Method for producing a plant extract dispersion, plant extract dispersion and use of the plant extract dispersion

Abstract

The present invention relates to a process for producing a plant extract dispersion (D) comprising a stationary lipophilic phase (LP) and a dispersed phase (DP) based on a plant extract (PE) with at least two hydrophilic components. The invention further relates to a plant extract dispersion (D) obtained according to the inventive process, and to the use of the plant extract dispersion (D) according to the invention, inter alia, as a food supplement.

Description

[0001] The present invention relates to a process for producing a plant extract dispersion (D) containing a stationary lipophilic phase (LP) and a dispersed phase (DP), based on a plant extract (PE) with at least two hydrophilic components.

[0002] The invention further relates to a plant extract dispersion (D) obtained according to the inventive method, which contains a stationary lipophilic phase (LP) and a dispersed phase (DP), wherein the dispersed phase (DP) is based on a plant extract (PE) with at least two hydrophilic components.

[0003] The invention also relates to the use of the plant extract dispersion (D) according to the invention as a food supplement. In particular, the plant extract dispersion (D) according to the invention can be used for the treatment of elevated or high blood pressure and / or for the treatment of elevated cholesterol levels. The plant extract dispersion (D) according to the invention can contribute to maintaining normal cholesterol levels, developing a healthy blood lipid profile, and protecting blood lipids from oxidative stress. The plant extract dispersion (D) according to the invention can be used in humans and animals.

[0004] The worldwide production of olive oil generates, among other things, large quantities of olive vegetation water, also called "olive (mill) wastewater".

[0005] It was found that this murky, often dark-colored vegetation water with a slightly acidic pH value (< 6.8 at 20°C) decomposes extremely poorly in sewage treatment plants, so this waste product was subjected to closer investigation.

[0006] The resistance of olive grove vegetation water to decomposition could be attributed to its antimicrobial and antioxidant properties. These properties are based, among other things, on the increased concentrations of phenols, diphenols, and polyphenol derivatives (hereinafter referred to as "polyphenol derivatives") in the vegetation water.

[0007] These polyphenol derivatives have also been found to have anti-inflammatory and anti-tumor effects in humans and generally have a positive impact on human health (see Razmpoosh et al., “The effects of olive leaf extract on cardiovascular risk factors in the general adult population: a systematic review and meta-analysis of randomized controlled trials”, Diabetology & Metabolic Syndrome (2022) 14:151; Jemai et al., “Lipid-Lowering and Antioxidant Effects of Hydroxytyrosol and Its Triacetylated Derivative Recovered from Olive Tree Leaves in Cholesterol-Fed Rats”, J. Agric. Food Chem. 2008, 56, 2630-2636; Perrinjaquet-Moccetti et al., “Food supplementation with an olive (Olea europaea L.) leaf extract reduces blood pressure in borderline hypertensive monozygotic twins”, Phytother Res. 2008; 22:1239-42; Ismail et al., „Olive leaf extract effect on cardiometabolic profile among adults with prehypertension and hypertension: a systematic review and meta-analysis“, PeerJ. 2021; 9: e11173; Lockyer et al., „Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomized controlled trial“, Eur. J. Nutr. (2017) 56:1421-1432; Yaghoobzadeh et al., „Determining Cardiometabolic and Antioxidant Effects of Olive Leaf Extract in Patients with Essential Hypertension“, Journal of Inflammatory Diseases, 2019).

[0008] The health benefits of olive oil have been known for decades, and its cosmetic uses have also been frequently described. However, the byproducts of its production, such as olive vegetation water, have not yet been studied in detail. This may be because the vegetation water, due to its bitter taste, is barely palatable or even unpalatable in its pure form. Furthermore, it should theoretically be used quickly to prevent oxidation of the delicate components it contains, especially the polyphenol derivatives.

[0009] Therefore, there is a need for an extraction method to recover the constituents from the aqueous waste phase of olive products. It has been found that the common extraction methods, which require high concentrations of solvent(s) and high temperatures, lead to the degradation of some of the constituents, such as the polyphenol derivatives (Ahmad-Qasem et al., “Drying and storage of olive leaf extracts. Influence on polyphenols stability”, Industrial Crops and Products 79 (2016) 232-239).

[0010] In particular, older studies show that the stability of phenolic compounds in virgin olive oil decreases when the temperature exceeds 27°C (Lavelli, V et al., “Comparison of the antioxidant activities of extra virgin olive oils”, Journal of Agricultural and Food Chemistry, 2002, 50(26), 7704-7708).

[0011] It is also known that the instability of phenolic compounds impairs their antioxidant properties (Servili et al., “Phenolic compounds in olive oil: Antioxidant, health and organoleptic activities according to their chemical structure”, Inflammopharmacology, 2009, 17(2), 76-84; Kiritsakis et al., “Chemical analysis, quality control and packaging issues of olive oil”, European Journal of Lipid Science and Technology, 2002, 104(9-10), 628-638; Aparicio et al., “Characterisation of monovarietal virgin olive oils”, European Journal of Lipid Science and Technology, 2002, 104(9-10), 614-627).

[0012] The demand for the development of new methods for the gentle extraction of ingredients from olive products is therefore high.

