Composition comprising sideritis derivatives and olive derivatives for memory enhancement

Abstract

The present invention relates to compositions for oral administration, for memory enhancement, which comprise one or more tea derivatives, preferably derivatives of sideritis tea (Sideritis spp.), more preferably derivatives of Sideritis syriaca and / or Sideritis scardica and / or Sideritis perfoliate and / or Sideritis raeseri and / or Sideritis euboa and one or more olive derivatives (Olea europaea).

Description

[0001] COMPOSITION COMPRISING SIDERITIS DERIVATIVES AND OLIVE DERIVATIVES FOR MEMORY ENHANCEMENT

[0002] Description of the invention The present invention relates to compositions for oral administration, for memory enhancement, which comprise one or more tea derivatives, preferably derivatives of sideritis tea (Sideritis spp.), more preferably derivatives of Sideritis syriaca and / or Sideritis scardica and / or Sideritis perfoiiata and / or Sideritis raeseri and / or Sideritis euboa avd one or more olive derivatives (Olea europaea).

[0003] Sideritis tea is full of flavonoids, polyphenols, phenolic acids, glycosides, resulting in beneficial effects on the intestinal microbiome, the digestive system, the prevention of insulin resistance and hyperlipidemia, helping to alleviate the common consequences of overweight and obesity, exerting a beneficial effect on lipid parameters and cardiovascular risk factors, as well as a positive effect on improving memory and mood, especially in elder adults [Dorota Zyzelewicz, Kamila Kuibat-Warycha, Joanna Oracz, and Kacper Zyzelewicz. 2020. "Polyphenols and Other Bioactive Compounds of Sideritis Plants and Their Potential Biological Activity” Molecules 25, no. 16: 3763],

[0004] Hydroxytyrosol can be extracted from olive leaves and fruit and is a molecule with antioxidant, anti-inflammatory, antiatherogenic and antithrombotic properties. In vitro studies show that, in addition to its antioxidant activity, it can improve endothelial dysfunction, lipid profile and has anti-inflammatory properties. It can therefore be considered as a neuroprotective, cardioprotective and chemoprotective agent [Bertelli M, Kiani AK, Paolacci S, Manara E, Kurti D, Dhuli K, Bushati V, Miertus J, Pangallo D, Baglivo M, Beccari T, Michelin! S. Hydroxytyrosol: A natural compound with promising pharmacological activities. J Biotechnol. 2020; 309: 29-33]. Hydroxytyrosol has also been considered as an antithrombotic agent, since it reduces endothelial cell activation, significantly reducing platelet aggregation, which is one of the stages of thrombus formation [DelTAgli M, et al. Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase. Br J Nutr. 2008; 99(5): 945-51]. Document EP2608798B1 relates to an extract from aerial plant parts of Sideritis ssp. for use in improving cognitive performance, wherein said aerial plant parts are fresh or dried plant parts selected from the group Sideritis euboa, Sideritis scardica, Sideritis raised or mixtures thereof. Document EP2515922B1 relates to siderite extracts obtained by extraction with water or aqueous-alcoholic solvents for use in the treatment or prevention of neurodegenerative diseases, wherein said neurodegenerative disease is associated with aggregated proteins / peptides, including Alzheimer’s disease.

[0005] In the study of Hofrichter et al., 2.016 [Hofrichter J, Krohn M, Schumacher T, Lange C, Feistel B, Walbroel B, Pahnke J. Sideritis spp. Extracts Enhance Memory and Learning in Alzheimer’s p-Amyioidosis Mouse Models and Aged C57BI / 6 Mice. J Alzheimers Dis. 2016; 53(3): 967-80] it was found that daily oral treatment with extracts of Sideritis spp. {Sideritis euboea and Sideritis scardica} significantly enhanced cognitive performance in aged, non-transgenic, as well as in transgenic mice with amyloid precursor protein (APP), an effect that was even more pronounced when the extracts of both species were applied in combination.

[0006] In the study of Moussavi et al., 2022 [Moussavi N, Azizullah H, Malterud KE, Inngjerdingen KT, Wangensteen H. Immunomodulating polyphenols from Sideritis scardica. Journal of Functional Foods, 2022; 96: 105197] it is reported that S’, scardica comprises a pool of compounds that indicate multifaceted activities according to the results of various in vitro bioassays and therefore may serve as a potential candidate for adjunctive treatment of Alzheimer's disease.

[0007] It is noteworthy that sideritis extract is also present in commercial products, e.g. Powerhealth® effervescent tablets with lOOmg sideritis extract, being available in the Greek market.

[0008] Document CN106138016A refers to the use of hydroxytyrosol for the prevention and treatment of Alzheimer’s disease. When administered to mice suffering from Alzheimer's disease, hydroxytyrosol was found to be able to cross the blood-brain barrier to remarkably improve the functions of cerebral nerves, as well as learning and memory abilities. However, in the prior art, there are no mentions yet of compositions comprising the combination of tea derivatives and olive derivatives, nor their use in enhancing memory.

