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

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

 

The invention relates to the field of pharmacy and relates to new pharmaceutical compositions for local application on the basis of epigallocatechin-3-gallate (EGCG) and ionized silver and treatment of skin and mucosal manifestations of herpes infection.

The creation of a drug with broad spectrum antiviral activity is an important practical task.

In clinical practice it is often necessary for the purpose of antiviral therapy in the absence of a precise understanding of the nature of the infectious agent. For example, such a need, have to face during seasonal outbreaks of acute respiratory diseases and influenza. The etiological agent of these outbreaks can be influenza viruses A and B, parainfluenza, respiratory syncytial virus, adenoviruses, each of which has individual sensitivity to drugs. In most cases it is treated without laboratory analysis confirming the nature of the disease. In this case it will be better to recommend the preparation of a wide spectrum of antiviral activity, the medicine causal actions. For example, the appointment of the drug Rimantadine" with symptoms of the common cold, can hardly be justified, since it is known that it acts only in relation to the attachment of influenza virus a (I. Kiselev (2012) Chemotherapy and chemotherapy flu. St. Petersburg, 272 C.). In addition, antiviral drugs causal actions induce the development of drug resistance. There are numerous data that the use of the drug "Rimantadine in the treatment of influenza is accompanied by the appearance of resistant strains of the virus. Treatment of herpes medicine "Acyclovir" leads to the development of resistance due to mutations in the gene for thymidine kinase, which significantly limits their use in clinical practice (Kiselev V.I., Zverev V.V., I. Kiselev, Stukau M.A., Rudenko V.I. (2002) drugs against herpes virus infections. St-Petersburg, 132 S.).

To create drugs with a broad spectrum combination of substances acting on the General mechanisms of reproduction of viruses, such as the synthesis of viral proteins or intracellular Assembly of viral capsid. In respect of latent viral infections, these mechanisms are powerless, as the virus does not replicate. In this case, the antiviral effect of the drug can be implemented only through the activation of apoptosis of infected cells.

Thus, the ideal drug with broad spectrum antiviral activity must contain substances that provide three types of antiviral action: virucides - ability in tigerbeat viral particles, inhibitory activity against the Assembly of viral capsid or viral penetration into the cell and the ability to induce apoptosis of cells containing the viral genome in a latent state.

It is known that EGCG has the ability to inhibit the infection of herpes simplex virus types 1 and 2, preventing its penetration into cells (Isaacs, S.E., et al. (2008) epigallocatechin gallate gallate inactivates clinical isolates of herpes simplex virus, Antimicrob, Agents Chemother, 52, 962-970). Were also obtained evidence that green tea catechins can inhibit the replication of herpes virus and 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).

Describes the ability of catechins to induce apoptotic death of transformed cells carrying the gene of human papilloma virus (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 implemented and in respect of other viruses, in particular in chronic carriers of the virus of herpes, and possibly viruses causing acute viral respiratory infections. However, this assumption is not obvious and can only be tested by experiment.

It is known the use of a composition containing the extract of green h is I, contains EGCG, and pomegranate extract, for the treatment of viral lesions of the skin by topical application to the affected skin, as well as by oral administration (RU 2009107699 A, published. 10.09.2010).

In recent years we have demonstrated antiviral properties of colloidal solutions of silver, including nano particles colloid (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 E.A., V.I. Baranov, Gankovsky O.A., Lavrov V.F., Zverev, V.V. (2010) the Effect of nano-silver and silicon dioxide 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 mercaptoethane sulfonate, Bioconjug Chem, 20(8), 1497-1502).

Known composition antifungal, antimicrobial and antiviral agents in the form of a cream, ointment or gel containing colloidal silver and designed for the treatment of skin diseases and lesions, as well as antiviral medication for treatment and prophylaxis of influenza, acute respiratory infections, viral respiratory infections (EN 2004137031 A, published. 27.05.2006).

However, the use of silver preparations when herpes infection gave only short-term effect, since these drugs are not acted on the latent form of infection.

Thus, despite protivovirusnoe the activity of catechins of green tea and colloidal silver each of these compounds separately does not provide a high efficiency of the drug.

Closest to the proposed pharmaceutical composition is a pharmaceutical agent for the prevention and treatment of skin diseases (EN 2437672 C1, published. 11.06.2011), which includes green tea extract with a content of 70-75% of epigallocatechin-3-gallate (EGCG) and as auxiliary components propylene glycol, sodium polyacrylate, Dimethicone, nipagin, nipazol and purified water in the following ratio, wt. %:

green tea extract with a content of 70% EGCG7,0-40,0
propylene glycol1,0-10,0
sodium polyacrylate0.5 to 10.0
Dimethicone0,1-5,0
nipagin0,02-0,5
nipazol0,01-0,5
purified water100

Known drug has antigyerpyetichyeskoi, anti-inflammatory and antioxidant properties, and also has an antiviral effect. When the is effective against the herpes virus, and also against influenza and acute respiratory viral infections are not shown.

