RU2739212C1 - Preparation for complex therapy of diseases caused by beta-coronaviruses - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: present invention refers to medicine and pharmaceutics, namely to application of 2-ethyl-6-methyl-3-hydroxypyridine succinate as an adjuvant preparation in complex therapy of diseases caused by beta-coronaviruses.

EFFECT: present invention provides higher effectiveness of complex therapy of coronavirus infection and reduced duration of treating the disease.

1 cl, 3 ex, 19 tbl, 1 dwg

Description

Technology area

The invention relates to medicine and pharmacy, namely to the use of 2-ethyl-6-methyl-3-hydroxypyridine succinate in the complex therapy of diseases caused by coronaviruses.

Prior art

Coronaviruses (Coronaviridae) are a large family of RNA viruses that can infect humans and some animals. The modern classification includes four groups - alpha, beta, gamma and delta coronaviruses [6]. For mammals, the danger is mainly represented by the first two groups. In humans, coronaviruses can cause a range of illnesses, from mild acute respiratory infections to severe acute respiratory syndrome.

For the treatment of coronavirus infections, drugs from the group of antiviral drugs (umifenovir, ingavirin, remdesivir, a combination of lopinavir + ritonavir), interferon drugs, and some drugs from the group of antimalarial drugs (chloroquine, hydroxychloroquine) are currently used [1, 2, 3].

The use of antiseptic Miramistin for inactivation of coronaviruses is known [4].

Antioxidants and antihypoxants are widely used in outpatient and clinical practice for the treatment of various diseases and can be used in the complex therapy of patients with coronavirus infection. Thus, the prior art describes the parenteral use of high doses of vitamin C in the therapy of COVID-19 in the early stages of the disease [5]. The mechanism of action of the drug is associated with its prooxidant effect, which helps to weaken the expression of pro-inflammatory mediators, improve the clearance of alveolar fluid, and due to the antioxidant effect, the function of epithelial cells improves.

The disadvantage of the described technical solution is the narrow spectrum of the pharmacological action of the drug. Diseases caused by coronaviruses have complex pathophysiological mechanisms of development. Acting on several "targets" at once, coronaviruses cause multiple lesions in human organs and tissues and thus have a systemic effect on the body [6, 7, 10]. In addition, the use of vitamin C in high doses can lead to osmotic death of immune cells and the development of a local inflammatory reaction in the alveolar environment [5].

2-ethyl-6-methyl-3-hydroxypyridine succinate (trade name Mexidol®) refers to drugs with antioxidant and antihypoxant effects. It is widely used in various types of ischemic and hypoxic conditions: in acute and chronic disorders of cerebral circulation, traumatic brain injury, vegetative dystonia syndrome, cardiovascular diseases, in high-altitude hypoxia and other extreme conditions accompanied by hypoxia and oxidative stress. The drug improves cerebral metabolism and blood supply to the brain, improves microcirculation and rheological properties of blood, and reduces platelet aggregation. It stabilizes the membrane structures of blood cells (erythrocytes and platelets) during hemolysis. [8].

Mexidol has already shown its effectiveness in the treatment of influenza [9]. At the same time, the drug has not been previously used to treat infections caused by coronaviruses.

Disclosure of invention

The objective of the invention is to expand the arsenal of drugs for the treatment and prevention of diseases caused by coronaviruses, reduce toxicity and increase the effectiveness of treatment.

The task is solved by using 2-ethyl-6-methyl-3-hydroxypyridine succinate in the complex therapy and prevention of coronavirus infection.

The technical result of the claimed invention is to increase the effectiveness of complex therapy for coronavirus infection and reduce the duration of treatment of the disease.

The specified technical result is achieved due to a multimodal mechanism of action and a wide range of pharmacological effects of 2-ethyl-6-methyl-3-hydroxypyridine succinate, which makes it possible to influence different pathophysiological pathways of the disease and use it as an adjuvant drug (auxiliary therapy drug).

In patients with coronavirus infection, Mexidol exhibits the following effects:

- inhibits serine, metal-dependent proteinases of viruses, helping to reduce their virulence;

- inhibits trypsin-like proteinases, preventing infection of epithelial cells with viruses;

- inhibits lipid peroxidation and neutralizes free radicals involved in inflammation and cell death, increases the activity of antioxidant enzymes superoxide dismutase and glutathione peroxidase, which are responsible for neutralizing reactive oxygen species;

- exhibits a membrane-protective effect, which is manifested in the ability to stabilize the membrane structures of blood cells (erythrocytes and platelets), reducing the likelihood of hemolysis;

- has an antihypoxic effect, improves energy metabolism in the cell;

- has chelating properties and is used to treat iron overload.

