RU2437672C1 - Method of green tea extract purification, based on it medication and method of prevention and treatment of skin diseases - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry and medicine. Method of purification consists in the following: extract of green tea is washed with methylene chloride, or chloroform, or trichloroethylene by slurryfication with further mixing of suspension at room temperature during 20-40 minutes, and ratio of green tea extract and chlorine-containing hydrocarbon constitutes 1:28-30. Then sediment is separated and dried at temperature 28-32°C and residual pressure 12-14 mm Hg during one and a half hours. Medicine represents gel, containing purified by claimed method extract of green tea with 70-75% content of epigallocatechine-3-gallate (EGCG) and additional components with specified ratio in wt %. Gel is applied on damaged areas of face and body skin in thin layer until cvomplete drying 1-3 times per day during 5 days - 12 weeks.

EFFECT: gel has expressed antihyperplastic, anti-inflammatory and antioxidant properties, activates natural process of tissue regeneration, normalises metabolic processes, inhibits premature ageing, increases skin stability against unfavorable iimpact of environment.

3 cl, 2 tbl, 10 ex

Description

The group of inventions relates to the pharmaceutical industry and medicine and relates to a method for purification of green tea extract, development of a medicine based on it having anti-inflammatory, antibacterial and cytostatic effects, as well as a method for using the obtained medicine.

Recently, interest in polyphenol-containing substances with anti-inflammatory, antibacterial and cytostatic properties due to the high biological activity of catechins has increased.

The greatest number of catechins is found in young shoots and leaves of a green tea plant. Among catechins, the main one in terms of quantity and bioeffects is epigallocatechin-3-gallate (EGCG).

A known method of producing polyphenolic fractions from green tea, involving the extraction of plant biomass with an aqueous-alcoholic solution or aqueous-ketone mixtures, complete or partial evaporation of the extraction solvent, suspension of the residue in an aqueous mixture of 30-60% by volume of methanol, extraction of the hydromethanol suspension with chlorinated solvents, filtration insoluble residues and concentration of the hydromethanol phase, optional acidification with organic acids, extraction of concentrated hydromethanol phase and arbitrary acidification with solvents selected from aliphatic esters, alcohols or ketones, provided that they do not mix with the hydromethanol mixture, adding optionally an aromatic or aliphatic hydrocarbon, followed by washing with dilute solutions of mineral acids, concentration of an immiscible aqueous-organic phase and its dilution with chlorinated solvents (RU 2185070 C2, 07.20.2002).

The disadvantage of this method is the complexity of the process of obtaining a mixture of catechins and the insufficiently high content of EGCG in the final product - 50-65%. In addition, the resulting drug based on a mixture of catechins is produced in the form of tablets, gelatin capsules, sachets, syrups, ampoules and is not used to treat skin diseases.

It is known a medicinal product containing, as an active principle, a polyphenol-containing substance with a concentration of catechins of at least 70%, preferably green tea and / or its extract and fluoroquinolone, as well as auxiliary components. The drug can be made in the form of a gel or cream, while the auxiliary components contain lipophilic, hydrophilic or hydrophilic-lipophilic substances, as well as preservatives, surfactants (RU 2372933 A1, 11/20/2009),

A disadvantage of the known agent is that the final product is not characterized by the value of EGCG, and also that it additionally contains an antibacterial agent - fluoroquinolone. A known tool is used to treat urological diseases.

Known drug for the treatment of precancerous lesions of the skin, containing a mixture of catechins isolated from green tea, about 2-20% (wt./wt.) Epicatechin, about 2-20% (wt./wt.) Epicatechin gallate, about 1-25 % (wt./wt.) epigallocatechin, about 40-75 wt.% (wt./wt.) epigallocatechin gallate, about 0.05-5% (wt./wt.) gallocatechin and / or 0.5-20% (w / w) gallocatechin gallate, as well as auxiliary components, including propylene glycol.

The drug can be made in the form of a gel, cream and / or ointment with a catechin content of 10-15%. Apply this tool by applying it to problem areas of the skin 1 to 5 times a week for 6-12 weeks (RU 2366447 C2, 09/10/2009).

