg. 12. The method of preceding claims 9 to 11, wherein said composition comprises a daily effective dose of gintonine of at least 0.1 mg and at most 10 mg. 13.A process for preparing a composition according to any one of preceding claims 1 to 7 and / or a composition according to preceding claim 8, the composition for use as a medicament, preferably a medicament for the treatment or prevention of stress in a subject, preferably the medicament comprising: a daily effective dose of rare ginsenoside of at least 1 mg and at most 100 mg; a daily effective dose of ginsan of at least 0.3 mg and at most 30 mg; and a daily effective dose of gintonine of at least 0.1 mg and at most 10 mg, the method comprising the steps of: cultivating ginseng in a hydroponic environment; harvesting a root of said adult ginseng; and crushing said harvested root to obtain said medicament. 14.A kit comprising one or more aliquots of a composition, said composition comprising a rare ginsenoside, a ginsan and a gintonine, preferably wherein said composition is a composition according to any one of the preceding claims 1 to 7 and / or a composition according to the preceding claim 8.