RU2195300C1 - Antidiabetic agent - Google Patents

Abstract

FIELD: pharmacology. SUBSTANCE: invention provides a novel antidiabetic agent representing dry extract of galingale tubers. Antidiabetic effect is revealed on subcutaneous administration of aqueous solution of agent in dose 10 mg per 1 kg body weight. EFFECT: extended choice of sugar-reducing drugs. 5 tbl, 6 ex

Description

 The invention relates to the field of pharmacology, in particular to new antidiabetic agents.

 Traditional antidiabetic agents are known. In insulin-dependent diabetes, insulin is used. In case of insulin-independent treatment with synthetic drugs, such as sulfonylureas, biguanides, alpha-glucosidase inhibitors, etc. [1]. In mild forms of diabetes, metabolic control of the disease can be achieved by using extracts of medicinal plants as sugar-lowering drugs [2]. In moderate diabetes, herbal medicine is used as an adjunct to treatment with synthetic drugs and insulin [2].

 The sugar-lowering properties of water-ethanol extracts of ginseng root [4; 5], roots and rhizomes of Eleutherococcus [3-5], leaves of Averrhoa bilimbi [7], and tubers Dioscorea dumetomm [8] are known.

 With all the advantages of known herbal hypoglycemic agents, the possibility of widespread use of preparations of this group is largely limited by the cultural characteristics of plants that are raw materials for the preparation of dosage forms (long vegetation cycle, low productivity), as well as their growth outside the European territory of the Russian Federation.

 An object of the present invention is to provide a highly effective, widely available herbal antidiabetic agent for parenteral use.

 This goal is achieved by using a dry extract of tubers of the plant Cyperus esculentus L. (chufa, edible raw) as an antidiabetic agent, prepared by extraction with 40% ethanol. The antidiabetic effect of a dry extract of plant tubers is manifested in a dose of 10 mg / kg body weight per day with a subcutaneous route of administration.

 The tubers of the plant Cyperus esculentus L. in Chinese traditional medicine are used as a remedy for pain in the stomach, as well as an antidepressant agent [6]. In the available literature there is no information on the use of extracts of the plant Cyperus esculentus L. in medicine.

 The claimed solution is patentable, since a new drug has been proposed (dry extract of tubers Cyperus esculentus L.) as an antidiabetic agent. The claimed solution is widely applicable, since the culture of Cyperus esculentus L. is developed in the European territory, including in the territory of the Russian Federation. Examples confirming the antidiabetic effect of the dry extract of Cyperus esculentus L. and the method for its preparation are given below.

 Example 1. Obtaining a dry extract of tubers of the plant Cyperus esculentus.

Freshly picked tubers of the Cyperus esculentus plant were washed with running hot water for 15 minutes, then placed on a cotton cloth and dried for 1 month in a well-ventilated room at an air temperature of 20-25 ^o C to constant weight.

 Then the tubers were crushed using the MUB-030 installation to a powder state with a particle size of 150-250 microns.

The resulting powder was poured with extractant (40% ethanol) in a ratio of 1: 5. The extraction was carried out at a temperature of 37 ^o C for 7 days in a dark place.

Extractive components of the plant were separated from the solvent in a Unipal type 350 vacuum rotary evaporator at a temperature of 60 ^{° C.} to constant weight.

 Example 2. The effect of the dry extract of tubers of the plant Cyperus esculentus on the glucose level of healthy animals.

The sugar-lowering properties of the dry extract of tubers of the plant Cyperus esculentus were studied on healthy male white rats weighing 190-230 g under standard conditions (air temperature - 20-22 ^o C, humidity - 70-80%). Previously, rats were subjected to food deprivation for 16 hours with free access to water. Blood glucose was determined by the glucose oxidase method. Blood was taken from the tail vein. After initial determination of glucose level, rats of the control group (n = 6) were injected subcutaneously with 0.5 ml of a 0.9% sodium chloride solution, and experimental groups (n = 6) were injected with 0.5 ml of an aqueous solution of C.esculentus dry extract calculated 1.0, 10.0 and 100.0 mg of dry matter per 1 kg of body weight. The results presented in table. 1, allow us to conclude about the direct sugar-lowering effect of the drug.

