UA125809C2 - Anti-diabetic collection of medicinal plants - Google Patents

Abstract

The invention relates to an antidiabetic collection of medicinal plants, which includes rosehips and blueberry leaves, additionally, it further contains nettle leaves, dandelion roots and peppermint leaves.

Description

(54) ANTIDIABETIC COLLECTION OF MEDICINAL PLANTS (57) Abstract:

The invention relates to an antidiabetic collection of medicinal plants, which includes rosehip fruits and blueberry leaves, and additionally contains nettle leaves, dandelion roots and peppermint leaves.

The invention belongs to pharmacy and medicine, namely to medicinal preparations of plant origin, and can be used for the prevention and treatment of type 2 diabetes mellitus and its complications both independently and as part of complex therapy.

Diabetes mellitus is a global social and medical problem caused by the rapid spread and development of serious complications in the form of micro- and macroangiopathy, which significantly reduce the quality and life expectancy of patients 11.

An important problem of modern pharmacovigilance is that existing pharmacotherapy can effectively reduce hyperglycemia, but it is not always able to stabilize fluctuations in glycemia during the day and maintain it at an optimal level. This leads to the formation of a cascade of pathological processes - excessive glycation and inactivation of the body's antioxidant defense system (ADS), triggering the processes of free radical oxidation of lipids and, as a result, the development of oxidative stress, which leads to the formation and progression of diabetic angiopathies. In addition, a frequent trigger for the development of diabetic complications is a violation of the lipid profile, manifested by dyslipidemia, hypercholesterolemia, and/or hypertriglyceridemia (1, 2). Therefore, the optimization of pharmacotherapy with the help of the collection of medicinal plants will be expedient and effective, because thanks to the combination of medicinal plant raw materials with various groups of biologically active substances, it will be able to comprehensively influence all pathogenetic mechanisms of the development of diabetes mellitus and its complications. It is also important that phytoremedies have a number of advantages over synthetic oral antidiabetic drugs, namely, they are low-toxic, have a mild pharmacological effect and can be used for a long period without significant side effects, are well combined with synthetic drugs, and have a wide spectrum of pharmacodynamics. .

Today, two anti-diabetic herbal collections are registered in Ukraine - the "Arfazetin" collection, which includes blueberry shoots and common bean leaves for 20 95 each, rhizome with the roots of Echinopanax talla (Zamanykh) and rosehip fruits for 15 95 each, horsetail grass, St. John's wort and chamomile flowers for 10 95 and the "Sadifit" collection, which includes blueberry shoots, broad beans, Jerusalem artichoke tubers and stevia leaves for 20 95, green leafy tea 15 95, peppermint leaves 5 95 |4|.

However, the rhizome with the roots of Echinopanax tall and St. John's wort belong to

From plants, which with long-term use can be dangerous and cause side effects. In addition, rhizomes with the roots of zamanikha have a tonic effect and are contraindicated in coronary heart disease, heart failure and arterial hypertension, which are often complications of diabetes.

The task of the invention is to create a new anti-diabetic collection with a component composition of plant raw materials, which, thanks to various groups of biologically active substances, will affect all links of the pathogenesis of type 2 diabetes and its complications, as well as on versatile disturbances of metabolic processes that occur in this pathology.

The task is solved in such a way that the antidiabetic collection of medicinal plants, which includes rose hips and bilberry leaves, additionally contains nettle leaves, dandelion roots and peppermint leaves, and all components are taken in the following ratio, weight. h.: nettle leaves 3-4 dandelion roots 3-4 mint pepper leaves 3-4 rose hips fruits 3-4 blueberries leaves 3-4.

The qualitative and quantitative composition of the declared collection of medicinal plants was determined experimentally and is unknown from 3 information sources. The optimal antidiabetic collection of medicinal plants with the following component composition, mass: nettle leaves 1 dandelion roots 1 peppermint leaf 1 rosehip fruit 1 blueberry leaves 1.

The declared collection is obtained by mixing crushed dry medicinal plant raw materials in a given proportion.

