Composition possessing multicomponent mechanism of antidiabetic effect

FIELD: medicine, endocrinology, pharmaceutical industry.

SUBSTANCE: invention relates to composition possessing the pathogenetic antidiabetic effect that comprises dry aqueous extracts of forest gymnema, tall elecampane and grape bunches taken in the definite ratio. The composition show effective action on all pathogenetic links of insulin-dependent diabetes mellitus: it normalizes blood carbohydrates level in prediabetic period, normalizes carbohydrate metabolism in diabetes mellitus of II type based on regeneration of β-cells in pancreas islet producing insulin, normalizes autoimmune responses in diabetes mellitus of II type and normalizes metabolism in diabetes mellitus based on antioxidants and trace elements. Invention is used in treatment and prophylaxis of diabetes mellitus.

EFFECT: valuable medicinal properties of composition.

6 cl

 

The invention relates to the creation of drugs that normalize carbohydrate metabolism and providing pathogenetic treatment-and-prophylactic action in the pre-diabetic period and diabetes type II.

It is known that the development of type II diabetes is caused by insulinrezistentnost dysfunction β-cells of the pancreas (Balabolkin M.I. Endocrinology M, 1998; Dedov I.I., diabetes mellitus, No. 1, 1998). The ratio of these two components of the pathogenesis of non-insulin-dependent diabetes is different in specific populations and specific patients one population. Therefore tactically correct and clinically justified should recognize the use of drugs, directionally affect different pathogenetic link non-insulin-dependent diabetes mellitus. But despite the fact that in medical practice, there are drugs that allow this kind of correction that is similar to the tactics of treatment of non-insulin dependent diabetes mellitus is currently not acceptable. On the one hand, this is due to a disability diagnosis, on the other - dependent changes in the ratio of components of pathogenesis in different periods of the disease. As a rule, it is not possible to determine which of the two defects in the development of the disease (insulinrezistentnost or dysfunction β-cleto is) is primary. To draw a clear boundary between them is quite difficult, because in different periods of the disease causal relationships between the components of the pathogenesis of the disease changed.

Also used in clinical practice as monotherapy drugs, mainly with peripheral or Central mechanism of action, often do not provide compensation of diabetes and improvement of metabolic control comes only with the combined use of medicines these groups, which, apparently, caused by the synergy of their actions. In current clinical practice, the drugs of choice are antidiabetic agents, while providing impact on all pathogenetic links of non-insulin-dependent diabetes mellitus.

Moreover, for most modern synthetic drugs is characterised by a large number of adverse effects that degrade quality of life of patients, and in some cases lead to irreversible consequences for the health of the patient (Dedov I.I., 1998; Bailey C.J. Potential new treatments for type diabetes. // Diabetologia. - Vol.43. No. 21, P.259-265., 2000).

Undoubtedly, all these factors make clear the need for new safe antidiabetic drugs, providing prevention and treatment of complications due to specificheskogo the impact on the pathogenic components of the disease, that will ensure maximum compensation of diabetes taking into account the individual characteristics of each patient. In addition, at present there are practically no polyfunctional drugs having therapeutic activity in pre-diabetic States and in the early stages of developing diabetes. In clinical practice it is used only compensation of carbohydrate metabolism diet, the purpose of physical therapy and therapeutic exercises.

The present invention is to provide a composition, possessing a multicomponent mechanism of antidiabetic action aimed at the prevention of complications of diabetes and is non-toxic, which determines the safety of long-term or even lifetime use of the drug. One of the promising directions in this situation is the creation of highly effective drugs based on natural raw materials, which allows to minimize the occurrence of side effects in patients and creates opportunities for long-term, secure compensation for violations of hydrocarbon metabolism.

The problem is solved as follows.

The proposed composition with pathogenic anti-diabetic action. The composition comprises a dry aqueous extracts of Gymnema forest, virgins is power and high ridges of grapes in a ratio of 8:10:4, 10:6,3:2,2.

The composition may be used for the normalization of carbohydrate blood in the pre-diabetic period.