The present invention was to develop a highly effective drug with broad spectrum antiviral activity.

The technical result of the invention is to provide a high efficiency compositions for the treatment of local manifestations of herpetic infection in the treatment of cutaneous manifestations of varicella and in the prevention of influenza and SARS.

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 with a content of epigallocatechin-3-gallate (EGCG) 70-90 wt. %, colloidal silver and gel-forming the basis for the following content, wt. %:

green tea extract EGCG 70-90 wt. %1,0-10,0
colloidal silver0,1-1,0
gel-forming baserest

In addition, in the preferred embodiment, the gel-forming base includes gelling, solubilizer, emulsifier, preservative is demineralized water with the following content of components, % by weight of the composition:

gelling4,0-6,0
the solubilizer0,3-0,7
emulsifier0,3-0,7
preservative0,08-0,12
water demineralizedrest

In particular cases as a gelling composition includes propylene glycol, as a solubilizer - carbopol, as emulsifier - triethanolamine and as preservative - nipagin in the amount of 0.07 to 0.09 wt.% and nipazol in an amount of 0.01-0.03 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. Clinical effects in the treatment of herpes were not only higher than that of well-known drugs as Acyclovir and Zovirax, but were suddenly solved two important practical problems that have not been solved previously by the use of traditional medicines. Namely the use of the developed drug allows after the first application to inactivate viral particles in the loci for the e lesions, that dramatically reduces the risk of infection of others and stop the spread of herpes virus in genital and other contacts. The second unexpected finding was the increase magnetizing period when the use of a combined preparation, which indicates its ability to suppress latent viral infection.

Evidence that the pharmaceutical composition significantly exceeds its effectiveness closest analogue and existing medicines, are presented in the following examples.

Example 1

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

Study of the efficacy of the drug was carried out on healthy volunteers aged 18 to 65 years who had contact with patients with influenza or SARS in majapidamisi or in the epidemic period for these diseases, not contraindications to prophylaxis with the help of the developed gel. The total number of subjects was 198, randomized in 2 groups. The first group in the amount of 111 people were used to prevent the combined gel, the second group (control) in the amount of 87 people no preventive measures were not received.

Survey methods

Re usemost and safety of the drug was evaluated on the basis of accounting for the subjective assessment of the volunteers, receiving a combined gel for the prevention and clinical assessment. A survey of all observed health status conducted once a week in the diary. If there are complaints on health conducted a medical examination registration results in the medical record.

The effectiveness of the prevention of influenza and ARVI in observation groups were evaluated by the following parameters:

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

- the development of allergic reactions.

The destination schema drug

For the prevention of ARVI applied gel containing 10 wt. % epigallocatechin-3-gallate, and 1 wt. % solution of colloidal silver. The gel was laid in both nasal stroke using a cotton applicator 2 times a day for 21 days. The entire period of observation for volunteers included a 3-week course of prophylaxis and four weeks of observation after the end of prophylaxis. The total observation period was 7 weeks.

Evaluation of the effectiveness of treatment

According to the following plan visits, patients were observed 8 times. The study included a visit for screening and randomization (visit-screening and randomization). Visit on the seventh day after the first application of the drug - "Visit 1, visit on the fourteenth day after the first application of the drug - "Visit 2", the visit to the twenty-first the day - "Visit 3", on the twenty-eighth day - Visit 4", at the thirty-fifth day - Visit 5", at the forty-second day - "Visit 6", on the forty-ninth day - Visit 7". In case of any symptoms of the disease, the patient was supposed to go to the doctor, watching him, not waiting for the date of the next visit.

Final evaluation of the effectiveness of the prevention of influenza and ARVI combined gel was carried out on the basis of the analysis of clinical data, the number of people affected, severity and duration of infection, the number of complications.

Completed the study considered all the volunteers who completed all visits. All observed, prematurely terminated their participation in the study was considered to be eliminated. They were not replaced. Information about any side effect listed in the Individual registration card.

Assessment of tolerance

The main factor of safety considered the absence of a systemic reaction to the drug. For the entire period of observation (prophylactic drug and the month after graduation) with active clinical examination of the observed individuals responsible physician did not identify any adverse reactions from various organs and systems, and had not observed the development of reactions where the application of the drug (mucous membranes), what evidence is the olza absolute safety and complete security of the combined gel. Subjective data about drug intolerance, on the negative side, allergic or other adverse events in the diaries of observations were recorded. Thus, when conducting preventive course of ARVI and influenza among healthy adults 10% gel epigallocatechin-3-gallate containing 1% solution of colloidal silver shows its complete harmlessness and good tolerability.