The disadvantage of this tool is a long course of treatment of 6-12 weeks.

A drug is known for the treatment and prevention of proliferative diseases, mainly of the anogenetic sphere, such as prostate and breast tumors, containing (wt.%): EGCG - 30-80, Indo-3-carbinol - 20-70 (RU 2276993 C2, 05/27/2006). This drug is produced in the form of capsules, which does not allow its use in problem areas of the skin with its diseases.

The objective of the present group of inventions is to purify green tea extract in order to increase the content of epigallocatechin-3-gallate and to create, on its basis, a medicine for the treatment of skin diseases such as vitiligo, excessive scarring after surgical interventions and various injuries.

The developed product has pronounced antihyperplastic, anti-inflammatory and antioxidant properties.

The problem in part of the first object of the invention is solved due to the fact that the green tea extract used as a raw material is pre-purified in order to increase the content of the active substance in it - epigallocatechin-3-gallate (EGCG) and reduce the caffeine content.

According to the invention, the green tea extract is washed with a chlorine-containing hydrocarbon, wherein the green tea extract is washed by suspending it in a chlorine-containing hydrocarbon, followed by stirring the suspension at room temperature for 20-40 minutes, while egallochite and chlorine-containing hydrocarbon are used in a ratio of 1: 28-30. then the precipitate is separated and dried at a temperature of 28-32 ° C and a residual pressure of 12-14 mm Hg for an hour and a half.

As chlorine-containing hydrocarbons, methylene chloride, or chloroform, or trichlorethylene is used.

The problem in part of the second object - the drug is solved due to the fact that, according to the invention, the drug is made in the form of a gel, as an active substance it contains purified green tea extract according to the above method with a content of 70-75% epigallocatechin- 3-gallate (EGCG), and as auxiliary components it contains propylene glycol, sodium polyacrylate, dimethicone, nipagin, nipazole and purified water in the following ratio of components (wt.%):

Green Tea Extract with 70% EGCG 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

The problem in part of the 3rd object - a method for the prevention and treatment of skin diseases - is solved by the fact that on the damaged areas of the skin of the face and body with a thin layer until complete drying 1-3 times a day for 5 days - 12 weeks, the claimed drug is applied.

The technical result of the proposed group of inventions is the creation of a medicinal product with pronounced antihyperplastic, anti-inflammatory and antioxidant properties. At the same time, the obtained drug activates the natural processes of tissue regeneration, normalizes metabolic processes, inhibits the processes of premature aging, and increases the skin's resistance to adverse environmental influences.

The invention is illustrated by the following examples, which do not cover, but do not limit the scope of the claims of the applicant.

Example 1

The product arriving at the enterprise - dry green tea extract “Green Tea P.E.” (manufactured by Zhejiang Cathaya International Co., Ltd, China) has the following indicators:

Fine powder

Color - Brown, Yellow

Particle sizes - 90% through 80 t mesh

Polyphenol content - not less than 90.0%

The content of kakhetins - not less than 70.0%, the content of EGCG - 55-60%

Caffeine content - not less than 10%

Humidity - no more than 8%

Ash - no more than 10%

Heavy metals - no more than 20 ppm.

Green tea extract is purified to increase EGCG and reduce caffeine.

For this, 0.208 kg of green tea extract is suspended in 6.18 L of methylene chloride. The suspension is stirred vigorously for half an hour at room temperature, and then filtered through a dense filter. The precipitate is separated and dried at a temperature of 30 ° C and a residual pressure of 13 mm Hg. for an hour and a half. Get 2.02 kg of the target product with a basic substance content of epigallocatechin-3-gallate 75.0%, the quality of which allows it to be used for the manufacture of dosage forms of the drug (HPLC). The caffeine content in the final product is 0.5%.

Example 2

Purification is carried out analogously to example 1. Take 0.205 kg of green tea extract, use chloroform in the amount of 6.15 l as a solvent. Get 2.0 kg (97.9%) of the target product with a basic substance content of 73.0%. The caffeine content in the final product is 0.5%.