[0009] Despite of the positive properties of the isolated components mentioned above, there is a continuous need for compositions with even more intense ability of memory enhancement and simultaneous action on cardiometabolic diseases, with even more intense antioxidant action against the oxidation of LDL cholesterol, as well as against atherosclerosis.

[0010] The present invention, taking into account all the aforementioned data, solves ail the above problems of the state of the art, and indeed with unexpectedly advantages and better results in terms of enhancing the mental function of individuals and treating symptoms related to dementia, especially in the elderly, enhancing memory and treating symptoms related to memory' loss in patients with Alzheimer's Disease, while exerting a simultaneous cardioprotective effect, taking advantage of the synergistic, as found, action of tea and olive derivatives, both in enhancing memory and cardioprotection,

[0011] More specifically, the present invention is defined by the following:

[0012] Definition 1, Composition for oral administration, which comprises one or more tea derivatives, preferably derivatives of sideritis tea (Sideritis spp.), more preferably derivatives of Sideritis syriaca and / or Sideritis scardica and / or Sideritis perfoliata and / or Sideritis raeseri and / or Sideritis euboa and one or more olive derivatives (Olea europaea).

[0013] Definition 2. Composition according to definition 1, which is formulated in granules for oral suspension or granules for immediate ingestion or tablets or soft capsules or hard capsules or oral solutions or oral suspensions or syrups or powders, preferably soft capsules or hard capsules. Definition 3. Composition according to any of the definitions 1 to 2, wherein the tea derivative is a tea extract of Sideritis spp., said extract ranges preferably from 1 to 1000 mg per formulation, more preferably is at 100 mg or at 500 mg per formulation. Definition 4. Composition according to definition 3, wherein the tea extract of Sideritis spp. is derived from Sideritis scardica, said extract comprises flanonoids in a concentration range from 0,1 to 10 %, preferably at 2,95 % and acteoside in a concentration range from 0,1 to 10 %, preferably at 1,38 %. Definition 5, Composition according to any of the definitions 1 to 4, wherein the olive derivative is an olive extract and / or solid hydroxytyrosol in concentration range from 0,2% to 6% per formulation and / or one or more additional substances derived from the olive, preferably oleuropein and / or oleocanthal. Definition 6. Composition according to definition 5, wherein said olive extract is derived from olive fruit and / or from olive leaves and said extract comprises hydroxy tyrosol in a concentration range from 0,2% to 6% per formulation.

[0014] Definition 7. Composition according to any of the definitions 1 to 6, which comprises hydroxytyrosol at a range from 0,5 to 10 mg per formulation, preferably comprises 2,5 or 5 mg hydroxytyrosol per formulation.

[0015] Definition 8. Composition according to any of the definitions 1 to 7, which additionally comprises one or more honey derivatives.

[0016] Definition 9. Composition according to any of the definitions 1 to 8, which additionally comprises one or more excipients, including one or more diluents and / or one or more lubricants and / or one or more anti-caking agents and / or one or more flavor enhancers and / or one or more sweeteners and / or one or more binders and / or one or more disintegrants and / or one or more surfactants. Definition 10. Composition according to any of the definitions 1 to 9, for use in enhancing the mentai function, treating symptoms related to dementia, especially in the elderly, enhancing memory and treating symptoms related to memory loss in patients with Alzheimer's Disease.

[0017] Definition 11. Nutritional supplement comprising the composition according to any of the definitions 1 to 10. It was surprisingly found that the specific composition of the present invention, comprising the combination with one or more tea derivatives, preferably derivatives of sideritis tea {Sideritis spp.), more preferably derivatives of Sideritis syriaca and / or Sideritis scardica and / or Sideritis perfoiiata and / or Sideritis raeseri and / or Sideritis euboa and one or more olive derivatives (Oiea europaea) exhibits significantly more intense results in terms of enhancing the mental function of individuals and treating symptoms related to dementia, especially in the elderly, compared to corresponding compositions comprising only tea derivatives or only olive derivatives.

[0018] Furthermore, it was surprisingly found that the specific composition of the present invention comprising the combination with one or more tea derivatives, preferably derivatives of sideritis tea {Sideritis spp.), more preferably derivatives of Sideritis syriaca and / or Sideritis scardica and / or Sideritis perfoiiata and / or Sideritis raeseri and / or Sideritis euboa and one or more olive derivatives (Oiea europaea) exhibits a significantly more enhancing effect specifically for memory enhancement, compared to corresponding compositions comprising only tea derivatives or only olive derivatives. It was surprisingly found that the specific composition of the present invention, comprising the combination with one or more tea derivatives, preferably derivatives of sideritis tea {Sideritis spp.), more preferably derivatives of Sideritis syriaca and / or Sideritis scardica and / or Sideritis perfoiiata and / or Sideritis raeseri and / or Sideritis euboa and one or more oiive derivatives (O / ea europaea) exhibits significantly extended treatment of symptoms related to memory loss specifically in patients with Alzheimer's Disease, compared to corresponding compositions comprising only tea derivatives or only olive derivatives. In addition, it was surprisingly found that the specific composition of the present invention comprising the combination with one or more tea derivatives, preferably derivatives of sideritis tea (Sideritis spp.\ more preferably derivatives of Sideritis syriaca and / or Sideritis scardica and / or Sideritis perfoliata acdrir Sideritis raeseri and / or Sideritis euboa and one or more olive derivatives (Olea europaea) exhibits significantly more enhanced antioxidant activity against LDL cholesterol oxidation and cardioprotection, compared to corresponding compositions comprising only tea derivatives or only olive derivatives.