The results of the study

Before taking the drug test and control group did not differ significantly in the incidence of viral respiratory infections, the severity and the duration of the course of diseases.

Conducted preventive course of the drug helped reduce the incidence of influenza and ARVI in the main group. The incidence rate among persons regularly using the combined gel (2,7%)differed from the corresponding rate in the control group (8.0 per cent). The effectiveness index (EI) was 2.9. It can be assumed that at higher intensity of the epidemic process and long-term rate of application protective properties of the drug would have been even more pronounced.

Within 4 weeks after discontinuation of prophylactic rate in the control group became infected with influenza and ARVI 6 (6.9 per cent), whereas in the study group identified 4 cases (36%). During the observation period (from the first day of use - just 7 weeks) incidence was 6.3% and 14.9% in experimental and control groups, respectively. IE is 2.3; however, the rate of protection was 57%. This indicates a stable, rather than short-term prophylactic effect of the drug, with a positive aftereffect. Analysis of the duration of disease did not reveal significant differences in the groups studied.

Example 2

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

Processing elements rash varicella has always been an important part of the comprehensive treatment of all clinical forms of the infection.

Currently, however, the Arsenal of external funds used for this purpose, not so great, especially since almost all of them do not allow you to quickly get rid of the negative and painful manifestations of varicella. Moreover, widely used at present, external funds have certain disadvantages, to which the relatively low compliance. The most frequently used solution of brilliant green (or a solution of potassium permanganate) does not reduce itching of the skin and creates a cosmetic inconvenience.

In affect, the, the choice of external tools for item processing rash varicella is not big enough, hence the urgency of the problem.

The study of clinical effectiveness developed 10% gel epigallocatechin-3-gallate containing 1% colloidal silver, were compared to ointment Zovirax", 10% gel on the basis of epigallocatechin-3-gallate, and the preparation of a 1% solution of colloidal silver.

The purpose of the study

The aim of this work was to study the efficacy and safety of topical application of the proposed gel containing 10 wt. % epigallocatechin-3-gallate, and 1 wt. % colloidal silver, with the purpose skin treatment items rash in patients with chickenpox before the age of 18 years.

Objectives of the study

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

2. To determine the frequency and nature of side effects of the combined gel in his appointment in the specified in the study Protocol doses.

Research design

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

Materials and methods

Under our supervision there were 30 patients with skin lesions varicella were on outpatient treatment in KL is nick the research Institute of influenza.

The age of patients was less than 18 years. Gender men was 66% (22 patients), women - 34% (8 patients).

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

Criteria for inclusion in the study

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

Survey methods

Examination of patients was performed according to the following scheme:

1. The collection of history according to a standardized card of the patient, including passport data, medical history, diagnosis.

2. Clinical examination with a description of the Status localis.

3. Registration card.

4. Evaluation of the patient or the parents of application of the external preparation after 1, 2, 3, 7 and 14 days from first use.

The destination schema drug

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

Evaluation of the effectiveness of treatment

Was conducted as a subjective evaluation of the effectiveness of treatment by patients, and objective evaluation of the effectiveness of treatment as measured by physician-researcher.

Criteria for evaluating the effectiveness of treatment:

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

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

3. The severity of side effects and their list.

Assessment of tolerance

Assessment of tolerability of the combined gel was made on the basis of patient complaints and objective examination of the physician-researcher and was assessed as "excellent" in the absence of any side effects and complications, "good" - with mild symptoms and do not require discontinuation of the drug, "satisfactory" - with mild symptoms requiring temporary discontinuation of the drug, "bad" - when expressed symptoms of any of the organs and systems that lead to drug withdrawal.

The results of the study

Under our observation of 30 patients. All patients (100%) had widespread skin lesions caused by the virus varicella.

In the structure of subjective sensations (complaints) during the history taking in patients with chickenpox largest number of patients reported itching in the lesion. In 2 patients was marked by a combination of subjective sensations as pain and itching.

Table 1 shows the distribution of subject the different symptoms in patients with varicella.

Table 1
Subjective symptoms in the lesionThe number of patients
(n=30)
Pain3
Itching29
Burning1
Pain and itching (including)3
Itching and burning (including)1

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

When evaluating clinical data on the day 3 showed a significant improvement (vesicles or pustules dried in peel, the swelling has decreased considerably, which was noted in 27 (91%) patients, 2 (6%) had marked improvement (part vesicles or pustules dried in peel, swelling decreased slightly), and 1 (3%) patient (common form) dynamics of skin status was not recorded, besides reducing the pain symptom. When viewed on the 7th day of the transition of all elements in Corinthians is his recorded at 29 (96%) patients, significant improvement in 1 (4%). On the 14th day of observation all patients had a clinical recovery.