The latter two effects are of particular importance for the treatment of COVID-19 infections. It has been shown that in most patients with this coronavirus infection, the level of hemoglobin, a protein that carries oxygen and provides gas exchange in the lungs, significantly decreases in the blood. The virus attacks hemoglobin, on the one hand, binding porphyrin, and on the other, interacting with the protein beta-chains of hemoglobin, and the consequence of these effects is the displacement of the iron ion from the heme, which plays an important role in the formation and metabolism of reactive oxygen species. The iron released into the circulatory system is so toxic that it causes severe oxidative damage. In this case, hemoglobin loses its ability to bind oxygen, hypoxia of the hemic (transport) nature of all organs and tissues occurs [10].

2-ethyl-6-methyl-3-hydroxypyridine succinate binds free iron, thereby reducing its toxic effect on the body, and also has an antihypoxic, energotropic effect.

It was also found that a special marker for the development of infection caused by COVID-19 is an increased level of ferritin, a protein responsible for the absorption of iron [11]. Some researchers associate the development of a "cytokine storm" (the main symptom of the severe course of COVID-19) with a sharp increase in the amount of ferritin in the blood [12]. It was found that Mexidol helps to reduce this indicator, thus blocking another mechanism of the development of the disease.

Additionally, a wide range of pharmacological activity of Mexidol makes it possible to reduce the dose and the number of drugs administered in combination with it, which makes it possible to reduce the frequency of possible side effects.

The drug Mexidol practically does not give side effects and has no contraindications, therefore it can be used in a contingent of patients over 70 years old, adolescents, as well as in severe concomitant pathology (tuberculosis, diabetes mellitus, etc.).

The route of administration (intravenous and / or oral) and the dosage regimen of 2-ethyl-6-methyl-3-hydroxypyridine succinate are selected depending on the stage and severity of the disease. At the same time, single and daily doses do not exceed the well-known dosages in which the drug is used for other nosologies. Preferably, the drug is administered intravenously or intramuscularly at 100-1200 mg 1-3 times a day. After the end of therapy with the injectable form, they switch to taking the drug in the form for oral administration (tablets, capsules, etc.), 100-750 mg 1-3 times a day.

The invention is illustrated by the following examples.

Example 1.

Therapy without Mexidol

Patient P. 60 years old, height - 174 cm, body weight - 76 kg; BMI of 25.5 kg / m ^2, RT = 75 cm.

Anamnesis: For about 15 years he has been suffering from hypertension with a maximum rise in blood pressure up to 160/110 mm Hg. Type 2 diabetes mellitus was diagnosed about 3 years ago. He denies leaving the territory of permanent residence in the last 6 months.

7 days before hospitalization, he noted a deterioration in his general condition, weakness appeared, body temperature 37.6 ° C. By the time of treatment, shortness of breath, dry cough, and an increase in body temperature to 38.1 ° C appeared. I turned to the City Clinical Hospital.

On admission: a state of moderate severity, temperature 38.1 ° C, complaints of shortness of breath at rest, dry cough, pale pink skin, no edema.

When examining the respiratory system: palpation of the chest - painless, percussion pulmonary sound, auscultatory breathing is hard, oxygen saturation - 92%, respiratory rate - 22 / min, dry rales are heard in the lower lungs on both sides, crepitus - no, pleural friction - no.

Circulatory system: clear heart sounds, correct rhythm. NPV - 76 beats / min, noises - no, blood pressure 150/90 mm Hg, heart rate 76 beats / min, satisfactory filling and tension.

The digestive system: the abdomen is soft, painless, the liver is at the edge of the costal arch, the spleen is not palpable, the symptom of "tapping" in the lumbar region is negative on both sides, physiological functions are normal.

CT scan of the chest organs was performed, according to which CT signs of a viral infection are observed, with a high probability of COVID-19, moderate (2 tbsp.) CT severity (Table 3).