The composition may be used for the normalization of carbohydrate metabolism in diabetes type II by regenerating producer of insulin β-cells of islet apparatus of the pancreas.

The composition may be used for the normalization of autoimmunity in diabetes type II.

The composition may be used for the normalization of metabolism in diabetes due to the antioxidants and trace elements.

The composition may be used for the production of biologically active additives or medicines in the form of tablets, granules, powder, capsules.

To implement this purpose, an attempt was made to create a composition which would have a multicomponent mechanism of antidiabetic action. Previously was a thorough literary analysis of prospective inclusion in the composition of components with the following types of biological activities:

1. Means of influencing the specific mechanisms of carbohydrate metabolism - the extract of Gymnema forest;

2. Means for preventing the development of complications of diabetes: an extract of Valerian extract, white grape;

Thus, the extract of the leaves of Gymnema forest is Sperimentale revealed an inhibitory effect on glucose absorption in the small intestine and increase glucose utilization (Shanmugasundaram K.R. et al. The Insulinotropic activity of Gymnema sylvestre. // Pharmacol Res Commun. 1981; 13: PAPS-486, Y. Okabayashi et al. Effect of Gymnema sylvestre. // Diabetes Res din Pract, 1990; 9: P.143-148).

Then also installed the influence of Gymnema forest on absorption of oligosaccharides and fatty acids in the intestine (Wang LF. et al. Inhibitory effect of gymnemic acid on intestinal absorption of oleic acid in rats. // Can J Physiol Pharmacol, 1998; 76: P.1017-1023).

Antidiabetes properties found in extract of Valerian, which had a pronounced inhibitory effect on the production of cytokines in immunogenicity form of diabetes (Y. Okabayashi et al. Effect of Gymnema sylvestre. // Diabetes Res din Pract, 1990; 9: P.143-148.

In earlier studies of the pharmacological properties of the composition based on the crests of grapes (bioflavonoids), was identified antioxidant and radical scavenging activity in a wide range of models in vitro (Spasov AA, and others report on the study of antidiabetic activity of the composition based on an extract of Gymnema forest 2003, P.95-100).

The inclusion of this component in hypoglycemic therapy may lead to a marked reduction in the incidence of severe complications of diabetes.

The proposed composition is created by mixing dry extracts in a standard mixer with the addition of minor components (starch and so on)required to obtain dosage forms and to improve the operation of the dispenser in the production of capsules.

One is concern for biologically active additives in absolute terms were: dry aqueous extract of Gymnema forest 80 mg, dry aqueous extract of elecampane 100 mg, ridges grapes 40 mg Single dose for medicines in absolute terms were: dry aqueous extract of Gymnema forest 460 mg, dry aqueous extract of elecampane 290 mg, ridges grape 100 mg

Studied the hypoglycemic properties of the composition upon oral administration of five doses in the blood of intact rats in comparison with maynila. The effect of the composition upon oral administration to the level of glucose in the blood of rats with streptozotocin diabetes in comparison with maynila.

Studied the hypoglycemic activity of the composition on the model of the sugar load in rats (scheme sugar load - standard outlined in the report). The influence of composition upon oral administration the absorption of maltose in the intestine intact rats compared with acarbose.

Studied the hypoglycemic activity of the composition, on the model of prediabetes:

Alimentary obesity

The latent form of diabetes

Exogenous hyperinsulinemia.

Investigated the preventive effect of biologically active compositions in oral application on the development of experimental immunosensing diabetes.

The influence of biologically active compositions in oral application on the morphology of the pancreas.

Studied the antioxidant properties of biologically active composition.

The influence of biologically active composition on the rheological properties of blood.

Performed study of acute toxicity multicomponent biologically active composition in rats (males and females) with the introduction of per os.