Example 3

Purification is carried out analogously to example 1. Take 0.200 kg of green tea extract, use trichlorethylene in an amount of 6.10 as a solvent. Get 2.0 kg (97.9%) of the target product with a basic substance content of 70%. The caffeine content in the final product is 0.5%.

The claimed method of purification of green tea extract allows to significantly increase the content of the most valuable biologically active substance - epigallocatechin-3-gallate, reduce the caffeine content, simplify the process, increase its economic efficiency and yield of the target product while maintaining high quality. The resulting product meets the requirements for pharmaceutical substances.

Example 4

Preparation of a medicinal product in the form of a gel.

The drug is manufactured according to the technological scheme in stages:

- Preparation of equipment, premises, equipment, workwear. Unloading raw materials.

- Weighing raw materials.

- Loading of raw materials into the homogenizer.

- Preparation of the gel.

- Filling or filling of bottles, tubes, cans.

- Corking of bottles, cans of finished products.

- Quarantine storage until a positive conclusion is received from the technical control department.

- Labeling and / or packaging in individual packaging.

- Formation of group packaging and labeling.

- Storage at the warehouse of finished products.

The calculated amount of water is poured into the reactor through the loading hatch, a weighed portion of propylene glycol and sodium polyacrylate is added, mixed and dimethicone, nipagin, nipazole are added. Stir until completely dissolved. After mixing, add the calculated amount of green tea extract, EGCG 70%, to the previously prepared mixture. Mix, homogenize. Get the tool of the following composition, wt.%:

Green Tea Extract with 70% EGCG 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

After mixing and dissolving the components, the gel is homogenized and packaged.

We give specific examples of therapeutic efficacy of the drug.

Example 5. External therapy after laser therapy.

In place of the laser remains the wound surface, which was treated with gel. Dressings were performed 3 times a day.

The antitumor mechanism of the gel is based on a wide spectrum of activity of the main substance of epigallocatechin-3-gallate. This is a powerful antioxidant, a ligand to acrylic receptors (activation of this receptor leads to an increase in oncogenic potential), has a powerful antiproliferative property and the ability to selectively induce programmed death processes in tumor cells of epithelial origin - apoptosis, and inhibit pathological neoangiogenesis.

A gel is a preparation that, after laser surgical procedures, can cope with the acceleration and completion of tissue defect regeneration processes: it stimulates the regeneration of tissue that has undergone ablation, as well as the growth of granulation and marginal epithelization during excision of skin formations; improves blood circulation in the wound; It has a bactericidal and dehydrating effect. In the presence of pain, it eliminates or reduces it. It normalizes trophism, prevents the formation of contractures and keloid scars. It has an antiviral effect. Quickly restores efficiency and promotes early rehabilitation of the patient.

The absence of relapses and a cosmetic effect is ensured by the combination of laser therapy of the antineoplastic drugs Indol-3 - carbinol with external use of the gel and immunotherapy according to the example: removal of all existing neoplasms and the purpose of the gel - 5 days, Indole-3-carbinol 400 mg daily from 3 to 6 months. Conducting general immunostimulation (immunomax, lycopid, intron-A, panavir), begun 1.5-2 weeks before and lasting for 4 weeks after surgery. Possible preoperative infiltration of lesions and adjacent tissues with solutions of inducers of the synthesis of endogenous interferon (cycloferon, neovir). A positive effect, especially in the treatment of relapses of warts, is given by postoperative irradiation of affected areas with ultraviolet light, laser and UV irradiation of blood, adaptogens, vitamin therapy, antioxidants (vitamins C, A, E, echinacea, ginseng, lemongrass, eleutherococcus). After recovery, up to a year or more is necessary.

Table 1 Assessment of the clinical efficacy and treatment of genital warts Relapse Period Treatment method Laser destruction (n = 49) Laser destruction + Indole-3-carbinol + Egallochite (n = 55) Relapse after 30 days 2 (4.08%) Only 8 (16.3%) 2 (3.6) Total 3 (5.5) Relapse after 90 days 3 (6.12%) 1 (1.8) Relapse after 180 days 3 (6.12%) 0

The reduction in the number of relapses of tumor formation more than twice registered in the experimental group compared to the control shown in the table indicates the adequacy of the use of laser therapy, Indole drug and external use of the claimed gel.

