RU2514103C1 - Pharmaceutical composition for treating local manifestations of herpex simplex infections and for preventing influenza and acute respiratory viral infections - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention represents a pharmaceutical composition for treating local manifestations of herpes simplex infections and for preventing influenza and acute respiratory viral infections, containing green tea extract and epigallocatechin-3-gallate (EGCG) 70-90 wt %, colloidal silver and a gel-forming base with the ingredients of the composition taken in certain ratio, wt %.

EFFECT: high clinical effectiveness.

6 cl, 8 ex, 5 tbl

Description

The invention relates to the field of pharmacy and relates to new pharmaceutical compositions for topical application based on epigallocatechin-3-gallate (EGCG) and ionized silver and methods for treating mucocutaneous manifestations of herpes virus infection.

The creation of drugs with a wide range of antiviral activity is an essential practical task.

In clinical practice, it is often necessary to prescribe antiviral therapy in the absence of an accurate idea of the nature of the infectious agent. For example, you have to deal with this need during seasonal outbreaks of acute respiratory illness and flu. The etiological agent of these outbreaks can be influenza A and B viruses, parainfluenza, respiratory syncytial virus, adenoviruses, each of which has an individual sensitivity to drugs. In most cases, treatment is prescribed without laboratory tests confirming the nature of the disease. In this case, it would be more advisable to recommend a drug with a wide spectrum of antiviral activity than an etiotropic drug. For example, the prescription of the drug “Remantadin” for the common cold can hardly be justified, since it is known that it acts only against the influenza A virus (Kiselev O.I. (2012) Chemotherapy and chemotherapy for the flu. St. Petersburg, 272 from.). In addition, antiviral drugs of etiotropic action induce the development of drug resistance. There is numerous evidence that the use of the drug "Remantadine" in the treatment of influenza is accompanied by the appearance of resistant strains of the virus. Treatment of herpes with the drug Acyclovir leads to the development of resistance due to a mutation in the thymidine kinase gene, which significantly limits their use in clinical practice (Kiselev V.I., Zverev V.V., Kiselev O.I., Stukova M.A. ., Rudenko V.I. (2002) Medicines against herpes virus infections. St-Petersburg, 132 pp.).

To create a wide range of drugs, a combination of substances acting on the general mechanisms of reproduction of viruses, for example, the synthesis of viral proteins or the intracellular assembly of viral capsids, is required. With respect to latent viral infections, these mechanisms are powerless since the virus does not replicate. In this case, the antiviral effect of the drug can be realized only through the activation of apoptosis of infected cells.

Thus, an ideal preparation with a wide spectrum of antiviral activity should contain substances that provide three types of antiviral activity: virucidity - the ability to inactivate viral particles, inhibitory activity against the assembly of viral capsids or the penetration of viruses into the cell and the ability to induce apoptosis of cells containing the viral genome in latent condition.

It is known that EGCG has the ability to suppress infection of the herpes simplex virus type 1 and 2, preventing its penetration into cells (Isaacs, C.E., et al. (2008) Epigallocatechin gallate inactivates clinical isolates of herpes simplex virus, Antimicrob, Agents Chemother, 52, 962-970). Evidence has also been obtained that green tea catechins can interfere with herpes virus replication through other mechanisms (Lyu SY, Rhim JY, Park WB (2005) Antiherpetic activities of flavonoids against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro, Arch Pharm Res, Nov28 (11), 1293-1301).

The ability of catechins to induce apoptotic death of transformed cells carrying the human papillomavirus genome has been described (Singh M, Singh R, Bhui K, Tyagi S, Mahmood Z, Shukla Y. (2011) Tea polyphenols induce apoptosis through mitochondrial pathway and by inhibiting nuclear factor-kappaB and Akt activation in human cervical cancer cells, Oncol Res, 19 (6), 245-257).

It is likely to assume that this activity will be realized in relation to other viruses, in particular for chronic carriage of the herpes virus, and possibly viruses that cause acute viral respiratory infections. However, this assumption is not obvious and can only be verified experimentally.