[0013] From EP-A 1157701, a process for obtaining extracts of the olive tree (Olea europaea) with a yield of over 25% is known, the process comprising the steps of extraction, purification, and solvent evaporation. Olive tree leaves are dried at a temperature of less than 35°C, and extraction with an alkanol is carried out at a temperature of less than 20°C. An extract with an oleuropein content of up to 5% is obtained, whereby the less polar components of the extract, such as chlorophylls, polyphenols, fats, and alkylphenols, are eliminated by membrane filtration.

[0014] Numerous extraction methods are known from the prior art in which individual compounds are extracted from olive tree leaves, as has been shown for oleuropein, for example. However, the valuable properties of the separated compounds are lost in these processes, or they are present in concentrations too low to exert their health-promoting effects.

[0015] Application ES-A 2395032 discloses a phenolic extract obtained from by-products of olive oil production, containing over 5% by weight of total phenolic alcohols and over 0.3% by weight of total phenolic acids.

[0016] In a first step, a heat treatment between 50°C and 200°C is carried out, which is intended to increase the concentration of polyphenols that can be extracted.

[0017] It is known that some polyphenol derivatives are sensitive to heat and decompose at high extraction temperatures. Furthermore, it has been found that many of the hydrophilic substances contained in olive tree leaves require a lipophilic carrier in order to be absorbed in the human or animal body (Partridge et al., “Food additives: Assessing the impact of exposure to permitted emulsifiers on bowel and metabolic health - introducing the FADiets study”, Nutrition Bulletin, 2019, Volume 44, Issue 4, 303-395; Chassaing et al., “Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome”, Nature, 2015, Volume 519, 92-96; Chassaing et al., “Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation”, 2017, Gut, 66, 1414-1427).

[0018] Consuming a purely water-based olive extract therefore seems, at least from a health perspective, to be of little use. However, it is difficult to dissolve the extracted hydrophilic compounds in a lipophilic carrier, preferably the lipophilic olive oil itself, after the extraction process. It is also a challenge to ensure that these compounds remain dissolved and do not precipitate even after prolonged storage, such as for several weeks.

[0019] US Patent 2021 / 0076697 discloses a food composition comprising an edible, water-soluble active ingredient derived from a byproduct of olive oil production, and a fat phase. The food composition is produced by processing the aqueous phase containing the edible active ingredient and the fat phase containing emulsifiers, thickeners, gelling agents, and stabilizers into an emulsion under high-shear stirring, and pasteurizing the emulsion at temperatures of 75°C to 90°C.

[0020] The creation of an oil-in-water emulsion is achieved by adding auxiliary agents such as emulsifiers, thickeners, gelling agents and stabilizers.

[0021] However, such additives have been criticized for several years for triggering or promoting allergies. Emulsifiers, in particular, are said to have negative effects on gut health, especially promoting chronic inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease (Chassaing et al., "Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome", Nature, 2025, 519(7541), 92-96).

[0022] It has been established that certain emulsifiers in food can alter the composition of the gut microbiome in mice, resulting in inflammation, colitis, and metabolic disorders (Viennois et al., “Dietary Emulsifier-Induced Low-Grade Inflammation Promotes Colon Carcinogenesis”, Cancer Research, 2017, 77(1), 27-40). Further research has shown that the consumption of certain emulsifiers not only promotes intestinal inflammation but can also increase the risk of developing colorectal cancer (Chassaing et al., “Gut Microbiota Drives Intestinal Inflammation by Altering Host Gene Expression via Microbial Metabolites”, Cell Reports, 2017, 21(13), 3884-3896).

[0023] The present invention was therefore based on the objective of providing a plant extract dispersion (D) that does not suffer from the disadvantages of the prior art, in particular by dispensing with the use of additives. It also aims to provide a process that can be carried out under mild conditions so that the hydrophilic components retain their health-promoting effects.

[0024] The process should be technically simple and cost-effective, both on a small (laboratory) scale and on an industrial scale. The resulting plant extract should be dispersed, with a concentration of plant extract in the dispersion high enough to avoid the need for large oral doses. Furthermore, the resulting plant extract dispersion (D) should be stable and, when stored appropriately in dry, light-protected containers at a temperature of up to 25°C, should have a shelf life of several months, for example, 3 or 6 months.

[0025] To solve the problem, a method for producing a plant extract dispersion (D) is proposed according to the invention, comprising a continuous lipophilic phase (LP) and a dispersed phase (DP) based on a plant extract (PE) with at least two hydrophilic components, comprising the following steps: a) Drying and shredding of plant material b) Extraction of the plant material from step a) with a hydrophilic solvent under ultrasonic treatment to obtain a crude solution (RL) c) Filtration of the crude solution (RL) from step b) to obtain a filtrate d) Concentrating the filtrate from step c) to obtain a plant extract (PE) e) Provision of a vegetable oil-ethanol mixture f) Mixing the plant extract (PE) from step d) and the vegetable oil-ethanol mixture from step e) under ultrasonic treatment, keeping the temperature of the mixture below 20°C during treatment, to obtain a plant extract-vegetable oil-ethanol mixture g) Cooling the plant extract-vegetable oil-ethanol mixture from step f) to a temperature < -80°C h) Treatment of the cooled plant extract-vegetable oil-ethanol mixture from step g) with ultrasound, keeping the temperature of the mixture at < 20°C i) Concentrating the mixture obtained from step h) to obtain the plant extract dispersion (D).