We studied the allergenicity of biologically active compositions. Based on the results of experimental studies of the composition in rats when administered orally, it follows that this drug can be attributed to non-toxic substances (LD 50>5 g/kg), providing a strong hypoglycemic effect, both in terms of norms and diabetes. Despite the fact that in healthy animals, the composition is inferior in activity to the Comparators to Mannila and gliclazide, on the model of streptozotocin diabetes demonstrates the effect comparable to the activity of synthetic drugs. It should be note that the largest ED (effective dose, which causes reduced blood sugar by 20%, for example, a multicomponent composition for the BAD is 100,31 mg/kg) identified in models of diabetes, the composition is significantly greater than the activity known hypoglycemic agents of plant origin. So, hypoglycemic dose of the extract of the root of Alpinia galanga, is at the level of more than 3 grams per kg of body weight of the animal (M.S. Akhtar et al. Hypoglicaemic activity ofAlpinia galanga a rhizome and its extracts in rabbits // Fitoterapia - 2002. - Vol.73, No. 1-2. - P.623-628).

Moreover, it was shown multicomponental impact of natural compositions on various aspects of carbohydrate metabolism. Thus, in the intravenous test glucose tolerance was clearly illustrates the increase in the rate of glucose utilization by peripheral tissues that may be associated with increased insulin secretion and increased glucose utilization by peripheral tissues. Furthermore, in rats with streptozotocin diabetes, the composition when administered orally resulted in normalization of the disturbed glucose utilization in peripheral tissues. In terms of the magnitude of the effect of the composition was comparable with maynila (increase criterion glucose utilization by tissues composition - 68,45% (p<0,01), Mannila - 73,63% (p<0,01)).

It was found that the investigated composition improved utilization of glucose in peripheral tissues in animals with experimental syndrome of insulin resistance (model of obesity rats). Because this state is accompanied by an increased content of insulin in the body, it is primarily a normalizing effect of drugs on glucose utilization in peripheral tissues can be associated with improved insulin sensitivity.

In the literature there is some disagreement regarding the pathogenetic mechanisms of insulin resistance in Osiris the farm animals. Mainly discussed issues about the role of insulin receptors in this process (their number, nature and extent of binding to the hormone). Most authors are of the opinion that the basis of insulin resistance in these animals is decreasing sensitivity to insulin transport systems and to a lesser extent of intracellular glucose metabolism. It is believed that the hyperinsulinemia of any etiology, as when excess insulin in vitro, significantly reduced the number of receptors in adipose tissue, liver, lymphocytes and muscles. No less intense effects were installed on models of oral carbohydrate load. The introduction of the composition resulted in a significant decrease in the rate and intensity of absorption of glucose from the intestines. When this was revealed almost equal effect on glucose absorption as in normal rats and in animals with diabetes. Maninil did not exert any influence on the processes of absorption of glucose. The proposed composition by oral administration resulted in a significant reduction of the absorption of maltose in the gut. When this composition is practically not inferior in activity drug comparison - acarbose. Apparently, these effects may be related to the ability of glucose-lowering drugs to slow the metabolism of disaccharides and absorption of gluco what s in the gut.

Taking into account all the above, the presumed mechanism of antidiabetic action of the composition is as follows: glucose-lowering effect of the drug is due to its Central and peripheral effects. Pancreatine effect on the pancreatic islets, probably due to the stimulation of insulin secretion and restoring the physiological profile of hormone secretion. Extrapancreatic action appears to be associated with normalization processes insulinretseptorny interaction and decrease the absorption of carbohydrates in the intestine. The results of studies on rats with impaired glucose tolerance has also identified the prospects for further study composition. So, it is known that when the concentration of glucose within the physiological norm of the transportation system is operating normally, with increased content of carbohydrates in animals with obesity glucose transporters do not fulfill their functions. Apparently, the composition in such cases improves the functioning of transport systems. Antihyperglycemic effect in rats with experimental insulin resistance syndrome confirms the presence of the composition in addition to pancreatology actions that cannot be implemented in this experimental model, extrapancreatic efficiency is tov on the receptor or postreceptor levels.