Diagnosis: Type 2 diabetes mellitus, grade 2 hypertension, community-acquired bilateral pneumonia (COVID-19 positive) of moderate to severe course.

The patient was admitted to the infectious diseases department.

Therapy: Omez 20 mg, Azithromycin 500 mg i.v. per day, Plaquenil 2 tablets. × 2 p. on the 1st day, then 1 table. × 2 p., Kaletra 2 tab. × 2 p. per day, Fragmin 2.5 thousand × 2 p. p / c, Bisoprolol 1.25 mg, Tocilizumab 600 mg (on the 2nd day), Human immunoglobulin at a dose of 10 g (on the 3rd day). Maxiktam 1 + 1 g 4 times a day, Amikacin 1500 mg 1 r. per day.

Treatment results

On the 5th day, the patient's condition remains moderate, however, there is a slight positive trend: the body temperature has returned to normal, CT shows a positive trend. There is a slight positive trend in general and biochemical blood tests (Table 1, Table 2).

On the 12th day of therapy, there is a significant positive trend. The patient's condition is satisfactory, the temperature is 36.7 ° C. Respiratory organs: auscultatory breathing in the lungs is vesicular, carried out in all departments, no wheezing, respiratory rate - 16 / min. On CT, there are residual effects of the transferred pneumonia (Table 3). The levels of erythrocytes and hemoglobin increased slightly, but remained below normal (Table 1). The levels of glucose, CRP and ferritin have decreased, but remain above normal (Table 2).

The levels of superoxide dismutase and malondialdehyde (MDA) practically did not change during therapy, which indicates an insufficient activity of the antioxidant defense of the body and, as a result, an active course of lipid peroxidation (LPO) processes (Table 2).

Dynamic control is recommended. The patient was discharged.

Therapy with Mexidol

Patient R. 62 years old, height - 172 cm, body weight - 74 kg; BMI of 25.0 kg / m ^2, RT = 74 cm.

Anamnesis: More than 10 years suffering from hypertension with a maximum rise in blood pressure up to 180/110 mm Hg. Type 2 diabetes mellitus was diagnosed 5 years ago. He denies leaving the territory of permanent residence in the last 6 months.

5 days before hospitalization, he noted a deterioration in his general condition, weakness appeared, body temperature 37.8 ° C. By the time of treatment, a dry cough appeared, an increase in body temperature up to 38.3 ° C. I turned to the City Clinical Hospital.

On admission: a state of moderate severity, temperature 38.3 ° C, dry cough, pale pink skin, no edema.

When examining the respiratory system: palpation of the chest - painless, percussion pulmonary sound, auscultatory breathing is hard, oxygen saturation - 93%, respiratory rate - 20 / min, dry rales are heard in the lower parts of the lungs on both sides, crepitus - no, pleural friction - no.

Circulatory system: clear heart sounds, correct rhythm. NPV - 78 beats / min, noises - no, blood pressure 160/90 mm Hg, heart rate 78 beats / min, satisfactory filling and tension.

The digestive system: the abdomen is soft, painless, the liver is at the edge of the costal arch, the spleen is not palpable, the symptom of "tapping" in the lumbar region is negative on both sides, physiological functions are normal.

CT scan of the chest organs was performed, according to which CT signs of a viral infection are observed, with a high probability of COVID-19, moderate (grade 2) CT severity (Table 6).

Diagnosis: Hypertension grade 3, type 2 diabetes mellitus, community-acquired bilateral pneumonia (COVID-19 positive) of moderate to severe course.

The patient was admitted to the infectious diseases department.

Therapy: Omez 20 mg, Azithromycin 500 mg i.v. per day, Plaquenil 2 tablets. × 2 p. on the 1st day, then 1 table. × 2 p., Kaletra 2 tab. × 2 p. per day, Fragmin 2.5 thousand × 2 p. s / c, Bisoprolol 1.25 mg. Tocilizumab 600 mg (on the 2nd day), Human immunoglobulin at a dose of 10 g (on the 3rd day). Maxiktam 1 + 1 g 4 times a day, Amikacin 1500 mg 1 r. per day, Mexidol 50 mg / in cap. × 2 rubles / day.

