UA121452C2 - PHARMACEUTICAL COMPOSITION OF ANTIDIABETIC ACTION IN THE FORM OF TABLETS - Google Patents

Abstract

The pharmaceutical composition of antidiabetic action in the form of tablets contains as active pharmaceutical substance plant extract and pharmaceutically acceptable excipients, as the extract use dry ginger extract, as pharmaceutically acceptable excipients use Galen IQ 721, Kollidon k30, Neusilin UFL 2, calcium stea.

Description

The invention belongs to pharmacy and medicine, in particular it relates to pharmaceutical compositions in the form of tablets for the treatment and prevention of type 2 diabetes, containing as an active pharmaceutical ingredient a substance of natural origin.

Type 2 diabetes is a metabolic disease characterized by insulin resistance and insufficient production of insulin by the pancreas and is manifested by a chronic increase in the level of glucose in the blood. Recently, type 2 diabetes mellitus has been recognized as one of the most common diseases, the complications of which affect the vision, kidneys, nervous and cardiovascular systems, and are the cause of high mortality and disability in most countries of the world.

The main means of treatment for T2DM are hypoglycemic oral drugs of synthetic origin, which with long-term use can cause serious side reactions and complications, as well as the inevitability of switching to insulin therapy.

Therefore, the development of sugar-lowering drugs based on plant raw materials is an actual area of pharmacy and medicine.

The pharmaceutical industry offers them both in the form of single-component extracts, infusions, decoctions, products of deep processing of plant raw materials, and in the form of multi-component pharmaceutical and parapharmaceutical products.

In order to reduce the absorption of carbohydrates in the gastrointestinal tract, the drug guarem is used, which contains guar resin, which is obtained from the endosperm of the seeds of Suatorzvii ieitadopoioriv - pea tree, a herbaceous plant of the legume family. When taking granules of the drug orally, guar gum, interacting with water, forms a viscous gel that significantly swells in the stomach. This helps to slow down the time of emptying the stomach, as well as reduce the absorption of carbohydrates and cholesterol in the small intestine, increase the secretion of bile acids and accelerate the metabolism of cholesterol in the liver (Compendium Op ipe: poru//rda.sotrepaiit.sot.tsa).

Bean pods contain betaine, arginine, lysine, tryptophan, tyrosine, leucine, asparagine, choline, hemicellulose (45-50 95), macro- and microelements (silicon, copper, cobalt, nickel). Their use improves carbohydrate and other types of metabolism in the body, has hypoglycemic, vasodilating, diuretic and antibacterial effects. Blueberry shoots contain

From tannins of the pyrocatechin series, flavonoids (quercetin, quercitrin, isoquercitrin, etc.), triterpene acids (ursolic, etc.), saponins, phenolic acids (hinna, chlorogenic), arbutin glycoside, hydroquinone, ascorbic acid, carotenoids. Their use, in addition to a favorable effect on the level of glycemia, has an anti-inflammatory, diuretic, choleretic, astringent effect, and stimulates the activity of PP. Bean pods and common blueberry shoots are prescribed in the form of an infusion of 1/3-1/2 cup 3 times a day, 15-30 minutes before meals (medicinal plants: Encyclopedic reference / Rep. editor. A.M. Grodzinsky. - Kyiv.: Chief Ed. URE. 1990. - 544 p.)

Of particular interest is the drug from the group of Ayurvedic remedies Diaveda - a complex herbal preparation, which includes extracts of six medicinal plants: clove jambolana (Jimnema lisova, Ssutpeta z5uimezigte), Indian azadirachta (Agadigasna ipais), momordica harantia (Chinese bitter melon, Motogaisa sNagapiya), Malabar kino (pterocarpus bag-shaped, Riegosagrie tagziriip), gunba hay (Fenugreek hay, T/idopeMya tepyt-dgaesit), Javan plum (Zuludiyt sitipi). Gymnemic acids, containing jambolan clove extract, cause a dose-dependent increase in insulin secretion by B-cells of the PZ due to the reverse increase in the concentration of calcium ions (Ca-:) in the VD-cells of the PZ, reduce the sensation of the sweet taste of many carbohydrates (glucose, fructose), as well as sweeteners (natural - stevioside, artificial - saccharin, aspartame), and certain amino acids (glycine), which with regular use can help reduce the need for sweets. This effect is reversible, and the taste is restored within two hours. Fredelin, an active component of jambolan cloves, increases the absorption of glucose by peripheral tissues in insulin resistance. Indian azadirachta leaf extract blocks the inhibitory effect of serotonin on increasing glucose-dependent insulin secretion, reduces gluconeogenesis in the liver and reduces insulin resistance. Glycosides isolated from Chinese bitter melon (momordicosides) increase the utilization of blood glucose through the activation of 5'-AMP-activating protein kinase, as a result of which the activity of the SI OT4 glucose transporter on the surface of myocytes and adipocytes increases. The components of the hayfever extract reduce insulin resistance, reduce the level of blood triglycerides (Interesting Botany: pyr:/boijapis.sot.cha/).