[0019] Furthermore, it was surprisingly found that the specific composition of the present invention comprising the combination with one or more tea derivatives, preferably derivatives of sideritis tea (Sideritis spp.}, more preferably derivatives of Sideritis syriaca and / or Sideritis scardica and / or Sideritis perfoliata and / or Sideritis raeseri and / or Sideritis euboa and one or more olive derivatives (Olea europaea) presents unexpectedly better results in simultaneously enhancing the mental function of individuals and treating symptoms related to dementia, especially in the elderly, enhancing memory and treating symptoms related to memory loss in patients with Alzheimer's disease and with simultaneous cardioprotective effect.

[0020] Moreover, all the above advantages, specifically the addressing of memory problems and Alzheimer's disease memory consequences with the simultaneous cardioprotective effect, were observed to exhibit synergy at a much greater intensity than the person skilled in the art would expect, when combining sideritis derivatives on the one hand and olive derivatives on the other.

[0021] Finally, it was surprisingly found that the more is restricted the scope of the claims, the more intense are the effects and the advantages of the present invention.

[0022] The compositions of the present invention can be prepared by methods already known In the state of art.

[0023] The present invention is further described by the following indicative, but non-limiting example. Example 1: In a preferred embodiment the composition of the present invention comprises the following:

[0024] The composition of the Example 1 is formulated into soft capsules. The composition of the present Example 1 exhibits ali the advantages of the present invention mentioned above.

[0025] In fact, the composition of the present Example 1 comprising both sideritis derivatives and olive derivatives was compared with the same composition comprising either only olive derivatives in the same quantities and without sideritis derivatives or only sideritis derivatives in the same quantities and without olive derivatives and it was found that the composition of the above Example 1 exhibits more improved properties than by receiving simultaneously the two compositions with individual olive derivatives and individual sideritis derivatives.

Claims

Claims1. Composition for oral administration, which comprises one or more tea derivatives, preferably derivatives of siderite tea (Sideritis spp.}, more preferably derivatives of Sideritis syriaca and / or Sideritis scardica and / or Sideritis perfoiiata and / or Sideritis raeseri and / or Sideritis euboa and one or more olive derivatives [Gies europaea}.

2. Composition according to claim 1, which is formulated in granules for orai suspension or granules for immediate ingestion or tablets or soft capsules or hard capsules or oral solutions or oral suspensions or syrups or powders, preferably soft capsules or hard capsules.

3. Composition according to any of the claims 1 to 2, wherein the tea derivative is a tea extract of Sideritis spp., said extract ranges preferably from 1 to 1000 mg per formulation, more preferably is at 100 mg or at 500 mg per formulation.

4. Composition according to claim 3, wherein the tea extract of Sideritis spp, is derived from Sideritis scardica, said extract comprises flanonoids in a concentration range from 0,1 to 10 %, preferably at 2,95 % and acteoside in a concentration range from 0,1 to 10 %, preferably at 1,38 %.

5. Composition according to any of the claims 1 to 4, wherein the olive derivative is an olive extract and / or solid hydroxytyrosol in concentration range from 0,2% to 6% per formulation and / or one or more additional substances derived from the olive, preferably oleuropein and / or oleocanthal.

6. Composition according to claim 5, wherein said olive extract is derived from olive fruit and / or from olive leaves and said extract comprises hydroxytyrosol in a concentration range from 0,2% to 6% per formulation.

7. Composition according to any of the claims 1 to 6, which comprises hydroxytyrosol at a range from 0,5 to 10 mg per formulation, preferably comprises 2,5 or 5 mg hydroxytyrosol per formulation,8. Composition according to any of the claims 1 to 7, which additionally comprises one or more honey derivatives.

9. Composition according to any of the claims 1 to 8, which additionally comprises one or more excipients, including one or more diluents and / or one or more lubricants and / or one or more anti-caking agents and / or one or more flavor enhancers and / or one or more sweeteners and / or one or more binders and / or one or more disintegrants and / or one or more surfactants,10. Composition according to any of the claims 1 to 9, for use in enhancing the mental function, treating symptoms related to dementia, especially in the elderly, enhancing memory and treating symptoms related to memory loss in patients with Alzheimer's Disease.

11. Nutritional supplement comprising the composition according to any of the claims 1 to 10.