Table 1

Pharmacodynamics of the components of the declared antidiabetic collection of medicinal plants. Pharmacological action of plant raw materials

Biologically active substances have hemostatic, diuretic, tonic, anti-inflammatory and vasoconstrictive effects,

Nettle leaves help increase the hemoglobin content and the number of erythrocytes, normalize blood composition, reduce blood sugar, promote the regeneration of the mucous membranes of the digestive tract, normalize lipid metabolism.

Biologically active substances have a choleretic, diuretic,

Dandelion roots have an antispasmodic, relaxing effect; increase appetite and improve digestion, increase bile production; is used as a hypoglycemic agent in folk medicine.

Biologically active substances have a choleretic, sedative and weak hypotensive effect; increase the secretion of digestive glands, excite

Peppermint leaves suppress the appetite, suppress the processes of rotting and fermentation in the digestive tract, reduce the tone of the smooth muscles of the intestines, biliary and urinary tracts, and increase the secretion of bile.

Biologically active substances have an anti-sclerotic, anti-inflammatory effect; activate enzyme systems and redox processes in the body, contribute to the elimination of vitamin C deficiency, normalize

Rosehip fruits improve carbohydrate metabolism, enhance hormone synthesis and tissue regeneration, increase the body's resistance to adverse environmental factors, increase bile secretion, increase diuresis, and reduce capillary fragility and permeability.

Biologically active substances have a hypoglycemic effect in mild and moderate type 2 diabetes, which gives

Bilberry leaves can in some cases reduce daily doses of oral antidiabetic agents; and also have anti-inflammatory, diuretic, choleretic, astringent effects.

The invention is illustrated by examples.

Example 1. The study of the antihyperglycemic activity of the claimed plant collection was conducted on normoglycemic white purebred male rats weighing 180-200 g, which were kept in the vivarium nursery of the Central Research Laboratory of Ternopil National Medical University named after I.Ya. Gorbachev's Ministry of Health of Ukraine" in accordance with sanitary and hygienic norms. All research was performed in accordance with the general ethical principles of conducting experiments on animals, established by Directive 2010/63/EU on the protection of animals used for experimental and other scientific purposes. (5).

The declared anti-diabetic plant collection in the form of an aqueous decoction (1:10) in doses of 6 ml/kg, 9 ml/kg and 12 ml/kg and comparative drugs - an aqueous decoction (1:20) of the "Arfazetin" collection (PJSC "Viola", Ukraine) at a dose of 9 ml/kg, and a suspension of metformin tablets SANDOZ (Lek S.A., Poland) at a dose of 60 mg/kg were administered intragastrically to rats for 20 days. The state of glucose homeostasis in animals was assessed by the level of basal glycemia and glucose tolerance, which was determined using the intraperitoneal glucose tolerance test (IPG).

The test was performed by intraperitoneal injection of 2 g/kg glucose solution into rats after overnight fasting (16-18 hours). The concentration of glucose in the blood, which was obtained from the tail vein of animals, was determined before the introduction of glucose and after 15, 45 and 60 min by the glucose oxidase method with the help of test kits "cSlyukose-D" of the company "Filisit-Diagnostika" (Ukraine).

The obtained experimental data were processed using the standard package of statistical programs "iaiviisa 6.0", the differences were considered statistically significant when p-0.05.

The obtained data are presented in Table 2.

Table 2

Antihyperglycemic activity of the declared antidiabetic collection of medicinal plants during a 20-day prophylactic administration to normoglycemic rats in comparison with the "Arfazetin" collection and metformin tablets under the conditions of an intraperitoneal glucose tolerance test (teapzh5E, p-8)

Notes: 1.7 - the differences are statistically significant in relation to the values of the intact group, p « 0.05 (according to 0- Mann-Whitney criteria); 2.7 - the differences are statistically significant with respect to the values of the comparison drug of the collection "Arfazetin", p « 0.05 (according to Mann-Whitney O-criteria);

Z. n - the number of animals in each group.

The study showed that the declared antidiabetic collection of medicinal plants in a dose of 12 ml/kg/day shows a pronounced reliable (p<0.05) antihyperglycemic activity, because a decrease in glucose in the blood of animals by 26 9o was observed compared to the control group at the 15th minute of the test ( peak hyperglycemia). As for the comparison drugs, metformin tablets showed a similar effect - they reduced hyperglycemia by 27 95, and the collection "Arfazetin" was somewhat inferior in effectiveness - it reduced hyperglycemia by 2195 compared to the control group. The results of the experiment testify to the high ability of the declared antidiabetic collection of medicinal plants to reduce the manifestations of impaired glucose tolerance, which play a leading role in the development of type 2 diabetes.

