RU2625737C2 - Effervescent phytomineral complex with antidiabetic action - Google Patents

Abstract

FIELD: pharmacology.

SUBSTANCE: effervescent phytomineral complex with antidiabetic action, containing an extract of forest dry gurmar, calcium carbonate, sodium chloride, potassium iodide, potassium bromide, anhydrous sodium sulfate, anhydrous magnesium sulfate, anhydrous citric acid, sodium hydrogen carbonate, trilon-B, medium molecular polyvinylpyrrolidone, polyethylene glycol with a molar mass of 6000, MAE 100P kolliecoat. The complex contains acidic and carbonate fractions obtained by separate granulation, where the acid fraction includes an extract of forest dry gurmar, citric acid, sodium chloride, potassium chloride, anhydrous sodium sulfate, anhydrous magnesium sulfate, and the carbonate fraction includes sodium bicarbonate, calcium carbonate, potassium iodide and potassium bromide. At the stage of carbonate fraction formation, prior to granulation, trilon-B, medium molecular polyvinylpyrrolidone are added to the carbonate fraction, after carbonate fraction granulation, polyethylene glycol 6000 is added to it, and MAE 100P kolliecoat is added to the composition of the acid fraction for granulation. The complex contains components at a certain ratio.

EFFECT: complex has improved adsorption, has a predictable and stable pharmacokinetic profile, transport time in the small intestine is reduced to 20 minutes.

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Description

The invention relates to medicine, namely to pharmaceuticals and the food industry, for the prevention of diseases of the endocrine and gastroenteropancreatic systems.

It is known that the primary prophylactic effect of mineral waters is mediated by the emerging urgent and long-term adaptation reactions in hormonal systems of various levels of regulation - the pituitary-adrenal, thyroid, gastroenteropancreatic and endocrine systems [1, 2, 3].

Recently, various phyto-additives containing flavonoids, tannins, anthracene derivatives, essential oils, and others have been used to enhance and direct the pharmacological action of mineral waters [1, 4]. This area is called balneophytotherapy. In addition to its use in gastroenterological practice, the Esentuki type mineral waters are successfully used in the treatment of diabetic complications, in particular diabetic gastroparesis and gastroenterological manifestations of autonomous diabetic neuropathy [5, 6].

One of the directions in the development of new approaches to the treatment of type 2 diabetes is the creation of drugs based on incretinomimetic action, i.e. possessing properties aimed at restoring the natural physiological mechanisms of glucose level regulation [7]. In recent years, there has been a steady trend of increasing interest of doctors in the use of herbal remedies. Therefore, studies are being conducted to verify the sugar-lowering effect of various medicinal plants used in domestic and foreign traditional medicine for this category of patients. Therapy with herbal preparations for diabetes mellitus is auxiliary and is used as an addition to the main treatment complex, since in addition to the sugar-lowering effect, some herbal agents can help restore damaged pancreatic cells [8].

A well-known vitamin-mineral complex [9], in which the distribution of micronutrients in time and place of their absorption is implemented within the same preparative form, which is made in the form of a tablet or capsule containing several independent elements - pellet. At the same time, pellets have their own dissolution time, depending on the acidity of the environment. When the finished form moves along the gastrointestinal tract, the time of the beginning of the release of substances from one pellet follows the time of the end of the release of substances from the other pellet so that at the same time there are no active substances in the solution that have an antagonistic interaction. Negatively interacting during the assimilation, storage or production of vitamins and minerals are included in different forms. The administration of individual formulations is timed so as to exclude mixing of the components of each of them.

However, regular intake of such a vitamin-mineral complex is necessary, which is not always convenient; the effectiveness of the preventive properties of the known composition is relatively low, and the costs of preparing the air and equipping the premises for granulation with locks and sealing systems in low humidity are quite high.

The task is to create an effective phytomineral complex convenient for use, which has prophylactic and therapeutic properties, and to reduce the cost of its manufacture.

The task is achieved by the composition of an effervescent phytomineral complex containing components: calcium carbonate, sodium chloride, potassium iodide, sodium sulfate anhydrous, magnesium sulfate anhydrous, anhydrous citric acid, sodium bicarbonate, Trilon-B, dry extract of forest anthem, potassium bromide, potassium chloride, binders and release agents polyvinylpyrrolidone, polyethylene glycol with a molar mass of 6000 and a collicut MAE 100P.

The composition of the phytomineral complex with antidiabetic action includes mineral, plant and auxiliary components.

The composition of the mineral components is selected similarly to the composition of natural mineral waters, based on stoichiometric calculations, and includes:

- Sodium bicarbonate;

- Calcium carbonate;

- Potassium bromide;

- Potassium iodide;

- Sodium chloride;

- Potassium chloride;

- Sodium sulfate anhydrous;

- Magnesium sulfate anhydrous.

- A plant component in the form of a dry extract of forest anthem, which has an incretin-mimetic effect.

Forest anthem has been known in Indian folk medicine for over 2 thousand years. It is this plant that has an incretin-mimetic effect and is the most promising for the treatment and prevention of diabetes [8, 10, 11, 12, 13, 14, 15, 16, 17].

