RU2553308C1 - Pletnev's drops possessing antiviral and immunomodulatory effects - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: drops possessing antiviral and immunomodulatory effects characterised by the fact that they represent a 95% ethanol infusion of wild strawberry leaves and fruit specified in: red raspberry fruit, mountain ash fruit, bilberry fruit, blood-red hawthorn fruit, cinnamon rose fruit; 15-25 mg of the substance in 1 ml of the infusion.

EFFECT: drops possess pronounced antiviral and immunomodulatory effects.

15 tbl, 5 ex

Description

The invention relates to the field of pharmacology, molecular biology and can be used in clinical medicine for the treatment of various diseases in the pathogenesis of which there is a violation of protein synthesis caused by various infectious agents, injuries and burns.

Recently, interest in drugs of natural origin has been growing, due to both the features of their chemical composition, whose components are structurally similar to the metabolites of the human body, and the relative safety of their use, which makes it much wider than synthetic to recommend them for the prevention and treatment of various diseases.

An important feature of galenic preparations is that they contain a significant amount of biologically active substances with varying degrees of severity of healing properties, which can be significantly enhanced or leveled when combined. It is the therapeutic effects of medicinal plants that are fundamental in compiling the prescriptions of complex herbal preparations (Phytotherapy with the basics of clinical pharmacology / Edited by V.G. Kukes. - M .: Medicine, 1999, p.7).

V.V. Pletnev proposed an original approach for creating new complex herbal preparations for medicine based on pharmacopoeial plants with the addition of biologically active components of plant or other nature. Using this approach, an integrated herbal medicine Selecartin (RF patent for the invention No. 2294209 dated 02.27.2007) and Pletnev drops (RF patent for the invention No. 2466734 dated November 20, 2012) were created.

It is known that modern medications used for antiviral and immunomodulating therapy often cause side effects, for example, when taking: amixin - allergic reactions, dyspeptic symptoms, short-term chills; acyclovir - abdominal pain, nausea, vomiting, diarrhea, transient increase in liver enzyme activity, hyperbilirubinemia, leukopenia, erythropenia, headache, weakness, tremor, dizziness, increased fatigue, drowsiness, hallucinations, skin rash, allergic dermatitis, alope, increased levels of urea and creatinine (Federal guidelines for the use of medicines. Issue XII. - M .: ″ Echo ″, 2011, pp. 47, 280, 282, 297, 435, 529, 530, 548, 585, 662, 680, 719, 826).

Known means based on herbal preparations with hepatoprotective, antimicrobial, antiviral, immunomodulating and antioxidant activity.

Also known is a composition for preparing a non-alcoholic jelly drink containing, kg / 100 kg: mangosteen extract 0.2-0.4, gellan gum 0.05-0.1, fruit, and / or vegetable, and / or vegetable puree 2, 0-5.0, fructose syrup 14.0-16.0, stevioside 0.02-0.03, citric acid 0.04-0.06 and water - the rest. The composition gives the prepared jelly soft drink antioxidant, antibacterial, antiviral, anti-inflammatory, immunomodulating and hepatoprotective properties and serves to prevent diseases and improve human health.

This product is a non-alcoholic drink and cannot be used as a medicine.

Closest to the proposed are Pletnev drops for restoring the metabolism and energy supply of tissues and organs, which are a tincture of one or two types of plant material on 95% ethanol containing 15-25 mg of substance in 1 ml of tincture, including tincture of strawberry leaves and the second type of plant material, such as nettle leaves (drops No. 1B), or leaves of a large plantain (drops No. 2B), or leaves of coltsfoot (drops No. 4), or shoots of blueberries (drops No. 39), or grass yarrow o (drops No. 68). Drops contribute to the restoration of the structure and functions of biomembranes of cells, endothelium of blood vessels, liver, nervous and immune systems without side effects and addiction to drugs (RU 2466734 C1, publ. 20.11.2012).

However, known drops have very weak immunomodulatory and antiviral effects. Those that were used in the treatment of viral diseases, such as HIV (drops No. 39) or chronic viral hepatitis C (drops No. 4 and No. 5), were used for rehabilitation when some of the indicators of the immune status were already within normal limits (with treatment of chronic viral hepatitis C), and those that were outside the norm, as a result of the use of drops did not reach the norm.

