WO2022159055A1

WO2022159055A1 - An olive leaf extract and production method thereof

Info

Publication number: WO2022159055A1
Application number: PCT/TR2021/050614
Authority: WO
Inventors: İlhan Sari
Original assignee: Medi̇cal Farm İlaç Ve Sağlik Ürünleri̇ Sanayi̇ Ve Ti̇caret Li̇mi̇ted Şi̇rketi̇
Priority date: 2021-01-25
Filing date: 2021-06-16
Publication date: 2022-07-28
Anticipated expiration: 2023-07-25
Also published as: TR202101093A1

Abstract

The present invention particularly relates to the aqueous total Olea europaea L. (olive) leaf extract which is developed for use within the scope of traditional and herbal medicinal products in the food supplement and pharmaceutical industry, contains a highly valuable plant chemical substance effective against diabetes, cancer, cardiovascular, gastrointestinal diseases and covid-19 and loss of weight and its production method. In order to fulfill this, the inventive olive leaf extract contains active substances and water that the plant has synthesized during its life, the inventive method comprises the following process steps; minimizing olive leaves dried with a standardized method, mixing and keeping the leaves in the presence of water at maximum surface film forming capacity and removing the solvent from the obtained filtrate under vacuum.

Description

AN OLIVE LEAF EXTRACT AND PRODUCTION METHOD THEREOF

Field of the Invention

The present invention relates to the aqueous total Olea europaea L. (olive) leaf extract which contains a highly valuable plant chemical substance effective against diabetes, cancer, cardiovascular, gastrointestinal diseases and covid-19 and loss of weight and its production method.

The present invention particularly relates to the aqueous total Olea europaea L. (olive) leaf extract which is developed for use within the scope of traditional and herbal medicinal products in the food supplement and pharmaceutical industry, contains a highly valuable plant chemical substance effective against diabetes, cancer, cardiovascular, gastrointestinal diseases and covid-19 and loss of weight and its production method.

State of the Art

The olive tree plant, which is called Olea europaea L. in Latin, has been widely used against different diseases in phytotherapy, which is a sub-practice of traditional and alternative medicine, for many years. In order to see this effect of the olive tree leaf, it shall have drugs that are compatible with human metabolism with its ingredient, whose all valuable herbal chemical substances that have protective and/or therapeutic power against diseases are obtained after drying the leaves obtained by producing in the right geography with the correct agricultural production method with correct drying methods.

According to the European Pharmacopoeia monograph "Oleae folium" dated 01/2009: 1878, Olea europaea L., folium is defined as the dried leaf of the plant containing a minimum of 5% oleuropein (C25H32O13; Mr 540.5) (European Pharmacopoeia 01/2009: 1878). In phytotherapy, Olea europaea L. leaf total extract is effective against diabetes, cancer, cardiovascular, gastrointestinal diseases and covid-19 due to its antiviral effect.

There is not so much information about olive cultivation in Turkey historically; however archaeological evidence shows that the first olive types were brought to Anatolia before B.C. 1000. Its economy is very important because olive is one of the main products of the agricultural sector in our country. In Turkey, approximately 87 local olive types have been documented. In the Mediterranean region, olive leaves have been used for folk medicine and as table olives throughout the history of civilization. In addition to this, the main product of the olive plant is its oil, which is valued worldwide for its unique aroma and nutrients. Homeros has defined this as "liquid gold". Among the phenolic and flavonoid composition of olive leaf extracts, there are components such as gallic acid, chlorogenic acid, caffeic acid, ellagic acid, epicatechin, rutin, quercetin, querthrin and kaempferol. The polyphenols and flavonoids obtained from olive leaves exhibit the abovementioned properties as herbal chemical substances, anti-carcinogen, anti-inflammatory, antihypertensive and antimicrobial. For this reason, these substances are necessary for the pharmacological effects of olive leaves.

In addition to the phenols commonly found in other plants, olive leaves contain secoiridoid phenols specific to Oleaceae. Olive leaves are useful sources of by-products with high phenolic value because they are cheap. The leaves of the tree are composed of secoiridoid phenolic compounds, flavonoids and volatiles.

The active component of olive leaf is oleuropein which is a secoiridoid reported to be a powerful antioxidant with anti-inflammatory properties. Oleuropein has pharmacological and health improving properties including hypoglycemic, antioxidant, antimicrobial, antimycoplasmal, antiviral, anti-tumor and angiogenic activities. It has been found that it inhibits the activity of androstenedione 6p-hydroxylase, a cytochrome P450 3A marker, in human liver microsomes, prevents lipid peroxidation on rat liver microsomes. It has also been shown that oleuropein inhibits LDL (Low Density Lipoprotein) oxidation and has vascular protective activity by inhibiting platelet aggregation induced by platelet activating factor.