Treatment results

Against the background of ongoing therapy, which includes Mexidol at a dose of 500 mg IV cap. × 2 r. / Day, on the 5th day the patient's condition remains moderate, however, there is a significant positive trend: body temperature has returned to normal, CT shows a positive trend. In the general analysis of blood, an increase in erythrocytes and hemoglobin is noteworthy (Table 4). In the biochemical analysis, a decrease in glucose levels is noted (Table 5).

On the 10th day of therapy, which includes Mexidol at a dose of 500 mg IV cap. × 2 rubles / day, there is a significant positive trend. The patient's condition is satisfactory, the temperature is 36.6 ° C. Respiratory organs: auscultatory breathing in the lungs is vesicular, carried out in all departments, no wheezing, respiratory rate - 16 / min. On CT, there are residual effects of the transferred pneumonia (Table 6). The levels of erythrocytes and hemoglobin returned to normal (Table 4). The glucose level has returned to normal. CRP and ferritin levels decreased significantly (Table 5).

While taking Mexidol, a significant increase in superoxide dismutase was noted, which indicates an increase in the antioxidant defense of the body. A significant decrease in malondialdehyde (MDA) was recorded, which indicates a positive effect of the drug Mexidol on the processes of lipid peroxidation (LPO) (Table 5).

Dynamic control is recommended. The patient was discharged.

Example 2.

Therapy without Mexidol

Patient A. 37 years old, height - 178 cm, body weight - 65 kg; BMI = 20.5 kg / m ² , OT = 67 cm.

Anamnesis: Previous diseases - denies. Chronic diseases - denies. Bad habits - denies. He denies leaving the territory of permanent residence in the last 6 months.

6 days ago, the temperature rises to 39.0 ° C, dry cough. I took paracetamol, then Klacid for 4 days, with no visible effect. Due to persistent complaints, he was hospitalized on the emergency room.

On admission: a state of moderate severity, temperature 37.8 ° C, complaints of dry cough, shortness of breath. The skin is pale pink, no edema.

When examining the respiratory system: palpation of the chest - painless, percussion pulmonary sound, auscultatory breathing is hard, oxygen saturation - 94%, respiratory rate - 23 / min, dry rales are heard in the lower parts of the lungs on both sides, crepitus - no, pleural friction - no.

Circulatory system: clear heart sounds, correct rhythm. NPV - 76 beats / min, noises - no, blood pressure 110/70 mm Hg, heart rate 76 beats / min, satisfactory filling and tension.

The digestive system: the abdomen is soft, painless, the liver is at the edge of the costal arch, the spleen is not palpable, the symptom of "tapping" in the lumbar region is negative on both sides, physiological functions are normal.

CT scan of the chest organs was performed, according to which CT signs of a viral infection are observed, with a high probability of COVID-19, moderate (2 tbsp.) CT severity (Table 9).

Diagnosis: Community-acquired bilateral pneumonia (COVID-19 positive) of moderate-severe course. DN 1 Art.

The patient was admitted to the infectious diseases department

Therapy: Hydroxychloroquine 200 mg peros, Azithromycin 400 mg i.v. × 2 r./day the first day, then 200 mg i.v. × 2 r./day per day.

Treatment results

On the 5th day, the patient's condition remains moderate, however, there is a slight positive dynamics in the general and biochemical blood tests (Table 7, Table 8), the body temperature dropped to 37 ° C.

On the 13th day of therapy, there is a significant positive trend. The patient's condition is satisfactory, the temperature is 36.6 ° C. Respiratory organs: auscultatory breathing in the lungs - vesicular, is carried out in all departments, no wheezing. On CT, there are residual effects of the transferred pneumonia (Table 9). Erythrocyte and hemoglobin levels have normalized, but remain below normal (Table 7) CRP and ferritin levels have decreased, but remain above normal (Table 8).

The levels of superoxide dismutase and malondialdehyde (MDA) changed insignificantly, which indicates insufficient activity of the body's antioxidant defense and, as a result, the active course of lipid peroxidation (LPO) processes (Table 8).

Dynamic control is recommended. The patient was discharged.

Therapy with Mexidol

Patient N., 41 years old, height - 181 cm, body weight - 69 kg; BMI of 21.1 kg / m ^2, RT = 73 cm.

Anamnesis: Previous diseases - denies. Chronic diseases - denies. Bad habits - smoking, up to 1 pack / day. He denies leaving the territory of permanent residence in the last 6 months.