The combined use in the treatment of condylomatosis of the drugs Indole-3-carbinol and the claimed gel reduces its relapse and prevents the development of malignancy.

Example 6

Scarring is a normal function of damaged tissue, without which no living organism can exist. Scar tissue is not identical to the tissue that it replaces, and has lower functional properties (Iashvili B.P., Belikov Yu.N., 2005, Dirk M Elston, 2001).

The need to prevent excessive scarring after surgery, various injuries, etc. is an actual scientific and practical task. Despite the continuous improvement of the methods of treating injuries (of various origins) and the tactics of postoperative management of patients, the formation of gross deforming scars is one of the serious problems of modern medicine. Having appeared once, scars remain for life. Cosmetic and functional defects cause psychological discomfort to the patient, disrupting the social adaptation of a person after injuries and operations, and significantly affect the quality of life.

On the basis of the oncological clinic, clinical experience was obtained aimed at identifying the effectiveness of the use in the early stages of the preparation of a gel in the form of a gel as an antihyperplastic agent in the prevention of pathological scar formation after removal of pathological skin formations.

For 4 months, 37 patients with various benign skin formations (skin fibromas, skin papillomas, various pigmented nevi) were under observation.

The study involved patients with benign skin tumors who underwent removal using the cryosurgical unit ERBO Cryogus 12 (two-time application for 2-3 minutes) and the Atkus-15 semiconductor laser knife (exposure energy - 11-14 W in continuous radiation mode) )

In all cases, pathomorphological and cytological studies were performed. All formations are confirmed as benign.

Patients were divided into 2 groups: the 1st group of 19 people who received traditional postoperative treatment without subsequent prevention of excessive scarring, and the 2nd group of 16 people who, from 6-9 days, applied a gel drug to the area of remote education . Application mode - daily 2 times a day, for 2 weeks with a break of 1 week, during which patients underwent a course of magnetotherapy, and repeated courses of use of the drug.

The effectiveness of therapy was evaluated according to clinical data at routine examinations after 2 weeks, 1 month, 3 months.

The clinical results in the 1st group were distributed as follows: in 12 of 19 patients at 2 and 3 examinations, the development of a typological scar was revealed at the site of previously removed skin formation, 4 scar had a mild hypertrophic character, and normotrophic began to form in 3 patients, practically not visualized scar.

In the 2nd group, after drug therapy, normotrophic scars that were not disturbing from the cosmetic point of view formed in 11 of 16 cases, the scar 3 was mildly hypertrophic, and in 2 cases the scarring went like hypertrophy with a clear cosmetic defect.

Evaluation of the effectiveness of the drug and the degree of development of scar tissue was carried out on a modified Vancouver scale. As a result of the analysis of the obtained data, the least number of points and, as a result, the best cosmetic and morphofunctional result was obtained in patients who used gel for prevention.

Thus, early prophylaxis of pathological scar formation is necessary to achieve the best aesthetic and functional effect and to a large extent avoids such negative consequences of removing benign formations as scar formation and a decrease in the quality of life due to stress factor and cosmetic defects. The drug in the form of a gel as a preventive agent with antihyperplastic effect has proved to be quite effective and worthy of attention of surgeons of various profiles. The application of the proposed methodology for the prevention of the formation of pathological scars allows expanding the possibilities of selecting adequate rehabilitation schemes for patients after removal of benign skin formations.

Example 7

Treatment of hypertrophic and keloid scars.

The claimed gel was included in the scar treatment method. The gel accelerates and shortens the growth phase of new vessels, which leads to stimulation of the deposition of the collagen matrix in the first days and to suppression in the future. The gel inhibits the activity of kinases and growth factors that transmit collagen enhancement signals, inhibits the synthesis of pro-inflammatory cytokines (IL-1, IL-6, IL-8, TNF), which leads to a decrease in the inflammatory effects (erythema, pruritus) associated with thermal damage to the skin . The gel prevents the formation of atrophic and hypertrophic scars, reduces the size of existing ones, and maintains normal skin pigmentation after laser exposure or photodynamic therapy.