Example 2. Determination of the effect of the declared antidiabetic collection of medicinal plants on insulin sensitivity was carried out on the experimental model of dexamethasone-induced insulin resistance in rats.

The research was conducted on white male rats weighing 180-200 g in the number of 40 laboratory animals, which were kept in the vivarium nursery of the Central Research Laboratory of Ternopil National Medical University named after I.Ya. Gorbachevskii

Ministry of Health of Ukraine in accordance with sanitary and hygienic norms. During the entire experimental period, the animals received a standard diet and water ai Irisht.

The experimental model was reproduced by subcutaneous injection of dexamethasone solution (KAKA, Slovenia) at a dose of 0.125 mg/kg/day for 15 days. A group of intact animals - received injections of 0.9 95 Massi solution in a similar mode.

Aqueous decoction (1:10) of the declared collection of medicinal plants at a dose of 12 ml/kg/day and comparative drugs - an aqueous decoction (1:20) of the "Arfazetin" collection at a dose of 9 ml/kg/day and a suspension of metformin tablets at a dose of 60 mg /kg"/day was administered intragastrically for 15 days. A group of control pathology animals received purified water according to a similar scheme.

Glucose content in the blood of animals was determined on an empty stomach after the end of the experiment by the glucose oxidase method.

The state of insulin resistance of animals was assessed using the NOMA-YIV index, which

Z was calculated according to the formula: NOMA-IV - fasting glucose (mmol/l) x fasting insulin (μU/ml)/22.5.

After the end of the experiment, the rats were euthanized under thiopentane anesthesia, blood was collected for biochemical analysis.

As a result of the introduction of a diabetogenic agent, the development of basal hyperglycemia was observed in animals from the control pathology group, which was 2.6 times higher than in intact animals.

The results of the study showed that the declared antidiabetic collection of medicinal plants in a dose of 12 ml/kg exhibits pronounced antihyperglycemic activity in animals with experimental dexamethasone-induced insulin resistance, which was manifested by a reliable decrease in basal glycemia by 41 95 relative to the control pathology (Table 3).

The confirmation of the development of insulin resistance, as a decrease in the sensitivity of tissues to the action of insulin, in the group of control animals was an increase in the NOMA-IV index by 3.7 times compared to the intact group of animals. According to the results of the study, it was established that the declared antidiabetic collection of medicinal plants increased the sensitivity of tissues to the action of insulin, which was manifested by a decrease in the NOMA-IV index by 2.3 times compared to the control pathology. As for the comparison drugs, the collection "Arfazetin" reduced the NOMA-IV indicator by 1.8 times, and metformin tablets by 2.5 times (Table 3).

Table C

The influence of the declared antidiabetic collection of medicinal plants on the state of insulin resistance in animals with dexamethasone-induced diabetes, (teape5E), p-8

NOT WITH. WITH

Animal groups fasting, NOMA-IV, 95 fasting, μU/ml mmol/l ml/kg/day ml/kg/day 60 mg/kg

Notes: 1.7 - the differences are statistically significant in relation to the values of the intact group, p<0.05 (according to 0- Mann-Whitney criteria); 27 - the differences are statistically significant in relation to the values of control pathology, p«0.05 (according to 0- Mann-Whitney criteria);

Z. n - number of animals in each group;

Example 3. On the model of insulin resistance induced by dexamethasone, the state of lipid metabolism was assessed according to the following indicators: the content of total cholesterol (CH), triglycerides (TG), cholesterol of high and low density lipoproteins (HDL-C, LDL-C), and the atherogenicity index was calculated ( IA) by the formula: IA - (ЗХ - ХС ЛЛВШХУЧС HDLVSH.

