TREATMENT

Technical Field

The invention relates to herbal tea with antidiabetic therapy properties.

The invention relates in particular to the use of fruit extracts of the Jerusalem thorn (Paiiurus spina-christi Mill.) fruits which has been discovered to be able to compete with oral antidiabetic drugs in the treatment of diabetes patients.

Prior Art

Diabetes is a disease which is one of the most common causes of death in recent times that negatively affects human life and can cause serious and permanent damage to vital organs if not treated. Due to the fact that the incidence and treatment costs of diabetes mellitus are high and the exact treatment method has not been developed yet, the world of science has been searching for a wide range of treatment methods for diabetes. Phytochemical compounds obtained from plants have started to find an area of use in the treatment of diabetes in recent years. There are many herbs that are used in the treatment of diabetes. In the literature search, there are many studies on the antidiabetic effects of various plant extracts on the experimentally created diabetic animals. Some of the many plants used in there studies are Ajuga iva (El Hilaly ve Lyoussi, 2002), Rubus fructicosis (Jouad vd., 2002), Fraxinus excelsior (Mag h rani vd., 2004), Tamarindus indica (Maiti ve ark., 2004), Urtica dioica (Farzami vd., 2004), Momordica charantia (Virdi vd. , 2003), and Brassica juncea (Grover vd., 2004). The most important factor in the development of the idea according to the invention is the emergence of anti-diabetic effect of the Paiiurus spina-christi Mill, plant known as Jerusalem thorn .

Paiiurus spina-christi Mill, plant is a well-known plant in Asia and the Mediterranean region. It is seen as a thorny bush with zigzag branches, two to three meters high, which grows in almost all Anatolia in Turkey (Kirca et al., 2007). Its leaves are oval, stipules are thorn-shaped, flowers are yellow, fruits are circle shaped; and it is a flat, winged, three seeded and dry plant (Syie et al., 2002). As a result of the literature studies conducted on the mature fruits of Paliurus spina-christi Mill, which is known to be biologically active, it has been observed that the plant is rich in polyphenolic substances (Kirca et al., 2007). Paliurus spina-christi Mill, with different medical uses among the public, is also important in terms of the substances it contains. Four cyclopeptide structured alkaloids, flavonoids glycosides (routine, isoceritrin and hyperositis found in the leaves), polyphenols, tannins, methyl esters of natural fatty acids, sterols, free fatty acids, normal and methyl-branched isoprenoidit hydrocarbons are isolated from this plant (Guner, 2005). In the isolation study on the Paliurus spina chiristi Mill, plant by chromatographic methods, 3 monomer tannins that are quercetin, isoceritrin, routine, quercetin-3-Ο-α- rhamnosyl (6→ 1 )-p-galactoside, quercetin-3-O-a-rhamnosyl (6→ 1 )-p-galactoside-7- O-a-ramnositide and quercetin-3-0-[-p-xylosyl(2→ 1 )-a-rhamnosyl(6→ 1 )]-p-glucoside, including 6 flavonoid and (+) catechin, (-) catechin and (-) gallocatechin were isolated (Guner, 2005). In another study on Paliurus spina chiristi Mill, plant, 15 flavonoids were isolated and the structure was enlightened. From the secondary metabolites including glycoside flavonoids, quercetin, isokersitrin, routine, quercetin-3-O-galactoside (hyperoside), quercetin 3-ramnoside, quercetin-3-0-ramnoglycoside-7-ramnoside, quercetin-3-0-ramnoglycoside-4'-glucoside, kaemferol, astragaline , kaemferol-3-O- ramnoglycoside-7-ramnositis, apigenin, luteolin, vitexin, myricetin, scoparin-7- ramnoglycoside were obtained (Medic-Saric et al. , 1 996).