Auxiliary components provide the technological cycle of obtaining the phytomineral complex:

- Anhydrous citric acid;

- Trilon-B;

- Polyvinylpyrrolidone;

- Polyethylene glycol (PEG) with a molar mass of 6000;

- KollikutMAE 100R.

Anhydrous citric acid in an amount of 15-30 wt. % serves as a component of the gas-forming mixture in the interaction with sodium bicarbonate, partially neutralizing the composition.

Polyvinylpyrrolidone with a molar mass of 25 to 55 thousand is used as a binder component for the carbonate fraction in the form of a 20% solution in alcohol; it also in the composition with PEG improves the solubility of the phytocomplex in water due to the solubilizing effect.

Polyethylene glycol with a molar mass of 6000 serves simultaneously as an antifoam, component, and also as a release agent for tabletting.

The collicut MAE 100P is introduced into the composition of the acid fraction in an amount of 0.1-0.5% in the form of a 10% alcohol solution, which forms an insoluble film when interacting with acids, which prevents the reaction of fractions in an anhydrous medium. When the composition is dissolved in water, the alkaline components prevailing in the composition dissolve this film.

The quantitative composition of the effervescent phytomineral complex with antidiabetic action is presented in table 1.

The effervescent phytomineral complex granules are obtained by the method of separate granulation in conditions of low humidity, which allows you to include hygroscopic components, including dry plant extracts, in the effervescent form. The essence of the method is the separate granulation of the acid and carbonate fractions to prevent premature reaction of the mixture. In order to maintain the acid-base balance and stability of the components of the mixture, neutral or acid-stable salts, including anhydrous ones, are included in the acid fraction, and alkali-resistant ones are included in the carbonate fraction.

The acid fraction includes dry forest anthem extract, citric acid, sodium chloride, potassium chloride, sodium sulfate anhydrous and magnesium sulfate anhydrous. The carbonate fraction contains sodium bicarbonate, calcium carbonate, potassium iodide and potassium bromide. At the stage of formation of the carbonate fraction, before granulation, trilon-B, which is a complexing agent, is added to the composition, improves dissolution and increases stability. Medium molecular weight polyvinylpyrrolidone is used as a binder in the preparation of the granulate of the carbonate fraction, which is added to the components of the fraction in the form of a 20% alcohol solution, granulated through a stainless steel mesh sieve with a hole size of 2.5 mm, and dried in an oven at a temperature not exceeding 50 ° C to a residual moisture content of not more than 2%. Then add polyethylene glycol with a molar mass of 6000, which is a defoamer, as well as a release agent for tabletting.

For granulation of the acid fraction, a 10% alcohol solution of a copolymer of methacrylic acid and ethyl acrylate (collicut MAE 100P) is used.

After drying, each granulate is again wiped through a stainless steel sieve with a hole diameter of 1.5 mm. Both granules are mixed, thereby obtaining granules of the phytomineral complex.

The granules thus obtained are packed in sealed, moisture-proof sachets or subjected to a tabletting process to produce effervescent tablets with a diameter of 20 mm. Pack them in plastic pencil cases.

The inhibitory effect of hymnema extract in combination with the mineral composition of salts is that under the influence of hymnemic acids, Na ⁺ -K ⁺ -ATPase is blocked, which is one of the features of the mechanism of antidiabetic activity of the proposed effervescent phytomineral complex.

The effervescent form of the developed phytomineral complex has several advantages over traditional forms [9]:

1) ease of administration and increased compliance does not require ingestion of solid components;

2) improved absorption;

3) the active substance enters the stomach in an aqueous buffer, which prevents its degradation and inactivation under the influence of the acidic environment of the stomach;

4) the presence of an aqueous buffer reduces the transport time of the drug into the small intestine up to 20 minutes (more favorable conditions for the absorption of the active substance);

5) a decrease in the irritating effect on the gastrointestinal tract due to less local contact;

6) a more predictable and stable pharmacokinetic profile.

Information sources

1. Arnold A.P. To the question of the effect of the mineral water of the resort "Lake Shira" on bile secretion and bile formation / A.P. Arnold // Issues of resort climatology, climatotherapy and the study of mineral waters of Siberia. - Tomsk, 1971. - S. 108-112.

2. Polushina N.D. Hormonal mechanisms of the primary prevention of gastroduodenal ulcers under the action of drinking mineral waters: Abstract. dis. ... doctors honey. sciences. - Pyatigorsk, 1993 .-- 36 p.

3. Gloria, Y. Systematic Review of Herbs and Dietary Supplements for Glycemic Control in Diabetes / Y. Yeh Gloria, M. David Eisenberg, Ted J. Kaptchuk [et al.] // Diabetes Care 26: 1277-1294, 2003 by the American Diabetes Association, Inc.

4. Kozhevnikov S.A. The combined use of rutin and mineral water "Essentuki N 17" to increase the resistance of the gastric mucosa: abstract. dis. ... cand. farm. sciences. - Pyatigorsk, 1998.20 s.