[0026] A plant extract according to the present invention can be produced from fresh, air-dried, or freeze-dried parts of the olive tree, such as seeds, leaves, stems, buds, flowers, bark, peels, roots, nuts, fruits, or mixtures thereof. Preferably, the plant extract dispersion (D) according to the invention is obtained from leaves.

[0027] In a preferred embodiment, the process according to the invention relates to olive tree leaves as possible plant parts, which are particularly rich in water-soluble polyphenol derivatives. The substances to be extracted from olive tree leaves can include, but are not limited to: simple phenol derivatives, flavonoids, secoiridoids, secologanosides, tyrosols, tyrosol glucosides, elenolic acid glucosides, luteolin diglucosides, demethyloleuropein, quercetin, isorhamnetin, catechin, apigenin, rutin, luteolin, luteolin rutinoside, luteolin glucoside, verbascoside, apigenin rutinoside, oleorupein, oleuroside, oleuropein diglucoside, oleuropein aglycone, and mixtures thereof.

[0028] The term polyphenol derivatives according to the invention includes aromatic compounds with at least two phenolic hydroxyl groups, in particular diphenols, polyphenols and their derivatives.

[0029] In a further embodiment, the process according to the invention relates to the flowers, seeds, and leaves of the rockrose (Cistus x incanus L.), which also has a high content of polyphenol derivatives and contains flavonoids and terpenoids. Furthermore, the rockrose comprises hydrolyzable tannins, such as ellagitannins, proanthocyanidins, essential oil, and resins. In further alternative embodiments, the process according to the invention can be applied to other plant parts whose components exhibit phytoactive properties. In particular, the process according to the invention is intended to make substances accessible that are normally sparingly soluble or insoluble in lipophilic substances, such as olive oil.

[0030] The following plants are listed as examples, although the list only shows several possibilities and is not limited to these plants: Arnica montana (mountain arnica), Calendula officinalis (marigold), Matricaria chamomilla (chamomile), Hypericum perforatum (St. John's wort), Glycyrrhiza glabra (licorice root), Mentha piperita (peppermint), Salvia officinalis (sage), Thymus vulgaris (thyme), Echinacea purpurea (purple coneflower), Urtica dioica (stinging nettle), Griffonia simplicifolia (African black bean), Taraxacum officinale (dandelion), Ginkgo biloba (ginkgo), Allium sativum (garlic), Cynara scolymus (artichoke), Valeriana officinalis (valerian), Sideritis (Greek mountain tea), Crataegus monogyna (hawthorn), Aesculus hippocastanum (horse chestnut), Foeniculum vulgare (fennel), Ruscus aculeatus (butcher's broom), Passiflora incarnata (passionflower), Achillea millefolium (yarrow), Althaea officinalis (marshmallow), Anemone pulsatilla (pasque flower) Angelica archangelica (Engelwurz), Berberis vulgaris (Sauerdorn), Birke pendula (Birke), Brassica nigra (Schwarzer Senf), Capsicum anumum (Paprika, Cayennepfeffer), Carum carvi (caraway), Chelidonium majus (celandine), Cichorium intybus (chives), Cinnamomum verum (cinnamon), Eucalyptus globulus (eucalyptus), Filipendula ulmaria (mallow root), Galega officinalis (goat's rue), Hamamelis virginiana (witch hazel), Hedera helix (Ifeu), Humulus lupulus (Hopfen), Juglans regia (Walnuss), Lavandula angustifolia (Lavendel), Leonurus cardiaca (Herzgespann), Melilotus officinalis (Steinklee), Melissa officinalis (Zitronenmelisse), Petroselinum crispum (Petersilie), Plantago lanceolata (Spitzwegerich), Primula veris (Schlüsselblume), Rheum palmatum (Rhabarber), Rosmarinus officinalis (rosemary), Rubus idaeus (raspberry), Sambucus nigra (elderberry), Silybum marianum (milk thistle), Solidago virgaurea (goldenrod), Tilia cordata (small-leaved lime), Urtica dioica (stinging nettle), Verbena officinalis (vervain), Viburnum opulus (Giant Viburnum), Viscum album (Mistletoe), Zingiber officinale (Ginger), Symphytum officinale (Comfrey), Aloe (Aloe vera), Marrubium vulgare (Horehound), Pimpinella anisum (Anise), Arnica montana (Arnica), Cynara scolymus (Artichoke), Valeriana officinalis (Valerian), Arctostaphylos uva-ursi (Bearberry), Artemisia vulgaris (Mugwort), Symphytum officinale (Comfrey), Cnicus benedictus (Blessed Thistle), Berberis vulgaris (Barberry), Betula pendula (Birch), Solanum dulcamara (Bittersweet Nightshade), Potentilla erecta (Tormentil), Borago officinalis (Borage) Rubus fruticosus (Blackberry), Nasturtium officinale (Watercress), Fagopyrum esculentum (Buckwheat), Vaccinium macrocarpon (Cranberry), Hedera helix (Ivy), Althaea officinalis (Marshmallow), Quercus robur (Oak), Angelica archangelica (Angelica), Gentiana lutea (Gentian), Fumaria officinalis (Fumitory), Frangula alnus (Bulberry), Menyanthes trifoliata (Bogbean), Plantago afra (Psyllium), Alchemilla vulgaris (Lady's Mantle), Bellis perennis (Daisy), Potentilla anserina (Silverweed), Panax ginseng (Ginseng), Glechoma hederacea (Ground ivy), Ononis spinosa (Restless), Rosa anina (dog rose), Vaccinium myrtillus (blueberry), Leonurus cardiaca (motherwort), Graminis flos (hay flowers), Capsella bursa-pastoris (shepherd's purse), Tussilago farfara (coltsfoot), Cetraria islandica (Iceland moss), Acorus calamus (sweet flag), Cinnamomum camphora (Kampferbaum), Pelargonium sidoides (Kapland-Pelargonie), Tropaeolum majus (Nasturtium), Verbascum thapsus (Mulberry), Cucurbita pepo (Pumpkin), Curcuma longa (Turmeric), Linum usitatissimum (Flax), Levisticum officinale (Lovage), Mahonia aquifolium (Mahogany), Malva sylvestris (Mallow), Armoracia rusticana (Horseraddish), Tanacetum parthenium (Motherwort), Oenothera biennis (Evening primrose), Geum urbanum (Clove root), Agrimonia eupatoria (Odermennig), Populus nigra (poplar), Petasites hybridus (butterbur), Citrus aurantium (orange), Vaccinium vitis-idaea (lingonberry), Rhodiola rosea (rose root), Serenoa repens (saw palmetto), Hippophae rhamnoides (sea buckthorn), Equisetum arvense (horsetail), Chelidonium majus (celandine), Senna alexandrina (formerly Cassia angustifolia) (senna), Geranium robertianum (crane-bill), Eleutherococcus senticosus (taiga root), Centaurium erythraea (centenarian), Camellia sinensis (tea bush), Harpagophytum procumbens (devil's claw), Juniperus communis (juniper), Salix alba (willow), Epilobium angustifolium (willow rose), Boswellia serrata (frankincense), Vitis vinifera (red grapevine), Artemisia absinthium (wormwood), Allium cepa (onion).