The obtained data to determine the prospects for further development based on the composition of the finished medicinal product used for the treatment of pre-diabetic conditions and early stages of diabetes. In addition, the composition exhibits antihyperglycemics action, probably by influencing the dynamics of insulin secretion. Improved glucose utilization to model latent streptozotocin diabetes, most likely, testifies to the restoration of first phase insulin secretion. Restoring the physiological profile of insulin secretion under the influence of antidiabetic drugs serves as a reliable basis for effective glycemic control and prevention of distant vascular complications, as this prevents excessive release of the hormone and decreases the resistance of peripheral tissues to insulin. The composition with the course introduction to healthy animals leads to an increase in functional activity of islet apparatus of the pancreas, which in turn determines the gain of hypoglycemic activity of the composition during the course introduction. In addition, the compositions in exchange receive identified the presence of treatment-and-prophylactic effect of composition on the course of alloxan diabetes in rats. However, changes to the islet apparatus of pagelogo the second cancer was characterized by statistically significant differences in percentage β cells to all cells of the insular apparatus as in the experimental group and control groups, however, regeneration was more intense in the group of rats treated with the composition, which is determined by the nature of the changes in the content of glucose in blood plasma.

Antidiabetic effects of the composition are shown and in exchange prophylactic introduction there is a reduction in the severity of hyperglycemia, polydipsia, loss of body weight and the change in the morphological structure of the pancreas in rats with immunogenicity diabetes. Thus, the obtained data to determine the prospects of taking a course composition for the prevention and treatment of diabetes. The song has a strong antioxidant and radical scavenging activity in a wide range of models in vitro. So, on the model askarruttavista FLOOR proved its antioxidant properties and it is shown that the use of complex substances has the highest activity compared to the individual components.

Based on the results of experimental studies indicate that the composition has an antioxidant effect in rats with streptozotocin diabetes, mainly reducing the formation of the final product FLOOR - malondialdehyde in the liver and slightly red eye reduction the I key indicators hemilaminectomy plasma and tissue homogenates. Given the information about the activation processes of peroxidation in diabetes accumulated to date, and that the basis of the composition is a natural balanced composition with the inclusion of plant flavonoids, we can assume its effectiveness as a potential means to improve the quality of life of patients with diabetes mellitus. When studying the hemorheological effects of composition on the model of streptozotocin diabetes in rats noted a marked hypoglycemic effect of the composition in the blood of rats with streptozotocin diabetes during the course of administration of the drug, accompanied by the improvement of the General condition of the animals. Composition and Tanakan in exchange introduction led to a decrease in blood viscosity over the entire range of shear rates in rats. Thus, the studied drugs have an impact on the aggregation and deformation components of the rheological properties of red blood cells. This is confirmed by the positive changes recorded filtration methods and viscosity of erythrocyte suspensions. In the result, it was found that the greatest effect the composition has on the viscosity of the membrane and the cell geometry of the cells, determining the degree of erythrocyte deformability. When this composition was much higher than ffecti the comparison drug for this type of activity. An important contribution to reducing the intensity of the processes of aggregation of erythrocytes in diabetes contributes and installed the influence of composition on the value of the electronegativity of erythrocyte membranes. In addition, the composition with the course introduction leads to normalization of hyperaggregation platelets and hypercoagulation status detected diabetes in rats.

The advantages of the composition in relation to synthetic drugs are:

low toxicity composition is an opportunity of lifetime use of antidiabetics;

the influence of the composition immediately on all parts of the disturbed carbohydrate homeostasis - both Central and peripheral, which ensures the stability of therapeutic and prophylactic effects while taking the drug;

the composition with the course introduction leads to weight loss that can be used for normalization of the weight in obese persons.

The composition has a preventive effect on the development of immunosensing of diabetes that can be used in the clinic to delay the progression of this form of the disease in patients. The composition improves hemorheological properties and antioxidant status of the organism, thereby preventing the development of side effects and complications of diabetes that contributes to the improvement to the quality of life of patients.

In addition to the hypoglycemic effect the composition has a modulating and protective properties due to the presence of trace elements and antioxidants in its composition, which is especially important for the regulation of disturbed metabolism in diabetes mellitus.