7 days ago, the temperature rose to 39.5 ° C, dry cough, heaviness in the chest. Took paracetamol for 5 days. Due to persistent complaints, he was hospitalized on the emergency room.

On admission: a state of moderate severity, temperature 38.0 ° C, complaints of heaviness in the chest, shortness of breath, dry cough. The skin is pink, no edema.

When examining the respiratory system: palpation of the chest - painless, percussion pulmonary sound, auscultatory breathing is hard, oxygen saturation - 92%, respiratory rate - 25 / min, dry rales are heard in the lower parts of the lungs on both sides, crepitus - no, pleural friction - no.

Circulatory system: clear heart sounds, correct rhythm. NPV - 82 beats / min, noises - no, blood pressure 130/80 mm Hg, heart rate 82 beats / min, satisfactory filling and tension.

The digestive system: the abdomen is soft, painless, the liver is at the edge of the costal arch, the spleen is not palpable, the symptom of "tapping" in the lumbar region is negative on both sides, physiological functions are normal.

CT scan of the chest organs was performed, according to which CT signs of a viral infection are observed, with a high probability of COVID-19, moderate (2 tbsp) CT severity (Table 12).

Diagnosis: Community-acquired bilateral pneumonia (COVID-19 positive) of moderate-severe course. Respiratory failure. DN 1 Art.

The patient was admitted to the infectious diseases department.

Therapy: Hydroxychloroquine 200 mg peros, Azithromycin 400 mg i.v. × 2 r./day the first day, then 200 mg i.v. × 2 r./day per day, Mexid 200 mg i.v. cap. × 2 rubles / day.

Treatment results

Against the background of ongoing therapy, which includes Mexidol at a dose of 200 mg / cap. × 2 r / day, on the 5th day there is a significant positive trend: body temperature returned to normal, CT shows a positive trend. In the general analysis of blood, attention is drawn to the increase in erythrocytes and hemoglobin to normal (Table 10).

On the 10th day of therapy, which includes Mexidol at a dose of 200 mg IV cap. × 2 rubles / day, there is a significant positive trend. The patient's condition is satisfactory, the temperature is 36.6 ° C. Respiratory organs: auscultatory breathing in the lungs is vesicular, carried out in all departments, no wheezing, respiratory rate - 16 / min. On CT, there are residual effects of the transferred pneumonia (Table 12). The levels of erythrocytes and hemoglobin increased (Table 10). CRP and ferritin levels decreased significantly (Table 11).

While taking Mexidol, a significant increase in superoxide dismutase was noted, which indicates an increase in the antioxidant defense of the body. A significant decrease in malondialdehyde (MDA) was recorded, which indicates a positive effect of the drug Mexidol on the processes of lipid peroxidation (LPO) (Table 11).

Dynamic control is recommended. The patient was discharged.

Example 3.

Therapy without Mexidol

Patient V., 72 years old, height - 167 cm, body weight - 98 kg; BMI of 35.1 kg / m ^2, RT = 119 cm.

Anamnesis: Past diseases - 5 years ago suffered a myocardial infarction, followed by CHF. Chronic diseases - hypertension, chronic heart failure, type 2 diabetes mellitus, obesity. Bad habits - denies.

He denies leaving the territory of permanent residence in the last 6 months.

4 days ago, the temperature rose to 38.6 ° C, dry cough, shortness of breath, feeling of lack of air. I took paracetamol, but the symptoms continued to increase. Due to persistent complaints, he was hospitalized on the emergency room.

On admission: a state of moderate severity, temperature 38.1 ° C, complaints of dry cough, shortness of breath, feeling of lack of air. The skin is pale pink, swelling of the feet and legs.

When examining the respiratory system: palpation of the chest - painless, percussion pulmonary sound, auscultatory breathing is hard, oxygen saturation - 91%, respiratory rate - 24 / min, dry rales are heard in the lower parts of the lungs on both sides, crepitus - no, pleural friction - no.

Circulatory system: clear heart sounds, correct rhythm. NPV - 82 beats / min, noises - no, blood pressure 160/90 mm Hg, heart rate 82 beats / min, satisfactory filling and tension.

The digestive system: the abdomen is soft, painless, the liver is not palpable due to obesity, the spleen is not palpable, the “tapping” symptom in the lumbar region is negative on both sides, physiological functions are normal.