Modeling of dexamethasone-induced insulin resistance caused a change in the lipid profile in rats from the control pathology group, in particular, an increase in the concentration of ХХ in the blood plasma by 22 95 was observed compared to the intact group. The introduction of the declared antidiabetic collection of medicinal plants, collection "Arfazetin" and metformin tablets reduced the level of ХХ almost to the values of the intact group. Regarding the concentration of TG in blood serum, the administration of glucocorticosteroid increased it by 3595 compared to the group of healthy animals. The declared antidiabetic collection of medicinal plants showed the ability to reduce hypertriglyceridemia induced by dexamethasone by 34 95 compared to the group of control pathology.

The introduction of the comparison drug - metformin tablets showed a result similar in effectiveness. During the experiment, a significant decrease in the concentration of HDL-C and an increase in the concentration of LDL-C in animals with control pathology was observed. Administration of the declared antidiabetic collection of medicinal plants caused a decrease in LDL-C by 2095 and an increase in HDL-C by 3395. The "Arfazetin" collection showed a similar, but slightly lower, result. In the group of animals receiving metformin tablets, it was observed

There was a two-fold increase in the level of LDL-C and a decrease in the level of HDL-C by 20 9o compared to the control pathology group (Table 4).

Table 4

The effect of the declared antidiabetic collection of medicinal plants on the lipid profile in animals with dexamethasone-induced insulin resistance, (teape5E), p-8

Pathology of it Pathology Same Collection Pathology Same

Indicators, Intact Control and sbi " " tablets mmol/l group pathology | The reported drug, Arfazetin", metformin, 60 12 ml/kg 9 ml/kg mg/kg ' ziznoov | 2025012 3.0950.19 Z2bzh-02 3.0840.13 mmol/l

TG, 0.8740y17 1.3450.16 0.890.09 1.09:0.09 0.83x0.09 mmol/l / ho LINshC, 2124017 2.875016 2.31 0.18 2.63x50.18 2.295018 mmol/l / / ho LIVSH, 2524016 1.0650.17 1.59-0.21 1465019 215018 mmol/l / / /

Ogazoli | Lov bo oo 046014

Notes: 1.7 - the differences are statistically significant in relation to the values of the intact group, p<0.05 (according to 0- Mann-Whitney criteria); 2.77 - the differences are statistically significant in relation to the values of the control pathology, p«e0.05 (according to 0О- Mann-Whitney criteria);

Z. n - the number of animals in each group.

The declared antidiabetic collection of medicinal plants showed the ability to regulate lipid metabolism due to a decrease in the level of cholesterol and an increase in HDL-C, which was manifested by a decrease in the atherogenicity index (A) by 6695 relative to the control pathology, compared to the collection "Arfazetin", the use of which reduced IA by 56 95 and tablets of metformin at 84 95 (Table 4).

Example 4. According to 3 modern concepts, oxidative stress is important in the development of insulin resistance, which is formed as a result of a violation of the balance between the body's health system and the system of lipid peroxidation (LPO).

The state of the system was evaluated on the model of insulin resistance induced by dexamethasone

AOZ - the activity of catalase (KAT) and superoxide dismutase (SOD), the content of reduced glutathione (C5H) in the blood and liver, as well as the state of the lipid peroxidation system according to the content of malondialdehyde (MDA) in the blood and liver.

Table 5

The influence of the declared antidiabetic collection of medicinal plants on the state of AOZ/POL systems in animals with dexamethasone-induced insulin resistance, (teape5E), p-8. Pathology t Pathology What

Pathology I

Control - |Pill collection

Indicators Intact group and declared |, n" . pathology and Arfazet", 9Imetformin, 60 collection, 12 ml/kg ml/kg mg/kg 332.04 | 790.24 Z64u029 | Z7810.26 3.4740.21 μmol/l / 14124037 | 1772034" | 1Bgovu ie 14 480.61 4.85-0.38 6b.57-0.26 4.92-0.27 5.13-40.29 4.99-0.16 um.od/l с5Н , mmol/l | 72.15:0.56 | 950.86 75584057 68124089 | 67.7810.93 4.82-0.24 5.46v0.21 | 46940177 | 4.7740.237 4.89--0 ...