[0031] A plant extract dispersion (D) according to the present invention is a heterogeneous mixture comprising components or substances that are either insoluble or practically insoluble in one another. Preferably, according to the invention, the at least two hydrophilic components of the plant extract form the dispersed phase. This means that they are finely dispersed in a continuous phase, also called the dispersion medium. According to the invention, the continuous phase is a lipophilic phase (LP) in liquid to viscous form, in particular an oil phase.

[0032] According to the invention, the at least two hydrophilic components can be obtained during extraction as a solid, as a liquid, as a (highly) viscous oil or as mixtures thereof.

[0033] According to the invention, a plant extract dispersion (D) can comprise a plant extract-vegetable oil emulsion (E), wherein the at least two hydrophilic components of the plant extract are present as (highly) viscous oils in the vegetable oil-oil phase, or a plant extract-vegetable oil suspension (S), in which the at least two hydrophilic components of the plant extract are present as solids in the vegetable oil-oil phase. Alternatively, the plant extract dispersion (D) according to the invention may form a mixture of the plant extract-vegetable oil emulsion (E) and the plant extract-vegetable oil suspension (S), which occurs when some of the hydrophilic components of the plant extract are obtained as solids during extraction and others as (highly) viscous oils.

[0034] In the case of a plant extract-plant oil suspension (S), the dispersed plant extract solid particles preferably have a mean particle diameter d50 (volume-based) of 1 to 100 µm, in particular of 1 to 50 µm, and particularly preferably of 1 to 20 µm. In a preferred embodiment of the process according to the invention, the plant material in step a) comprises olive tree leaves, wherein the at least two hydrophilic components comprise polyphenol derivatives, in particular selected from a group consisting of phenolic acids, phenolic alcohols, flavonoids and secoiridoids.

[0035] The plant material can be dried in air at room temperature, in a climate-controlled drying chamber (preferably not exceeding 25°C), or under vacuum at a reduced temperature (freeze-drying). The comminution of the plant material can yield coarsely ground or powdered plant material. The crushers and mills suitable for this purpose are known to those skilled in the art.

[0036] In preferred embodiments of the inventive process, the drying and comminution are preceded by cleaning the plant material. This cleaning of the plant material is intended to ensure that the plant material is free of pests or beneficial insects, and essentially free of dust and dirt. Preferably, the plant material is rinsed with water for this purpose, with the temperature preferably being kept at about 15°C or lower; in particular, no pesticides, cleaning agents, or similar substances should be used.

[0037] In one embodiment of the process according to the invention, the hydrophilic solvent for extraction in step b) comprises ethanol. In a preferred embodiment, the ethanol has a purity of at least 96%. In a preferred embodiment, the solvent is ethanol; alternatively, an ethanol-water mixture can also be used.