The objective of the invention is the creation of new highly effective complex herbal medicines with antiviral and immunomodulating effects, not causing side effects, getting used to them and used both independently and in combination with standard therapy.

The technical result of the invention is the provision of effective antiviral and immunomodulating therapy without side effects and addiction to drugs.

To solve this problem, drops are proposed that have antiviral and immunomodulating effects, which are called "Pletnev's drops." They are a tincture obtained by extraction from plant materials with an organic solvent.

Pletnev drops are a tincture of two types of plant materials, which together contain selenium, zinc, vitamin P, chlorophyll, 95% ethanol (FS 42-3072-00) with a content of 15-25 mg of substance in 1 ml of tincture.

The following formulation options for Pletnev drops are possible.

1. Pletnev’s drops No. 204 is a tincture of strawberry leaves (FS 42-134-72) and ordinary raspberries (GOST 3525-75) containing selenium, chlorophyll (strawberry leaves), zinc and vitamin P (raspberry fruit).

2. Pletnev’s drops No. 207 is a tincture of strawberry leaves (FS 42-134-72) and the fruits of mountain ash (GF XI, issue 2, article 25) containing selenium, chlorophyll (strawberry leaves), zinc, vitamins P, C ( rowan fruits).

3. Pletnev’s drops No. 212 is a tincture of wild strawberry leaves (FS 42-134-72) and common blueberries (GF XI, issue 2, article 25) containing selenium, chlorophyll (wild strawberry leaves), zinc, vitamins P, C, quercetrin (blueberries).

4. Pletnev’s drops No. 236 is a tincture of strawberry leaves (FS 42-134-72) and blood-red hawthorn fruits (GF XI, issue 2, article 25) containing selenium, chlorophyll (strawberry leaves), zinc, vitamins P, C, E (hawthorn fruit).

5. Pletnev’s drops No. 245 is a tincture of strawberry leaves (FS 42-134-72) and May hips (GF XI, issue 2, article 25) containing selenium, chlorophyll (strawberry leaves), zinc, vitamins P, C, PP (rose hips).

Pletnev drops are made as follows.

Two types of vegetable raw materials are selected as the starting products, which together contain selenium, zinc, vitamin P and chlorophyll: strawberry leaves, as well as fruits of common raspberry, or mountain ash, or blueberry, or blood-red hawthorn, or may rose hips. 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. 100 g of dried and crushed green mass is placed in a glass container and poured with 95% ethyl alcohol in a ratio of 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 pharmacological properties and toxicity of Pletnev drops No. 204, 207, 212, 236, 245 showed:

1. Pletnev drops No. 204, 207, 212, 236, 245 possess immunomodulating and antiviral properties.

In the range of doses tested, Pletnev drops No. 204, 207, 212, 236, 245 stimulate humoral and cellular immunity, increase phagocytic activity, lymphocyte proliferation and production of TNF-α by human mononuclear cells.

With prophylactic administration 24 hours before infection of mice with a lethal dose of Staphylococcus pyogenes, Pletnev drops No. 204, 207, 212, 236, 245 increase their survival to 75% with 84% death in the control.

In in vitro experiments, Pletnev drops No. 204, 207, 212, 236, 245 in the tested dilutions completely inhibit the growth of Staphylococcus aureus and Escherichia coli, completely inhibit the growth of Pseudomonas aeruginosa and Acinetobacter calcoaceticus.

Pletnev’s drops No. 204, 207, 212, 236, 245 in various administration schemes (before, during and after infection of cell cultures) exhibit pronounced antiviral activity against a number of viruses pathogenic for humans and animals. Pletnev’s drops No. 204, 207, 212, 236, 245 inhibit in the cell culture the replication of A / H5 bird viruses in the tested doses, while reducing their infectious titer by 2.0-3.0 lg.