Components of olive leaf are iridoid monoterpenes, triterpenes, flavonoids, kalkols, phenolic acids and coumarins. Herein, iridoid monoterpenes; among others oleuropein (5-9%), in addition 6-O-oleuropeine consists of sucrose, ligstroside, oleoroside and similar components. Triterpenes consist of oleanolic acid, maslinic acid and similar components. Flavonoids consist of luteolin, kaempferol, chrysoeriol and apigenin derivatives and similar components. Kalkols consist of olivine, olivine-4'-0-diglucoside and similar components. Phenolic acids consist of cumaric acid, caffeic acid, ferulic acid, vanillic acid and similar components. Coumarins consist of aesculetin, scopoletin and aesculin components.

The main components of olive leaves are oleuropein, ligstroside, I methyloleuropein and oleoside, and flavonoids (apigenin, kaempferol, luteolin, chrysoeriol) and phenolic compounds (caffeic acid, tyrosol, hydroxytrozole). Secoiridoids are a very specific group found in plenty of in Oleaceas. Secoiridoids are produced from the secondary metabolism of terpene as precursors of various indole alkaloids in many other plants. Generally, the oleoside-type glucoside is derived from oleosides. It is characterized by a combination of ellenolic acid and a glucosidic residue. These compounds can be considered to advance through the acetate/mevalonate pathway.

Oleuropein which is the main component of the secoiridoid family in olive trees, is a complex phenol found in high amounts in olive tree leaves and low in olive oil and has a bitter taste and strong aroma. Olive leaves contain approximately 60-90 mg/g (dry weight) of oleuropein as well as significant levels of elenolic acid and hydroxytyrosol (3,4- dihydrophenylethanol) glucosidic ester. Furthermore, oleuropein and its hydrolysis, oleuropein aglycon, elenolic acid, beta-3, 4-dihydroxyphenethyl alcohol and methyl-o- methyl enolate products emerge as the main molecules of biological interest.

In traditional use, olive leaf extract has been used against cardiovascular diseases in Germany since 1976 in the state of the art, in European drug agency records. Furthermore, olive leaf and its extracts are used in the complementary and alternative medicine community for their ability to act as the killer of natural pathogens by inhibiting the replication process of many pathogens. Olive leaf extract has also been used as a household remedy so as to battle against other illnesses such as fever and malaria. Furthermore, various reports have shown that olive leaf extract has the capacity to lower blood pressure, increase blood flow in coronary arteries, relieve arrhythmias, and prevent intestinal muscle spasms in animals. Olive leaf is also widely used to battle against viral infections such as cold and flu, yeast infections, and difficult to treat Epstein-Barr disease, shingles, and herpes etc. Furthermore, olive leaves are used to support the heart. It has been shown that olive leaf reduces low-density lipoproteins (LDL), lowers blood pressure and increases blood flow by relaxing the arteries.

There are two main independent historical sources regarding the potential benefits of extracts from olive trees. The first official disclosing of the medicinal effect of olive leaf, which explains its ability to treat severe cases of fever and malaria, occurred about 150 years ago. Pharmaceutical Journal published a report by Daniel Hanbury in 1854. The author wrote that he/she discovered the effective tenture and used it successfully in 1843. The second source records that Spanish physicians sometimes prescribed olive leaves as a "febrifuge" (high antipyretic) in the early 19^th century and as a result French officers recorded that de Sante used these frequently in treating "cases of intermittent fever” during the Spanish war of 1808-1813. This method has become well known in England for the treatment of sick British people who return from tropical colonies. The author believes that a bitter substance in the leaves is the key healing component.

Subsequently, scientists isolated a bitter substance from the leaf and called it oleuropein. It is reported that oleuropein makes the olive tree particularly durable and resistant to insect and bacterial damage. Oleuropein is iridoid which is a structural class of chemical compounds found in plants. It is found in the olive tree, along the olive tree, and is a bitter material that is eliminated from the olives when they are dried. An Italian researcher has reported that oleuropein lowers blood pressure in animals in 1962. This triggered scientific interest in the olive leaf. Other European researchers confirm this interesting finding. Furthermore, it has been found that olive leaf can increase blood flow in coronary arteries, relieve arrhythmias, and prevent intestinal muscle spasms. Dried or fresh leaves have also been used as an antipyretic and as a diuretic against malaria. Today, in addition to these, today, it is known to be effective against covid-19, which became a pandemic in December 2019 due to the antiviral, antimicrobial and historical use of olive tree leaf against malaria.

In addition to the abovementioned many effects, it is known that leaf and essential oil extracts obtained from olives are also used in anti-aging creams, hand creams, soaps and pediatric creams in the cosmetics sector.