Patients with abnormal scars underwent laser therapy with a wavelength of 578 nm, 07-1.0 W and an exposure of 0.2 s. The surface was treated densely with pulses at 1 mm intervals without damaging the epidermis until visible whitening. Depending on the effect, 1-2 procedures were performed with an interval of 2 weeks. During the experiment, the scar area was not taken into account, as for the height of the scar, if it was more than 0.5 mm from the skin level, then laser resurfacing was first performed. In all cases, after laser exposure, the claimed gel was prescribed for 5 days. The effectiveness of the method was 82%, the follow-up period was up to three years, no relapses were noted.

Thus, in the treatment of hypertrophic and keloid scars, it is better to use the combined method - laser therapy with the mandatory use of the claimed gel as an epithelizing, anti-relapse agent, including in the complex treatment of patients with local erosive surfaces prone to scar formation (after peeling, dermabrasion). The gel has an antiproliferative property. Therapy using the claimed gel is non-aggressive, painless, well tolerated, with no side effects, with the possibility of use both in the form of monotherapy and in combination with various treatment methods (peels, laser therapy, dermobrazia).

Example 8

The study was conducted on 80 patients with hypertrophic and keloid skin scars aged 19 to 58 years. To normalize scarring, we used a gel-based drug containing 10% epigallocatechin-3-gallate. Patients were randomly divided into two groups. Patients of group 1, the gel was applied after laser resurfacing (scar ablation) with a laser power of 15 W and a radiation wavelength of 810 them. Next, the gel was applied 2 times a day for 30 days. Patients of the 2nd group - the control - received the same laser surgery, but instead of the gel they were applied the gel Kontraktubeks or ointment Levomekol. Next, patients were observed on 3, 10, 30 and 90 days after laser resurfacing. To control the healing process, all patients underwent video dermatoscopy (BS-888ProSMP dermatoscope) with polarizing 5x and 200x multiple lenses and digital video recording on the 3rd, 10th, 30th and 90th days after the PDT session.

For statistical data processing, the SPSS for Windows software package (SPSS Inc.) was used. To assess the normality of the data distribution, the Kolmogorov-Smirnov test was used.

In the first group, the main share was patients with hypertrophic scars - 37 people, three patients had keloid scars. In the control group of patients with hypertrophic scars was 36, and with keloids - 4. Patient groups did not differ among themselves by the presence of a certain type of scar (criterion x ² , p = 0.69). In terms of the sex ratio, the groups did not differ among themselves (criterion x ² , p = 0.26).

The main criterion for the effectiveness of the treatment we chose was the type of scar formed on the 90th day after laser surgery. All patients of the first group (receiving the drug in the form of a gel) formed a normotrophic scar after 3 months. Patients of the second group (receiving Kontraktubeks or Levomekol) in 13% of cases formed pathological scars. This difference is statistically significant (criterion x ² , p = 0.021). Among patients of the control group with pathological forms of scarring, a relapse of a hypertrophic scar was mainly observed (10%), and only one patient had an atrophic scar. Differences in the proportion of patients with relapse are also statistically significant (criterion x ² , p = 0.037).

Laser resurfacing of hypertrophic and keloid scars provides a significant reduction in the area of cosmetic defect after treatment. In the control group, the ratio of the scar area on 90 days to the area of the initial scar was 0.27 × 0.09. Against the background of the use of the drug in gel form, this indicator was 0.23 ± 0.04, which is 18% less. Differences between groups are statistically significant (Mann-Whitney test, p = 0.009).

It should be noted that significant differences in the ratio of the area of the final and initial scar appear only after 30 days from the date of laser resurfacing. When comparing this indicator on day 30, it turned out that it was 0.48 ± 0.09 in group 1, and 0.48 ± 0.21 in group 2. Thus, the claimed gel has the main therapeutic effect in the first days of its use, which affects the further process of maturation of scar tissue.