The main advantage of phytotherapy is that it can be used as monotherapy in combination with diet in the case of a mild course of the disease, and in combination with the main oral hypoglycemic drugs and insulin as adjunctive therapy. Such a complex approach to the treatment of T2DM helps to stabilize the course of the disease and reduce the doses of synthetic drugs, and in some cases to completely abandon them.

Phytopreparations are low-toxic and have a physiological effect on the body, unlike synthetic means. Antidiabetic medicinal plants contain a complex of biologically active substances that simultaneously affect several body systems, therefore the search for new medicinal plants that can be used in the treatment of T2DM is urgent.

Medicinal ginger is known in official medicine as a plant that exhibits analgesic, anti-inflammatory, disinfectant, anti-allergic and antioxidant effects, and can also be used in meteotropic reactions, vegetative disorders, anorexia, hypotrophy, increased fatigue and stress, and it also improves the distribution and assimilation of fats in the digestive system.

Ginger rhizomes are used to treat coughs, as an expectorant with mucolytic, anti-inflammatory, local irritant and distracting effects. In folk medicine, the plant is able to relieve headaches, heart and rheumatic pains and eliminate fatigue and apathy. According to the literature, the chemical composition of medicinal ginger contains such a phenolic compound as 6-gingerol, which restores the state of pancreatic islets "- and VD-cells of the pancreas, and due to its antioxidant effect, models insulin secretion.

In phytotherapy of T2DM, single-component medicinal products are used - common blueberry shoots and common bean leaves, as well as multi-component collections "Arfazetin" and "Sadifit".

Phytozbir "Arfazetin" is produced in filter bags, 1 g of the collection contains: common blueberry shoots - 0.2 g; common beans with fruit flaps - 0.2 g; Eleutherococcus of spiny rhizomes and roots - 0.15 g; rose hips - 0.15 g; field grass horsetail - 0.1 g; St. John's wort - 0.1 g; chamomile flowers - 0.1 g.

The medicinal effect of the collection is provided by: flavonoids and myrtilin of blueberry shoots; triterpene glycosides, robinin and rutin of bean leaves; organic acids, carotenoids, vitamins C and P in the composition of rose hips; saponins, silicic acid, flavonoids in horsetail grass; hypericin and flavonoids in St. John's wort; flavonoids, mucilage and essential oil in chamomile flowers.

Together, the components of the drug provide hypoglycemic, angioprotective and immunomodulating effects.

The "Sadifit" collection is produced in filter bags, 1 g of the collection contains: Jerusalem artichoke tubers - 0.2 g, stevia leaves - 0.2 g, blueberry shoots - 0.2 g, beans, fruit flaps - 0.2 g, green tea - 0.15 g, peppermint leaves - 0.05 g.

Despite the complex effect in the treatment of T2DM, these drugs have a dosage form that is inconvenient for the patient to use, which consists in the fact that it is necessary to prepare a decoction or infusion that has a short shelf life, which does not allow to prepare it in reserve. It was established that there are no drugs containing medicinal ginger that have a hypoglycemic effect. This indicates the urgency of developing a new herbal preparation in a convenient dosage form for the treatment of Tsde2 based on it.

The invention is based on the task of developing a pharmaceutical composition with antidiabetic action in the form of tablets, which contains a dry extract of medicinal ginger as an active pharmaceutical ingredient.

The task is solved in such a way that the pharmaceutical composition of antidiabetic action in the form of tablets contains as an active pharmaceutical substance a plant extract and pharmaceutically acceptable excipients, according to the invention, dry extract of medicinal ginger is used as an extract, Saiep IS) 721 is used as a pharmaceutically acceptable excipient, KoPidop KZO, Meiziip ORI 2, calcium stearate, with the following ratio of components (mg/cap.): dry medicinal ginger extract 278.0-444 0

Saiyep IO 721 170.0-175.0

Koidop KZO 16.25-18.75

Meizviip ORI 2 4.75-5.25 calcium stearate 4.0-5.0.

Dry extract of medicinal ginger was used as an active pharmaceutical ingredient in the development of tablets with a sugar-lowering effect, and tablets were used to ensure stability, ease of dosing and use of the oral dosage form.

The dry extract of medicinal ginger, which is included in the pharmaceutical composition, is manufactured by "Medagroprom" LLC, Dnipro. This extract is obtained by the percolation method, which is a finely dispersed, hygroscopic powder, light brown in color with its characteristic smell. Preliminary chemical studies have established that it contains 0.1153 g/g of phenolic compounds in terms of b-gingerol.