[0038] In the processes according to the invention, where extraction is carried out with ethanol, the extraction is performed at temperatures from -40°C to 78°C (boiling point of ethanol), preferably at temperatures from -40°C to 27°C with ultrasonic treatment. For extractions with an ethanol-water mixture, the extraction can be carried out at 90°C to 95°C under reflux, but preferably at temperatures between -20°C and 27°C. Cold extraction is therefore preferred, particularly when working on a laboratory scale, wherein the comminuted plant material from step a) is immersed in the hydrophilic solvent for an extended period, preferably for at least 12 hours.

[0039] In a suitable embodiment of the method according to the invention, the inserted plant material is treated with ultrasound to support the extraction process.

[0040] In alternative embodiments, the extraction process is treated with ultrasound at least at suitable intervals, but at least once before the crude solution (RL) is filtered in step c). During the ultrasound treatment, a temperature of 27°C, preferably 20°C, and particularly preferably 15°C, is not exceeded, as otherwise some of the phytoactive ingredients may be degraded.

[0041] In a further step c) of the process according to the invention, the resulting crude solution (RL) is filtered. On a laboratory scale, glass funnels with a pore size of 0 to 5 are used for this purpose in suitable embodiments. Glass funnels with a pore size of 3 and a filter porosity of 16 to 40 µm are particularly suitable, as these are small enough to trap excess plant material and suspended solids and still large enough to allow all the active ingredients to pass through. On an industrial scale, centrifugation can be carried out, or suitable column systems, membranes, vacuum funnels, Bernoulli filters, belt filters, gravity filters, sheet filters, or other separation systems familiar to those skilled in the art can be used.

[0042] The process according to the invention comprises, after obtaining the filtrate from the crude solution (RL), a step d) in which the filtrate is concentrated. Preferably, the temperature of the filtrate is also kept at a maximum of 27°C, so that it is advantageous to carry out the concentration at reduced pressure. This can take place, for example, on a rotary evaporator at room temperature and a reduced pressure of 0.6 to 30 mbar, particularly when working on a laboratory scale, or in the form of vacuum distillation.

[0043] Steam distillation is also a gentle method. Alternatively, but less preferred, the ethanolic filtrate can be heated under reflux, allowing the excess ethanol to evaporate. In this case, it is advisable to use boiling aids, a practice familiar to experts. The final concentration yields a highly viscous plant extract, which, in the case of olive leaves as the starting material, has a deep green color.

[0044] The resulting extract is hydrophilic and therefore water-soluble. According to the prior art, additives such as emulsifiers would be necessary to dissolve this extract in a continuous lipophilic phase; however, these are to be dispensed with according to the invention. To nevertheless enable the hydrophilic plant extract to be incorporated into the lipophilic phase, an intermediary is required that exhibits both hydrophilic and lipophilic properties, i.e., that is miscible to a certain extent with both the aqueous phase and the oil phase.

[0045] According to the invention, in a subsequent step e), a vegetable oil-ethanol mixture is prepared, with the ethanol acting as an intermediary. Ethanol is initially supplied and cooled to -5°C to 0°C. The vegetable oil, in particular olive oil, is then gradually emulsified while stirring and preferably under ultrasonic treatment.

[0046] The amount of ethanol should be at least twice the amount of vegetable oil. To avoid having to concentrate unnecessarily large quantities of solvent later in the process, it has proven advantageous if the amount of ethanol is no more than four times, in particular no more than three times, and most preferably exactly 2.5 times the amount of vegetable oil.

[0047] According to the invention, in a further step f), the plant extract (PE) is incorporated into the vegetable oil-ethanol mixture, resulting in a plant extract-vegetable oil-ethanol mixture. The resulting plant extract-vegetable oil-ethanol mixture is further cooled in step g) to a temperature of < -80°C, preferably < -85°C, and treated with ultrasound in step h), whereby the temperature of the mixture is maintained at < 20°C.

[0048] In preferred embodiments of the inventive method, the temperature of the mixture in step h) is kept at < 7°C.

[0049] In some embodiments of the invention, the ultrasonic treatment in step h) can cause the temperature of the plant extract-vegetable oil-ethanol mixture to become too warm, meaning that the temperature rises above 20°C. In such cases, the ultrasonic treatment should be interrupted and the plant extract-vegetable oil-ethanol mixture should be cooled again to < -80°C so that at least part of this mixture solidifies in order to continue the ultrasonic treatment.

[0050] Upon treatment with ultrasound, the plant oil forms a highly viscous to solid mixture with the plant extract, with the ethanol depositing as a liquid on top of this mixture. During a second ultrasound treatment, the cold ethanol can serve as a cooling liquid, and the highly viscous to solid mixture of plant oil and plant extract begins to melt. This process yields the plant extract dispersion (D) according to the invention.

[0051] In a final step i) of the process according to the invention, the mixture is concentrated under vacuum to obtain the plant extract dispersion (D). Here too, the temperature of the filtrate is preferably kept below 27°C and the concentration is carried out at reduced pressure, which can be done, for example, using a rotary evaporator or by means of vacuum distillation.

[0052] The plant extract dispersion (D) according to the invention can, as described above, comprise or consist of a plant extract-vegetable oil emulsion (E) and / or a plant extract-vegetable oil suspension (S), wherein the dispersed plant extract solid particles have a maximum mean particle diameter d50 (volume-based) of 1 to 100 µm, in particular of 1 to 50 µm, and particularly preferably 1 to 20 µm, wherein the mean particle diameter was determined according to the invention using a light microscope.

