Composition comprising a toxicodendron derivative and an olive derivative for enhancing memory

Abstract

The present invention relates to a composition for oral administration for enhancing memory, comprising one or more tea derivatives, preferably derivatives of Aloysia citriodora (Lippia citriodora), more preferably derivatives of Aloysia citriodora, and / or Aloysia recutita, and / or Aloysia scoparia, and / or Aloysia vaseyana, and / or Aloysia yubja, and one or more derivatives of Olea (Olea europaea), preferably derivatives of Olea europaea, and / or Olea capitate, and / or Olea europaea subsp. cuspidata, and / or Olea europaea subsp. cerasiformis, and / or Olea europaea subsp. maritima, and / or Olea europaea subsp. cerasoides.

Description

Technical Field

[0001] This invention relates to compositions for oral administration and for enhancing memory, the compositions comprising one or more tea derivatives and one or more olive derivatives (Olea europaea), wherein the tea derivatives are preferably derivatives of Sideritis spp., more preferably derivatives of Sideritis syriaca and / or Sideritis scardica and / or Sideritis perfoliata and / or Sideritis raeseri and / or Sideritis euboa. Background Technology

[0002] Sideritis tea leaves are rich in flavonoids, polyphenols, phenolic acids, and glycosides, leading to beneficial effects on the gut microbiome and digestive system, preventing insulin resistance and hyperlipidemia, helping to alleviate common consequences of overweight and obesity, exerting beneficial effects on lipid parameters and cardiovascular risk factors, and having positive effects on improving memory and mood, especially in older adults (Dorota Żyżelewicz, Kamila Kulbat-Warycha, Joanna Oracz and Kacper Żyżelewicz, 2020, “Polyphenols and Other Bioactive Compounds of Sideritis Plants and Their Potential Biological Activity”, Molecules 25, no. 16: 3763).

[0003] Hydroxytyrosol can be extracted from olive leaves and fruit and is a molecule with antioxidant, anti-inflammatory, anti-atherosclerotic, and antithrombotic properties. In vitro studies have shown that, in addition to its antioxidant activity, it can also improve endothelial dysfunction, lipid distribution, and has anti-inflammatory properties. Therefore, it can be considered 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, and Michelini S, “Hydroxytyrosol: A natural compound with promising pharmacological activities”, J Biotechnol. 2020; 309: 29-33). Hydroxytyrosol is also considered an antithrombotic agent because it reduces endothelial cell activation and significantly reduces platelet aggregation, a stage of thrombosis (Dell'Agli M et al., "Inhibition of platelet taggregation by olive oil phenols via cAMP-phosphodiesterase", Br J Nutr. 2008;99(5): 945–51).

[0004] Document EP2608798B1 relates to extracts from epiphytic parts of the genus *Eriocaulon* for improving cognitive performance, wherein the epiphytic parts are fresh or dried plant parts selected from the group consisting of: *Eriocaulon yuboa*, *Eriocaulon skardica*, *Eriocaulon razerii*, or mixtures thereof.

[0005] Document EP2515922B1 relates to siderite extracts for the treatment or prevention of neurodegenerative diseases, obtained by extraction with water or an aqueous-alcohol solvent, wherein the neurodegenerative diseases are associated with aggregated proteins / peptides, including Alzheimer's disease.

[0006] In a 2016 study by Hofrichter et al. (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 administration of Sideritis spp. extracts (Sideritis yuboa and Sideritis cardica) significantly enhanced cognitive performance in aged non-transgenic mice and transgenic mice with amyloid precursor protein (APP). The effect was even more pronounced when the extracts of the two species were used in combination.

[0007] In a 2022 study by Mousavi et al. (Moussavi N, Azizullah H, Malterud KE, Inngjerdingen KT, Wangensteen H, “Immunomodulating polyphenols from Sideritis scardica”, Journal of Functional Foods, 2022; 96: 105197), it was reported that Sideritis scardica contains a pool of compounds with multifaceted activities indicated by the results of various in vitro bioassays, and therefore could be used as a potential candidate for adjunctive therapy for Alzheimer’s disease.

[0008] It is worth noting that horsetail extract is also found in commercial products, such as Powerhealth, which sells products containing 100mg of horsetail extract in the Greek market. ® Effervescent tablets.

[0009] Document CN106138016A refers to the use of hydroxytyrosol for the prevention and treatment of Alzheimer's disease. When administered to mice with Alzheimer's disease, hydroxytyrosol was found to cross the blood-brain barrier, significantly improving brain function and learning and memory abilities.

[0010] However, in the prior art, there is no mention of compositions containing a combination of tea derivatives and olive derivatives, nor is there any mention of their use in enhancing memory.