Pharmacological studies have proven the ability to stimulate metabolic processes in the body, to reduce the level of cholesterol and glucose in the blood.

In the claimed pharmaceutical composition, the amount of dry medicinal ginger extract was determined experimentally and is 278-444 mg per tablet. The optimal content of dry medicinal ginger extract is 300 mg per tablet.

The qualitative and quantitative composition of excipients was experimentally determined, which allows obtaining tablets by the direct pressing method with the necessary technological and biopharmaceutical characteristics with the following ratio of components.

Saiep 10 721 is a crystalline water-soluble sugar alcohol (isomalt), which is a filler, improves the technological properties of the extract, in particular, the density before and after shrinkage and flowability.

KoPidop KZO is a binder that allows you to obtain tablets of the required strength.

Meshviip ORI. 2 is used as a moisture regulator, and calcium stearate is a lubricant that improves the fluidity of the mass for tableting and prevents it from sticking to the press tool of the tablet machine.

The claimed pharmaceutical composition can be produced using standard equipment as follows: weigh out the required amount of dry medicinal ginger extract, Saiep I 721, KoPidop KZO, Meiziip ORI 2 and calcium stearate, mix thoroughly and tablet.

The invention is illustrated by examples:

Example 1. To obtain the claimed product in the form of tablets, 300 mg of medicinal ginger extract was weighed, 172.5 mg of Saiep IO 721, 17.5 mg of Koiydop KZO, 5 mg of Meshviip ORI2 and 5 mg of calcium stearate were added, and thoroughly mixed. The obtained homogeneous mass was tableted.

Receive tablets with the composition of components in mg per 1 tablet: dry extract of medicinal ginger 300

Saiyep IO 721 172.5

Koidop KZO 17.5

Meshzviip ORI 2 5.0 calcium stearate 5.0.

Example 2. The hypoglycemic effect of the claimed pharmaceutical composition was studied on a model of experimental diabetes mellitus (DM) type 2 caused by dexamethasone. Diabetes mellitus was modeled in 18-month-old rats weighing 220-230 g by subcutaneous administration of dexamethasone (Dexamethasone-KKKA, produced by KEKA, Slovenia), at a dose of 0.125 mg/kg for

From 13 days Rats were divided into the following experimental groups: intact control; control pathology; From the group of animals that received the declared pharmaceutical composition at a dose of 50, 80 and 100 mg/kg; 2 groups of animals, which were administered the comparative drugs "Arfazetin" at a dose of 16 ml/kg and metformin at a dose of 60 mg/kg. On the 14th day, basal glycemia and basal insulinemia were measured in the blood serum of rats, which were used to assess the hypoglycemic activity of the claimed agent.

The results of the study of the hypoglycemic effect of the pharmaceutical composition are shown in the table.

Table

Notes: " - differences are significant relative to the values of the intact control, p<0.05; 7" - differences are significant relative to the values of the control pathology, p<0.05; a - differences are significant relative to the values of the Arfazetin collection, p<0.05.

The analysis of the results of the table shows that in the rats of the control pathology group, a pronounced increase in the level of glucose by 2.6 times and an increase in the level of insulin by 1.7 times was observed, which testified to the formation of type 2 diabetes mellitus with insulin resistance in animals.

The level of glucose in the blood under the influence of the declared pharmaceutical composition at a dose of 50 mg/kg probably decreased by 1.6 times, when the dose was increased to 80 and 100 mg/kg, the hypoglycemic effect was more pronounced and prevailed over arfazetin and was not inferior to metformin. In terms of its ability to reduce insulin resistance by reducing hyperinsulinemia, the claimed pharmaceutical composition did not differ from metformin and was probably superior to arfazetin.

Thus, the claimed composition will expand the range of herbal antidiabetic drugs for the treatment of type 2 diabetes and correction of insulin-resistant states, both as monotherapy and in combination with oral hypoglycemic agents.

Claims (1)

FORMULA OF THE INVENTION A pharmaceutical composition of antidiabetic action in the form of tablets, containing as an active pharmaceutical substance a plant extract and pharmaceutically acceptable excipients, which is characterized by the fact that dry extract of medicinal ginger is used as an extract, and Saiyep I 721 is used as a pharmaceutically acceptable excipient, KoPidop KZO, Meiziip ORI 2, calcium stearate, with the following ratio of components (mg/tablet): dry extract of medicinal ginger 278.0-444 0 Saiyep IO 721 170.0-175.0 Koidop KZO 16.25-18.75 Meizviip ORI 2 4.75-5.25 calcium stearate 4.0-5.0.