It is known to use a composition containing green tea extract containing EGCG and pomegranate extract for the treatment of viral skin lesions by topical application to affected skin areas, as well as by oral administration (RU 2009107699 A, publ. 09/10/2010).

In recent years, the antiviral properties of colloidal silver solutions have been demonstrated, including those with nanoscale colloid particles (Galdiero S, Falanga A, Vitiello M, Cantisani M, Marra V, Galdiero M. (2011) Silver nanoparticles as potential antiviral agents, Molecules, 16 (10), 8894-8918; Sopova EA, Baranov V.I., Gankovskaya OA, Lavrov V.F., Zverev V.V. (2010) Effect of silver and silicon dioxide nanopowders on the development of herpes virus infection in vitro. Hygiene and sanitation , 4, 89-91) and particles with a modified surface (Baram-Pinto D, Shukla S, Perkas N, Gedanken A, Sand R. (2009) Inhibition of herpes simplex virus type 1 infection by silver nanoparticles capped with mer captoethane sulfonate, Bioconjug Chem, 20 (8), 1497-1502).

The known composition of an antifungal, antimicrobial and antiviral agent in the form of a cream, ointment or gel containing colloidal silver and intended for the treatment of skin diseases and lesions, as well as an antiviral drug for the treatment and prevention of influenza, acute respiratory infections, acute respiratory viral infections (RU 2004137031 A, publ. 05/27/2006).

However, the use of silver preparations for herpes virus infection gave only a short-term effect, since these drugs did not act on the latent form of the infection.

Thus, despite the antiviral activity of catechins of green tea and colloidal silver, each of these compounds alone does not provide high drug efficacy.

Closest to the proposed pharmaceutical composition is a drug for the prevention and treatment of skin diseases (RU 2437672 C1, publ. 06/11/2011), including green tea extract containing 70-75% epigallocatechin-3-gallate (EGCG) and as auxiliary components propylene glycol, sodium polyacrylate, dimethicone, nipagin, nipazole and purified water in the following ratio, wt. %:

70% EGCG green tea extract 7.0-40.0 propylene glycol 1.0-10.0 sodium polyacrylate 0.5-10.0 dimethicone 0.1-5.0 nipagin 0.02-0.5 nipazole 0.01-0.5 purified water up to 100

Known drug has antihyperplastic, anti-inflammatory and antioxidant properties, and also has an antiviral effect. At the same time, efficacy against the herpes virus, as well as against influenza and acute respiratory viral infections, has not been shown.

The present invention was the development of a highly effective drug with a wide range of antiviral activity.

The technical result of the invention is to ensure the high efficiency of the composition in the treatment of local manifestations of herpes infection, in the treatment of skin manifestations of chickenpox and in the prevention of influenza and SARS.

The technical result is achieved by a pharmaceutical composition for the treatment of local manifestations of infections caused by the herpes simplex virus, and for the prevention of influenza and acute viral infections, including green tea extract containing epigallocatechin-3-gallate (EGCG) 70-90 wt. %, colloidal silver and a gelling base in the following components, wt. %:

EGCG green tea extract 70-90 wt. % 1.0-10.0 colloidal silver 0.1-1.0 gelling base rest

In addition, in a preferred embodiment, the gelling base includes a gelling agent, a solubilizer, an emulsifier, a preservative and demineralized water in the following components,% by weight of the composition:

gelling agent 4.0-6.0 solubilizer 0.3-0.7 emulsifier 0.3-0.7 preservative 0.08-0.12 demineralized water rest

In particular cases, the composition includes propylene glycol as a gelling agent, carbopol as a solubilizer, triethanolamine as an emulsifier, and nipagin in an amount of 0.07-0.09 wt.% And nipazole in an amount of 0.01-0.03 as a preservative wt. %

The results of studies of the antiviral activity of the combination of EGCG and colloidal silver according to the proposed invention unexpectedly exceeded all expectations. The clinical effects in the treatment of herpes were not only higher than those of well-known drugs like Acyclovir and Zovirax, but unexpectedly two important practical problems were solved that were not previously solved using traditional drugs. Namely, the use of the developed drug allows, after the first application, to inactivate viral particles in the lesion, which dramatically reduces the risk of infection of others and stops the spread of the herpes virus during sexual and other contacts. The second unexpected observation is to increase the inter-relapse period when using the combined drug, which indicates its ability to suppress latent viral infection.

