RU2589260C1 - Pletnev drops possessing coagulating agent action, and method of treating thrombocytopenia in hepatic diseases and leukaemia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to drops possessing coagulating action. Drops represent 95 % ethyl alcohol infusion of great nettle leaves and common motherwort grass, taken at ratio of 1:9 to 9:1, with 250-450 mcg substance content in 1 ml of infusion. Present invention also relates to method of treating thrombocytopenia in hepatic diseases and leukaemia, involving peroral introduction of said drops to patient.

EFFECT: invention promotes normalisation of platelet content in blood volume unit.

2 cl, 2 tbl, 2 ex

Description

The invention relates to the field of pharmaceuticals, pharmacology and can be used in clinical medicine for the treatment of thrombocytopenia in liver diseases and leukemia.

Thrombocytopenia is a condition characterized by a decrease in the number of platelets in a unit of blood volume below normal.

Thrombocytopenia (TP), which, along with damage to the thyroid gland and autoimmune diseases, can become an insurmountable obstacle for doctors and patients during their treatment, one of the important places in the diverse spectrum of formidable adverse events in the medical treatment of liver diseases, cancer and leukemia.

It has been established that TP is one of the first signs of a far-reaching progressive chronic liver disease [McHutchison J.G., Afdhal N., Shiffinan M.L. et al. Efficacy and safety of eltrombopag, an oral platelet growth factor, in subjects with HCV associated thrombocytopenia: preliminary results from a phase II dose-ranging study. J. Hepatol. 2006; 44 (Suppl. 2): A 745], which may be due to the development of hypersplenism syndrome as a consequence of portal hypertension and the manifestation of the duration of the pathological process in the hepatobiliary system. At the same time, with a number of acute liver lesions, clinically significant changes in the cellular composition of peripheral blood are also noted. So, TP is diagnosed in 52% of patients with fulminant hepatitis, in 16% of patients with acute hepatitis, in 6% of cases of chronic liver diseases with mild to moderate fibrosis, and in 64-76% of cases of patients with advanced liver cirrhosis [McHutchison J., Manns M. , Patel K. et al. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology 2002; 123: 1061-1069]. According to a number of studies, the severity and incidence of TA is higher in patients with cirrhosis of the liver of viral etiology [Resk-Radosavljevic M. Thrombocytopenia in liver disease. Can. J. Gastroenterol. 2000; 14 (Suppl. D): 60-66].

Along with substitution therapy, surgical methods such as splenectomy, embolization of the splenic artery, pharmacological methods for the correction of TP have recently been most developed.

Thrombomass transfusion has long been regarded as the “gold standard” for TP correction, especially in urgent cases, being the fastest way to increase platelet count (by 10,000-20000 cells / μl per transfusion) and effectively reduce the risk of bleeding [Giarmini E. Review article : Thrombocytopenia in chronic liver disease and pharmacologic treatment options. Aliment. Pharmacol Ther. 2006; 23: 1055-65; Trotter J. Coagulation abnormalities in patients who have liver disease. Clin. Liver. Dis. 2006; 10: 665-678]. This method was usually used before prescribing diagnostic and therapeutic procedures, or surgical interventions in patients with TA. However, a large number (about 30%) of various infectious, immune complications, as well as technical difficulties (the need for transfusion of thrombomass within 3 days after harvesting) reduces the effectiveness and limits the use of this method for the treatment of TP [Giannini E. Review article: Thrombocytopenia in chronic liver disease and pharmacologic treatment options. Aliment. Pharmacol Ther. 2006; 23: 1055-65].

Splenectomy with laparotomy due to the high risk of severe complications in patients with liver disease and hypersplenism syndrome for the correction of TP is currently not used.

Total vascular embolization of the spleen parenchyma was used as one of the first methods of surgical treatment of hypersplenism, but due to frequent complications (bleeding, purulent processes in the spleen, abdominal cavity), this method has lost its relevance. Currently, partial (30-50% parenchyma) spleen embolization is being carried out, the purpose of which is to reduce platelet sequestration by reducing organ volume [Trotter J. Coagulation abnormalities in patients who have liver disease. Clin. Liver. Dis. 2006; 10: 665-678], which allows in most cases to avoid the above complications [N'Kontchou G., Seror O., Bourcier V. et al. Partial splenic embolization in patients with cirrhosis: efficacy, tolerance and long-term outcome in 32 patients. Eur. J. Gastroenterol. Hepatol. 2005; 2: 179-84].