High efficiency designed for external use is illustrated by the following example.

Patient Z., 12 years. According to the patient and his parents got sick 3 days ago. Prescription rash is 1 day. When viewed on the skin revealed widespread vesicles, sometimes pustules and traces of scratches. Exhibited diagnosed with chickenpox. Appointed external treatment: combined gel on the affected areas 2 times a day for 7 days. According to the registration card itching stopped after 1.5 hours from the beginning of the drug. On the day 3 the patient in the dynamics of skin lesions showed a significant improvement in the redness faded, the swelling has decreased considerably, all vesicles have dried up in the crust. To 14 days of treatment, all inflammation in the lesions completely disappeared (hyperemia, edema and new vesicles was not, cover partially disappeared with the formation of minor pigmentation), a clinical recovery.

Thus, the combined gel for skin treatment items rash in patients with chickenpox accelerated the reduction of subjective sensations (pain, itching, burning and inflammation, as well as the acceleration of epithelialization in the pockets of time is possible.

The portability of the test combo gel is marked as "excellent" in 28 (93%) patients, good in 2 (7%) patients. No adverse effects were observed.

The above indicates high effectiveness and safety of the developed gel processing elements skin rashes in patients with varicella.

Other drugs tested in this study gave significantly less pronounced effect.

Example 3

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

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

Comparative effectiveness of drugs was assessed by the following parameters: the disappearance or weakening of symptoms of pain or itching and timing of the disappearance of the rash. For all parameters the effectiveness of the gel is about 30% higher than traditional drugs to treat herpes as ointments "Acyclovir" and "Zovirax"and 10% gel on the basis of epigallocatechin-3-gallate, and ven is at 1% solution of colloidal silver.

Conclusion

Use gel for skin treatment items rash in patients with herpetic infection accelerated the reduction of subjective sensations (pain, itching, burning and inflammation, and accelerate epithelization of skin lesions.

Example 4

Studying the activity of the virus in the lesions

The presence of viable virus particles in the lesions is the main cause of transmission of the virus upon contact. Therefore, evaluation of effectiveness of new drugs on its ability to inactivate viral particles in the lesions is extremely important. The viability of the viruses of herpes lesions examined by 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 suggested gel containing 10 wt. % epigallocatechin-3-gallate, and 1% colloidal silver on the ability to inactivate viral particles was performed in comparison with the ointment "Zovirax", a gel containing 10% epigallocatechin-3-gallate, and a 1% solution of colloidal silver. The study involved 20 volunteers.

The study was performed according to the following Protocol.

Of the lesions were sampled for quantitative assessment of viable viral particles. Then on the AGI of the lesion was treated with drugs and after 3 hours of exposure again samples were taken for determination of 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 proposed use of the gel for the treatment of recurrent genital herpes

Recurrent genital herpes is a specific clinical scenario of disease infection. With some categories of patients clinical episodes occur with a frequency of 2-3 weeks. The reasons for this course of herpes is associated with features of the immune system and possibly yet unknown mechanisms of reactivation of latent viral infections. Increase magnetizing period is achieved by the so-called suppressive therapy. Its essence lies in a constant reception antiherpetic drugs in high dosages. This very expensive treatment does not always lead to the desired results and is accompanied by abnormal liver function. The search for alternative therapy is an important clinical task.

Study of the efficacy of the developed composition in relation to reducing the frequency of relapses was performed in comparison with the drug "Zovirax"and 10% gel on the basis of epigallocatechin-3-gallate, and the treatment with 1% solution colloides the silver.

For the study we selected patients with recurrent type of the current infection. The average interval between relapses was 14-20 days. The results are shown in Table 2.

Table 2
Drug for the treatmentThe combined gel (EGCG+colloidal silver)"Zovirax"10% gel on the basis of epigallocatechin-3-gallate1% colloidal silver
The interval between relapsesMore than 3 months14-20 days14-20 days14-20 days

Example 6

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

NO
Table 3
AcyclovirA combination of hydrated gel (EGCG+colloidal silver)10% gel on the basis of EGCG1% colloid
Noah silver
Engibarov the e virus replication YESNONONO
Inhibition of the Assembly of viral particlesNOYESYESYES
Suppression of the virus from entering healthy cellsNOYESYESNO
Anti-inflammatory effect (suppression of the synthesis of cytokines)NOYESYESYES
Direct inhibition of viral particles in the lesionNOYESNONO
Apoptosis of cells carrying the viral genomeNOYESYESNO
Reducing contagionist (transmission contact path)NOYESNO
The speed of onset of therapeutic effect3-5 days1-3 days5-6 days5-6 days
Increase magnetizing periodNOYESNONO

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

1. Rapid anti-inflammatory and analgesic effect (due to the suppression of EGCG Cox-2 and proinflammatory signaling cascades).