Data confirming that the developed pharmaceutical composition significantly exceeds the closest analogue and existing drugs in their effectiveness, are presented in the following examples.

Example 1

A study of the use of a gel containing 10 wt. % epigallocatechin-3-gallate and 1 wt. % colloidal silver, for the prevention of influenza and acute respiratory viral infections (ARVI)

A study of the effectiveness of the drug was carried out on healthy volunteers aged 18 to 65 years who had contact with patients with influenza or acute respiratory viral infections in the epidemic or epidemic period for these diseases, which have no contraindications to prevention using the developed gel. The total number of subjects was 198 people randomized to 2 groups. The first group of 111 people used a combined gel for prophylaxis, the second group (control) of 87 people did not receive any preventive measures.

Survey methods

Tolerance and safety of the drug was evaluated based on the subjective assessment of volunteers who received a combination gel for prevention and clinical examination data. A survey of all health observables was carried out once a week with registration in the observation diary. If there are complaints about the state of health, a medical examination was performed with the results recorded in a medical record.

The effectiveness of the prevention of influenza and SARS in the observation groups was evaluated by the following parameters:

- the number of cases of influenza and / or SARS;

- the development of allergic reactions.

Scheme of drug administration

For the prevention of acute respiratory viral infections, a gel containing 10 wt. % epigallocatechin-3-gallate and 1 wt. % solution of colloidal silver. The gel was placed in both nasal passages using a cotton applicator 2 times a day for 21 days. The entire observation period for volunteers included a 3-week course of prevention and four weeks of follow-up after completion of prevention. The total follow-up period was 7 weeks.

Evaluation of the effectiveness of treatment

According to the visit plan below, patients were observed 8 times. The study included a visit for screening and randomization (visit screening and randomization). The visit on the seventh day after the first use of the drug is “Visit 1”, the visit on the fourteenth day after the first use of the drug is “Visit 2”, the visit on the twenty-first day is “Visit 3”, on the twenty-eighth day is “Visit 4”, on the thirty-fifth day - “Visit 5”, on the forty-second day - “Visit 6”, on the forty-ninth day - “Visit 7”. In case of symptoms of the disease, the patient should consult a doctor observing him, without waiting for the date of the next visit.

The final assessment of the effectiveness of the prevention of influenza and SARS with a combined gel was carried out on the basis of an analysis of clinical data, the number of cases, the severity and duration of the infection process, and the number of complications.

All volunteers who completed all visits were considered to have completed the study. All those observed who prematurely terminated their participation in the study were considered retired. They have not been replaced. Information about any side effect was entered into the Individual Registration Card.

Portability Assessment

The main indicator of safety was considered the lack of a systemic reaction to the use of the drug. Over the entire period of observation (the preventive course of taking the drug and a month after its completion) during an active clinical examination of the observed persons, the responsible doctor did not reveal any adverse reactions from various organs and systems, and the development of the reaction at the places of application of the drug was not recorded ( mucous membrane of the nose), which testifies in favor of absolute harmlessness and complete safety of the combined gel. There were no subjective data on intolerance to the drug, adverse adverse, allergic or any other adverse events in the diaries of observation. Thus, when carrying out a preventive course of influenza and acute respiratory viral infections among healthy adults, 10% epigallocatechin-3-gallate gel containing 1% colloidal silver solution shows its complete harmlessness and good tolerance.

Research results

Before taking the drug, the experimental and control groups did not significantly differ in terms of the incidence of acute respiratory viral infections, the severity and duration of the course of the disease.

The prophylactic course of the drug provided a decrease in the incidence of influenza and acute respiratory viral infections in the main group. The incidence rate among people who regularly used the combined gel (2.7%) differed from the corresponding indicator in the control group (8.0%). The performance index (IE) was 2.9. It can be assumed that with a higher intensity of the epidemic process and a long course of use, the protective properties of the drug would be even more pronounced.