Given the rather high risk of developing various complications with surgical methods of treatment, pharmacotherapy is considered as the most promising way in the treatment of TP.

Known folk coagulating agent for the treatment of thrombocytopenia in the form of a decoction of dioica nettle leaves, obtained, for example, by brewing 3 tablespoons of nettle in a glass of boiling water and insisting for 10 minutes. A method of treating thrombocytopenia is to take the resulting broth 3-4 times a day (see http://medresept.ru/trombotsitopeniya-lechenie).

A disadvantage of the known agent is: 1) contraindications for use with an increased tendency to thrombosis with a previous ischemic stroke of the brain, postinfarction cardiosclerosis, thrombophlebitis; 2) the need to prepare a decoction immediately before taking it.

The objective of the invention is the creation of a new highly effective integrated herbal drug for the treatment of thrombocytopenia in diseases of the liver, cancer and leukemia, not causing side effects, getting used to it and used both independently and in combination with standard therapy.

The technical result of the invention is the normalization of platelet count per unit volume of blood.

To solve this problem, drops are proposed that have a coagulating effect, characterized in that they are a tincture of 95% ethyl alcohol of dioecious nettle leaves and common motherwort grass, taken in a ratio of 1: 9 to 9: 1, with a content of 250- 450 mcg of substance in 1 ml of tincture.

A method for treating thrombocytopenia in liver diseases and leukemia using the proposed drops is also proposed, which consists in administering to the patient orally said drops of at least 3 drops once a day. The proposed drops were called "Pletnev drops No. 257."

Dioecious nettle leaves contain selenium and vitamin K, and the chemical composition of the grass of the common motherwort includes stachydrin.

Deficiency of selenium and a decrease in the activity of glutathione peroxidase leads to impaired platelet function [Vitoux D., et al. Selenium, glutathione peroxidase, peroxides and platelet functions. Ann Biol Clin, Paris, 1996]. It is proved that vitamin K is a regulator of the formation of coagulants in the human body [N. Mashkovsky. Medicines A guide to pharmacotherapy for doctors. M .: Medicine, 1984. T. 1, 624 p., T. 2, 576 p.]. It was found that stachidrin possesses coagulating properties [Plant resources of the USSR. L. - St. Petersburg: Science, 1985-1993. Vol. one].

Drops Pletnev No. 257 are made as follows.

As the initial products, two types of plant materials are selected, which together contain selenium, vitamin K, and stachydrin: dioecious nettle leaves and

grass motherwort. The plant mass is pre-dried and ground. To select the technological mode, the kinetics of extraction of plant material is studied and the time to establish dynamic equilibrium in the solid-liquid system is determined by the active substances. 30-70 g of dried and crushed leaves of the nettle dioica and 30-70 g of dried and crushed grass of the common motherwort (the ratio of the mass of nettle and motherwort can be from 1: 9 to 9: 1) is placed in a glass container and filled with 95% ethanol in bulk the ratio of plant materials and alcohol is 1:10. The extracts obtained by extraction of the raw materials are defended in the sump during the time specified in the ND. The resulting extract was filtered through membrane ultrafiltration (pore size 0.2 microns). The made tincture is packaged by the batcher in bottles or ampoules of various capacities, sealed and packaged.

An experimental study of the toxicity of Pletnev’s droplets No. 257 showed that the drug is low toxic with a single administration to laboratory animals and is well tolerated with prolonged administration to Wistar rats (3 months) and dogs (1 month), does not have a damaging effect on the main organs and body systems of experimental animals and does not show local irritating effect.

Pletnev's drops No. 257 do not possess embryotoxicity, mutagenicity, and DNA-damaging effects. In the tested doses and administration schemes, the drug does not exhibit allergenic and immunotoxic properties.

A method of treating thrombocytopenia in liver diseases and leukemia is as follows.

The resulting Pletnev drops No. 257 are a solution of the active substance in 95% ethanol, 1 ml of which contains 250-450 μg of drug substance. Drops of Pletnev No. 257 are administered orally.

