Cocarboxylase (amp. 50 mg No. 5 + solution), Microgen (Allergen FSUE)

Pharmacological properties of the drug Cocarboxylase

Thiamine diphosphoric ester, a coenzyme of enzymes involved in carbohydrate metabolism. In combination with protein and magnesium ions, it is a component of carboxylase, which catalyzes the decarboxylation and carboxylation of alpha-keto acids. To participate in these processes, exogenous vitamin B1 (thiamine) must be metabolized by phosphorylation to cocarboxylase, the active form of coenzyme formed from thiamine during its metabolism in the body. It should be noted that the properties of cocarboxylase are only partially adequate to those of thiamine; Cocarboxylase is not used to treat hypo- and vitamin B1 deficiency. After parenteral administration it is well absorbed and does not deposit in the body. Excreted in urine.

Cocarboxylase, vitamin B2 and lipoic acid in obstetric and gynecological practice

In recent years, against the background of a sharp decline in the birth rate in Moscow, there has been a significant increase in the frequency of perinatal pathology (1.5–2 times), a stabilization in the frequency and birth of premature babies (7–9%). There is a certain pathomorphism of diseases of the newborn period, pathogenetically associated with the deterioration of the health status of mothers. Most diseases in children are characterized by multisystem disorders, neurosomatic disorders, occurring against the background of significantly reduced resistance in the reparative period of diseases such as perinatal encephalopathy, sepsis, pneumonia, and respiratory distress syndrome. Most children experience persistent dysfunction of various organs and systems, and develop disadaptation syndrome (syndrome of increased excitability, dysbacteriosis, dyskinesia of the gastrointestinal tract, allergic reactions, prolonged and recurrent acute respiratory viral infections).

There is a direct relationship between the cytochemical parameters of a pregnant woman and the histochemical parameters of the developing fetus. Indicators of the enzyme status of a woman’s lymphocytes at 7–10 weeks are prognostically significant for assessing the state of energy metabolism in a developing child throughout pregnancy. No less important is dynamic monitoring of the state of energy metabolism in children of different ages, especially in newborns and children in the first year of life. Changes in the energy metabolism of brain cells, cardiomyocytes, and epithelial cells of the intestinal mucosa in a newborn child who has suffered chronic antenatal or acute intrapartum hypoxia lead to the formation of dysfunctions of the above organs, which disrupts the adaptation processes of the newborn child. Timely prescribed effective metabolite therapy allows you to correct disorders of cellular energy metabolism and prevent the development of such dysfunctions.

Monitoring the state of energy metabolism in a pregnant woman makes it possible to promptly detect fetal tissue hypoxia and take timely measures to correct it.

At the moment, a large amount of clinical material has been accumulated on the use of various metabolic therapy regimens, prescribed depending on the parameters of cytochemical blood tests and underlying the prevention of the development of pregnancy pathologies. The use of these schemes in preparation for pregnancy and during it allows optimizing energy exchange processes and reduces the risk of perinatal pathology in the unborn child.

The totality of identified cytochemical changes determines the direction of metabolite therapy. Currently, based on cytochemical studies of energy metabolism, a number of combined drugs with metabolic action have been developed. In particular, at low levels of activity of mitochondrial flavoproteins, the use of cofactors of the tricarboxylic acid cycle is justified. However, it is known that parenteral administration of metabolite drugs is more effective than enteral administration, and this sharply limits the use of these drugs in outpatient practice. As an alternative to the parenteral route of administration, metabolic complexes in the form of suppositories are offered. The bioavailability of drugs with this route of administration increases significantly and is not inferior in terms of effectiveness to that observed with the parenteral route of administration. When developing such complexes, the main attention is paid to the synergism of the action of drugs in the correction of biochemical processes in the cell.

As you know, all food products in the body are broken down into acetyl-CoA, which enters the final oxidation pathway - the tricarboxylic acid cycle. Activation of the di- and tricarboxylic acid cycle is possible by regulating two important stages: 1) oxidation of pyruvic acid to acetyl-CoA and then interaction with oxaloacetate to form citric acid; 2) oxidation of ketoglutaric acid to succinate (succinic acid). Both of these steps can be catalyzed by the Corylip multienzyme complex, which includes lipoic acid, cocarboxylase and riboflavin.