The raw material source used in olive leaf extract, which is observed to be effective against diabetes, cancer, cardiovascular, gastrointestinal diseases and covid-19 is obtained from the farm grown under the same conditions of two different types of olive trees, which were started to be cultivated in a certain geography and climate in Anatolia twenty years ago, without using chemical fertilizers, hormones or pesticides. It is important to standardize the agricultural cultivation method of the raw material so as to ensure that the products to be used in herbal treatment can always exhibit the same effect.

When Chinese patents related to the subject in the literature are taken into account, applications with publication numbers CN1422537 and CN1544007 have been encountered in the light of traditional Chinese medicine applications. In the abstract of the application with the publication number CN1422537, the immune system strengthening, thrombosis, blood sugar lowering, anti-aging, anti-cancer and hypertensive properties of the food containing olive leaf and gingko oil are disclosed. However, here the application of a different extraction method is not disclosed. In the abstract of the application with the publication numbered CN1544007, it is mentioned that the biological activity of olive leaf has anticancer, hepatotoxic (liver protective), anti-inflammatory effects. Herein, the extraction of olive leaves with ethanol is mentioned. As a result, there is not any total aqueous olive leaf extract containing active ingredients in both applications.

It is seen that there have been efforts in reducing the source of the biological effect in the olive leaf to a single substance when the studies in the literature are examined. It is focused on the oleuropein active ingredient in the olive leaf extract in the descriptions in the patent or scientific literature. The use of olive leaves in the 1970s is based on the products obtained by the infusion technique even in the monographs of the European pharmaceutical agency. However, improvements so as to obtain the total aqueous extract of olive leaves, which contain a plurality of highly valuable plant chemical substances are required.

As a result, due to the abovementioned disadvantages and the insufficiency of the current solutions regarding the subject matter, a development is required to be made in the relevant technical field.

Brief Description of the Invention

The present invention is related to an olive leaf extract and production method thereof which fulfills the abovementioned requirements, eliminates all disadvantages and brings some additional advantages.

The main aim of the invention is to develop an aqueous total olive leaf extract that contains multiple highly valuable plant chemical substances effective against diabetes, cancer, cardiovascular, gastrointestinal diseases and covid-19, in which the positive (synergistic) effect of all substances is observed together, in which this synergistic effect is obtained by revealing the protective or therapeutic properties of the diseases mentioned in human metabolism.

The aim of the invention is to develop an olive leaf extract which is a supporting or alternative treatment for diabetes, cancer, cardiovascular, gastrointestinal diseases and covid-19 patients, reduces undesired side effects, increases the quality of life by preventing the formation of other diseases that occur as a side effect after covid-19 treatment, which has been exposed to these diseases and has recently turned into a pandemic. A similar aim of the invention is to develop an aqueous total olive leaf extract whose effectiveness is increased against diabetes, cancer, cardiovascular, gastrointestinal diseases and COVID-19 with a synergistic effect between them by not isolating the active ingredients.

Another aim of the invention is to develop an aqueous total olive leaf extract containing more than 2000 active ingredients in their own proportions, which are synthesized during the life of the plant so as to be more effective against said diseases.

Another aim of the invention is to develop an olive leaf extract with reduced production cost.

Another aim of the invention is to develop an olive leaf extract that does not contain any of the preservatives or fillers added in most food supplements and traditional herbal products, thus that does not lead to the adverse effects caused by these substances.

Another aim of the invention is to develop a total aqueous extract of the olive leaf in the form of liquid extract that provides easy use for children, the elderly or people who have difficulty swallowing products produced in pellet form.

In order to fulfill the abovementioned aims, the inventive olive oil extract is a total aqueous extract of Olea europaea L. (olive) leaf, which contains a high percentage of valuable vegetable chemicals, the inventive method comprises the following process steps; minimizing olive leaves dried with a standardized method, mixing and keeping the leaves in the presence of water at maximum surface film forming capacity and removing the solvent from the obtained filtrate under vacuum.

The structural and characteristic features of the present invention will be understood clearly by the following detailed description and therefore the evaluation shall be made by taking the detailed description into consideration.

Detailed Description of the Invention

In this detailed description, the inventive olive leaf extract and the production method thereof is described only for clarifying the subject matter in a manner such that no limiting effect is created.

