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5SCIENTIFIC PROGRESS VOLUME 3 I ISSUE 8 I 2022 _ISSN: 2181-1601
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PROSPECTS FOR OBTAINING DOSAGE FORMS BASED ON LOCALIZED
INDIAN POMEGRANATE
Bakhodirjon Sharipovich Samadov, Feruza Sodiqovna Jalilova,
Bukhara state medical institute named after Abu Ali ibn Sino Fazliddin Sodiqovich Jalilov
Tashkent Pharmaceutical Institute
Introduction. The search for new drugs, their experimental and clinical study is connected with the solution of many scientific, technical, economic, ethnic, legal issues both within our country and on an international scale. Today, as in the pharmacy industry, special attention is also paid to the synthesis of new active substances and obtaining new dosage forms from them, and in our republic, the cultivation of medicinal herbs is also deeply supported, medicinal plants are localized and new dosage forms are obtained from them.
The aim of the work. Diabetes mellitus, as defined by the WHO and the UN, is classified as an endocrine disease, with an epidemic increase in prevalence, which led the UN to adopt a resolution to combat diabetes mellitus. In Uzbekistan, there are city and regional endocrinological centers, polyclinics, urban and rural family polyclinics, medical centers for early diagnosis and treatment of diabetes mellitus and its complications. Improper lifestyle, eating foods rich in pathogenic fats lead to dysfunction of the endocrine glands or a decrease in the sensitivity of cells to insulin. Under the influence of various etiological and pathogenetic factors, the body develops diabetes mellitus of the first or second type, leading to a violation of the amount of glucose in the blood. Applicants face a constant task to create new dosage forms to ensure the health of the population of each republic and to continue their average life expectancy. Many medicinal forms, as well as in their composition, contain components of medicinal plants, which lead to the return of medicinal herbs with pharmacological activity, in this study, hypolipidemic activity is the goal of our study. Medicinal plants belonging to the pumpkin family "Cucurbitaceae" Momordica charantia "Momordica charantia L" has been used for a long time in folk medicine against various diseases, including as a hypolipidemic agent for diabetes mellitus. Momordica charantia (lat. Momordica charantia L) is a climbing medicinal plant native to India and the Southeastern regions of Asia. [1]. The genus of plants includes about 20 species of annual or perennial lianas. Momordica charantia (Latin Momordica charantia L) is usually grown as cultivated plants [2, 3]. Fruits are rich in vitamins C, A, E, B, PP, F, contain trace elements and substances important for the human body (dietary fiber, lutein, beta carotene, etc.) [4].
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Materials and methods. Basing on the data of different authors, we conducted an experiment basing the lipid-lowering activity of a medicinal plant on laboratory mice to study. Since it is known from literary sources that it is also used in folk medicine, patients with diabetes mellitus were the experiments [6].
Preparation of an aqueous extract: In the Bukhara region of the Republic of Uzbekistan, the bark of momordica fruits grown at home was softened in an electric mixer. The softened powder of momordica fruits was soaked in the same amount of water and washed overnight [7]. After that, the resulting mass was sieved through a sieve with a large hole, the resulting mass was dried at a low temperature. The proportional mass was equal to the unit MX - 80.4 g/kg. To ensure shelf life and integrity, the extract "Krist" alpha 1-4 is dried with a special dryer, completely dried in vacuum for 54 hours. The mass of the MX was 64/100 grams [8].
Preparation of alcohol extract: 1 kg of MOSS fruit is mixed with 500 ml of 70% alcohol and kept for 36 hours at room temperature. The resulting clot is shaken for 2 hours and infused overnight. After that, the mixture is filtered and cleaned from the solution in a vacuum bag at a temperature of 35-45 ° C. To prevent foaming, drops of silicone emulsion were added at the end of distillation. The collected residue was in the form of a thick paste of a reddish color. The proportional mass of MX is equal to 29 g/kg of a unit in the form of raw materials [5, p.139-143].
Animals: the weight of old albino rats of two sexes is 150-180 grams, the creatures were divided into different therapeutic groups by a tasofdifi method, kept in the light for 12 hours and kept in a darkened room for 12 hours, fed with water and feed. After 3 days of acclimatization, all rats (uncontrolled), which was attributed to previous studies (Sleder et al., 1981), were transferred to a diet consisting mainly of 66% fructose, 12% fat and 22% protein [9]. This diet continued in perfect order for 15 days. The animals were divided into three groups: (i) a control group with supplements, that is, creatures on a standard diet; (ii) fructose control, that is, a diet rich in fructose; (iii) groups treated, that is, a group that received a fructose diet and aqueous and alcoholic extracts of cocaine in ascending order (100, 200 and 400 mg per day). The escorts reached the mouth of the living creatures at a well-defined time every day [10]. Experiments on living beings were carried out in accordance with the procedures established by the Institute. The creatures, who were described as not consuming nitrogen, were kept away from nitrogen for at least 16 hours, but were allowed to drink any water they wanted [11]. During this time, blood samples were taken from animals that showed a significantly effective hyperglycemic effect and received plant eclecticics that were tested for insulin levels. All studies were conducted using a set of insulin-related tools at the most significant moment of the study (Incstar, Inc., Minnesota, USA). The probing was carried out on an equal amount of BSA-borate buffer.