 Example 3. The effectiveness of a single use of dry extract of Cyperus esculentus L. in rat alloxan diabetes.

The antidiabetic properties of the dry extract of Cyperus esculentus L. were studied on 56 outbred male rats weighing 150-170 g in a model of alloxan diabetes. Animals were kept under standard conditions (air temperature - 20-22 ^o C, humidity - 70-80%). After a 12-hour fasting diet, animals were injected subcutaneously with a 2.6% solution of alloxan at a dose of 130 mg / kg once. Rats of the experimental group (n = 23) 2 hours before the administration of alloxan were subcutaneously injected with an aqueous solution of dry extract of C. esculentus at a dose of 10.0 mg / kg. Animals of the control group (n = 23) were subcutaneously injected with 1.0 ml of 0.9% NaCl solution 2 hours before the injection of alloxan. Animals of the fourth (intact) group (n = 10) with an interval of 2 hours were given 2 subcutaneous injections of 1.0 ml of isotonic NaCl solution.

 The animals were monitored for 14 days, the dynamics of glucose in the blood was recorded daily, and the presence of glucose in the urine was determined. The dynamics of glycemia are presented in table. 2. The development of alloxan diabetes was accompanied by the appearance of all signs of insulin-dependent diabetes mellitus (hyperglycemia, glucosuria, weight loss, polyuria, polydipsia, polyphagy, etc.). It was established that a single preliminary use of the dry extract of tubers Cyperus esculentus L. favorably affects the general condition of animals with diabetes, reduces the degree of manifestation of the main clinical symptoms of the disease, and also reduces the time of recovery. The duration of urinary glucose excretion in animals of the experimental group was 2 days versus 6 days in the control.

 Thus, the dry extract of Cyperus esculentus L. with a single subcutaneous prophylactic administration has antidiabetic properties.

 Example 4. The effect of long-term prophylactic use of the dry extract of Cyperus esculentus L. in alloxan diabetes.

 On the above model of rat alloxan diabetes mellitus, the effect of chufa preparations on the development of the disease was studied with their long-term preventive use. The experiment used 40 male white laboratory rats with an average body weight of 165.2 ± 6.56 g. Rats of 3 groups were injected with an alloxan solution at a dose of 150.0 mg / kg, while the animals of the 1st experimental group (n = 10 ) daily injected subcutaneously with an aqueous solution of dry extract of Cyperus esculentus L. at a dose of 10 mg / kg for 7 days, animals of the 2nd experimental group (n = 10) received the extract with the same ratio in the same dose for 21 days, control group (n = 10) for 7 days before the injection of alloxan was injected with the corresponding volumes of saline. Intact rats (n = 10) received only physiological saline in a volume of 1.0 ml. Within 15 days, the incidence of animals was recorded, the concentration of glucose in the blood and urine was determined. The results presented in table. 3, indicate that prolonged preliminary administration of chufa preparations reduces the intensity of the manifestation of the main symptoms of diabetes mellitus (hyperglycemia, glucosuria), and helps to reduce the recovery time. The most effective prophylactic use of the drug within 21 days.

 Example 5. The effect of prolonged therapeutic use of dry extract of chufa tubers in alloxan diabetes.

The therapeutic efficacy of the dry extract of tubers of Cyperus esculentus L. in rat alloxan diabetes was studied. For this, 40 male white laboratory rats with a body weight of 144.5-172.0 g contained in standard conditions (air temperature - 20-22 ^o C, humidity - 70-80%) were used. All animals were divided into 3 groups: - "experimental" (n = 10); - "control" (n = 20); - "intact" (n = 10). After a 12-hour fasting diet, rats of the experimental and control groups were once subcutaneously injected with a solution of alloxan at a dose of 150.0 mg / kg of body weight, saline in a similar manner was injected with saline in a volume of 1.0 ml. Starting from 2 to 20 days from the onset of the disease, animals of the experimental group were injected subcutaneously daily with 1 ml of an aqueous solution of dry extract of chufa tubers at a dose of 10.0 mg / kg, animals of the control group were daily injected subcutaneously with physiological saline in a volume of 1.0 ml. The animals were observed for 20 days, the dynamics of glycemia was recorded. In all animals, within 24 hours after the administration of alloxan, a symptom complex of diabetes mellitus developed. The results of the therapeutic use of the dry extract of tubers of Cyperus esculentus are presented in table. 4 and indicate the antidiabetic effect on the model of alloxan diabetes in therapeutic use.