[0053] The resulting plant extract dispersion (D) according to the invention is dimensionally stable, meaning that no agglomeration of particles or sedimentation is observed even after several days, weeks, and up to two months. Slight sedimentation and agglomeration may occur after three months, but this can be dissolved again by shaking the plant extract dispersion (D) according to the invention.

[0054] In suitable processes according to the invention, the concentration of plant extract (PE) in the plant extract dispersion (D) is approximately 1 to approximately 25 wt.%, in particular 2 to 20 wt.%, and most preferably 5 to 10 wt.%, based on the total mass of the plant extract dispersion (D).

[0055] The process according to the invention is characterized, among other things, by the fact that a plant extract dispersion (D) can be obtained which is based on a continuous lipophilic phase (LP) and a dispersed phase (DP) based on a plant extract (PE) with at least two hydrophilic components, wherein no emulsifiers, whether natural or artificial, need to be added for the production and also for the preservation of the plant extract dispersion (D).

[0056] The object of the present invention is further solved by a plant extract dispersion (D) containing a continuous lipophilic phase (LP) and a dispersed phase (DP) based on a plant extract (PE) with at least two hydrophilic components, obtained according to a method according to the invention.

[0057] The plant extract dispersion (D) according to the invention contains only a plant oil and a plant extract comprising at least two hydrophilic components. The plant extract dispersion (D) according to the invention is particularly free of emulsifiers, thickeners, gelling agents, and stabilizers, yet it exhibits a storage stability of several months.

[0058] The object of the present invention is further achieved by using the plant extract dispersion (D) according to the invention as a food supplement. In particular, the plant extract dispersion (D) according to the invention is to be taken orally. Tests on the effect of the plant extract dispersion according to the invention (D)

[0059] The following describes different effects of the plant extract dispersion (D) according to the invention, each relating to the administration of single doses according to Example 1 to test subjects.

[0060] Firstly, it was demonstrated that the plant extract dispersion (D) according to the invention can be successfully used to treat elevated blood pressure. It was found that when a single daily dose, prepared according to Example 1, was administered over a period of 4 weeks to test subjects with a baseline blood pressure of 140 to 159 / 90 to 99 mmHg, corresponding to grade 1 hypertension, this blood pressure could be reduced back to the normal range of 120 to 129 / 80 to 89 mmHg.

[0061] Compounds of the plant extract dispersion (D) according to the invention presumably act as AT-1 receptor antagonists and exhibit a vasodilating effect due to the inhibition of the blood pressure-raising hormone angiotensin II. Further compounds of the plant extract dispersion (D) according to the invention presumably act simultaneously as alpha receptor blockers and are based on competitive inhibition of alpha1-adrenergic receptors. The associated vasodilation leads to more efficient blood flow and a reduction in stress on the cardiovascular system.

[0062] Due to the vasodilating properties observed after administration of the plant extract dispersion (D) according to the invention, the invention also relates to its use as a pain reliever and has been successfully used for headaches, migraines, or menstrual cramps. For this purpose, a single dose according to Example 1 was administered during an acute pain attack. It was observed in test subjects with headaches that pain relief occurred as early as 30 minutes after ingestion of the single dose of the plant extract dispersion (D) according to the invention.

[0063] The plant extract dispersion (D) according to the invention also has a positive effect on the blood sugar level of diabetics. It was observed in test subjects with type 1 diabetes and the associated frequent hypoglycemia that taking the plant extract dispersion (D) according to the invention 30 minutes before a meal in the form of a single dose according to Example 1 leads to a steady rise in the blood sugar curve.

[0064] The rise in blood sugar levels is significantly less pronounced than with direct food intake. The compounds in the plant extract dispersion (D) according to the invention presumably act as inhibitors of digestive enzymes such as alpha-amylase and alpha-glucosidase. Furthermore, the sensitivity of the cells to insulin appears to be increased, which promotes glucose uptake into the cells and lowers blood sugar levels.

[0065] A positive effect of the plant extract dispersion (D) according to the invention on sperm count was also observed in male subjects. Following ten days of oral administration of the plant extract dispersion (D) according to the invention in the form of two daily single doses as shown in Example 1, an increase in sperm count from 6 million / ml to 147 million / ml was observed.

[0066] Furthermore, an improvement was observed in subjects with elevated cholesterol levels following the administration of the plant extract dispersion (D) according to the invention. In subjects with primary familial hypercholesterolemia and baseline LDL cholesterol levels of approximately 200 mg / dl, LDL cholesterol levels were reduced to 157 mg / dl after just 10 days of taking a single daily dose according to Example 1, while HDL cholesterol levels remained largely stable. Total cholesterol was also reduced from 316 mg / dl to 234 mg / dl.

[0067] In summary, the inventive method for producing a plant extract dispersion (D) according to the invention, as well as the inventive plant extract dispersion (D) containing a continuous lipophilic phase (LP) and a dispersed phase (DP) based on a plant extract (PE) with at least two hydrophilic components, can therefore provide a plant extract with health-promoting effects that can be easily taken in an oral dosage form.