A positive effect of the gel was noted on the concomitant phenomena common for laser surgical treatment, such as hyperemia and itching of the skin in the area of grinding. In the experimental group, the period of hyperemia disappearance was 5 days, and in the control - 7 days. Differences between groups are statistically significant (Mann-Whitney test, p <0.001).

Itching of the skin disappeared in the control group more often on day 10, and when using the drug in the form of a gel, on day 6. Differences between groups are statistically significant (Mann-Whitney test, p <0.001).

The positive effect of the gel on hyperemia and itching of the skin is apparently associated with the anti-inflammatory properties of epigallocachetin-3-gallate, which are realized by suppressing the synthesis of pro-inflammatory cytokines.

The study demonstrated the effectiveness of the external use of the claimed gel to normalize the scarring process. The study was conducted on a contingent of patients, obviously prone to the formation of hypertrophic and keloid scars. The use of a medicinal product in the form of a gel for laser resurfacing of skin scars allows you to ensure: the normal appearance of the scar after polishing without the formation of hypertrophic and atrophic scars; acceleration of the disappearance of hyperemia and itching; 18% smaller size of the final scar. These effects were also discovered earlier on the example of patients receiving photodynamic therapy of basal cell skin cancer.

This approach does not require long-term preventive exposure, as is the case with silicone gels. The reduction of treatment time and the almost complete absence of recurrence of hypertrophic and keloid scars after laser resurfacing using a gel allows us to recommend this approach as a method of choice for patients with this pathology.

Example 9

The aim of the study was a comparative assessment of the effectiveness of the treatment of scars using the declared gel based on the developed clinical diagnostic criteria.

The feasibility of using the gel is due to its high pharmacological effect, which consists in a two-phase effect on the pathogenesis of scar formation. In the first phase, there was a sharp stimulation of angiogenesis in the wound, followed by a rapid suppression of collagen formation in the second phase. The suppression of inflammatory cytokines leads to a decrease in the proliferation of fibroblasts and a decrease in the synthesis of coarse fibrous connective tissue.

The study was conducted in 20 patients of both sexes (8 men, 12 women) aged 21 to 62 years with cicatricial changes in the skin.

Patients of the 1st group (18 people) applied the gel 2 times a day for two months (60 days). The control was carried out on the 1st, 30th and 60th days of treatment. Patients of the 2nd control group of 23 patients (10 men and 13 women) applied Levomekol ointment according to a similar scheme.

To assess the clinical effectiveness of the drug, a study was made of the condition of scars in dynamics. A special scale was applied, in accordance with which changes in the indicator of the state of scars (RPS) were recorded.

The formula for calculating the RPS:

PSR = S cm ² × the total score of qualitative features (scar type, color, consistency, sensitivity).

During the treatment, in 18 patients who received topical gel treatment of scars, the average scar area was 2.22 ± 0.24 cm ² , after treatment 2.18 ± 0.24 cm ² , the difference was not significant. Clinically, changes in the area of scar defects in most patients were not noted. At the same time, the indicator of the state of scars (PSR) in patients of the main group before treatment was 15.54 ± 2.96, after treatment - 8.29 ± 1.95 (P <0.05). As a result of the treatment, a significant improvement in the condition of the scar was noted, statistically significant according to the Student criterion. When applying Levomekol ointment in the control group of patients, the average scar area was 2.17 ± 0.23 cm ² , after treatment, the reduction in the size of the average scar area was also not detected (2.15: 0.23 cm ² ). Clinical changes were insignificant, the PSR index changed from 14.8 ± 2.58 to 12.1 ± 2.22, the difference is unreliable.

Thus, when applying the gel, there was a significant decrease in the indicator of the state of scars (RPS) by about 2 times, which was clinically expressed in the resolution of scar hypertrophy, decrease in compaction, erythema, and unpleasant sensations. In the control group, PSR changed slightly; the clinical picture in this group of patients expressed changes did not undergo. These data make it possible to use the gel as an antihyperplastic and anti-inflammatory agent as monotherapy in patients with various types of cicatricial deformities, including those with significant periods of limitation.