Materials and methods

Research by the Research Institute of Pediatrics together with the Center for Obstetrics, Gynecology and Perinatology of the Russian Academy of Medical Sciences, with the Moscow Antiherpetic Center and with the 25th Maternity Hospital in Moscow with the participation of 64 women at risk and their children, observed for a year after birth, proved how important the use of energy-normalizing drugs is actions in women preparing for pregnancy and in pregnant women.

Korilip suppositories were used as part of basic therapy in 31 women during pregnancy under the mandatory control of quantitative cytochemical analysis. Only basic therapy was also received by 33 women in the comparison group. The enzymatic status of peripheral blood lymphocytes was studied in the classic version of the reaction (R.P. Nartsissov, 1969–1984), including determination of the activity of succinate dehydrogenase (SDH) and glycerophosphate dehydrogenase (GPDH), as well as in various modifications of the classic version, allowing to assess membrane permeability and stability of the mitochondrial locus containing succinate dehydrogenase. The permeability of the mitochondrial membrane was indirectly assessed by SDH activity after 10 min of incubation. It was assumed that the rate of formation of the reaction product when detecting SDH activity is maximum in the first minutes of exposure and minimum at an exposure time of 60 minutes.

This method made it possible to determine not only the average activity of the enzyme, as is done in biochemical studies, but also made it possible to consider as characteristics the parameters of the distribution of cells by enzyme activity - coefficients of the second, third and fourth order (coefficients of variation, asymmetry, kurtosis), as well as a measure cellular diversity (relative entropy of information). The totality of these distribution parameters according to enzyme activity constitutes the concept of the enzyme status of blood cells. Thus, analysis of the cell population made it possible to identify changes in various cell subpopulations against the background of still unchanged average activity, since these changes in cellular structure appear before the clinical signs of the disease.

To assess the functional activity of mitochondria, a cytomorphodensitometric method was used to determine SDH activity. Analysis of the functional activity of mitochondria based on cytomorphodensitometric parameters made it possible to identify the features of the pathological process at the subcellular level and evaluate the effectiveness of the treatment.

results

It was found that in pregnant women at risk who received a course of treatment with the Korilip complex against the background of basic therapy, the frequency of pregnancy complications with repeated acute respiratory viral infections was 2.5 times lower compared to the comparison group. They were less likely to experience exacerbations of chronic foci of infection. Hypochromic anemia in pregnant women was diagnosed 2.9 times less often in those receiving Corilip. The most effective use of Korilip in relation to the child was observed in women who received therapy 6–9 months before and during pregnancy. Early use of the drug ensured that the development of perinatal complications was minimized and contributed to better development of children in the first year of life by providing a higher level of energy to the tissues and cells of a pregnant woman, newborns and infants.

It was found that during pregnancy the prescription of metabolic benefits is more justified in critical periods (according to cytochemical indicators): 5–8 weeks, 10–12 weeks, 20th week, 27–28 weeks, 30–32 weeks, 35–37 weeks, and especially women at high risk of developing perinatal pathology in children. In women at high risk of developing perinatal pathology in children, as a rule, there is a decrease in the activity of SDH and alpha-GPDH against the background of deformation of the population structure in the form of a reduced number of lymphocytes with typical activity (kurtosis less than –0.8). For them, the prescription of the Korilip complex is justified, both as an independent treatment and in combination with specialized therapy. As a rule, at least 6–8 courses of 10 days with the Korilip complex are necessary to normalize the enzyme status and well-being of a woman.

The choice of course duration (10 days) is explained by the fact that 4–5 days after the start of taking the drugs, there is a positive trend in the cytochemical status of leukocytes, which consists, in particular, in an increase in the average activity of SDH and alpha-GPDH and a tendency towards normalization of other elements of the population structure . The number of courses prescribed is determined by the positive dynamics of cytochemical parameters and the stability of their changes. As a rule, at least 6–8 courses of the Korilip complex are necessary to normalize the enzyme status and well-being of a woman (Fig.).