[0068] Furthermore, the plant extract dispersion (D) according to the invention is based solely on a plant oil as a lipophilic carrier and the plant extract (PE) as a dissolved hydrophilic component, without the addition of any excipients in the form of emulsifiers, thickeners, gelling agents, or stabilizers. Nevertheless, the plant extract dispersion (D) according to the invention is simple and cost-effective to produce, both on a small and large scale, and yields storage-stable plant extract dispersions (D).

[0069] The method according to the invention ensures that the active ingredients contained are not decomposed due to high temperatures or broken down or oxidized by strong bases or acids. Example 1: Production of olive tree leaf extract on a laboratory scale Step a)

[0070] 500 g of olive tree leaves were air-dried for 30 days in a dark room. The dried leaves were then ground into a powder using a standard household blender. Step b)

[0071] The powdered olive leaves were transferred to a container with 2500 g of ethanol with a purity of 96.4% and stirred with a hand blender. This mixture was stored overnight for 12 hours at -45°C for complete extraction, before being stirred again the following day with a hand blender under ultrasonic stimulation at 35 ws / g. The temperature of the mixture was maintained below 10°C. Step c)

[0072] The resulting crude solution was filtered through a glass filter with a pore size of 3 under vacuum. Step d)

[0073] The filtered solution was concentrated on a rotary evaporator at a pressure of 18 mbar and a water bath temperature of 27°C, resulting in a hydrophilic olive extract. Step e)

[0074] Olive oil and ethanol with a purity of 96.4% were stirred together in a vessel under ultrasound to create an olive oil-ethanol emulsion.

[0075] The amount of ethanol was chosen to be 2.5 times the amount of olive oil. Step f)

[0076] The hydrophilic olive extract from step d) was placed in a reaction vessel and the olive oil-ethanol emulsion from step e) was mixed under high stirring speed of 200rpm.

[0077] After mixing, the mixture was cooled to -10°C to 0°C and stirred again under ultrasound, keeping the temperature of the mixture at a maximum of 20°C. Step g)

[0078] The resulting mixture was cooled to -85°C, whereby the olive oil and olive extract formed a frozen mass and the ethanol floated on this frozen mass. Step h)

[0079] The chilled mixture was treated again with ultrasound, gradually melting the frozen mass of olive oil and olive extract. The temperature of the mixture was maintained below 20°C. The ultrasound treatment was interrupted at certain points, and the mixture was cooled again to below -10°C before the ultrasound treatment was resumed. Step i)

[0080] Finally, the mixture was concentrated using a rotary evaporator at a pressure of 18 mbar and a water bath temperature of 27°C. This resulted in an olive leaf extract in which the majority of the olive extract is emulsified in the olive oil, while a small portion is finely dispersed. The dispersed particles had an average size of 20 µm, which was measured using a light microscope.

[0081] From the 500 g of olive tree leaves, 85 g of olive extract could be obtained after step d), which corresponds to an olive extract yield of 17%.

[0082] Preliminary tests have already shown that olive extract dispersions with a concentration of 8% are particularly stable. Single doses of 1 ml of olive extract dispersion also represent good portion sizes due to their small volume, making them easy to handle, for example, when the consumer is traveling.

[0083] Accordingly, the 85 g of olive extract obtained were emulsified in olive oil and individual doses of 1 ml olive extract dispersion were produced, which have a concentration of olive extract of 8 mg / 1 ml olive extract dispersion.

[0084] These single doses were used in the various tests on the effect of the plant extract dispersion (D) according to the invention and have proven to be advantageous products. QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] EP-A 1157701

[0013] ES-A 2395032

[0015] US-A 2021 / 0076697

[0019] Cited non-patent literature

[0000] Razmpoosh et al., “The effects of olive leaf extract on cardiovascular risk factors in the general adult population: a systematic review and meta-analysis of randomized controlled trials,” Diabetology & Metabolic Syndrome (2022) 14:151

[0007] Jemai et al., „Lipid-Lowering and Antioxidant Effects of Hydroxytyrosol and Its Triacetylated Derivative Recovered from Olive Tree Leaves in Cholesterol-Fed Rats“, J. Agric. Food Chem. 2008, 56, 2630-2636

[0007] Perrinjaquet-Moccetti et al., „Food supplementation with an olive (Olea europaea L.) leaf extract reduces blood pressure in borderline hypertensive monozygotic twins“, Phytother Res. 2008; 22 :1239-42

[0007] Ismail et al., „Olive leaf extract effect on cardiometabolic profile among adults with prehypertension and hypertension: a systematic review and meta-analysis“, PeerJ. 2021

[0007] 9: e11173; Lockyer et al., „Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomized controlled trial“, Eur. J. Nutr. (2017) 56:1421-1432

[0007] Yaghoobzadeh et al., „Determining Cardiometabolic and Antioxidant Effects of Olive Leaf Extract in Patients with Essential Hypertension“, Journal of Inflammatory Diseases, 2019

[0007] Ahmad-Qasem et al., „Drying and storage of olive leaf extracts. Influence on polyphenols stability“, Industrial Crops and Products 79 (2016) 232- 239

[0009] Comparison of the antioxidant activities of extra virgin olive oils“, Journal of Agricultural and Food Chemistry, 2002, 50(26), 7704-7708