Example 10

Vitiligo is an autoimmune disorder with loss of skin pigment as a result of pathological changes that occur in melanocytes. According to statistics, the incidence of this disease is 1-2% of the entire dermatological pathology.

Clinical studies of the gel were carried out on 20 vitiligo patients, in 15 concomitant diseases were noted: thyroid gland diseases, vegetative dystonia, diseases of the gastrointestinal tract, etc.

In 15 people, a common type of vitiligo was observed, in 5 patients it was limited.

The duration of therapy was 3 months. Patients applied the gel once a day. Prior to the use of the drug, patients underwent biochemical and clinical blood tests, as well as photographs of the affected areas of the skin. After completing the course of therapy, blood tests were repeated and repeated photographs were taken. The gel was used against the background of complex therapy of vitiligo. The results of the data are summarized in table.

table 2 Dynamics of blood biochemical parameters in 20 vitiligo patients before and after applying the drug in gel form Indicators Before treatment After Total protein 71.9 75 Urea 5.37 5.05 Creatinine 67 74 Cholesterol 4.75 4.92 Bilirubin 13,4 13.1 ALT 31,2 30.5 ACT 33.5 33,2 Alkaline phosphatase 330 293 Glucose 5.3 4.7

From the table it follows that the use of the drug in the form of a gel did not significantly change the biochemical parameters of the blood, which confirms its safety.

Throughout the course of admission, patients were regularly observed by a dermatologist. Clinical observations, as well as an active questioning of patients about the presence of side effects, indicated good tolerability of the drug, as well as the absence of side effects during its use.

For an objective and more complete assessment of the effectiveness of the drug in patients, affected areas of the skin were photographed before and after the course of their use. A month after the start of the drug administration, the borders of depigmentation sites were smoothed out in most patients (17 patients), in some the color of depigmented areas (3 patients) also changed, in 3 patients there were no changes. After 3 months of use in some patients, the background of the “white spot” approached the color of normal skin (3 patients), i.e. ceased to stand out so sharply against normal skin, in 2 patients the small foci of depigmentation in the face area completely closed, in 2 patients who had no changes during the first month, the borders of the spots were smoothed and a change in the tone of the spots appeared. After using the drug against the background of “white spots”, the number of pigmented areas increased, in 4 patients the spots decreased in size by more than 30% and by more than 50% in 4 patients, in other patients, spots of pigmentation began to appear in the spots.

As a result of the use of the drug in most patients, a good effect was noted, stabilization of the process was noted.

Thus, on the basis of clinical trials of the drug, we note that the gel is well tolerated by patients, in no case was there any side effects. These data are confirmed by biochemical studies of the blood of patients in dynamics. Its effectiveness in vitiligo patients has been proven, which gives reason to use the gel as a tool in the treatment of this disease.

As follows from the data presented, the claimed technical result is achieved.

Claims (3)

1. The method of purification of green tea extract, characterized in that the green tea extract is washed with a chlorine-containing hydrocarbon, which is used methylene chloride, or chloroform, or trichlorethylene, and the green tea extract is washed by suspending it in a chlorine-containing hydrocarbon, followed by stirring the suspension at room temperature temperature for 20-40 minutes, while green tea extract and chlorine-containing hydrocarbon are used in a ratio of 1: 28-30, then the precipitate is separated and dried at that erature 28-32 ° C and a residual pressure of 12-14 mmHg for an hour and a half. 2. A medicine for the prevention and treatment of skin diseases, containing an active ingredient and auxiliary components, characterized in that it is made in the form of a gel and as an active ingredient contains purified green tea extract according to claim 1 with a content of 70-75% epigallocatechin-3-gallate (EGCG), and as auxiliary components it contains propylene glycol, sodium polyacrylate, dimethicone, nipagin, nipazole, purified water in the following ratio, wt.%:
Green Tea Extract with 70% EGCG 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 3. A method for the prevention and treatment of skin diseases, including applying to the damaged areas of the skin of the face and body of the drug, characterized in that on the damaged areas of the skin of the face and body with a thin layer until complete drying 1-3 times a day for 5 days - 12 weeks apply the drug according to claim 2.