To study the degree of tension in energy metabolism in response to the administration of the Korilip suppository complex, a test with isocitrate, SDH (IZO) was used (M. N. Kondrashova et al., 1987; S. V. Petrichuk et al., 1990). It is known that in response to the action of an intense external stimulus, there is a sharp increase in the production of energy resources in the cells of the body, which are used to ensure a response. To prevent excessive consumption of energy cycle substrates and depletion of mitochondrial activity, there is a protective mechanism by blocking the main mitochondrial enzyme, succinate dehydrogenase. This block is inactivated during a reaction to detect SDH activity with the addition of isocitric acid to the main substrate. An increase in enzyme activity in a sample with isocitric acid, compared to a sample on the main substrate, indicates an increase in energy metabolism. To assess the degree of tension in energy metabolism, the coefficient K is calculated:

K = SDH (ISO)/SDG = 1.15 or 115%

The value of the coefficient K > 1 is an unfavorable cytochemical sign, indicating the stress of cellular metabolism and the instability of the mitochondrial membrane. In relatively healthy patients, the K coefficient is 80–90%.

It has been proven that during treatment with Korilip suppositories, the value of the K coefficient decreases and approaches normal values ​​().

conclusions

1. The most effective use of Korilip in relation to the child is observed in women receiving therapy 6–9 months before and during pregnancy under the control of cytochemical analysis.
2. The duration of courses of therapy with the Korilip complex (10 days) and their frequency are determined by the activity of peripheral blood leukocyte enzymes.
3. During pregnancy, it is justified to prescribe metabolic benefits during critical periods (according to cytochemical indicators): 5–8 weeks, 10–12 weeks, 20th week, 27–28 weeks, 30–32 weeks, 35–37 weeks.
4. Preparing a married couple for pregnancy should begin at least 6–9 months before pregnancy; optimally, the year of life of the parents before conception should be attributed to the ontogenesis of the child.
5. Metabolite correction of energy metabolism disorders in women should be the first step of medical care. It represents the most physiological medication that allows, in most cases, to increase the effectiveness of any basic treatment, and in some cases to avoid it.

Literature

1. Shcheplyagina L. A., Nesterenko O. S., Kurmacheva N. A. et al. Prevention and correction of vitamin and mineral deficiency in children and mothers (information letter). M., 2006. 16 p.
2. Petrichuk S. V., Shishchenko V. M., Dukhova Z. P. Cytomorphometric method in assessing the functional activity of lymphocyte mitochondria in normal and pathological conditions / In: “Mitochondria in pathology”, Pushchino, 2001. pp. 19–20 .
3. Aripova A. A. Pathogenetic basis of metabolic therapy of perinatal encephalopathy in premature infants. Diss. Doctor of Medical Sciences M., 1983. 303 p.
4. Kondrashova M. N. Metabolic states of mitochondria in different physiological states of the body. Molecular mechanisms and regulation of experimental metabolism. Pushchino, 1987. pp. 140–153.
5. Usmanov U. Kh., Kiseleva G. S., Tseytina A. Ya., Shishchenko V. M., Valyulis A. A. Creation and research of children's suppositories with vitamins of the V. M. group: Pharmacy. 1991. No. 1. P. 20–24.
6. Mukhamedova Kh. T. Efficiency of metabolic therapy for infectious and inflammatory diseases of premature infants. Author's abstract. diss. Ph.D. honey. Sci. M., 1988. 23 p.
7. Sukhorukov V. S. Heterogeneity and clinical and morphological heterogeneity of mitochondrial pathology in children. Author's abstract. diss. Doctor of Medical Sciences M., 1998.
8. Nikoleva E. A., Semyachkina S. V., Vasiliev S. Ts. Basic methods of drug treatment for children with mitochondrial diseases. Guide to pharmacotherapy in pediatrics and pediatric surgery, volume 2, “Clinical genetics” under the general editorship of A. D. Tsaregorodtsev, V. A. Tabolin. M.: Medpraktika-M. 2002. pp. 32–44.
9. Samsygina G. A., Dementieva G. M., Talalaev A. G. Health of the newborn fetus: current status and prognosis // Pediatrics. 1999, no. 5, p. 4–5.
10. Klembovsky A.I., Sukhorukov V.S. Mitochondrial failure in children // Archives of Pathology. 1997; 59: 5, p. 3–7.
11. Nartsissov R.P. Cell image analysis is the next stage in the development of clinical cytochemistry in pediatrics // Pediatrics, 1998, 34, p. 101–105.
12. Nartsisov R.P. et al. Health, disease and medicine (cytochemical examination using an image analyzer). M., 1999. 25 p.
13. Khripunova G. I., Gribova S. N., Budelenko G. B., Orlova V. M. Abstracts for the 9th All-Russian Forum “Mother and Child”: Experience with the use of the drug “Corilip” in the postoperative period in the complex treatment of background and precancerous diseases of the cervix.