2. Effect of accelerating the resolution of rash elements regardless of the strain of the virus and how early initiated drug use (due to the combination of direct antiviral action of EGCG and silver in relation to herpesvirus and non-specific proapoptotic actions of EGCG).

3. Prevention of secondary infections (due to the antibacterial action of silver).

4. The presence of two components in the drug significantly accelerate therapeutic effect due to the above mechanisms and the strongest anti-inflammatory activity of EGCG.

5. Also noted the increase is of magnetizing interval, which is associated with inhibition of latent viral infection through activation of apoptosis.

6. Virucides of the drug in the lesion dramatically reduces the infectivity of the virus, i.e. the transmission of the virus by contact way, including sexual partners.

Example 7

Technology of preparation of the proposed gel

Dosing of raw materials

The water is poured into the mixer on the counter.

All components are weighed into a special, marked container on the scale according to the recipe in Table 4.

Table 4
№ p/pName of the componentName INCI nameMass fraction, %
1The green tea extract, EGCG 70-90Camellia sinensis, Extract (INCI)1,00-10,00
2Propylene glycolPropylene Glycol (INCI)5,00
3Colloidal silverColloidal Silver (INCI)0,1-1,00
4The carbopol (Carbomer) Carbomer (INCI)0,50
5TriethanolamineTriethanolamine (INCI)0,50
6NipaginMethylparaben (INCI)0,08
7NipazolPropylparaben (INCI)0,02
8Water demineralizedAqua (INCI)up to 100%

Preparation of a gel

1. In the homogenizer pour the calculated amount of water, add a portion of the gel, mix until smooth.

2. In a portion of the propylene glycol type hitch preservatives, mix until dissolved. The solution is poured into the homogenizer, mix.

3. In the calculated amount of water is added a portion of green tea, colloidal silver, stirred until dissolved, add in the homogenizer, mix.

4. A portion of carbopol is added to the homogenizer, mix, produce emulsification of the mixture.

5. After making the last component of the gel mix on low speed of mixer.

6. After sampling the laboratory and the positive conclusion of the gel are transferred into the filling.

Example 8

Antiviral effect developed compositions with various concentrations of 90%epigallocatechin-3-gallate, colloidal silver and 70%epigallocatechin-3-gallate.

Testing of gels with different concentration of active ingredients was carried out on the example of the treatment of genital herpes. As the main criterion for the effectiveness of investigational drugs used, such factors as the speed of onset of therapeutic effect. The results of the study are displayed in Table 5.

Table 5
The gel →10% EGCG(90%) +
1% colloidal silver
1% EGCG(90%) + 0.5% of colloidal silver5% EGCG (90%) + 0.1% of colloidal silver10% EGCG (70%) + 1% colloidal silver
The rate of occurrence of therapeutics-one effect1-3 days4-5 days3-4 days1-3 days

Conclusions

The study of clinical effectiveness of the combined gel with different ratios of active substances showed that EGCG (90%) in the concentration range of 1-10% and to Rodnoe silver in the concentration range of 0.1-1% have medicinal effects, although to a lesser extent than the bulk composition. Use as active ingredient EGCG (70%) is also possible in the production of combined drugs. The possibility of using different concentrations of active substances with retention of therapeutic effect is an important parameter, as it allows to reduce the cost of the final product when its mass production.

1. 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 with a content of epigallocatechin-3-gallate (EGCG) 70-90 wt. %, colloidal silver and gel-forming the basis for the following content, wt. %:

Green tea extract EGCG 70-90 wt. %1,0-10,0
Colloidal silver0,1-1,0
Gel-forming baserest

2. The composition according to claim 1, characterized in that the gelling base includes gelling, solubilizer, emulsifier, preservative and water demineralized with the following content of components, % by weight of the composition:

Gelling4,0-6,0
The solubilizer0,3-0,7
Emulsifier0,3-0,7
Preservative0,08-0,12
Water demineralizedrest

3. The composition according to claim 2, characterized in that the gelling 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 the emulsifier contains triethanolamine.

6. The composition according to claim 2, characterized in that as preservative contains nipagin in the amount of 0.07 to 0.09 wt. % nipazol in an amount of 0.01-0.03 wt. %.



 

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43 cl, 2 tbl, 2 ex, 19 dwg

FIELD: medicine.