The drugs are effective in the experiment on chicken embryos, on the replication of the virus and exhibit a virucidal effect. In an experiment in mice, they have a protective effect in the tested doses for viral pneumonia, increasing the survival of animals to 60-100% with 100% death in the control.

In in vitro experiments, Pletnev drops No. 204, 207, 212, 236, 245 in the tested dilutions have antiviral and virucidal effects on the herpes simplex virus-1. The drugs have a virucidal effect on the extracellular virus not only of herpes simplex-1, but also on strains of the virus that are sensitive and resistant to acyclovir.

Pletnev drops No. 204, 207, 212, 236, 245 in the tested dilutions introduced into the cell culture 24 hours before its infection with hepatitis C virus protect 100% of infected cells from the cytopathogenic effect of the virus with 100% cell death in the control. The antiviral effect of the drugs is preserved when they are introduced during and 24 hours after infection of the cells with this virus.

In in vitro experiments, Pletnev drops No. 204, 207, 212, 236, 245 in the tested dilutions have antiviral and virucidal effects on human immunodeficiency virus-1.

2. Pletnev’s Drops No. 204, 207, 212, 236, 245 are low-toxic drugs with a single administration to laboratory animals and are well tolerated with long-term administration to Wistar rats (3 months) and dogs (1 month), do not have a damaging effect on the main organs and systems organisms of experimental animals and do not show a local irritant effect.

Pletnev’s drops No. 204, 207, 212, 236, 245 do not have mutagenicity and DNA damaging effect. In the tested doses and administration schemes, the preparations do not exhibit allergenic and immunotoxic properties.

When pregnant rats are prescribed, Pletnev drops No. 204, 207, 212, 236, 245 show embryotoxicity, therefore pregnancy is a contraindication to the administration of drugs.

The use of the proposed drops for antiviral and immunomodulatory therapy is as follows.

The resulting Pletnev drops are a solution of the active substance in 95% ethanol, 1 ml of which contains 15-25 mg of the drug substance. Drops of Pletnev No. 204 are administered orally.

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

20 drops of the solution contain 15-25 mg of the drug substance;

10 drops (1/2) of the solution contain 7.5-12.5 mg of the drug substance;

5 drops (1/4) of the solution contain 3.75-6.25 mg of the drug substance;

3 drops (1/7) of the solution contain 2.25-3.75 mg of the drug substance.

The duration of treatment is 2-3 months, depending on the condition of the patient. Conducting repeated courses of treatment on the recommendation of a doctor. During the treatment period, the patient's condition is monitored according to the results of a blood test, urine test, biochemical blood test, immunogram, virological and instrumental studies.

When applying Pletnev drops, a relative normalization of the indicators of blood analysis, urine, biochemical blood tests, immunograms, virological and instrumental studies is observed, which manifests itself as an improvement in the patients' clinical well-being.

Examples of antiviral and immunomodulatory therapy using the proposed drops.

Example 1

Patient M., 19 years old. Clinical diagnosis: Chronic viral hepatitis C, phase of active replication of the virus.

Considers herself ill since March 2011, when dull pains appeared, a feeling of heaviness in the right hypochondrium and jaundice, the color of urine became dark. In the infectious diseases hospital, anti-HCV and HCV RNA were detected during the examination. In 2011, combination antiviral therapy (Pegasis + Ribavirin) was started over a period of 6 months with a positive trend.

Patient M. turned to us on 08/26/2013. Complaints of dull pain and a feeling of heaviness in the right hypochondrium, nausea, fatigue in the evening. Consciousness is clear. The skin is yellow. The sclera is icteric. Visible mucous membranes are yellow, moist, clean. The tongue is coated with white plaque. Body temperature 36.5 ° C. Vesicular breathing. NPV: 16 / min. Heart sounds are rhythmic. HELL: 110/70 mm Hg Pulse: 57 / min. Pain in the right hypochondrium during palpation is noted. In other areas, the abdomen is soft, painless. The edge of the liver with a dense-elastic consistency, sharp, comes out from under the edge of the costal arch by 3 cm, the surface of the liver is smooth. The urine is dark. The chair is light, mushy - 1 time per day. No swelling.