Zh. Kh. Kushkhova , Candidate of Medical Sciences

GP No. 153 UZ NEAD , Moscow

Contact information about the author for correspondence

Indications for use of the drug Cocarboxylase

Hepatic and renal failure, hepatic and diabetic coma, precomatous conditions, acidosis in diabetes mellitus, respiratory acidosis in chronic pulmonary heart failure, coronary circulatory failure, heart disease accompanied by extrasystole, paroxysmal tachycardia, atrial fibrillation and other rhythm disturbances, mild forms of disseminated sclerosis, preeclamptic conditions and eclampsia, peripheral neuritis, pathological processes with impaired carbohydrate metabolism.

Use of the drug Cocarboxylase

Administer intramuscularly (sometimes intravenously and subcutaneously) after dissolving in water for injection. As a rule, they are prescribed in complex treatment regimens. Adults are administered 0.05–0.1 g intramuscularly once a day. The course of treatment is 15–30 days. If necessary (diabetic coma), cocarboxylase can be administered again in the same dose after 1–2 hours. Subsequently, they switch to a maintenance dose of 50 mg once a day. Children up to the 3rd month of life - 25 mg (0.025 g) 1 time per day; from 4 months to 7 years - 0.025–0.05 g 1 time per day; patients aged 8-18 years - 0.05-0.1 g 1 time per day. If necessary, the indicated daily dose can be divided into 2 administrations.

Cocarboxylase 50 mg No. 10 por.liof.d/in.