SUBSTANCE: composition to be used for the purpose of inhibiting the infecting ability of viruses accompanying viral infections, including cold with a primary infection caused by rhinoviruses, adenoviruses and/or coronaviruses, influenza, and a viral infection caused by retroviruses; the above composition contains an aqueous extract of Ribes leaves and branches. Using the aqueous extract of Ribes leaves and branches for preparing a drug preparation for inhibiting the infecting ability of viruses accompanying viral infections, including cold with the primary infection caused by rhinoviruses, adenoviruses and/or coronaviruses, influenza, and the viral infection caused by retroviruses The composition containing the aqueous extract of Ribes leaves and branches is effective for inhibiting the infecting ability of viruses accompanying viral infections, including cold with the primary infection caused by rhinoviruses, adenoviruses and/or coronaviruses, influenza, and the viral infection caused by retroviruses.

EFFECT: improved properties of the composition.

14 cl, 3 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to otorhinolaryngology, and may be used in conducting the antiviral therapy in treating antiviral and hyperplastic nasopharyngeal diseases in children. That is ensured by prescribing cyclopheron in the period of acute clinical manifestations in a clinically effective daily doses prescribed considering patient's weight and age in the five- or ten-day therapeutic course in a combination with the local administration of 20% aqueous sulphacyl sodium 2-3 drops in both nostrils with patient's head lag 3 times a day in the ten-day therapeutic course. Cyclopheron is prescribed in rarely ill patients suffering ARVIs in the five-day therapeutic courses. In recurrently ill patients and in the setting of hyperplastic nasopharyngeal conditions, in chronic nasopharyngitis, chronic adenoiditis and pharyngeal lymphoid tissue ring hyperplasia, the patient undergoes the ten-day therapeutic course in each aggravation of clinical manifestations to reduce the rate of acute clinical manifestation and stable clinical remission. Local sanitation of the inflammation centre with sulphacyl sodium in all cases is performed within the ten-day therapeutic courses.

EFFECT: invention enables reducing the length and rate of the aggravations of inflammatory and hyperplastic nasopharyngeal diseases in children.

3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine and deals with pharmaceutical composition for local application in form of gel, which contains enzyme deoxyribonuclease (DNA-ase) and/or ribonuclease (RNA-ase) and liposomes, which can be applied in medicine for treatment and prevention of viral infection.

EFFECT: invention ensures obtaining stable pharmaceutical compositions.

1 cl, 7 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention refers to veterinary virology, microbiology and biotechnology and may be used in developing the agents for specific prevention, particularly for preparing cattle viral diarrhoea vaccine. To improve the quality of an end product by using an oxidant solution as an inactivating agent prepared by the electrolysis of sodium chloride solution, as well as to activate the method for preparing the cattle viral diarrhoea vaccine involving preparing a virus-containing material of the cattle viral diarrhoea vaccine strain, infecting a continuous cell culture with the virus-containing material, culturing the cattle viral diarrhoea virus, collecting a virus-containing fluid, inactivating and preparing the end product in the liquid form, with the cattle viral diarrhoea virus being inactivated by the oxidant solution prepared by electrolysis of 10.0-20.0% sodium chloride with the electrolysis carried out to pH 7.0-8.0, oxidant concentration 0.7-0.9% and redox potential +1000±50 mV; the processing is one-staged with the active chlorine content Cax=400-600 mg/l for 60-70 min with inactivating agent consumption 4.5-5.0 cm3 per 0.8-1.0 l of the virus-containing fluid.

EFFECT: higher quality of the end product.

3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present group of inventions refers to medicine, namely therapy, and concerns treating bacterial infections. That is ensured by a combined drug containing an activated potentiated form of human gamma-interferon (IFN-γ) antibodies, an activated potentiated form of CD4 receptor antibodies and an activated potentiated form of histamine antibodies.

EFFECT: invention provides the effective treatment of bacterial infections due to potentiating the antibacterial action of the activated potentiated forms of gamma-interferon antibodies.

11 cl, 1 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: present group of inventions refers to medicine, namely therapy, and concerns treating viral infections. That is ensured by administering a combined drug containing human activated potentiated gamma-interferon, CD4 receptor and histamine antibodies.

EFFECT: administering the same combined drug provides treating various viral diseases, such as acute respiratory viral infections, herpes viral infections, acute intestinal viral infections, etc, by action on the various components of the immune system.

10 cl, 5 ex, 2 dwg, 8 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are presented: using nalbuphine salt in the form of a hydrophilic emulsion suppository for treating moderate to severe pain syndrome, a pharmaceutical composition for the same application in the form of suppositories comprising nalbuphine hydrochloride as an active substance and a hydrophilic emulsion base in the following ratio, g/100 g of the composition: nalbuphine hydrochloride 0.0125-5.00, hydrophilic emulsion base up to 100 g, and a method for preparing the same.

EFFECT: effective and prolonged analgesic action with no laxative action has been shown.