The patient was recommended a course (90 days) of treatment with Pletnev drops No. 204.

With the patient’s oral consent, Pletnev’s drops No. 204 were treated according to the following scheme: 5 drops of the drug inside, dissolving in 50 ml of boiled water at room temperature, 1 time a day in the morning before meals for 20 minutes.

- Laboratory research:

After the first course of treatment on 11/22/2013: notes improvement in well-being. There are no complaints. Body temperature 36.6 ° C. Vesicular breathing. NPV: 18 / min. Heart sounds are rhythmic. HELL: 110/70 mm Hg Pulse: 60 / min. The abdomen is soft, painless. Liver, spleen not palpable. There are no dysuric phenomena. No swelling.

Conclusion: a 90-day course of treatment with Pletnev drops No. 204 was carried out with a positive effect. Recommended therapy in the same volume. It is under dynamic observation.

Example 2

Patient A., 36 years old. Clinical diagnosis: HIV infection 4A stage (herpes zoster in history, onychomycosis), phase of progression. Chronic viral hepatitis C.

Anamnesis of the disease: sick since 05/25/2011, when the examination revealed HIV-1 RNA, anti-HCV and HCV RNA. The path of infection is genital. No treatment has been performed.

Patient A. turned to us on 08.02.2012. Complaints of headache, fever up to 38.5 ° C, cough, nasal congestion, weakness, fatigue, enlarged lymph nodes, increased irritability. Body temperature 38.5 ° C. The breath is hard. NPV: 20 / min. Heart sounds are rhythmic, muffled. HELL: 110/70 mm Hg Pulse: 75 / min. The abdomen is soft, painless. Liver, spleen not palpable. There are no dysuric phenomena. No swelling.

The patient was recommended to undergo a course (90 days) of treatment with Pletnev drops No. 207.

With oral consent, the patient was treated with Pletnev drops No. 207 according to the following scheme: inside 15 drops of the drug, dissolving in 50 ml of boiled water at room temperature, 2 times a day in the morning and in the evening before meals for 20 minutes.

- Laboratory research:

After the first course of treatment on 05/05/2012: notes improvement in health. There are no complaints. Became active. There is no weakness. Body temperature 36.6 ° C. Vesicular breathing. NPV: 18 / min. Heart sounds are rhythmic. HELL: 120/80 mmHg Pulse: 60 / min. The abdomen is soft, painless. Liver, spleen not palpable. There are no dysuric phenomena. No swelling.

Conclusion: a 90-day course of treatment with Pletnev drops No. 207 was carried out with a positive effect. It is recommended to carry out therapy in the same volume. Since 05/05/2012, the patient’s treatment with Pletnev’s drops No. 207 has not passed due to relocation to another region of Russia.

Example 3

Patient A., 36 years old. Clinical diagnosis: Cirrhosis of the liver in the outcome of chronic viral hepatitis C. Edema-ascitic syndrome. Varicose veins of the esophagus I tbsp. Thrombocytopenia. Jaundice.

Considers herself a patient since 2008, when the examination revealed anti-HCV and HCV RNA. In 2008, combined antiviral therapy (pegasis + ribavirin) was performed for 6 months with a positive trend.

Patient A. turned to us on 02/14/2013. Complaints of weakness, sweating, loss of appetite, dark urine, yellowing of the skin and sclera. When handling a state of moderate severity. The skin, sclera jaundice. Single hemorrhages on the skin of the trunk, face, limbs. Body temperature 36.8 ° C. Vesicular breathing. NPV: 20 / min. Heart sounds are rhythmic. HELL: 135/80 mmHg Pulse: 70 / min. The abdomen is soft, painless. Liver at the edge of the costal arch, dense, spleen palpated in the left hypochondrium, dense. There are no dysuric phenomena. The formation of ascites according to ultrasound.

- Instrumental research:

Ultrasound from 02/04/2013: the liver is typically located in the right hypochondrium. Subphrenic space without additional inclusions. Liver motility during breathing is not limited. The capsule in the visualized areas is not thickened, not deformed. The body contour is clear, even, traced throughout. The edge is rounded, does not protrude. The shape is typical without defects. Liver size increased: right lobe: anteroposterior - 168 mm (up to 130 mm); cranio-caudal - 91 mm (up to 125 mm); left lobe: anteroposterior - 87 mm (up to 70 mm); caudate lobe: anteroposterior - 37 mm (up to 35 mm).