[0011] Despite the positive properties of the aforementioned isolated components, there remains a continued need for compositions that possess even stronger memory-enhancing properties and act on cardiometabolic diseases, with even stronger antioxidant effects to combat LDL cholesterol oxidation and atherosclerosis. Summary of the Invention

[0012] This invention takes into account all the above-mentioned data, solves all the aforementioned problems of the prior art, and actually has unexpected advantages and better results in enhancing individual psychological function and treating symptoms associated with dementia (especially in the elderly), enhancing memory and treating symptoms associated with memory loss in Alzheimer's patients, while exerting a simultaneous cardioprotective effect, utilizing the synergistic effect of tea and olive derivatives in enhancing memory and cardioprotection.

[0013] More specifically, the present invention is defined as follows:

[0014] Definition 1. A composition for oral administration, the composition comprising one or more tea derivatives and one or more olive derivatives (oil olive), wherein the tea derivative is preferably a derivative of *Tea scabra* (*Tea scabra*), more preferably a derivative of *Tea scabra*, and / or *Tea scabra*, and / or *Tea scabra*, and / or *Tea scabra*, and / or *Tea scabra*, and / or *Tea scabra*, and / or *Tea scabra*.

[0015] Definition 2. The composition according to Definition 1 is formulated as a granule for oral suspension, or a granule for immediate consumption, or a tablet, or a soft capsule, or a hard capsule, or an oral solution, or an oral suspension, or a syrup, or a powder, preferably a soft capsule or a hard capsule.

[0016] Definition 3. The composition according to any one of Definitions 1 to 2, wherein the tea derivative is a tea extract of the genus *Achyranthes*, preferably 1 mg to 1000 mg per formulation, more preferably 100 mg or 500 mg per formulation.

[0017] Definition 4. The composition according to Definition 3, wherein the tea extract of the genus *Scadica* is derived from *Scadica scadica*, the extract comprising 0.1% to 10%, preferably 2.95%, of flavonoids and 0.1% to 10%, preferably 1.38%, of vervainin.

[0018] Definition 5. A composition according to any one of Definitions 1 to 4, wherein the olive derivative is an olive extract and / or solid hydroxytyrosol at a concentration of 0.2% to 6% per formulation, and / or one or more other substances derived from said olive, preferably oleuropein and / or oleocanthal.

[0019] Definition 6. The composition according to Definition 5, wherein the olive extract is derived from olive fruit and / or olive leaves, and the extract contains hydroxytyrosol at a concentration of 0.2% to 6% per formulation.

[0020] Definition 7. A composition according to any one of Definitions 1 to 6, comprising 0.5 mg to 10 mg of hydroxytyrosol per formulation, preferably comprising 2.5 mg or 5 mg of hydroxytyrosol per formulation.

[0021] Definition 8. A composition according to any one of definitions 1 to 7, further comprising one or more honey derivatives.

[0022] Definition 9. A composition according to any one of Definitions 1 to 8, further comprising 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.

[0023] Definition 10. The composition according to any one of Definitions 1 to 9 is used to enhance mental function, treat symptoms associated with dementia (especially in older adults), enhance memory, and treat symptoms associated with memory loss in patients with Alzheimer's disease.

[0024] Definition 11. A nutritional supplement comprising a composition according to any one of Definitions 1 to 10.

[0025] Surprisingly, it has been found that, compared with corresponding compositions containing only tea derivatives or only olive derivatives, specific compositions of the present invention containing a combination of one or more tea derivatives and one or more olive derivatives (oil olives) exhibit significantly stronger effects in enhancing individual psychological function and treating symptoms associated with dementia (especially in the elderly), wherein the tea derivatives are preferably derivatives of *Hypericum spp.* (Hypericum genus), more preferably derivatives of *Hypericum spp.*, and / or *Hypericum skadika*, and / or *Hypericum perforatum*, and / or *Hypericum reze*, and / or *Hypericum yoboa*.

[0026] Furthermore, it was surprisingly found that, compared with corresponding compositions containing only tea derivatives or only olive derivatives, specific compositions of the present invention containing a combination of one or more tea derivatives and one or more olive derivatives (oil olives) exhibit a significantly stronger effect on enhancing specific memory, wherein the tea derivatives are preferably derivatives of *Hydrocotyle spp.* (Hydrocotyle genus), more preferably derivatives of *Hydrocotyle sydrocotyle scadicica*, and / or *H ....

[0027] Surprisingly, it has been found that, compared with corresponding compositions containing only tea derivatives or only olive derivatives, certain compositions of the present invention containing a combination of one or more tea derivatives and one or more olive derivatives (oil olives) exhibit a significant prolongation of the treatment of memory loss-related symptoms (particularly memory loss-related symptoms in patients with Alzheimer's disease), wherein the tea derivatives are preferably derivatives of *Hypericum spp.* (Hypericum genus), more preferably derivatives of *Hypericum spp.*, and / or *Hypericum skadika*, and / or *Hypericum perforatum*, and / or *Hypericum razei*, and / or *Hypericum yoboa*.