CT scan of the chest organs was performed, according to which CT signs of a viral infection are observed, with a high probability of COVID-19, severe (grade 3) CT severity (Table 15).

Diagnosis: Hypertension grade 3, CHF II FC, Type 2 diabetes mellitus, Obesity, Community-acquired bilateral pneumonia (COVID-19 positive) of severe course. Respiratory failure. DN 2 tbsp.

Therapy: Ambroxol 30 mg peros × 3 p./d; Hydroxychloroquine 400 mg peros × 2 times a day on the 1st day, then 200 mg × 2 times a day; Paracetamol 0.5 IV drip when the temperature rises> 38 ° C; solution of NaCl 0.9% 500.0 w / w cap; Enalapril 10 mg × 2 r / d Bisoprolol 1.25 mg; Heparin 7.5 thousand units × 2 r./d pc, Ksarelto 15 mg × 2 r./d, Omez 20 mg.

Treatment results

Against the background of the therapy on the 5th day, the patient's condition remains moderate. There is a slight positive trend in general and biochemical blood tests (Table 13, Table 14).

On the 15th day of therapy, there is a significant positive trend. The patient's condition is satisfactory, the temperature is 36.6 ° C. Respiratory organs: auscultatory breathing in the lungs is vesicular, carried out in all departments, no wheezing, respiratory rate - 16 / min. On CT, there are residual effects of the transferred pneumonia (Table 15). The levels of erythrocytes and hemoglobin increased slightly, but remained below normal (Table 13). Glucose, CRP, and ferritin levels have decreased, but remain above normal (Table 14).

The level of superoxide dismutase and malondialdehyde (MDA) practically did not change during therapy (Table 14).

Dynamic control is recommended. The patient was discharged.

Therapy with Mexidol.

Patient S. 75 years old, height - 172 cm, body weight - 104 kg; BMI of 35.1 kg / m ^2, RT = 125 cm

Anamnesis: Long-term obese. More than 20 years ago, arterial hypertension was diagnosed with maximum blood pressure up to 210/130 mm Hg. and type 2 diabetes. CHF was diagnosed about 7 years ago. 2 years ago she suffered a myocardial infarction. Bad habits - denies. He denies leaving the territory of permanent residence in the last 6 months.

7 days ago, the temperature increased to 39.1 ° C, dry cough, shortness of breath, feeling of shortness of breath. I took paracetamol and ampicilin, but the symptoms continued to increase. Due to persistent complaints, he was hospitalized on the emergency room.

Upon enrolment; a state of moderate severity, temperature 39.3 ° C, complaints of dry cough, shortness of breath, feeling of lack of air. The skin is pale pink, swelling of the feet and legs.

When examining the respiratory system: palpation of the chest - painless, percussion pulmonary sound, auscultatory breathing is hard, oxygen saturation - 92%, respiratory rate - 22 / min, dry rales are heard in the lower lungs on both sides, crepitus - no, pleural friction - no.

Circulatory system: clear heart sounds, correct rhythm. NPV - 76 beats / min, noises - no, blood pressure 170/100 mm Hg, heart rate 76 beats / min, satisfactory filling and tension.

The digestive system: the abdomen is soft, painless, the liver is not palpable due to obesity, the spleen is not palpable, the “tapping” symptom in the lumbar region is negative on both sides, physiological functions are normal.

CT scan of the chest organs was performed, according to which CT signs of a viral infection are observed, with a high probability of COVID-19, severe (3st) CT severity (Table 18).

Diagnosis: Hypertension grade 3, CHF III FC, Type 2 diabetes mellitus, obesity, community-acquired bilateral pneumonia (COVID-19 positive) of severe course. Respiratory failure. DN 2 tbsp.

Therapy: Ambroxol 30 mg peros × 3 p./d; Hydroxychloroquine 400 mg peros × 2 times a day on the 1st day, then 200 mg × 2 times a day; Paracetamol 0.5 IV cap. when the temperature rises> 38 ° С; solution of NaCl 0.9% 500.0 w / w cap; Enalapril 10 mg × 2 r./d; Bisoprolol 1.25 mg; Heparin 7.5 thousand units × 2 r./d pc, Ksarelto 15 mg × 2 r./d, Omez 20 mg; Mexidol 1000 mg IV cap. 1 r / day.