Liver parenchyma with a cellular, coarse, coarse-grained echostructure. Echogenicity of the parenchyma is unevenly moderately elevated throughout. The vascular pattern of the portal system is depleted. Vessels are sufficiently traced in the main departments, poorly visible on the periphery. The periportal structures are not densified.

The spleen is usually located, enlarged: 197-76 mm (up to 130-50 mm). The lumen of the vessels of the portal system is expanded. The portal vein (transcostally) 12.8 mm, the splenic vein (at the gate) 14.4 mm. Speed indicators of blood flow are reduced by 14.5 and 13 cm / sec. Free fluid meager accumulations in the space of Marrison, interloop spaces. Conclusion: hepatosplenomegaly. Diffuse change in the structure of the liver. Portal hypertension with hemodynamic disorders. The formation of ascites.

Endoscopy from 02/06/2013. Conclusion: varicose veins of the esophagus I century, the risk of bleeding is low. Hemorrhagic antral gastritis. Superficial mixed gastritis of the body of the stomach. Superficial bulbit. Cardia insufficiency.

The patient recommended a course (90 days) of treatment with Pletnev drops No. 245.

With the patient’s oral consent, Pletnev’s drops No. 245 were treated according to the following scheme: 5 drops of the drug inside, dissolving in 50 ml of boiled water at room temperature, 2 times a day in the morning and evening before meals for 20 minutes.

- Laboratory research:

08/15/2013 year. Complaints of sweating persist. Notes improvement in well-being. Body temperature 36.6 ° C. Vesicular breathing. NPV: 18 / min. Heart sounds are rhythmic. HELL: 120/80 mmHg Pulse: 75 / min. The abdomen is soft, painless. Liver at the edge of the costal arch, dense, spleen palpated in the left hypochondrium, dense. There are no dysuric phenomena. No swelling.

Conclusion: after 2 courses of treatment with Pletnev drops No. 245 on 08/15/2013: notes improvement in well-being. Recommended therapy in the same volume. It is under dynamic observation.

Example 4

Patient V., 64 years old. Clinical diagnosis: HIV infection 3A stage (history of herpes simplex virus), transitional phase.

Anamnesis of the disease: sick since 1998, when an examination in the blood revealed HIV-1 RNA. He refused treatment.

Patient V. turned to us on 02.16.2013. Complaints of sore throat, frequent fever up to 38 ° C, night sweat, weakness, fatigue, irritability, weight loss up to 10%, skin rashes, herpetic rashes on the face, enlarged lymph nodes. Body temperature 37.3 ° C. The breath is hard. NPV: 22 / min. Heart sounds are rhythmic, muffled. HELL: 135/85 mmHg Pulse: 92 / min. The abdomen is tense, painless. Recurrent diarrhea. The symptom of Pasternadsky is negative. Urination is painless, free. No swelling.

The patient was recommended a course (90 days) of treatment with Pletnev drops No. 212.

With the oral consent of the patient, Pletnev No. 212 drops were treated according to the following scheme: inside, 20 drops of the drug, dissolving in 50 ml of boiled water at room temperature, 1 time a day in the morning before meals for 20 minutes.

- Laboratory research:

May 18, 2013. There are no complaints. Notes improvement in well-being. Active There are no complaints. Body temperature 36.6 ° C. Vesicular breathing. NPV: 18 / min. Heart sounds are rhythmic. HELL: 120/80 mmHg Pulse: 60 / min. The abdomen is soft, painless. Liver, spleen not palpable. There are no dysuric phenomena. No swelling. Continues taking Pletnev drops No. 212.

08/15/2013 year. There are no complaints. She feels well. Body temperature 36.7 ° C. Vesicular breathing. NPV: 18 / min. Heart sounds are rhythmic. HELL: 120/80 mmHg Pulse: 65 / min. The abdomen is soft, painless. Liver, spleen not palpable. There are no dysuric phenomena. No swelling.

