RU2580757C1 - Agent for treating metabolic syndrome - Google Patents

Abstract

FIELD: medicine; veterinary.

SUBSTANCE: invention relates to an agent for treating metabolic syndrome, including adsorbed on solid sorbent such as sorbitol, lactose or starch, at least, one polyprenylphosphate or polyprenylpyrophosphate with number of isoprene links from 7 to 30.

EFFECT: invention provides effective agent for reducing body weight, normalising carbohydrate and lipid metabolism.

6 cl, 1 dwg, 2 tbl, 5 ex

Description

The invention relates to medicine and veterinary medicine, in particular to agents for the treatment of metabolic syndrome (MS).

MS is a collective concept, uniting a group of diseases or pathological conditions, manifested in the form of certain metabolic, hormonal and clinical disorders.

MS is often characterized by an increase in body weight, a decrease in the sensitivity of peripheral tissues to insulin (insulin resistance) and hyperinsulinemia, as well as arterial hypertension, impaired carbohydrate, lipid and purine metabolism. If there are three or more of the above symptoms, it is customary to diagnose MS.

For the treatment of obesity with a non-systemic effect, the drug orlistat (orsoten, xenical) is used. The action of the drug is aimed at a key factor in obesity - food fats. Orlistat is a powerful specific and long-acting inhibitor of gastric and pancreatic lipases, prevents the breakdown and subsequent absorption of food fats. It reduces the amount of free fatty acids and monoglycerides in the intestinal lumen, leading to a decrease in cholesterol absorption and a decrease in its level in the blood. Thus, orlistat reduces the flow of energy, which leads to a loss of body weight. The drug has a therapeutic effect within the gastrointestinal tract and does not have a systemic effect.

When using the drug in the recommended therapeutic doses in combination with a moderate hypocaloric diet containing no more than 30% of the daily calorie fat, approximately 1/3 of the fat obtained from food is not absorbed, which leads to a noticeable decrease in body weight.

In a comparative study, orlistat therapy allowed most patients (47.6% in the orseten group and 51.2% in the xenical group) to achieve clinically significant body weight loss (> 5%) after 12 weeks of treatment, and a decrease body weight greater than 10% was observed in 7.1% and 5.9%, respectively. In addition, there were no statistically significant differences in secondary efficacy parameters, such as a decrease in waist volume, body mass index, and blood pressure. However, the use of orlistat leads to undesirable effects: fatty stools, increased bowel movements, oily discharge from the anus and flatulence with the passage of gases.

The authors are not aware of the means that provide the possibility of complex treatment of MS, which consists in reducing body weight while normalizing carbohydrate and lipid metabolism. The technical result from the use of the invention is to create a means to reduce body weight and normalize carbohydrate and lipid metabolism.

The specified technical result is achieved using a biologically active additive (BAA) containing a mixture of various polyprenyl phosphates and / or polyprenyl pyrophosphates with the number of isoprene units from 7 to 30 adsorbed on a solid sorbent, in particular sorbitol, lactose, starch (RU 2427284).

The specified technical result is also achieved by the fact that the content of polyprenyl pyrophosphates in the mixture of polyprenyl phosphates and polyprenyl pyrophosphates is 10 mass percent.

The specified technical result is also achieved by the fact that the sorbent content is 90-99.5 mass percent.

The specified technical result is also achieved by the fact that beta-sitosterol is added to the dietary supplement.

The specified technical result is also achieved by the fact that the content of beta-sitosterol is 1-10 mass percent.

The specified technical result is also achieved by the fact that the content of beta-sitosterol is 5 weight percent.

The action of the proposed Means is illustrated by the following examples of animal studies in which the Means in the form of a 250 mg tablet containing 10 mg beta-sitosterol, 8 mg sodium polyprenyl phosphate (a mixture of oligomer homologs with a chain length of 13 to 22 isoprene units) was used for the treatment of MS adsorbed on sorbitol, 2.5 mg magnesium stearate, sorbitol 229.5 mg. The tool was obtained by the method described in the patents RU 2427284 and RU 2542420. In this case, a single dose of the Meal fed to the animal was 3-6 mg / kg of animal weight.

Example 1

The study was conducted on 4 cats and 7 cats aged 6 to 9 years. All animals were sterilized, kept in one apartment. Food before treatment - dry food Friskas and Viskas in bags, food during treatment - diet food Hills L \ D. All animals were overweight. The tool was fed to each animal for 50 days with food 2 times a day. The table shows the mass of animals (kg) before and after treatment. In 10 of 11 animals, the weight after treatment decreased. At the same time, a decrease in total cholesterol and triglycerides was observed (see drawing). At the same time, the body weight of all animals continued to decrease and 2 months after discontinuation of the drug and reached the level of 6.39 ± 0.21 kg, which is statistically significantly different from the initial level (p <0.05).