Based on these data we can assume the perspective of the development of antidiabetic agents based on natural composition having severe hypoglycemic, antioxidant and hemorheological properties for use in clinical practice for the following purposes:

- patients with metabolic syndrome;

- prevention of the consequences of the unbalanced nutrition (fast-food);

- persons with overweight (BMI>24,9 kg/m2);

- in individuals with impaired glucose tolerance and the syndrome of insulin resistance;

- patients with diabetes for the prevention of micro - and macrocirculatory complications of the disease;

- prevention of dyscirculatory and diabetic encephalopathy;

for the correction of lipid and mineral metabolism in patients with diabetes mellitus.

1. Composition with pathogenic anti-diabetic effect, characterized in that it contains dried aqueous extracts of Gymnema forest, elecampane and crests of grapes in a ratio of 8:10:4 to 10:6, 3:2,2.

2. the song according to claim 1, can be used for normalization of carbohydrate blood in the pre-diabetic period.

3. The composition according to claim 1, can be used for normalization of carbohydrate metabolism in diabetes type II by regenerating producer of insulin β-cells of islet apparatus of the pancreas.

4. The composition according to claim 1, can be used for normalization of autoimmunity in diabetes type II.

5. The composition according to claim 1, can be used for normalization of metabolism in diabetes due to the antioxidants and trace elements.

6. The composition according to claim 1, can be used for the production of dietary supplements or medicines.



 

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EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

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16 cl, 2 tbl, 185 ex

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12 ex, 1 tbl

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EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

19 cl, 21 tbl, 54 ex

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EFFECT: valuable medicinal properties of derivatives.

14 cl, 2 tbl, 56 ex

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EFFECT: valuable medicinal properties of compounds.

20 cl, 6 tbl, 113 ex

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EFFECT: composition with increased glibenclamide bioavailability.

68 cl, 3 ex, 7 tbl, 3 dwg

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EFFECT: improved effective agent for treatment and prophylaxis of sheep gastrointestinal tract helminthoses.

FIELD: medicine, immunology.

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EFFECT: improved method of prophylaxis and treatment.

38 cl, 2 tbl, 9 dwg, 6 ex

FIELD: veterinary.

SUBSTANCE: claimed method includes administration of mixture of succinic and ascorbic acid in ratio of 1:1 in dose of 0.5-1.5 g/head/day per os for 20-25 days before calving and 20-25 days after calving.

EFFECT: method and agent for effective immunocorrection in cows.

2 cl, 4 tbl, 2 ex

FIELD: veterinary.

SUBSTANCE: claimed method includes administration of mixture of succinic and ascorbic acid in ratio of 1:1 in dose of 0.5-1.5 g/head/day per os for 20-25 days before calving and 20-25 days after calving.

EFFECT: method and agent for effective immunocorrection in cows.

2 cl, 4 tbl, 2 ex

FIELD: medicine, dermatology.

SUBSTANCE: method involves carrying out the complex therapy by using antibiotic griseofulvin and the immune modulating preparation "Anaferon" for children orally in the dose 1 tablet, 3 times per a day for 14 days. Method provides effectiveness of treatment based on the immune stimulating effect involving activation of cellular immune response for trichophyton antigens and inactivation processes of fungus-pathogen by cell phagocytes and the absence of transformation of infiltrative forms of disease to the suppurative form. Invention can be used in treatment of zooanthroponosis trichophytosis in children.

EFFECT: improved method of treatment, enhanced effectiveness.

6 tbl, 2 ex

FIELD: medicine, infectious diseases.

SUBSTANCE: method involves carrying out the conventional antibacterial, pathogenetic and symptomatic therapy of acute tick borreliosis (ATB) in standard doses. Since the first day of treatment the preparation "yantar antitoks" is prescribed orally in the dose 1 tablet, 2-3 times per 24 h after eating for 25-30 days; before 5-7 days from onset of anthelmintic therapy the preparation "allohol" is prescribed in the dose 1 tablet, 2-3 times per 2 4 h and the preparation No-Spa in the dose 0.04-0.08g, 2-3 times per 24 h; biltricid is prescribed in the first day after termination of antibacterial therapy of ATB in the dose 60 mg/kg of body mass for 3 intakes with break for 4 h for 24 h and 15 after eating. Invention promotes to prophylaxis of borrelia persistence and opisthorchia, reducing intoxication syndrome for the shortest period and decreasing adverse effects of antibacterial therapy. Invention can be used in treatment of ATB on background of chronic opisthorchosis.