Treatment results

Against the background of ongoing therapy, which includes Mexidol at a dose of 1000 mg / cap. × 1 r // day, on the 5th day, the patient's condition remains moderate, however, there is a significant positive trend: body temperature returned to normal, CT scan showed positive dynamics. In the general analysis of blood, an increase in erythrocytes and hemoglobin attracts attention (Table 16). Biochemical analysis shows a decrease in glucose and ferritin levels (Table 17).

On the 11th day of therapy, which includes Mexidol at a dose of 1000 mg / cap. × 1p / day, there is a significant positive trend. The patient's condition is satisfactory, the temperature is 36.6 ° C. Respiratory organs: auscultatory breathing in the lungs is vesicular, carried out in all departments, no wheezing, respiratory rate - 16 / min. On CT, there are residual effects of the transferred pneumonia (Table 18). Erythrocyte and hemoglobin levels returned to normal (Table 16). The glucose level has returned to normal. CRP and ferritin levels have significantly decreased, but remain above normal (Table 17).

While taking Mexidol, a significant increase in superoxide dismutase was noted, which indicates an increase in the antioxidant defense of the body. A significant decrease in malondialdehyde (MDA) was recorded, which indicates a positive effect of the drug Mexidol on the processes of lipid peroxidation (LPO) (Table 17).

Dynamic control is recommended. The patient was discharged.

Table 19 and FIG. 1 shows the general data of therapy with Mexidol and without.

From the above examples, it can be seen that the use of 2-ethyl-6-methyl-3-hydroxypyridine succinate in combinations with other drugs makes it possible to increase the effectiveness of the treatment of coronavirus infection, to normalize blood counts, which are markers of the development of the disease, in a shorter time, and to shorten the duration of the course of the disease in on average for 2-4 days. This effect is confirmed by experimental studies and could not be predicted empirically based on the prior art due to the nonlinearity of the course of diseases, as well as multicomponent therapy with a different combination of both positive and side effects.

Thus, the claimed invention meets the criteria of "industrial applicability", "novelty" and "inventive step" and can be recognized as patentable.

Bibliography

1. Directory of medicines VIDAL,

https://www.vidal.ru/drugs/umifenovir

2. Directory of medicines VIDAL,

https://www.vidal.ru/drugs/ingavirin_18284

3. Interim guidelines: prevention, diagnosis and treatment of coronavirus infection (COVID-19), ver. 6, 28.04.2020.

4. RF patent No. 2234313, C1 (Krivoshein Yu.S., Rudko A.P.), 20.08.2004.

5. Adrian Erol, High-dose intravenous vitamin C treatment for COVID-19 (a mechanistic approach), feb. 2020,

https://www.researchgate.net/publication/339511104_High_dose_intravenousvitaminCtreatmentf_for_COVID-19

6. Helena Jane Maier, Erica Bickerton, Paul Britton, “Coronaviruses: An Overview of Their Replication and Pathogenesis)), Coronaviruses, 2015; 1282: 1-23.

7. Abdul Mannan Baig, Areeba Khaleeq, Usman Ali, and Hira Syeda Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. Chem. Neurosci. 2020, 11, 995-998.

8. Directory of medicines VIDAL,

https://www.vidal.ru/drugs/mexidol_39928

9. Pavelkina V.F. Clinical and pathogenetic aspects of endogenous intoxication and its correction in diseases of viral and bacterial etiology. Abstract of dissertation Doctor of Medical Sciences, Moscow, 2010, 48 p.

10. Wenzhong Liu, Hualan Li "COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism", 04/27/2020,

https://chemrxiv.org/articles/COVID19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173

11. Stanislas Bataille, "Could ferritin help the screening for COVID-19 in hemodialysis patients?", 04.2020,

https://www.researchgate.net/publication/340852931_Could_ferritin_help_the_screening_for_COVID-19_in_hemodialysis_patients

12. Yehuda Shoenfeld, "Corona (COVID-19) time musings: Our involvement in COVID-19 pathogenesis, diagnosis, treatment and vaccine planning," Autoimmunity Reviews, v. 19, Issue 6, June 2020, 102538.

Claims (2)

1. The use of 2-ethyl-6-methyl-3-hydroxypyridine succinate as an adjuvant drug in the complex therapy of diseases caused by beta-coronaviruses. 2. Use according to claim 1, characterized in that the disease is caused by the coronavirus COVID-19.

Images