Data on the treatment of metabolic syndrome with the Agent have also been demonstrated in dogs.

The group of animals with metabolic syndrome included dogs with increased body weight and dyslipidemia in diseases such as hyperadrenocorticism (35%), diabetes mellitus (25%), hypothyroidism (20%), as well as in violation of the feeding regimen and nature ( obesity, fatty liver disease (45%)).

The treatment regimen, in addition to the specific treatment of hyperadrenocorticism (ketoconazole), diabetes mellitus (canisulin), hypothyroidism (L-thyroxine), violations of the regimen and nature of feeding (Hill's Metabolic diet), included the use of the Drug.

During the treatment, in addition to the disappearance / weakening of the clinical symptoms of the disease, it was also possible to achieve a decrease in body weight by an average of 10-15%.

Body mass index was determined by the formula I = m / h2, where m is body weight, h2 is the surface area of the body. Normal weight was determined according to the method presented by Hill's.

Example 2: dog, female, 5 years old, Chinese crested, Glasha. Diagnosis: hyperadrenocorticism, dyslipidemia, obesity. Clinical signs: polydipsia, polyphagia, polyuria, halitosis, increased body weight by 35% (weight was 8.2 kg with a normal weight of 5.5-6.0 kg).

After 1 month of therapy: weakening of polydipsia, polyuria, polyphagy and halitosis persisted, weight decreased to 7.8 kg. After 2 months of therapy: the disappearance of polydipsia, polyuria. The signs of halitosis weakened, the polyphagy could not be stopped, the weight was reduced to 7.3 kg.

Example 3: dog, female, 8 years old, dachshund, "Plush". Diagnosis: dyslipidemia, obesity. Clinical signs: polyphagy, halitosis, dull coat, hair was poorly kept in the hair bulb, weeping eczematous skin lesions, alopecia, increased body weight by 45% (weight was 14.7 kg with a normal weight of 10-11 kg).

After 1 month of therapy: the polyphagy was preserved, the coat was still dull, but the hair was well retained in the hair bulb, alopecia, weeping eczema turned into dry, body weight decreased to 13.9 kg. After 2 months of therapy: a new hair began to appear at the site of alopecia, the coat became more shiny, body weight decreased to 13.1 kg.

Example 4: dog, male, 4 years old, Chihuahua, Casper Diagnosis: diabetes mellitus, dyslipidemia. Clinical signs: polydipsia, polyuria, increased body weight by 25% (weight 4, 1 kg with an ideal weight of 2.5-3.0 kg), halitosis.

After 1 month of therapy: weakening of polydipsia, polyuria and halitosis, body weight decreased to 3.7 kg. After 2 months of therapy: the absence of polydipsia and polyuria, halitosis persisted, body weight decreased to 3.2 kg.

Example 5

Under observation were 45 heads of cats of different age and gender groups, divided into 3 groups of 15 goals each. The animals of the first group (experimental) The tool was fed 2 times a day for 2 months. To cats of the second group, the product was fed 2 times a day for 2 months; however, the animals of the second group were fed Hill's L / D according to the manufacturer's recommendations throughout the observation period. To cats of the third group (control) - Mexidolum inside in a dose of 3.5 mg / kg of body weight. During the work, clinical (n = 135), hematological (n = 810), biochemical (n = 2295), and statistical studies were carried out.

Clinical studies (examination, palpation, auscultation, thermometry, appetite, the study of visible mucous membranes) were carried out by methods generally accepted in veterinary medicine. They paid attention to body temperature, pulse, respiration, general condition of the animal, appetite, color of mucous membranes, position of the body in space, and fatness.

Biochemical studies of blood serum were performed on a BioSystems BTS-350 analyzer (Spain), using reagents from Deacon DDS. At the same time, the level of cholesterol, triglycerides, α-amylase, pancreatic lipase, and glucose were studied. Studies were carried out before treatment, after 30 and 60 days of therapy. Statistical processing of the obtained data was carried out using the Statistica 6 program.

When conducting biochemical studies, the data obtained are presented in table 2.

As the data shown in table 2 show, cat MS in all groups was characterized by an increase in all groups of cholesterol, triglycerides, pancreatic lipase, α-amylase, and glucose.

The prescribed therapy after a month gave a noticeable result, but there was a significant difference in groups of animals. The greatest therapeutic effect was achieved in the second group of animals, as evidenced by a decrease in the level of triglycerides, pancreatic lipase, α-amylase.