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Duplicates of sample samples (200 ^l) were also obtained [12]. The company that produced the tool kit was known for its non-exclusive fastening by 4.8% and maximum fastening by 52.9%, while the proportional fastening in the current study was 5.8 and 51.7% [5, pp.139-143].
Biochemical measurements: blood was taken from the inner opening of the eye by retroorbital method (under the influence of ether anesthesia) using capillary tubes (Micro Hematocrit Capillaries, Mucaps) into a vial with fluorosodium and sodium oxalate, which perform an anticovagulant function. The plasma T8 was in 2000 at a rotation speed of 2 minutes in an electric trifuge (Remi Udyog, New Delhi). It was divided into aliquots, frozen at -20°C, and then tested for glucose and triglycerides using existing devices [5, pp.139-143].
Results. Table No. 1. Serum glucose, insulin, and triglyceride levels in rats fed a fructose-rich diet for 15 days.
Metabolic parameters Trial day Standard control Fructose control
Body weight (g) 0 165.6±4.17 156.8±4.58
7 186.0±7.98 175.0±7.07
15 207.5±7.07 193.1±8.42
Glucose (mg/dl) 0 54.92±1.42 57.85±2.11
7 54.54±2.21 69.76±2.66b
15 55.59±2.89 75.46±2.41b
Insulin 0 9.31±3.00 6.26±1.27
(mg/dl) 15 8.00±1.27 15.04±2.43b
Triglycerides (ng/dl) 0 40.45±2.46 41.79±3.74
7 41.31±2.55 43.68±3.10
15 41.10±3.33 50.93±3.30b
After 15 days, the weight of rats in all groups was at the same indicator. However, during the transition to a fructose diet, food intake decreased at the first stage, but later it reached such a high level as in the control group [13,23]. The arrival of garbage in a scattered form was another phenomenon observed in rats caught on a diet rich in fructose. However, this is better in its own way. The effect of fructose supplements on weight, glucose, insulin and triglycerides as a result of taking fructose is shown in Table No. 1 above. The primary difference in glucose, insulin, and triglyceride levels was compared in groups receiving fructose, supplements, and plant extracts, and no significant difference was found. However, the fructose-rich diet ended from 7 days to the last day of the study (15 days) with hyperglycemia (P<0.001) and hyperinsulinemia (P<0.001). In rats fed with fructose, this indicator was equal to 1.2%, while an increase
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in serum glucose was recorded by 30% in rats fed with plain food [14,24]. At the end of the experiment, the glucose content in rats fed with fructose reached 140.25%, while in rats that consumed plain food, this indicator was equal to 14.07%. (15.0± 2.43 vs. 8.00± 1.27 mg/dl, proportionally, P<0.001). From this it can be seen that fructose caused hypertriglyceridemia in rats. In the current study, plasma triglyceride levels were higher in 15 days of the experiment than in 21% of the control group (41.10±3.33 vs. 50.93± 3.30 mg/dl, P<0.001). The effect of extracts on rats fed with fructose is shown in Table 1. Although alcoholic extracts are MX specific. Similar results were observed with low doses of aqueous extracts of this plant. However, doses of MX extract at a dose of 400 mg significantly eliminated hyperglycemia, taking into account the percentage increase in glucose levels over 15 days of the experiment. The increase in serum glucose was 15.3% and 14.62%, while in the control groups this indicator reached 30.44% (i.e. glucose 63.52±2.9 and 66.46±2.2, etc.). 75.46±2.4 mg/dl, proportionally, P<0.001). The effect demonstrated at the insulin level in rats after feeding MX (400 mg per day) is shown in Figure 3. In groups with a high insulin content, the levels of increase were equal to 23.1% and 60%, while in rats treated with fructose, this indicator reached 140.44%. (7.78±3.1 and 10.8±0.9 versus 15.04±2.43 ng/dl, P<0.01 and P<0.05, respectively) [5, pp.139-143].
Figure 1. The content of the cited information: ±S.E. Aq, aqueous extract; Alc, alcohol extract; digital units represent doses in milligrams. n = 8; the set number differs significantly from the group with fructose. *P<0.001.