Within 4 weeks after the cessation of the prophylactic course, 6 people (6.9%) fell ill with influenza and SARS in the control group, while 4 cases of the disease were detected in the main group (3.6%). Over the observation period (from the first day of use - only 7 weeks), the incidence rates were 6.3% and 14.9% in the experimental and control groups, respectively. IE is 2.3; the security indicator was 57%. This indicates a stable, and not short-term preventive effect of the drug, with a positive aftereffect. An analysis of the duration of the disease did not reveal significant differences in the study groups.

Example 2

A study of the clinical effectiveness of a gel containing 10 wt. % epigallocatechin-3-gallate and 1 wt. % colloidal silver, when processing skin manifestations of chickenpox.

The treatment of the elements of the rash with chickenpox has always been an important part of the comprehensive treatment of all clinical forms of this infection.

However, at present, the arsenal of external agents used for this purpose is not so large, especially since almost all of them do not allow you to quickly get rid of the negative and painful manifestations of chickenpox. Moreover, the currently widely used external products have certain disadvantages, to which rather low compliance. The most commonly used brilliant green solution (or potassium permanganate solution) does not reduce skin itching and creates cosmetic inconveniences.

Thus, the choice of external means for treating the elements of the rash with chickenpox is not large enough, which determines the urgency of the problem.

A study of the clinical effectiveness of the developed 10% epigallocatechin-3-gallate gel containing 1% colloidal silver was carried out in comparison with Zovirax ointment, 10% epigallocatechin-3-gallate ointment gel and the preparation of a 1% colloidal silver solution.

Purpose of the study

The aim of the work was to study the effectiveness and safety of the external application of the proposed gel containing 10 wt. % epigallocatechin-3-gallate and 1 wt. % colloidal silver, for the treatment of skin elements of a rash in patients with chickenpox under the age of 18 years.

Research objectives

1. To determine the dynamics of the main clinical symptoms in patients with chickenpox against the background of external use of the combined gel.

2. To determine the frequency and nature of side effects of the combined gel when it is prescribed in the doses indicated in the study protocol.

Study design

An open, comparative study of the efficacy and safety of 10% epigallocatechin-3-gallate gel containing 1% colloidal silver

Materials and methods

Under our supervision, there were 30 patients with skin lesions with chickenpox, who were outpatiently treated at the clinic of the Research Institute of Influenza.

Patients were less than 18 years old. By gender, men accounted for 66% (22 patients), women - 34% (8 patients).

Patients were included in the study in the presence of all inclusion criteria and the absence of any exclusion criteria.

Study Criteria

Patients (under 18 years old) with skin lesions associated with chickenpox.

Survey methods

The examination of patients was carried out according to the following scheme:

1. Collection of medical history in accordance with a standardized patient card, including passport data, medical history, diagnosis.

2. Clinical examination with a description of Status localis.

3. Registration card.

4. Evaluation by the patient or parents of the use of the external drug after 1, 2, 3, 7 and 14 days from the start of use.

Scheme of drug administration

To treat skin elements of a rash in patients with chickenpox, the proposed combined gel containing 10 wt. % epigallocatechin-3-gallate and 1 wt. % colloidal silver. The gel was applied to the elements of the rash 2 times a day (from 1-4 days from the onset of the disease) for 7-14 days.

Evaluation of the effectiveness of treatment

We conducted both a subjective assessment of the effectiveness of treatment by the patient himself and an objective assessment of the effectiveness of treatment, evaluated by a research physician.

Criteria for evaluating the effectiveness of treatment:

1. The severity of subjective symptoms (pain, itching, irritation, burning, skin sensitivity) in comparison with their initial manifestation.

2. Localization and severity of objective symptoms (presence of hyperemia, infiltration, edema, vesicles, pustules, crusts).

3. The severity of side effects and their list.

Portability Assessment

The tolerance of the combined gel was assessed on the basis of complaints from a patient and an objective examination by a medical researcher and was assessed as “excellent” in the absence of any side effects and complications, “good” for mild symptoms that did not require discontinuation of the drug, “satisfactory” for mild symptoms, requiring temporary discontinuation of the drug, “bad” - with severe symptoms from any organs and systems, requiring discontinuation of the drug.