It should be noted that the level of cholesterol by this time did not significantly change in any group of animals. By the end of the experiment (60 days), normalization of blood cholesterol levels was observed in groups 1 and 2 (group 1 - 6.5 ± 0.4 mmol / l, group 2 - 6.0 ± 0.4). At the same time, cholesterinemia (8.0 ± 0.3 mmol / l) was still observed in group 3.

Similar changes were observed in the concentration of triglycerides. Triglyceridemia (2.4 ± 0.6 mmol / L) was also observed in group 3. After a month of observation, the level of α-amylase in all groups corresponded to the physiological norm, however, the most striking changes were noted in group 2. A decrease in blood glucose was also observed. The level of pancreatic lipase, considered the most informative indicator of pancreatitis by this time, returned to normal in groups 1 and 2, while in group 3 it remained elevated (45.4 ± 1.2 U / L).

Clinical efficacy of the action of MS.

At the beginning of treatment, clinically sick MS had a weakening or lack of appetite, thirst, halitosis, and in some animals, vomiting. The mucous membranes were most often pale pink. On palpation, the abdominal wall is tense and painful. The coat is dull and disheveled, and the hair was poorly held in the hair follicle. Skin turgor is weakened, some animals on the skin had alopecia, eczematous lesions. Many animals have noted itching.

After 30 days of therapy, an improvement in appetite was clinically observed in animals of the 1st group (experimental), in four animals halitosis persisted, vomiting and diarrhea stopped. The abdominal wall during palpation is soft and painless. The coat is dull, the hair was poorly held in the hair bulb, in some animals alopecia, weeping eczema turned into dry. The turgor of the skin returned to normal. In addition, animals became more mobile, active, itching disappeared.

Clinical changes in animals of the 2nd group were largely consistent with those of the 1st group. It should be noted that cats of this group were more active, all had halitosis, shine of coat appeared, and feces consistency improved. In cats of the 3rd group there was a slight improvement in well-being, in particular, appetite improved, and halitosis was weakened.

After 2 months of therapy, animals of the 1st group showed good appetite, there was no halitosis. The coat is dull, the hair was well kept in the hair bulb, a new hair appeared at the site of alopecia, a weakening of the eczematous process was noted.

In cats of the 2nd group, no signs of disease were observed by this time. In particular, there was no halitosis, the hair shone, they became active and inquisitive, thirst disappeared, and skin lesions were absent.

In animals of the 3rd group, at the end of the observations, a certain positive dynamics was noted, which manifested itself in a significant weakening of halitosis, a decrease in thirst, an improvement in appetite, a shine of the coat, a weakening of inflammation at the site of eczematous lesions and itching.

The use of MS in cats has reduced the level of triglycerides, pancreatic lipase, α-amylase, glucose and normalized blood cholesterol (group 1 - 6.5 ± 0.4 mmol / l, group 2 - 6.0 ± 0.4 ) At the same time, cholesterinemia (8.0 ± 0.3 mmol / l) was still observed in group 3. Similar changes were observed in the concentration of triglycerides. Triglyceridemia (2.4 ± 0.6 mmol / L) was also observed in group 3. After a month of observation, the level of α-amylase in all groups corresponded to the physiological norm, however, the most striking changes were noted in the 2nd group. The level of pancreatic lipase, which is considered the most informative indicator of pancreatitis, returned to normal in groups 1 and 2 by this time, while in group 3 it remained elevated (45.4 ± 1.2 U / L).

Claims (6)

1. An agent for treating a metabolic syndrome containing adsorbed on a solid sorbent, in particular sorbitol, lactose, starch, at least one polyprenyl phosphate or polyprenyl pyrophosphate with the number of isoprene units from 7 to 30 or a mixture of different polyprenyl phosphates and polyprenyl pyrophosphates with the number of isoprene units from 7 up to 30. 2. The agent for treating the metabolic syndrome according to claim 1, characterized in that the content of polyprenyl pyrophosphates in the mixture of polyprenyl phosphates and polyprenyl pyrophosphates is 10 weight percent. 3. The tool for the treatment of metabolic syndrome according to claim 1, characterized in that the sorbent content is 90-99.5 weight percent. 4. The drug for the treatment of metabolic syndrome according to claim 1, characterized in that it additionally contains beta-sitosterol. 5. The drug for the treatment of metabolic syndrome according to claim 4, characterized in that the content of beta-sitosterol is 1-10 weight percent. 6. The drug for the treatment of metabolic syndrome according to claim 4, characterized in that the content of beta-sitosterol is 5 weight percent.

Images