MmMOl/kg

Notes: 1.7 - the differences are statistically significant in relation to the values of the intact group, p<0.05 (according to 0- Mann-Whitney criteria); 2.77 - the differences are statistically significant in relation to the values of the control pathology, p«e0.05 (according to Mann-Whitney O-criteria);

Z. n - the number of animals in each group.

Modeling insulin resistance by administering dexamethasone caused the development of oxidative stress in rats, which was manifested by a change in enzyme activity, namely an increase in the activity of CAT by 25 95 and SOD by 47 95 in the blood, as well as a decrease in CAT activity by 21 95 and an increase in SOD by 41 95 in the liver The biological role of CAT consists in the destruction of hydrogen peroxide molecules and providing effective protection of cellular structures against their damage. The declared antidiabetic collection of medicinal plants showed the ability to reduce the activity of CAT in the blood by 18 95 and increase its activity by 19 95 in the liver. SOD acts as an acceptor of oxygen free radicals, which inhibits the peroxidation of lipids. In the group of animals that received the declared antidiabetic collection, a decrease in the activity of SOD by 34 95 in the blood and by 36 95 in the liver was observed compared to the control group (Table 5).

Administration of dexamethasone to experimental rats caused accumulation of products

SEX - the amount of MDA increased by 4395 in the blood and by 18595 in the liver. The declared antidiabetic collection of medicinal plants showed the ability to reduce the MDA content by 31 95 in the blood and not significantly in the liver. In addition, it was established that the declared antidiabetic collection of medicinal plants increased the content of (35Н) by 62 95 in the liver (Table 5).

Thus, the declared antidiabetic collection of medicinal plants has pronounced hypoglycemic properties, and also shows the ability to regulate carbohydrate tolerance disorders and reduce the manifestations of insulin resistance, as the main triggers of the development of type 2 diabetes. Thanks to the herbal composition with different groups of biologically active substances, the declared antidiabetic collection exhibits a wide range of pharmacological properties covering various mechanisms of the pathogenesis of diabetes and its complications: it improves the sensitivity of target tissues to insulin, normalizes carbohydrate and lipid metabolism, improves the state of the AOZ system, reduces processes POL. According to the studied indicators of pharmacodynamics, the declared antidiabetic collection significantly outweighs the comparison drug - the herbal collection "Arfazetin".

The tool is obtained using a simple technology, which is implemented on standard industrial equipment. There is a sufficient domestic raw material base for production.

Sources of information: 1. Atepisap Oiabeiie5 Azzosiaiop. biapdaga5 oi Meadisa! Sage ip Oiareie5z. Riareiez sage. - Mine. 43.-2020.-1212 r. 2. InTeptaiyiopai! Oiabeiez Eedegaiiop. IUE Oiabreyez Ayav. 9Ip unit. - Vhyv5ei!5, VeiIdiit. - 2019. 3. Modern phytotherapy: education. manual /S.V. Garna, I.M. Vladimirova, N.B. Burda et al. H.: "Madrid Printing House". - 2016. - 580 p. 4. Compendium 2013 - medicinal product /ed. V. RI. Kovalenko, A. P. Viktorova. - K.: Morion. - 2013. - 2270 p. 5. EES. "Soishpsii aigesiime 2010/63/EU, "E pe 2279 Berietreg 2010 op te arrgohitaiop oi Iamuv, geashinop5 apa adtipivigaime rgomiviop5 oi She tetreg v5iagez gedagaipu She rgoyesiop oi apitai5 izey god ehregitepia! apa oineg zsiepiyys ritrozev". - ONisa! hilddaii oi She Eigoreap Sottypiyev. - 2010. - R. 1-29.

Claims (1)

FORMULA OF THE INVENTION Antidiabetic collection of medicinal plants, including rosehip fruits and blueberry leaves, which is distinguished by the fact that it additionally contains nettle leaves, dandelion roots and peppermint leaves, and all components are taken in the following ratio, wt. h.: nettle leaves 1 dandelion roots 1 peppermint leaves 1 rosehip fruit 1 blueberry leaves 1.