EFFECT: improved and enhanced method of treatment.

8 tbl, 4 ex

FIELD: medicine; phthisiology.

SUBSTANCE: method is based upon course of electric-vibration acupressure by means of massaging unit. Massage is applied to skin covers around surface of thorax, including biologically active points above area of projection of main and proximal bronchus. Covers are subject to influence at frequency of 35-40 Hz and with amplitude of 0,5-0,7 mm. Procedure is complete daily, its duration changes from 3 to 15 minutes during 12-14 days. As chemical preparations, isoniazid in amount of 0,3 g, rhyphampicine of 0,6 g and ethambutol of 1,2 g are introduced.

EFFECT: improved reflex stimulation of vegetative nervous system; improved secretion of bronchial glands.

1 ex, 2 tbl

FIELD: medicine; physiotherapy.

SUBSTANCE: two to here days after surgical operation, vibration massage is made by means of vibration apparatus on thorax area of root of lung being opposite to that one which was subject to operation. Vibration massage is made daily at frequency of 90-100 Hz and amplitude of 0,4-0,5 mm during 3-5 minutes for 13-14 days. Starting from the fourth f the fifth day after operation, when both drainages are removed from post-resection pleural cavity, electric-vibration acupressure is made in parallel on skin covers all around total area of thorax by means of massaging device. Vibration-acupressure is made daily at the second part of day after I-II row chemical preparations are given to patient. Frequency of procedure is 35-40 Hz and amplitude 0,5-0,6 mm. Duration of influence is increased gradually from 3 to 13-14 minutes during 11-12 days.

EFFECT: reduced number of pleural-pulmonary complications; uniform ventilation of all parts of segments of lung subjected to operation.

2 ex, 3 tbl

FIELD: medicine, oncology.

SUBSTANCE: in patients with prognostically unfavorable laryngeal and pharyngeal cancer therapy should be started with carrying out chemotherapy with preparations that enhance radiation action. Local hyperthermia should be conducted twice weekly at the background of radiation therapy. Moreover, during hyperthermal days a single focal dosage corresponds to 4 Gy - 2 Gyx2 at 4-h-long interval. The innovation enables to increase efficiency in treating patients with cerebral and cervical squamous cell cancer stage III-IV, improve viability values in this category of patients, decrease toxicity and improve therapeutic results at acceptable increase of topical radiation alterations and hematological toxicity.

EFFECT: higher efficiency of therapy.

1 ex

FIELD: otolaryngology.

SUBSTANCE: invention is intended to treat pseudoallergic rhinosinusopathy against a background of parasitic invasion of hepatobiliary system. Elimination of parasites is effected simultaneously with administration of hepatoprotectors and all-purpose membrane stabilizers until clinical is achieved, while cryoconchotomy is performed not later than elimination of parasites is ended.

EFFECT: achieved complete restoration of nasal respiration, reduced incidence of parasitic malady recurrences, and reliably eliminated symptoms of rhinosinusopathy owing to combination of cryoconchotomy and purposive action on hepatobiliary system.

5 cl, 2 ex

FIELD: agriculture, in particular sheep breading.

SUBSTANCE: agent for treatment and prophylaxis of sheep gastrointestinal tract helminthoses is produced from desiccated and ground snowdrop (Pulstatilla turczaninovii Krul.et Serg) grass, plant of family Ranunculuceae harvested in flowering time which is charged in glass vessel and extracted in three step with 40 % ethanol. Extracts are sequentially filtered and boiled down, separated and boiled down again to produce concentrated pappy dark-green extract followed by drying thereof. After administration of said agent in sheep strobile joints and parts of moniezia leave gastrointestinal tract over 5-12 h, haemonch, chabertia and bunostoma over 15 x-1.5 days, and sheep botfly grubs over 2-4 days.

EFFECT: improved effective agent for treatment and prophylaxis of sheep gastrointestinal tract helminthoses.

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