When administered orally, the required dose is calculated as follows:

20 drops of the solution contain 250-450 μg of the drug substance;

10 drops (1/2) of the solution contain 125-225 μg of the drug substance;

5 drops (1/4) of the solution contain 62.5-112.5 μg of the drug substance;

3 drops (1/7) of the solution contain 37.5-67.5 μg of the drug substance.

Under the control of a general blood test (every 10 days of therapy), the course of treatment is carried out with Pletnev drops No. 257 only when the platelet content is below normal.

With normalization of platelet count per unit volume of blood, the drug is stopped. Repeated courses of treatment on the recommendation of a doctor.

When applying Pletnev’s drops No. 257, normalization of platelet count per unit volume of blood is observed.

An example of a method for the treatment of thrombocytopenia in liver diseases and leukemia.

Example 1

Patient N., 65 years old.

Clinical diagnosis: chronic viral hepatitis C with the formation of cirrhosis. Thrombocytopenia.

Patient N. turned to us on September 10, 2014. Complaints of fatigue, dull pain in the right hypochondrium. Body temperature 36.7 ° C. Vesicular breathing. NPV: 19 / min. Heart sounds are rhythmic. HELL: 135/85 mmHg Art. Pulse: 70 / min. The abdomen is soft, painless. The liver at the edge of the costal arch is dense. The spleen is not palpable. There are no dysuric phenomena. No swelling. Thrombocytopenia (Table 1).

The patient was recommended treatment of thrombocytopenia with Pletnev’s drops No. 257 under the control of a general blood test (after 10 days of therapy).

With written consent, the patient was treated with Pletnev drops No. 257 according to the following scheme: 5 drops inside, dissolving in 50 ml of boiled water at room temperature 1 time a day in the evening before meals for 20 minutes under the control of a general blood test (after 10 days of therapy).

Laboratory research.

After conducting therapy for 30 days on 10/10/2014: complaints of dull pain in the right upper quadrant. Body temperature 36.6 ° C. Vesicular breathing.

NPV: 18 / min. Heart sounds are rhythmic. HELL: 130/70 mmHg Art. Pulse: 65 / min. The abdomen is soft, painless. Liver at the edge of the costal arch, dense. The spleen is not palpable. There are no dysuric phenomena. No swelling. The platelet count is normal (Table 1).

Conclusion: the treatment of thrombocytopenia with Pletnev drops No. 257 was carried out with a positive effect.

Example 2

Patient I., 37 years old.

Clinical diagnosis: acute myeloid leukemia (MO), remission from 09.2013. Relapse of the disease from 11.2014. 1 course FLAG-Ida. C92.0.

Patient I. turned to us on November 7, 2014. Complaints of headache, night cough. Fatigue, drowsiness. Body temperature is 37.8 ° C. The breath is hard. NPV: 22 / min. Heart sounds are rhythmic, muffled. HELL: 125/75 mmHg Art. Pulse: 75 / min. The abdomen is soft, painless. Liver, spleen not palpable. There are no dysuric phenomena. No swelling. Thrombocytopenia (Table 2).

The patient was recommended treatment of thrombocytopenia with Pletnev’s drops No. 257 under the control of a general blood test (after 10 days of therapy).

With the written consent of the patient, Pletnev’s drops No. 257 were treated according to the following scheme: 3 drops inside, dissolving in 50 ml of boiled water at room temperature once a day in the morning before meals for 20 minutes, under the control of a general blood test (after 10 days of therapy).

Laboratory research.

After conducting therapy for 20 days on 11/27/2014: notes improvement in well-being. There are no complaints. Body temperature 36.8 ° C. Vesicular breathing. NPV: 18 / min. Heart sounds are rhythmic. HELL: 120/70 mmHg Art. Pulse: 65 / min. The abdomen is soft, painless. Liver, spleen not palpable. There are no dysuric phenomena. No swelling. The platelet count is normal (Table 2).

Conclusion: the treatment of thrombocytopenia with Pletnev drops No. 257 was carried out with a positive effect.

Claims (2)

1. Drops with a coagulating effect, characterized in that they are a tincture of 95% ethyl alcohol of dioica nettle leaves and common motherwort grass, taken in a ratio of 1: 9 to 9: 1, with a content of 250-450 μg of substance in 1 ml of tincture. 2. A method for the treatment of thrombocytopenia in liver diseases and leukemia, which consists in administering to the patient oral drops according to claim 1, at least 3 drops once a day.