Patil et al. (2013) suggested that curculigo orchioides gaerthn Rhizom plant repaired histological deformities in the kidney, liver and pancreas of the diabetic rats to a certain extent, and has a therapeutic potential as antihyperglycemic plants. Anandakirouchenane et al. (2013) found that the methanol extract of curculigo orchioides had a positive effect on the recovery of histopathological abnormalities such as cytoplamic vacuolization of hepatocytes, leukococytic infiltration and edema in the kidney and liver. Rath et al. (2016) found that the Cuscuta reflexa roxb. methanol extract had a positive effect on body weight of the diabetic rats, significantly reduced their blood glucose levels, and did not cause abnormal disorders in their kidney, liver and pancreas such as histopathological damage and necrosis in long-term treatment.

Kaur et al. (2016) stated that Dillnia indica L. leaves have a beneficial effect on fasting blood glucose and related biochemical parameters of diabetic rats, and show itself as a good candidate as an alternative or supportive drug for diabetes mellitus. Jayaprasad et al. (2016) found that methanol and water extracts of the chloroxylon swiettenia bark plant had a positive effect on decreasing blood glucose levels and glycated hemoglobin of the diabetic rats moderately, elevated their plasma insulin levels, and improved the histopathological structure of the liver. Ozbek et al. (2017), examined the protective activity of methanolic water extracts of the air and root parts of alchem illa mollis (buser) rothmun on hypoglycemic activity and hepatotoxicity of diabetic rats. In their results, they found that plant extracts did not have any effect on blood sugar, and that both extracts significantly reduced the serum ALT value and significantly improved cellular damage in the liver. Carhoglu et al. (2014) examined the effect of zofenopril on liver, kidney and pancreatic damage in diabetic rats histopathologically. In the results obtained, they observed that zofenopril improved the histopathological changes in the kidney caused by diabetes, yet did not cause any significant histological changes in the pancreas and liver. Huang et al. (2017) found that allicin effectively inhibits kidney damage in rats with diabetic nephropathy. Lee et al. (2005) reported that water extract of eucommia ulmoides oliv. leaves reduce plasma glucose levels and help protect the histological structure of pancreatic islets and insulin positive beta cells in diabetic rats. Barky et al. (2016) found that holothuria thomus saponins significantly decreased serum glucose, adiponectin and IL-6 concentrations, significantly increased serum insulin and liver glycogen levels, and significantly reduced degenerative changes of beta cells.

In the patent applications, it is known that many studies have been carried out to find a the treatment of diabetes, and different plant species and combinations thereof have been used in these studies instead of chemical drugs. For example, in European patent no. EP2685997; for the prevention or treatment of diabetic peripheral neuropathy, a composition containing a herbal combination extract is used and details of this use are disclosed.

The European patent no. EP2768323 is also related to the use of whey protein micelles to improve insulin profile in diabetic patients. That application relates to whey protein micelles for use in the treatment and/or prevention of a condition associated with an increase in plasma postprandial insulin and/or plasma postprandial glucagon concentration in a subject. The invention also relates to the non-therapeutic use of whey protein micelles to reduce plasma postprandial insulin and/or glucagon concentration in healthy subjects.

The European patent no. EP2376077 is also a compound selected from combination of glutamine, a group of compounds that contain pharmaceutically acceptable salts and their combinations, and the combination is associated with a method for the treatment or prevention of a disease selected from diabetes, metabolic syndrome, hypertriglyceridemia, obesity and polycystic ovary syndrome, bearing a condition in which the secretion of a enterogastrone secreted from cells L is reduced or absent, this method involves the application of sufficient composition to the person to stimulate the secretion of enterogastrone from cells L in the colon.

The European patent no. EP 1954261 is also related to the use of fenofibrate or a derivative for the production of a drug to prevent and/or treat retinopathy.

Another European patent application no. EP2842563 which is developed for the treatment of diabetic patients is related to a combination containing the powder-reduced egg shell membrane for the treatment of pre-diabetic mammals.

In another European patent (EP2773331 ), formulations for the treatment of diabetes are described and a formulation for parenteral administration comprising an pH of 1 to 4 or 6 to 8 insulin and an aprotic polar solvent is disclosed, in this case the insulin is dissolved in the aprotic polar solvent, the soluble insulin here contains stable monomeric or dimeric forms of insulin or mixtures thereof, wherein the formulation has a water content of 15% (weight/volume) or less.