 Example 6. The use of dry extract of tuber chufa for the prevention of streptozotocin diabetes.

The antidiabetic properties of the dry extract of tubers of Cyperus esculentus were studied using rat streptozotocin diabetes model. The study was performed on 18 male non-linear laboratory rats aged 10-12 weeks, weighing 170-190 g. Streptozotocin diabetes was obtained by double intraperitoneal administration of streptozotocin in a total dose of 60 mg / kg (30 mg / kg with an interval of 24 hours). Animals were kept under standard conditions (air temperature - 20-22 ^o C, humidity - 70-80%). The experimental group 1 hour before each injection of streptozotocin was injected with 0.5 ml of an aqueous solution of dry extract of C. esculentus at a rate of 10 mg / kg body weight. The control animals were injected with the same volume of distilled water an hour before the administration of streptozotocin. Animals of the intact group for 2 days twice with an interval of 1 hour received injections of distilled water. The development of streptozotocin diabetes was accompanied by the appearance of all signs of diabetes. The animals were observed for 12 days, 1 time in 2 days, the concentration of glucose in the blood was determined. The results are presented in table. 5.

 It was established that a single preliminary use of chufa extract provides complete protection against the diabetic effect of streptozotocin in 33% of animals, as well as shortens the recovery time of rats in which hyperglycemia was observed on the 2nd day of the disease. Moreover, glycemia above 6 mM / L was observed on day 4 in 33% of the rats of the experimental group, on days 6 and 8 - in 16.5%, on day 12 - in all animals corresponded to the species norm.

 Thus, a dry extract of the tubers of the plant C. esculentus L. with a single prophylactic administration subcutaneously at a dose of 10 mg / kg 1 hour before streptozotocin has antidiabetic properties in the model of streptozotocin diabetes.

 Dry extract of tubers of Cyperus esculentus L. has an antidiabetic effect. The use of the extract reduces the level of glucose in healthy animals, reduces the degree of manifestation of the main clinical and laboratory symptoms of alloxan diabetes during prophylactic and therapeutic applications, and protects the body of laboratory animals from the diabetic effect of streptozotocin.

Literature
1. Balabolkin M.I. Diabetology - M .: Medicine, 2000.-671 p.

 2. Bogdanovich V.L. Diabetes mellitus (treatment and prevention). - N. Novgorod: NGMA, 1998.-192 p.

 3. Brekhman I.I. Eleutherococcus. - L .: Nauka, 1979.-186p.

 4. Dardymov I.V. Ginseng, Eleutherococcus. - M .: Nauka, 1976.-184 p.

 5. Molokovsky D. S., Davydov V.V., Tyulenev V.V. The effect of adaptogenic herbal remedies in experimental alloxan diabetes. // Problems of Endocrinology.-1989.- 6.-S. 82-87.

 6. Perry L.M., Metzger J. Medicinal Plants of East and Southeast Asia: attributed properties and uses.-Cambridge: MIT Press, 1980.-620 c.

 7. Pushparaj P., Tan S.N., Tan V.K. Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats. // J Ethnopharmacol.- 2000.- 1-2.-C. 69-76.

 8. Undie A.S., Akubue P.I. Pharmacological evaluation of Dioscorea dumetorum tuber used in traditional antidiabetic therapy. // J Ethnopharmacol-1986.- 2.- C. 133-144.

Claims (1)

 An antidiabetic agent based on plant materials, characterized in that it is a dry extract of edible tubers (chufa, Cyperus esculentus L.)

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