7 cl, 3 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and medicine, namely to a soft dosage form in the form of a topical oily gel used in treating purulent skin infections and containing sodium fusidine, methyluracil (dioxomethyl tetrahydropyrimidine), an oily gel base (mineral oil and polyethylene) and additionally hydroxymethyl quinoxaline dioxide.

EFFECT: developing the preparation for treating purulent wounds, degrees 3-4 burns, decubituses and ulcers, possessing the improved antibacterial effect and regenerative action.

2 cl, 8 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to veterinary science and medicine, and may be used to prevent and treat bacterial infections. An antibacterial injectable pharmaceutical composition comprises azithromycin, solvents and/or co-solvents, a preserving agent, and an antioxidant. The antioxidant is presented by ascorbic acid, or sodium ascorbate, or calcium ascorbate, or palmityl ascorbate, or 4-methyl-2,6-ditertbutylphenol, or tertbutylhydroquinone, 2,4,5-trihydroxybutyrophenone, or sodium metabisulphite, or alpha tocopherol, or thioglycerol, or combinations thereof; the preserving agent is presented in the form of benzyl alcohol, parabenes, chloroethanol or combinations thereof; the solvents or co-solvents are organic solvents, including dimethylacetamide, or dimethylsulphoxide, or N-methyl-2-pyrrolidone, or 2-pyrrolidone, or combinations thereof, or combinations of organic solvents with water in the following relations, wt %: azithromycin 5-50, antioxidant 0.1-0.2, preserving agent 1-2, pH regulator up to 5, solvents the rest.

EFFECT: antibacterial injectable pharmaceutical composition of azithromycin possesses a wide spectrum of the antimicrobial action, and is applicable to the intravenous, intramuscular, subcutaneous, intrauterine and intracisternal introduction.

3 cl, 1 dwg, 7 tbl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and represents a combined drug preparation for the local treatment of periodontics, including a complex of metronidazole and chlorhexidine in a combination with sodium fusidine, sweetening agents and a pharmaceutically acceptable gel base in the following proportions, g: sodium fusidine 1.8-2.2; metronidazole 0.9-1.1; chlorhexidine bigluconate (in the form of 20% chlorhexidine bigluconate) 0.42-0.58 in the amount equivalent to chlorhexidine 0.08-0.12; sodium saccharinate 0.1-0.3; monoammonium glycerrhizinate (MM100) 0.006-0.008; aerosil 200 (colloidal silicon dioxide) 5.5-6.0; paraffin oil (Vaselin oil) - the rest up to 100 g.

EFFECT: invention provides creating the therapeutic pharmaceutical composition in the form of gel possessing the antibacterial and anti-inflammatory action with an optimum combination of the ingredients to provide a stable depot of the active substances within an area of inflammation for the purpose of treating infectious-inflammatory periodontics of various aetiologies.

3 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to a method for preparing a therapeutic hydrogel material involving mixing an aqueous solution of sodium alginate and a drug preparation, dispersing a cross-linking agent that is presented by calcium sulphate in glycerol in the concentration of 0.8-2.5%, mixing the dispersion with the prepared mixture of sodium alginate with the drug preparation in ratio 1-2:4-6, placing the prepared product into a tiling pattern and keeping it till form-stable, conducting gamma sterilisation; the formation process involves the mechanical stability measurements with the diametral compression of the formed hydrogel; the hydrogel is considered to be formed once a thickness of the formed hydrogel varies with the diametral compression by 10-30%.

EFFECT: invention provides the wider medical variation of the drug concentrations, preparing high-thixotropy soft hydrogel materials (tablets) easy to administer, including through rectum, preparing the materials that preserve its all their physical-technical and mechanical properties after the gamma sterilisation along with the sterility.

4 cl, 10 ex

FIELD: medicine.

SUBSTANCE: invention represents a composition for the topical delivery of a composition containing a nitrogen oxide donor specified in L-arginine or its derivative; an adverse biophysical medium containing an ionic salt; a stabilisation polymer containing xantham gum; propylene glycol; a polysorbate surfactant containing Polysorbate 20; and ibuprofen and/or an ibuprofen salt, to the individual's skin.

EFFECT: creating the composition possessing temperature stability at high temperatures.