To discover the active ingredient of a plant that has therapeutic properties against any disease and to make it manufacturable in the industry is one of the most important investment areas of the pharmaceutical industry. In this context, the purpose of this study is to develop a new oral antidiabetic drug that will help diabetic patients to recover from the costly and hard to use insulin.

Although the presence of different plant species used in the treatment of diabetes patients is known in the prior art, when all technical literature and patent applications are examined, there is no data found about the use of antidiabetic effect of Paliurus spina-christi Mill, in this field and the obvious need in this field necessitates an improvement in the related technical field. The Object of the Invention

In order to eliminate the disadvantages of the current technique, the purpose of the invention is to develop the Jerusalem thorn (Paiiurus spina-christi Mill.) plant as a herbal tea, which is an endogenous antidiabetic agent that is capable of competing with oral antidiabetic drugs. The experimental studies that we have conducted have revealed that the tea prepared with these fruits reduce blood sugar in diabetic rats and people with diabetes and does not cause any organ damage, especially on liver. In addition, patients with diabetes reported that the taste is pleasant and it can be consumed on a daily basis, such as frequently used herbal teas. In this context, the main purpose of this study is to develop and launch a new oral antidiabetic herbal tea that will help diabetic patients to recover from the costly and hard to use insulin and oral antidiabetic pills.

A more specific purpose of the invention is the use of the Jerusalem thorn (Paiiurus spina-christi Mill.) plant for the treatment of diabetes patients. In the literature search, no data were found regarding the antidiabetic effect of Paiiurus spina-christi Mill. The study is unique in this aspect. The invention is important for isolating the effective antidiabetic drug active agent to be used in the prevention of diabetes and for constituting the source of the investigation of its mechanisms by trying on in vivo diabetic rats. This study will not only be specific to the Jerusalem thorn plant but will also serve as an example for other phytotherapeutic plants used for antidiabetic purposes among the public.

In order to accomplish the above-mentioned purposes, the invention is a method of producing herbal tea of Jerusalem thorn (Paiiurus spina-christi Mill.) plant for use in the treatment of diabetic patients. This method has an industrial property. Because our experimental studies have shown that the fruits of the Jerusalem thorn (Paiiurus spina- christi Mill.) are effective not after the brewing process, but after a rapid boiling period of 5 minutes. The reason for this is that during boiling, the phytochemical compound called naringene releases from the plant to the solvent environment and other antidiabetic compounds are enriched in this solvent environment. In addition, to increase the amount of naringenin in the tea, the root cinnamon is added to the combination. The combination of tea will be formed as follows; the first extract of the fruits of Jerusalem thorn (Paiiurus spina-christi Mill.) are obtained with a 5 min decoction (boiling), and then the herbal tea obtained by infusing root cinnamon in a ratio of 20% of the total herbal mixture to increase the amount of naringenin, malic acid, catechin, rutin, quinic acid, gallic acid, and fumaric acid compounds which is the most important agent of the extract obtained.

In order to accomplish all the advantages mentioned above and to be understood from the following detailed description, the present invention provides many advantages with respect to said features.

The structural and characteristic features and all advantages of the invention outlined in the drawings below and in the detailed description made by referring these figures will be understood clearly, therefore the evaluation should be made by taking these figures and detailed explanation into consideration.

Detailed Description of the Invention

The invention relates to the use of the Jerusalem thorn (Paliurus spina-christi Mill.) plant for the treatment of diabetes patients.

The use of plants for pharmaceutical, food and cosmetic purposes began with the existence of human beings and has continued to this day. The use of plants and the specific characteristics of each of these have been discovered by the humans in time for the presence of the usual diseases and their treatment, and have also been developed by positive or negative trials. Secondary substances synthesized in plants (essential oils, alkaloids, glycosides, phenolics, tannins and flavonoids) have a wide range of uses in food, cosmetics and pharmaceutical sectors due to their bioactive properties.