The subject of the present invention is the total aqueous Olea europaea L. (olive) leaf extract which contains a highly valuable plant chemical substance effective against diabetes, cancer, and cardiovascular, gastrointestinal diseases and covid-19. It’s being total is thought to be effective against diabetes, cancer, cardiovascular, gastrointestinal diseases and covid-19 with its high synergistic effect in terms of approximately 2000 active ingredients in the olive leaf content. In the subject of the invention, the positive (synergistic) effect of all the substances it contains is observed. This synergistic effect has protective or therapeutic properties in said diseases in human metabolism. The inventive olive leaf extract is a natural plant extract. Here olive leaves of two different types of olive trees, which were started to be cultivated in a certain geography and climate in Anatolia twenty years ago, without using chemical fertilizers, hormones or pesticides are used as raw materials. This total aqueous extract, which contains a high ratio of valuable herbal chemicals, also contains a certain amount of water. It does not require additional preservatives or fillers because it contains water. In order to obtain the invention, 2 to 20 ml water is used as solvent per gram of olive leaf. For example; 100 - 2000 ml of water can be used for olive leaves in the range of 50 - 100 grams.

The inventive production method invention aims to reveal the synergistic effect of the total extract and herbal chemicals and simultaneously to increase its applicability in the industry by reducing the production cost. The olive leaves, which have been first dried by a standardized method, are preferably reduced to the range of 0.2-4 cm so as to achieve this. Subsequently, olive leaves are extracted in a dark environment. Then, the leaves are preferably kept by stirring at a temperature of 18-100 °C at a rotation speed of 10-60 rpm in the range of 5-72 hours in the presence of water at maximum surface film forming capacity. Lastly, the solvent is removed from the obtained filtrate, preferably in the range of 1-10 hours, at a rotational speed of 10-70 rpm at a temperature of 18-100 ° C and a vacuum of 2-100 mbar. It is ensured that the active substances pass to the solvent in a certain time without deterioration at the same rate after all these steps are carried out. The aqueous total olive leaf extract obtained in this manner is much more appropriate in terms of production costs. At the same time, it has been observed that the active ingredients have not been isolated and have increased their effectiveness against diabetes, cancer, cardiovascular, gastrointestinal diseases and covid-19 with a synergistic effect between each other in olive leaf extract obtained by this production method.

It is important that the process steps are carried out under the specified temperature, rotation speed and pressure values and extracted in the same standardized manner each time so as to ensure that the active ingredients in the leaves of the olive tree, which has been produced with herbal production techniques in standardized form for 20 years, are effective against diabetes, cancer, cardiovascular, gastrointestinal diseases and covid-19 and loss of weight in human health, can pass to the solvent at the same rate within a certain period of time and to ensure that the active substances found naturally in the olive leaf to be protective and therapeutic against the diseases specified in human metabolism.

The inventive olive leaf extract can be used within the scope of food supplement in the food industry against diabetes, cancer, cardiovascular, gastrointestinal diseases and COVID-19 and as and traditional and herbal medicinal products in the pharmaceutical industry. Application of the invention may be encapsulated into a liquid drop or a slow release soft gel capsule in the stomach or intestine. Since there is a form in the application, it provides easy use for children, the elderly or people who have difficulty swallowing products produced in pellet form. This liquid form can be used orally in a practical manner.

Claims

1. An olive leaf extract characterized in that; Olea europaea L. (olive) leaf is a total aqueous extract containing a high percentage of valuable plant chemical substance.

2. The olive leaf extract according to claim 1 ; characterized in that; it is effective against diabetes, cancer, cardiovascular, gastrointestinal diseases and covid-19.

3. The olive leaf extract according to claim 1 ; characterized by comprising; active substances and water that the plant has synthesized during its life.

4. The olive leaf extract according to claim 3; characterized by comprising; the said active ingredients in the proportions that the plant has synthesized during its life.

5. The olive leaf extract according to claim 1 ; characterized by comprising; 2 to 20 times ml of water per gram of olive leaf.

6. The olive leaf extract according to claim 1 ; characterized in that; it is in liquid form suitable for oral use in a practical way or in the form of a slow-release soft gel capsule in the stomach or intestine.

7. An oil leaf extract production method according to any of the preceding claims, by comprising the following process steps; a. minimizing olive leaves dried with a standardized method, b. keeping the leaves by mixing in the presence of water at maximum surface film forming capacity, c. removing solvent from the obtained filtrate under vacuum.

8. The production method according to claim 7, characterized in that; in the step "a" olive leaf sizes in the range of 0.2-4 cm.

9. The production method according to claim 7, characterized in that; in the step “b” the processing time is 5-72 hours, the rotation speed is 10-60 rpm and the temperature is in the range of 18-100 °C. The production method according to claim 7, characterized in that; in the step “c” the processing time is 1-10 hours, the rotation speed is 10-70 rpm, the temperature is 18-100 O and the pressure is between 2-100 bar. The production method according to claim 7, characterized in that; in steps “b” and “c” the extraction is in the dark environment.