[0010] Servili et al., „Phenolic compounds in olive oil: Antioxidant, health and organoleptic activities according to their chemical structure“, Inflammopharmacology, 2009, 17(2), 76-84; Kiritsakis et al., „Chemical analysis, quality control and packaging issues of olive oil“, European Journal of Lipid Science and Technology, 2002, 104(9-10), 628-638; Aparicio et al., „Characterisation of monovarietal virgin olive oils“, European Journal of Lipid Science and Technology, 2002, 104(9-10), 614-627

[0011] Partridge et al., „Food additives: Assessing the impact of exposure to permitted emulsifiers on bowel and metabolic health - introducing the FADiets study“, Nutrition Bulletin, 2019, Volume 44, Issue 4, 303-395; Chassaing et al., „Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome“, Nature, 2015, Volume 519, 92-96; Chassaing et al., „Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation“, 2017, Gut, 66, 1414-1427

[0017] Chassaing et al., „Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome“, Nature, 2025, 519(7541), 92-96

[0021] Viennois et al., “Dietary Emulsifier-Induced Low-Grade Inflammation Promotes Colon Carcinogenesis”, Cancer Research, 2017, 77(1), 27-40). It has even been further investigated that the consumption of certain emulsifiers not only promotes intestinal inflammation but can also increase the risk of developing colorectal cancer (Chassaing et al., “Gut Microbiota Drives Intestinal Inflammation by Altering Host Gene Expression via Microbial Metabolites”, Cell Reports, 2017, 21(13), 3884-3896

[0022]

Claims

A process for producing a plant extract dispersion (D) comprising a continuous lipophilic phase (LP) and a dispersed phase (DP) based on a plant extract (PE) with at least two hydrophilic components, comprising the following steps: a) drying and comminution of plant material; b) extraction of the plant material from step a) with a hydrophilic solvent under ultrasonic treatment to obtain a crude solution (RL); c) filtration of the crude solution (RL) from step b) to obtain a filtrate; d) concentration of the filtrate from step c) to obtain a plant extract (PE); e) preparation of a vegetable oil-ethanol mixture; f) mixing of the plant extract (PE) from step d) and the vegetable oil-ethanol mixture from step e) under ultrasonic treatment, the temperature of the mixture being kept below 20°C during treatment.to obtain a plant extract-vegetable oil-ethanol mixture g) Cooling the plant extract-vegetable oil-ethanol mixture from step f) to a temperature < -80°C h) Treating the cooled plant extract-vegetable oil-ethanol mixture from step g) with ultrasound, maintaining the temperature of the mixture at < 20°C i) Concentrating the mixture obtained from step h) to obtain the plant extract dispersion (D). Method for producing a plant extract dispersion (D) according to claim 1, wherein the plant material in step a) comprises olive tree leaves, wherein the at least two hydrophilic components comprise polyphenol derivatives, in particular selected from a group consisting of phenolic acids, phenolic alcohols, flavonoids and secoiridoids. Method for producing a plant extract dispersion (D) according to at least one of claims 1 or 2, wherein the hydrophilic solvent in step b) comprises ethanol, preferably consists of ethanol, and the extraction is carried out at a temperature of -40°C to 78°C, in particular from -40°C to 27°C. Method for producing a plant extract dispersion (D) according to at least one of the preceding claims, wherein the concentration in step d) and in step i) takes place at reduced pressure, in particular wherein the temperature of the filtrate or the melt is kept at < 27°C. Method for producing a plant extract dispersion (D) according to at least one of the preceding claims, wherein the vegetable oil in step e) comprises olive oil, in particular wherein the vegetable oil is olive oil. Method for producing a plant extract dispersion (D) according to at least one of the preceding claims, wherein in the plant oil-ethanol emulsion the mass ratio of plant oil : ethanol = 1 : n, with n ≥ 2. Method for producing a plant extract dispersion (D) according to at least one of the preceding claims, wherein, prior to step f), the plant oil-ethanol emulsion is cooled to a temperature of < - 10°C. Method for producing a plant extract dispersion (D) according to at least one of the preceding claims, wherein the obtained plant extract dispersion (D) in step i) comprises a plant extract-vegetable oil emulsion (E) and / or a plant extract-vegetable oil suspension (S), wherein the dispersed plant extract solid particles have a mean particle diameter d50 (volume-based) of 1 to 100 µm, in particular of 1 to 50 µm, particularly preferably 1 to 20 µm. Method for producing a plant extract dispersion (D) according to at least one of the preceding claims, wherein the concentration of plant extract (PE) in the plant extract dispersion (D) is 1 to 25 wt.%, in particular 2 to 20 wt.%, particularly preferably 5 to 10 wt.%, based on the total mass of the plant extract dispersion (D). Method for producing a plant extract dispersion (D) according to at least one of the preceding claims, wherein no emulsifiers are added in the method. Plant extract dispersion (D) obtained according to a method according to at least one of claims 1 to 10 . Plant extract dispersion (D) according to claim 11 for use as a food supplement. Plant extract dispersion (D) according to claim 11 for use in the treatment of elevated blood pressure, in oral administration form. Plant extract dispersion (D) according to claim 11 for use in the treatment of elevated cholesterol levels, in oral administration form.