The most important factor in the discovery of the usage area of the invention is the research conducted on the recommendations from diabetes patients. On a recommendation from a Type-ll Diabetes patient using insulin 4 times a day; " I've prepared the Jerusalem thorn (Paliurus spina-christi Mill.) fruit with decoction and drink it after morning, noon and evening meals, and I don't need to use insulin anymore. It reduces my blood sugar to 90-110 mg/dL without causing hypoglycemia. " Together with this discourse, we carried out a study on this subject concerning the question "Does it have any side effects such as liver damage caused by phytotherapeutic plants?".

In this study which leads to the invention, we prepared Paliurus spina-christi Mill, fruits with decoction and applied 100, 250 and 500 mg/kg body weight concentrations on diabetic rats induced by streptococin for 1 month, and then measured body weight and blood glucose levels. At the end of the experiment, in order to investigate its effect on ALT and AST enzymes which are the telling signs of liver destruction, on the lipid profiles, and the effects on lipid profiles and the effects of antioxidant enzymes on catalase, glutathione peroxidase and superoxide dismutase enzymes, we took blood sample, liver, kidney and pancreatic tissues and conducted a study according to current methods in the literature. Indeed, as mentioned in the history of the study, we observed that the Jerusalem thorn fruits prepared with decoction reduced the blood sugar of diabetic rats from 500-600 mg up to 100-150 mg levels, also did not cause liver damage, and even prevented the damage caused by streptozotocin, in other words improved ALT and AST enzyme levels. We also noticed that it balances the levels of antioxidant enzymes. As a result of these experiments and researches, we revealed the necessity to produce a herbal tea with Jerusalem thorn plant and to use it in the treatment of diabetes patients. Usually herbal teas are prepared by two methods such as brewing and decoction (boiling). In addition, it can be applied in two different methods, by using a single type of plant or a herbal mixture.

In the production of herbal tea, the Jerusalem thorn plant (Paliurus spina-christi Mill.) was used. The results of our experiments showed that although the extracts of Jerusalem thorn (Paliurus spina-christi Mill.) plant prepared by the decoction method showed high antidiabetic effect, and the same effect was not observed in the brewing method. In the content analysis we performed to investigate this difference, we observed that in the extract obtained by decoction, the naringenin compound was formed which was different from the others. In the literature search, it is found that naringenin compound has an antidiabetic effect which can compete with oral antidiabetic drugs. In addition, other compounds responsible for the antidiabetic effect in the extract obtained by decoction are as follows: cinnamic acid increases insulin secretion. Malic acid regulates blood sugar and increases the absorption of magnesium. This extract contains a very high amount of minerals (magnesium, zinc, +3 valence chromium) and phenolics (malic acid catechin, rutin, quinic acid, gallic acid, and fumaric acid). Taking both together is widely used for antidiabetic therapy. Catechin, by binding glucose, prevents it from being absorbed through the intestine. Therefore, it helps to lower blood sugar. Because the high amount will cause hypoglycemia, it needs to be moderate. In the extract, the amount is moderate. The binding of glucose in the phase of the digestion of glucose from the food to the blood is a very effective method for lowering blood glucose. Therefore, it is expected that drinking the extract immediately after the food will be more effective for lowering blood glucose. The experiments revealed that the extract had a higher effect when used immediately after the meal. Quinic acid helps to reduce the expression of TNF-a and thus close the pathways that lead up to the diabetic conditions. On the other hand, there is enough of it in the extract to create such a condition.

To increase the amount of naringenin which is the most important agent of the extract in the tea that is obtained from Jerusalem thorn (Paliurus spina-christi Mill.) plant with a decoction method, the root cinnamon is added to the combination. The root cinnamon (20% of the total herbal mixture) was added to the Jerusalem thorn extract prepared with decoction to be brewed, kept at room temperature (20-25 °C) until it cooled, and then filtered. This mixture will be stored at + 4 °C and consumed within 7 days.

The extract from which the solvent is removed can be stored for longer (up to 1 year). With the herbal tea of the present invention, a new active substance of an antidiabetic drug has been developed which will relieve the severe diabetes patients from the use of insulin and the effects of its use have been proved by the experiments.