Conclusion: 2 courses (90 days each) of treatment with Pletnev drops No. 212 with a positive effect were carried out. Recommended therapy in the same volume. It is under dynamic observation.

Example 5

Patient E., 25 years old. Clinical diagnosis: HIV infection 2A stage (ARVI, tonsillitis in the anamnesis), initial phase (acute).

Anamnesis of the disease: sick since 07/22/11, when HIV-1 RNA was detected during the examination. No treatment has been performed.

Patient E. turned to us on 08.08.2011. Complaints of headache, sore throat, fever up to 38 ° C, cough, nasal congestion, weakness, fatigue, enlarged lymph nodes, increased irritability. Body temperature 38 ° C. The breath is hard. NPV: 20 / min. Heart sounds are rhythmic, muffled. HELL: 110/70 mm Hg Pulse: 80 / min. The abdomen is soft, painless. Liver, spleen not palpable. There are no dysuric phenomena. No swelling.

The patient is recommended to undergo a course (90 days) of treatment with Pletnev drops No. 236.

With oral consent, the patient was treated with Pletnev drops No. 236 according to the following scheme: inside 15 drops of the drug, dissolving in 50 ml of boiled water at room temperature, 1 time a day in the morning before meals for 20 minutes.

- Laboratory research:

11/27/2011: feeling good. There are no complaints. Became active. Body temperature 36.7 ° C. Vesicular breathing. NPV: 16 / min. Heart sounds are rhythmic. HELL: 110/70 mm Hg Pulse: 60 / min. The abdomen is soft, painless. Liver, spleen not palpable. There are no dysuric phenomena. No swelling. Therapy continues in the same volume.

10/10/2013: well-being. There are no complaints. Body temperature 36.5 ° C. Vesicular breathing. NPV: 18 / min. Heart sounds are rhythmic. HELL: 115/75 mmHg Pulse: 65 / min. The abdomen is soft, painless. Liver, spleen not palpable. There are no dysuric phenomena. No swelling.

Conclusion: after 8 courses of treatment with Pletnev drops No. 236 on 10/10/2013: well-being. HIV-1 RNA from 05/31/2012 and from 05/10/2013 - not detected. There are no complaints. Recommended: prophylactic course (90 days) of taking Pletnev drops No. 236 once a year; dynamic observation; blood test, biochemical blood test, immunogram - after 6 months.

The treatment of patients with HIV infection, viral hepatitis C, demyelinating diseases of the nervous system, blood diseases, oncological diseases is an extremely difficult task. We have to admit that at present, treatment according to accepted standards often does not prevent the dramatic course of these diseases.

The clinical examples cited No. 1, 2, 3, 4, 5 summarize the experience of using the Pletnev drop preparations No. 204, 207, 212, 236, 245 in the treatment of various diseases that have pathogenetic mechanisms uniting them: violation of the structure and functions of cell biomembrane, vascular endothelium , as well as immunopathological changes caused by a violation of the unified immuno-biochemical mechanism of homeostasis regulation.

Analysis of the dynamics of clinical and laboratory parameters in patients taking Pletnev drops No. 204, 207, 212, 236, 245 as monotherapy, indicate normalization of cellular immunity (CD3, CD4, CD8, CD16, CD56), peripheral blood (white blood cells, red blood cells , platelets, neutrophils, lymphocytes), biochemical parameters (aminotransferases, alkaline phosphatases, glutamate transpeptidases, bilirubin, total protein). In general, this may indicate a reliable correction of the immune system, as well as the restoration of a systematic relationship between hematological, endocrine, neurological and biochemical statuses.

Claims (1)

Drops having antiviral and immunomodulatory effects, characterized in that they are a tincture of 95% ethyl alcohol of wild strawberry leaves and fruits selected from the series: fruits of raspberry ordinary, fruits of mountain ash ordinary, fruits of blueberry ordinary, fruits of hawthorn blood red, May rose hips, with a content of 15-25 mg of substance in 1 ml of tincture.