20 cl, 1 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to use of 2-nitroheterylthiocyanates, particularly 4-rhodano-5-nitropyrimidine and 2-rhodano-3-nitripyridine derivatives of general formula (I), optionally in crystalline form or in form of pharmaceutically acceptable addition salts thereof with acids or bases, having activity on fungal strains, fungal infection agents, for producing pharmaceutical compositions that are suitable for local application. The compounds are also active on strains that are resistant to existing drugs. In general formula (I) X=N or C-R3, R1 denotes a proton, a saturated or unsaturated linear alkoxy radical having 1-5 carbon atoms; a cycloalkyloxy radical having up to 6 carbon atoms; a saturated linear alkylmercapto radical having 1-3 carbon atoms; an amino radical having 1-10 carbon atoms, selected from a saturated or unsaturated linear mono- or dialkylamino radical or a cycloalkylamino radical, cyclic amino radical. Each of the cyclic groups can be substituted with 1-2 methyl groups, or a benzylamino group; R2 denotes a proton, a saturated or unsaturated linear alkyl radical having 1-5 carbon atoms, or a cyclic aliphatic radical having up to 6 carbon atoms, trifluoromethyl, styryl or methylmercapto group; R3 denotes a trifluoromethyl, formyl, acetyl, nitro, benzoyl, cyano group or an alkoxycarbonyl substitute having 1-3 carbon atoms in the alkoxy group.

EFFECT: improved properties of compounds.

5 cl, 3 tbl, 21 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a method for preparing a water suspension of silicon nanocrystalline particles for biomedical applications. The declared method is characterised by the fact that a porous silicon film of the thickness of 1 to 100 mcm and the porosity of 50 to 80% is formed on the surface of silicon plates. The film is formed by electrochemical etching in a solution containing 40-50% aqueous solution of fluoric acid and alcohol in ratio 1:1 to 1:5 for a period of time of 10 to 60 minutes at specific current 20 to 60 mA/cm2. The prepared silicon plates coated with a porous silicon layer is washed in distilled water, dried and placed in a container with distilled water. Then, they are exposed to ultrasound for more than 10 minutes at the intensity of the silicon plate exposure in water of 100 Wt/cm2 at frequency 23 kHz. This provides forming the stable suspension in distilled water from nanoparticles of the lateral dimension of 10 to 500 nm.

EFFECT: invention provides preparing the biocompaticle suspension of silicon nanoparticles that penetrate into living cells preserving its useful biological properties and luminescence.

4 dwg, 1 ex

Biogel // 2503464

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics. There are developed agent for forming a biogel, biogels for hemostasis, wound closure, tissue engineering and targeted drug delivery. The agent contains a soluble carrier whereon a number of fibrinogen-binding groups is immobilised. The biogel that contains fibrinogen molecules and a number of soluble carriers applicable for intravenous and/or local administration; each carrier comprises a number of fibrinogen-binding groups immobilised on the carrier, and each fibrinogen molecule is bound to at least two fibrinogen-binding groups so that the fibrinogen molecules occurs to be bound to each other through the carriers by non-covalent bonds between the fibrinogen-binding groups and the fibrinogen molecules. The biogel containing fibrin monomers and a number of soluble carriers applicable for intravenous and/or local administration, wherein each carrier comprises a number of fibrinogen-binding groups immobilised on the carrier, while the fibrin monomers are bound to each other through the carriers by non-covalent bonds between the fibrinogen-binding groups and the fibrinogen monomers. The biogel containing fibrin and a number of soluble carriers applicable for intravenous and/or local administration, wherein each carrier comprises a number of fibrinogen-binding groups immobilised on the carrier with the fibrin monomers in fibrin are covalently bound to each other by peptide bonds, and the fibrin monomers in fibrin are bound to each other through the carriers by non-covalent bonds between the fibrinogen-binding groups and the fibrinogen monomers. A method for forming the biogel involving a contact of the fibrinogen molecules with a number of soluble carriers. A method for hemostasis by topical administration of the biogel at a haemorrhage or a wound. Using a number of soluble carriers applicable for intravenous and/or local administration. A pharmaceutical formulation for topical administration containing the biogel, agent or a number of soluble carriers.

EFFECT: using the declared invention enables preparing the agents requiring no toxic reagents to be used, have a minimal risk of allergic reactions, and are easy to prepare and use.

2 tbl, 4 dwg, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and cosmetology, and represents a composition for treating or preventing alopecia in the form of a gel containing sodium salt of non-fractionated heparin 0.08-0.8% , lipid nanocomplex emulsion 0.15-3%, gel former 0.5-2%, emulsifier 0.1-0.2%, neutralising agent 0.03-1.3%, preserving agent 0.01-0.03%, and a solvent specified in a group consisting of water, or polyol - the rest.

EFFECT: invention provides extending the range of products for treating alopecia with no side effects.

25 cl, 6 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, namely to enterosorbent and method of its obtaining. Enterosorbent based on peat, free from lipids, additionally contains cranberry cake, prebiotic with specified component ratio. Method of obtaining enterosorbent from preliminarily dried sphagnum peat includes extraction of lipids with solvents, mixing with cranberry cake, crushing, mixing with solution of prebiotics - lactulose or lactose and drying.

EFFECT: method makes it possible to extend assortment of natural enterosorbents with improved properties: high enterosorbing capability and prebiotic activity.

2 cl, 1 tbl, 2 ex

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