Instructions for medical use of the drug Cocarboxylase hydrochloride Trade name Cocarboxylase hydrochloride International nonproprietary name Cocarboxylase Dosage form Lyophilisate for the preparation of solution for injection 50 mg complete with solvent Composition 1 ampoule contains the active substance: cocarboxylase hydrochloride 50 mg, excipient: sodium carbonate, solvent - water for injection Description White porous mass with a slight specific odor. Hygroscopic. Pharmacotherapeutic group Vitamin B1 and its combinations with vitamins B6 and B12. Vitamin B1. ATX code A11DA Pharmacological properties Pharmacokinetics Cocarboxylase is rapidly absorbed after intramuscular administration. Penetrates into most tissues of the body. Subject to metabolic decomposition. Decomposition products are excreted primarily by the kidneys. Pharmacodynamics Cocarboxylase is a coenzyme of thiamine (vitamin B1), phosphorylated in the body to form mono-, di- and triphosphoric esters, it is part of the enzymes that catalyze the carboxylation and decarboxylation of alpha-keto acids, pyruvic acid, promotes the formation of acetyl-coenzyme A, which determines its participation in carbohydrate metabolism. To participate in these processes, exogenous vitamin B1 (thiamine) must be metabolized into cocarboxylase, a ready-made form of coenzyme, by phosphorylation. It should be noted that the properties of cocarboxylase are only partially adequate to those of thiamine; Cocarboxylase is not used for the prevention and treatment of hypo- and vitamin B1 deficiency. Improves the absorption of glucose, trophism of nervous tissue, and helps normalize the function of the cardiovascular system. Cocarboxylase deficiency causes an increase in the level of pyruvic and lactic acids in the blood, which leads to acidosis and acidotic coma. Indications for use: acidosis of diabetic origin; - hepatic and diabetic coma, precomatose states; - liver and kidney failure; - respiratory acidosis in pulmonary heart failure, heart disease accompanied by extrasystole, paroxysmal tachycardia, atrial fibrillation and other rhythm disturbances, mild forms of multiple sclerosis; — preeclamptic conditions and eclampsia; - peripheral neuritis; — pathological processes with impaired carbohydrate metabolism. Method of administration and dosage Usually used as a component of complex therapy. Cocarboxylase is administered intramuscularly, less often – subcutaneously or intravenously. Before administration, the contents of the ampoule are dissolved in 2 ml of water for injection. For intravenous jet administration, increase the volume to 10-20 ml, for drip administration - up to 200-400 ml, adding 0.9% sodium chloride solution or 5% glucose solution. The dose for administration is determined individually, taking into account the nature of the disease and the severity of the patient’s condition. Adults are administered 50-100 mg/day once. The course of treatment is 15-30 days. If necessary (diabetic coma), the indicated dose can be re-administered after 1-2 hours. In the future, you should switch to maintenance therapy - 50 mg 1 time per day. In case of acute renal and/or liver failure, the drug is used intravenously in a stream of 100-150 mg (4-6 ml) 3 times a day or drip (in a 5% glucose solution) in a dose of 100-150 mg (4-6 ml) for 1 -1.5 months. Children are administered subcutaneously or intramuscularly: from birth to the third month of life - 25 mg 1 time per day; from 4 months to 7 years – 25-50 mg 1 time per day, 8-18 years – 50-100 mg 1 time per day. If necessary, these daily doses can be administered in two doses. Side effects From the immune system: allergic reactions, including hypersensitivity reactions, are possible. Symptoms can vary from itching, skin rash, hives to the development of anaphylactic shock; with intravenous administration - hyperemia, itching, swelling at the injection site. Contraindications - individual hypersensitivity to the drug - pregnancy and lactation. Drug interactions Cocarboxylase enhances the cardiotonic effect of cardiac glycosides and improves their tolerability. Special instructions When carrying out complex therapy, it is necessary to take into account the property of cocarboxylase to enhance the cardiotonic effect of cardiac glycosides. For flickering arrhythmia, the drug should not be administered intravenously. The prepared solution should not be used with other medications. Use the solvent included in the package. Use during pregnancy and lactation. The effectiveness and safety of using Cocarboxylase hydrochloride for the treatment of pregnant women or during breastfeeding have not been established, so the drug is not recommended for use during this period. Childhood. Used from birth. Do not use the drug intravenously. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms No data Overdose Symptoms: increased adverse reactions Treatment: discontinuation of the drug. Symptomatic therapy. Release form and packaging 50 mg of the drug and 2 ml of solvent in glass ampoules or 50 mg of the drug and 2 ml of solvent in glass ampoules with a break ring. 5 or 10 ampoules of the drug and 5 or 10 ampoules of solvent (water for injection) together with instructions for medical use in the state and Russian languages ​​and a ceramic cutting disc for opening ampoules (if necessary) are placed in a pack of cardboard box (chrome-ersatz ) with partitions or a corrugated liner, or with a polymer liner made of polyvinyl chloride film for placement and fixation of ampoules. Storage conditions: Protected from light at a temperature not exceeding 25ºС. Keep out of the reach of children! Shelf life: 3 years Do not use after the expiration date indicated on the package. Conditions for dispensing from pharmacies By prescription, Ukraine Address: 03680, Kiev, st. N. Amosova, 9, Ukraine, tel. +38 (044) 275-16-04, 275-91-50, 521-15-39 Owner of the registration certificate LLC FZ BIOPHARMA, Ukraine Address of the organization that accepts claims from consumers on product quality in the territory of the Republic of Kazakhstan IP Tleubergenova G .S., Republic of Kazakhstan, 010000, Akmola region. Astana, st. Bosingen 8 [email protected]