Research results

Under our supervision there were 30 patients. All patients (100%) had a common skin lesion caused by chickenpox virus.

In the structure of subjective sensations (complaints) when collecting an anamnesis in patients with chickenpox, the largest number of patients noted itching in the lesion. In 2 patients, a combination of subjective sensations was noted in the form of both pain and itching.

Table 1 shows the distribution of subjective symptoms in patients with chickenpox.

Table 1 Subjective symptoms in the lesion Number of patients
(n = 30) Pain 3 Itching 29th Burning one Pain and itching (including) 3 Itching and burning (including) one

The use of an external combined gel in 30 patients with skin lesions contributed to the relief of subjective sensations (pain, itching, burning) in all patients (100%) on average 1-2 hours (with a gradual decrease in the intensity of sensation) after the start of use.

When evaluating clinical data on the 3rd day, a significant improvement was observed (vesicles or pustules dried up in the crusts, edema significantly decreased), which was noted in 27 (91%) patients, in 2 (6%) - an improvement was noted (part of the vesicles or pustules dried up in the crusts, edema decreased slightly), in 1 (3%) patient (with a common form), the dynamics of the skin status was not observed, except for a decrease in the pain symptom. When examined on the 7th day, the transition of all elements into crusts was recorded in 29 (96%) patients, a significant improvement in 1 (4%). On the 14th day of observation, all patients experienced clinical recovery.

The high efficiency of the developed external means is illustrated by the following example.

Patient Z., 12 years old. According to the patient and his parents, he fell ill 3 days ago. The rash is 1 day old. Examination of the skin revealed common vesicles, sometimes pustules and traces of scratching. Diagnosed with chickenpox. Appointed external treatment: a combined gel on the lesions 2 times a day for 7 days. According to the registration card, itching of the skin stopped after 1.5 hours from the start of the drug. On the 3rd day, the patient showed a significant improvement in the dynamics of skin rashes - hyperemia turned pale, swelling decreased significantly, all vesicles dried up in the crusts. By the 14th day of treatment, all inflammatory phenomena in the lesions completely disappeared (there was no hyperemia, edema and new vesicles, the crusts partially disappeared with the formation of slight pigmentation), and clinical recovery began.

Thus, the use of a combined gel for the treatment of skin elements of a rash in patients with chickenpox contributed to an accelerated relief of subjective sensations (pain, itching, burning) and inflammation, as well as acceleration of epithelization in the lesion foci.

The tolerance of the test combined gel was marked as “excellent” in 28 (93%) patients, good in 2 (7%) patients. No side effects.

The above indicates the high efficiency and safety of the developed gel when processing elements of the skin rash in patients with chickenpox.

The remaining drugs tested in this study gave a significantly less pronounced effect.

Example 3

A study of the clinical effectiveness of a gel containing 10 wt. % epigallocatechin-3-gallate and 1 wt. % colloidal silver, with local manifestations of herpes infection

The study of the combined gel of the proposed composition for the treatment of skin manifestations of herpes infection was carried out in comparison with ointments "Acyclovir" and "Zovirax", a gel containing 10 wt. % epigallocatechin-3-gallate, and 1% colloidal silver solution. The study involved 100 volunteers.

The comparative effectiveness of the drugs was evaluated by the following parameters: the disappearance or weakening of the symptoms of pain or itching and the timing of the disappearance of the rashes. In all respects, the effectiveness of the developed gel was approximately 30% higher than traditional herpes preparations such as Acyclovir and Zovirax ointments, as well as 10% epigallocatechin-3-gallate gel and a preparation with 1% colloidal silver solution.

Output

The use of a gel for the treatment of skin elements of a rash in patients with herpetic infection contributed to an accelerated relief of subjective sensations (pain, itching, burning) and inflammation, as well as accelerated skin epithelization in the lesion foci.