[0028] Furthermore, it was surprisingly found that, compared with corresponding compositions containing only tea derivatives or only olive derivatives, specific compositions of the present invention containing a combination of one or more tea derivatives and one or more olive derivatives (Olive) exhibit significantly enhanced antioxidant activity against LDL cholesterol oxidation and cardioprotection, wherein the tea derivatives are preferably derivatives of *Hydrocotyle spp.* (Hydrocotyle genus), more preferably derivatives of *Hydrocotyle sydrocotyle scadicica*, and / or *H ....

[0029] Furthermore, it has been surprisingly found that specific compositions of the present invention comprising one or more tea derivatives and one or more olive derivatives (olives) exhibit unexpectedly better results in simultaneously enhancing an individual's mental function and treating symptoms associated with dementia (especially in the elderly), enhancing memory and treating memory loss-related symptoms in patients with Alzheimer's disease, and simultaneously having cardioprotective effects. The tea derivatives are preferably derivatives of *Hypericum spp.* (Hypericum genus), more preferably derivatives of *Hypericum spp.*, and / or *Hypericum skadika*, and / or *Hypericum perforatum*, and / or *Hypericum razei*, and / or *Hypericum yoboa*.

[0030] Furthermore, when the derivatives of *Hypericum perforatum* and olive were used in combination, all the aforementioned advantages were observed, particularly in addressing memory problems and the memory sequelae of Alzheimer's disease, as well as providing cardioprotective effects, demonstrating a synergistic effect stronger than expected by those skilled in the art.

[0031] Finally, it was surprisingly found that the more limited the scope of the claims, the more significant the effects and advantages of the invention. Detailed Implementation

[0032] The compositions of the present invention can be prepared by methods known in the prior art.

[0033] The invention is further described by way of the following indicative but non-limiting embodiments.

[0034] Example 1: In a preferred embodiment, the composition of the present invention comprises the following substances:

[0035]

[0036] The composition of Example 1 was formulated into soft capsules.

[0037] The composition of this Example 1 exhibits all the advantages of the present invention described above.

[0038] In fact, when comparing the composition of Example 1 of the present invention, which contains both a strychnos derivative and an olive derivative, with the same amount of the same composition containing only an olive derivative and no strychnos derivative, or the same amount of the same composition containing only a strychnos derivative and no olive derivative, it was found that the composition of Example 1 exhibited superior properties compared to the two compositions that simultaneously received a single olive derivative and a single strychnos derivative.

Claims

1. A composition for oral administration, the composition comprising one or more tea derivatives and one or more olive derivatives (Olea europaea), wherein the tea derivative is preferably a derivative of Sideritis spp., more preferably a derivative of Sideritis syriaca and / or Sideritis scardica and / or Sideritis perfoliata and / or Sideritis raeseri and / or Sideritis euboa.

2. The composition according to claim 1, wherein it is formulated as granules for oral suspension, or granules for immediate consumption, 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. The composition according to any one of claims 1 to 2, wherein, The tea derivative is a tea extract of the genus *Achyranthes*, and the extract is preferably 1 mg to 1000 mg per preparation, more preferably 100 mg or 500 mg per preparation.

4. The composition according to claim 3, wherein, The tea extract of the genus *Scadica* is derived from *Scadica scadica*, and the extract contains 0.1% to 10%, preferably 2.95%, of flavonoids and 0.1% to 10%, preferably 1.38%, of verbascoside.

5. The composition according to any one of claims 1 to 4, wherein, The olive derivative is an olive extract and / or solid hydroxytyrosol at a concentration of 0.2% to 6% per formulation, and / or one or more other substances derived from olives, preferably oleuropein and / or olive oil stimulant aldehyde.

6. The composition according to claim 5, wherein, The olive extract is derived from olive fruit and / or olive leaves, and the extract contains hydroxytyrosol at a concentration of 0.2% to 6% per formulation.

7. The composition according to any one of claims 1 to 6, comprising 0.5 mg to 10 mg of hydroxytyrosol per formulation, preferably comprising 2.5 mg or 5 mg of hydroxytyrosol per formulation.

8. The composition according to any one of claims 1 to 7, further comprising one or more honey derivatives.

9. The composition according to any one of claims 1 to 8, further comprising 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. The composition according to any one of claims 1 to 9, for enhancing mental function, treating symptoms associated with dementia, enhancing memory, and treating symptoms associated with memory loss in patients with Alzheimer's disease, particularly in older adults.

11. A nutritional supplement comprising the composition of any one of claims 1 to 10.

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