Figure 2. Content of the cited information: ±S. E. Aq, aqueous extract; Alc, alcohol extract; digital units represent doses in milligrams. n = 8; the set number differs significantly from the group with fructose. *P<0.001.
Hyperinsulinemia affects the development and clinical course of at least three concomitant diseases, including: insulin-dependent diabetes mellitus, primary hypertension and arterial disease (Reaven, 1988). It is also a common metabolic disorder and dyslipidemia that occur in overweight people (Defronzo and Ferran - nini, 1991) [15]. Chronic nutrition of living beings in an experiment with fructose can lead to the development of glucose intolerance associated with hyperinsulinemia (Hill et al.,
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1954; Vrana et al., 1978; Zavaroni et al., 1980) and loss of insulin sensitivity in vivo (Beck-Nielsen et al., 1980; Zavarani et al., 1980; Sleder et al., 1981) and caused imitation of syndrome X. This model is recommended for evaluating the therapeutic effectiveness of insulin sensors and drugs that affect insulin sensitivity [16]. Therefore, a model of these creatures was chosen for the study. All previous work on this model was carried out on Sprag-Dowley and Long Evans rats (Curry et al., 1971; Zavarani et al., 1980; Sleder et al., 1981; Tobey et al., 1982; Hwang et al., 1987; Haurshid et al., 1995). However, due to the fact that these rats are difficult to find in India, albinos of white color were chosen for this study. Studies have shown that Wistar rats also gave almost similar results with a fructose-rich diet. In this study, it was shown for the first time that fructose nutrition leads to hyperinsulinemia and hyperglycemia in adult Vistar rats, however, when Sprag-Doly kalamushlari was not detected, it was described that Vistar kalamushlari is used for such studies. However, in this study, hypertriglyceridemia, as in previous studies, was not recorded. This is probably due to the shortening of the experimental period (15 days) and long experiments in earlier short experiments (Zavaroni et al., 1980), a relatively mild type of hypertriglyceridemia should be identified as the cause. Various oral agents that cause hypoglycemia are commonly used to control glucose levels in patients with insulin-dependent diabetes mellitus. However, the effectiveness of such drugs is limited, and it is known that various side effects may occur, such as hypoglycemia (Davis and Granner, 1996) [17]. Many patients are unable to take such drugs that are administered orally, but are forced to undergo insulin treatment, which has certain drawbacks (pronounced dosage, risk of hypoglycemia, parenteral therapy and a short shelf life). All such factors ultimately negatively affect the compatibility of the tool [18]. On the other hand, the plant extracts studied in this research paper are widely used in India as fruits and vegetables, and their juices are prepared at home and used as an antidiabetic. In the conditions of Uzbekistan, attention is now being paid to the study of this plant [19]. Earlier studies have shown that the effect of MX plant against hyperglycemia is known (Sharma et al., 1960; Krishnamurti, 1962; Chatterjee, 1963; Lal and Chowdhury, 1968; Dhawan et al., 1988). This research work was carried out because the action of this plant has not been studied in the framework of the body's fight against insulin. It was found that alcoholic extracts of the MX plant were ineffective in reducing plasma glucose levels, but aqueous extracts (in large doses, 400 mg per day) significantly inhibited the development of hyperglycemia and hyperinsulinemia [20]. A similar advantage of drugs that inhibit hyperinsulinemia is that (including the plants studied in this study), they have therapeutic properties, such as drugs that reduce the level of hyperinsulinemia, and can be effective in the treatment of primary hypertension and arterial diseases in people with insulin-dependent diabetes mellitus [21]. Although alcohol extracts have not shown a
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good result in this regard, water extracts are relatively more effective, this is due to the fact that the chemical components against hyperglycemia dissolve in water [22]. Experiments on rats have shown that a diet rich in fructose (Tobey et al., 1982; Hwang et al., 1987) has shown that skeletal slows down the effect of insulin on muscles and muscles. Although the exact mechanism of action of these plants is unknown, these extracts can be evaluated as an antidepressant against the weakening of skeletal muscles and ligamentous insulin under the influence of fructose. The current results allow us to draw new conclusions in this regard [5, pp.139-143].
Conclusions. In conclusion, it can be said that feeding healthy rats with fructose for 15 days led to hyperinsulinemia, the occurrence of hyperglycemia, which pushes insulin, and a slight increase in serum triglycerides. Among such side effects, only hyperglycemia and hyperinsulinemia were aggravated when taking a dose of 4 ml of MX aqueous extract. Such results can also be applied to humans, and these findings can confirm that the effectiveness of the course of treatment and the mechanism of mastering obesity or glucose eliminate the effects of insulin in the case of diabetes mellitus disorders.
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