Example 4

Study of virus activity in lesions

The presence of viable viral particles in the lesion is the main cause of transmission of the virus upon contact. Therefore, evaluating the effectiveness of a new drug by its ability to inactivate viral particles in the lesions is extremely important. The viability of herpes viruses in foci was investigated according to the method described in: F. Shimizu, Y. Shimizu and K. Kumagai (1976) Specific Inactivation of Herpes Simplex Virus by Silver Nitrate at Low Concentrations and Biological Activities of the Inactivated Virus, Antimicrob Agents Chemother 10 (1), 57-63.

The study of the proposed gel containing 10 wt. % epigallocatechin-3-gallate and 1% colloidal silver, on the ability to inactivate viral particles, was performed in comparison with Zovirax ointment, a gel containing 10% epigallocatechin-3-gallate, and 1% colloidal silver solution. The study involved 20 volunteers.

The study was carried out according to the following protocol.

Samples were taken from lesions to quantify viable viral particles. Then the lesions were treated with drugs and after 3 hours of exposure, samples were again taken to determine a viable virus.

Studies have shown that complete inactivation of the virus in the lesions was observed only when using the proposed gel containing 10 wt. % epigallocatechin-3-gallate containing 1 wt. % colloidal silver.

Example 5

The use of the proposed gel for the treatment of recurrent genital herpes

Recurrent genital herpes is a special clinical variant of the course of infection. In a certain category of patients, clinical episodes occur with a frequency of 2-3 weeks. The causes of this course of herpes are associated with the characteristics of immunity and, possibly, with yet unknown mechanisms of reactivation of latent viral infection. An increase in the relapse period is achieved by the so-called suppressive therapy. Its essence is the constant intake of antiherpetic drugs in high dosages. This very expensive therapy does not always lead to the desired results and is accompanied by impaired liver function. Finding alternative therapies is an important clinical task.

The study of the effectiveness of the use of the developed composition in relation to reducing the recurrence rate was carried out in comparison with the Zovirax drug, as well as 10% epigallocatechin-3-gallate gel and a preparation with 1% colloidal silver solution.

For the study, patients with a recurrent type of infection were selected. The average interval between relapses was 14-20 days. The research results are presented in Table 2.

table 2 Drug for treatment Combination gel (EGCG + colloidal silver) Zovirax 10% epigallocatechin-3-gallate gel 1% colloidal silver Relapse Interval More than 3 months 14-20 days 14-20 days 14-20 days

Example 6

Comparative characteristics of the therapeutic effects of the studied drugs in the treatment of herpes infections of the skin.

Table 3 Acyclovir Combination gel (EGCG + colloidal silver) 10% gel based on EGCG 1% colloid
silver Inhibition of virus replication YES NO NO NO Inhibition of viral particle assembly NO YES YES YES Suppression of virus entry into healthy cells NO YES YES NO Anti-inflammatory effect (suppression of cytokine synthesis) NO YES YES YES Direct inhibition of viral particles in the lesion NO YES NO NO Apoptosis of cells carrying the viral genome NO YES YES NO Decreased contagiousness (transmission of the virus by contact) NO YES NO NO The onset of therapeutic effect 3-5 days 1-3 days 5-6 days 5-6 days The increase in the relapse period NO YES NO NO

As follows from the data presented in Table 3, the developed combination preparation containing epigallocatechin-3-gallate and colloidal silver allows to achieve:

1. The rapid anti-inflammatory and analgesic effect (due to the suppression of EGCG cyclooxygenase-2 and pro-inflammatory signaling cascades).

2. The effect of accelerating the resolution of rash elements regardless of the strain of the virus and how early the use of the drug is started (due to the combination of the direct antiviral effect of EGCG and silver against herpes virus and the non-specific proapoptotic effect of EGCG).

3. Prevention of secondary infections (due to the antiseptic effect of silver).

4. The presence of two components in the preparation significantly accelerates the therapeutic effect due to the above mechanisms and the strong anti-inflammatory activity of EGCG.

5. An increase in the relapse interval was also noted, which is associated with the inhibition of the latent form of viral infection through the activation of apoptosis.