5. Botvineva L.A. A method for the prevention of the progression of microangiopathies in patients with diabetes mellitus: patent for an invention of the Russian Federation / L.A. Botvineva, G.M. Krashenitsa, G.M. Cherevashchenko [et al.], 2004. - Application No. 2002121177/14. - Patent No. RU (11) 2222312 (13) C1.

6. Deryabin V.M. The mechanisms of the physiological and therapeutic action of mineral waters // Medical mineral waters. - Pyatigorsk, 1971.- S. 69-98.

7. Antsiferov M.B. New approaches to the treatment of type 2 diabetes mellitus: glucagon-like peptide-1 and exenatide (Baeta) / M.B. Antsiferov, L.G. Dorofeeva // Farmateka, No. 11 (145), 2007. - 6 p.

8. Persaud, S.J. Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability / S.J. Persaud, H. Al-Majed, A. Raman [et al.] // J Endocrinol. 1999; 163: 207-212.

9. Optimized vitamin-mineral complex: patent for the invention of the Russian Federation No. 2423108 / patent holders M.I. Lazarev, R.Kh. Enileev, 2010.

10. Sorokina E.V. Antidiabetic activity of dry extract of forest anthem: abstract. dis. ... cand. biol. Sciences: 14.00.25 / EV Sorokina. Volgograd, 2008 .-- 24 p.

11. Ankit, Saneja. Gymnema Sylvestre (Gurmar): A Review / Ankit Saneja, Chetan Sharma, K.R. Aneja, Rakesh Pahwa // Der Pharmacia Lettre, 2010: 2 (1) 275-284.

12. Negi, J.S. Effect of bioadhesion on initial in vitro buoyancy of effervescent floating matrix tablets of ciprofloxacin HCL / J.S. Negi, A. Trivedi [et al.] // J Adv Pharm Technol Res 2 (2). - 2009. - c. 121-127.

13. Okabayashi, Y. Effect of Gymnema sylvestre, R. Br, on glucose homeostasis in rats. / Y. Okabayashi, S. Tani, T. Fujisawa [et al.] // Diabetes Res Clin Pract 1990; 9: 143-8.

14. Shanmugasundaram, ERB. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. / Erb. Shanmugasundaram, G. Rajeswari, K. Baskaran, Kumar B.R. Rajesh [et al.] // J Ethnopharmacol. 1990; 30: 281-294.

15. Sugihara, Y. Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema sylvestre leaves in streptozotocin-diabetic mice. / Y. Sugihara, H. Nojima, H. Matsuda [etal.] // J Asian Nat Prod Res, 2000; 2: 321-7.

16. Thakur, G. Gymnema sylvestre: An Alternative Therapeutic Agent for Management of Diabetes / Gulab S. Thakur, Rohit Sharma, Bhagwan S. Sanodiya [et al.] // Journal of Applied Pharmaceutical Science 2 (12); 2012: 001-006.

17. Terasawa, H. Effects of long-term administration of Gymnema sylvestre watery-extract on variations of body weight, plasma glucose, serum triglyceride, total cholesterol and insulin in Wistar fatty rats. / H. Terasawa, M. Miyoshi, T. Imoto // Yonago Acta Med 1994; 37: 117-127.

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Claims (2)

Effervescent phytomineral complex with antidiabetic effect, containing dry forest anthem, calcium carbonate, sodium chloride, potassium iodide, potassium bromide, sodium sulfate anhydrous, magnesium sulfate anhydrous, citric acid anhydrous, sodium bicarbonate, trilon-B, polyvinylpyrrolidone medium molecular weight polyethylene, polyethylene weighing 6000, collicut MAE 100P, while the complex contains acid and carbonate fractions obtained by separate granulation, where the acid fraction contains an extract of forest hymna Khoy, citric acid, sodium chloride, potassium chloride, anhydrous sodium sulfate, anhydrous magnesium sulfate, and the carbonate fraction includes sodium bicarbonate, calcium carbonate, potassium iodide and potassium bromide, and at the stage of formation of the carbonate fraction, before granulation, the composition trilon-B is added to the carbonate fraction, medium molecular weight polyvinylpyrrolidone, after granulation of the carbonate fraction, polyethylene glycol 6000 is added to it, and the MAE 100P collicut is added to the granulation acid composition, while the complex C contains components in the following ratio of components, in wt.%: Dry forest anthem extract 0.5-1.5 Sodium bicarbonate 45.0-60.0 Calcium carbonate 0.1-4.0 Potassium bromide 0.01-0.05 Potassium iodide 0.001-0.01 Trilon-B 0.5-1.0 Anhydrous Citric Acid 15.0-30.0 Sodium chloride 0.1-12.0 Potassium chloride 0.1-1.0 Sodium Sulfate Anhydrous 1,5-8,0 Magnesium sulfate anhydrous 0.1-1.5 Polyvinylpyrrolidone with a molar mass of 25 to 55 thousand 0.5-2.0 Polyethylene glycol with a molar mass of 6000 2.5-4.0 Collicut MAE 100P 0.1-0.5