6. The virucidity of the drug in the lesion sharply reduces the contagiousness of the virus, ie contact transmission of the virus, including sexual partners.

Example 7

The technology of preparation of the proposed gel

Dosing of raw materials

Prepared water is poured into the mixer by the counter.

All components are weighed in a special, labeled container on a balance according to the recipe in Table 4.

Table 4 No. p / p Name of components Name by INCI Mass fraction,% one Green Tea Extract, EGCG 70-90 Camellia sinensis Extract (INCI) 1.00-10.00 2 Propylene glycol Propylene Glycol (INCI) 5.00 3 Colloidal silver Colloidal Silver (INCI) 0.1-1.00 four Carbopol (carbomer) Carbomer (INCI) 0.50 5 Triethanolamine Triethanolamine (INCI) 0.50 6 Nipagin Methylparaben (INCI) 0.08 7 Nipazole Propylparaben (INCI) 0.02 8 Demineralized water Aqua (INCI) up to 100%

Gel Preparation

1. The calculated amount of water is poured into the homogenizer, a sample of the gelling agent is added, and mixed until a homogeneous mass is obtained.

2. In a sample of propylene glycol add a sample of preservatives, mix until completely dissolved. The solution is poured into a homogenizer, mixed.

3. A sample of green tea, colloidal silver is added to the estimated amount of water, mixed until completely dissolved, added to the homogenizer, mixed.

4. A portion of carbopol is added to the homogenizer, mixed, the mixture is emulsified.

5. After making the last component, the gel is stirred at low speed stirrers.

6. After sampling by the laboratory and a positive conclusion, the gel is transferred to the bottling.

Example 8

The study of the antiviral effect of the developed composition with various concentrations of 90% epigallocatechin-3-gallate, colloidal silver and 70% epigallocatechin-3-gallate.

Testing of gels with different concentrations of active ingredients was carried out on the example of the treatment of genital herpes. An indicator such as the rate of onset of the therapeutic effect was used as the main criterion for the effectiveness of the studied drugs. The results of the study are shown in Table 5.

Table 5 The composition of the gel → 10% EGCG (90%) +
1% colloidal silver 1% EGCG (90%) + 0.5% colloidal silver 5% EGCG (90%) + 0.1% colloidal silver 10% EGCG (70%) + 1% colloidal silver The speed of the onset of the therapeutic effect 1-3 days 4-5 days 3-4 days 1-3 days

findings

A study of the clinical efficacy of a combined gel with a different ratio of active ingredients showed that EGCG (90%) in the concentration range of 1-10% and colloidal silver in the concentration range of 0.1-1% have therapeutic effects, although to a lesser extent than the main composition . The use of EGCG as an active ingredient (70%) is also possible in the manufacture of a combined drug. The possibility of using various concentrations of active ingredients while maintaining the therapeutic effect is an important parameter, as it allows to reduce the cost of the final product in its mass production.

Claims (6)

1. The pharmaceutical composition for the treatment of local manifestations of infections caused by the herpes simplex virus, and for the prevention of influenza and acute respiratory viral infections, including green tea extract containing epigallocatechin-3-gallate (EGCG) 70-90 wt. %, colloidal silver and a gelling base in the following components, wt. %:
Green Tea Extract EGCG 70-90 wt. % 1.0-10.0 Colloidal silver 0.1-1.0 Gelling base rest 2. The composition according to claim 1, characterized in that the gelling base includes a gelling agent, a solubilizer, an emulsifier, a preservative and demineralized water with the following components,% by weight of the composition:
Gelling agent 4.0-6.0 Solubilizer 0.3-0.7 Emulsifier 0.3-0.7 Preservative 0.08-0.12 Demineralized water rest 3. The composition according to claim 2, characterized in that the gelling agent includes propylene glycol. 4. The composition according to claim 2, characterized in that as a solubilizer contains carbopol. 5. The composition according to claim 1, characterized in that as an emulsifier contains triethanolamine. 6. The composition according to claim 2, characterized in that as a preservative contains nipagin in an amount of 0.07-0.09 wt. % and nipazole in an amount of 0.01-0.03 wt. %