RU2744142C1 - Composition for prevention of fungal diseases - Google Patents

Abstract

FIELD: pharmaceutical industry.

SUBSTANCE: invention relates to pharmaceutical industry and is intended for the prevention and treatment of fungal diseases caused by Escherichia coli, Candida sp., Aspergillus niger, Saccharomyces cerevisiae. Capsule consists of a shell and a composition enclosed in it in the form of an oil suspension, including unrefined black cumin oil (29.7-44.7 wt.%), magnesium caprylate (5.8-8.8 wt.%), essential bark cinnamon oil (0.6-0.9 wt.%), CO2-extract of cloves (0.48-0.72 wt.%), edible tea tree essential oil (0.17-0.26 wt.%), essential garlic oil (0.12-0.18 wt.%) and filler. Shell weight of one capsule is 324-396 mg. The capsule shell consists of a suture soft gelatin shell containing gelatin, a humectant, and an enteric shell, containing Collicut MAE 100P, a humectant, anti-caking agent, thickener and colorants. Shell weights are equal.

EFFECT: provides increased capsule antimicrobial and antifungal activity due to the use of the claimed composition.

7 cl, 4 tbl, 12 dwg

Description

The field of application to which the invention relates

The invention relates to the pharmaceutical industry and is intended for the prevention and treatment of fungal diseases of various localization, namely: in the gastrointestinal tract, respiratory tract, genitourinary system. State of the art

Gastrointestinal diseases are one of the most common reasons for visiting a doctor. They deliver such unpleasant symptoms as belching, heartburn, flatulence, rumbling, transfusion, pain from colicky to bursting, stool disturbance, etc. At the same time, many other diseases such as cardiovascular, autoimmune disorders, diseases of the skin, liver, kidneys, allergies, depression is also associated with bowel function. There is a strong link between bowel dysfunctions and chronic diseases of the body. Intestinal activity has a direct and indirect effect on every cell in the body. Microbiota is an ideal indicator of the physiological state of the body, depending on the impact on it of various factors. Therefore, it is so necessary to restore the microbiocenosis in case of its violation.

More than half of the world's population is a carrier of fungi of the genus Candida. According to the WHO, a fifth of the world's population suffers or has at least once suffered clinical manifestations of various localizations and forms of candidiasis. In fact, Candida fungi are in fourth place in terms of frequency among microorganisms isolated from the blood and in first place in mortality from nosocomial septic conditions.

Standard courses of antifungal therapy are prescribed for up to 3-6 months. Patients often develop side effects as a consequence of the toxic effect on the liver of most of the synthetic antimycotics used in medical practice.

In this regard, the search for a combined complex of herbal components is becoming relevant, which would eliminate the negative consequences of long-term courses of antifungal therapy.

Known drug CANDIMIN (https://badavit.ru/kandimin), each capsule of which contains caprylic acid 125 mg; L-taurine 25 mg; biotin 10 mcg; chamomile extract of pharmacy 50 mg; Po d'Arco bark extract 50 mg; grapefruit seed extract 20 mg; garlic 125 mg; barberry fruits 20 mg; cinnamon 10 mg; cloves 10 mg.

The disadvantage of this drug is the lack of a functional enteric shell on the capsule. Therefore, the active components of the product, being released in the stomach, can cause nausea, heartburn, belching, and epigastric pain. Also, the absence of an enteric coating does not allow for targeted delivery of active components to the area of action of the drug (lower parts of the small and large intestine), which reduces its effectiveness.

Known drug "Kandigon", which contains black cumin oil 234.47 mg, magnesium caprylate 72.7 mg, cloves CO2-extract 5 mg, garlic essential oil 1 mg. The drug is available in the form of enteric capsules.

The disadvantage of this composition is that the insufficient thickness of the enteric shell of the capsule does not allow the active components of the product to be delivered directly to the area of action (lower parts of the small and large intestine).

The essence of the invention

The objective of the proposed invention is to provide a dosage form capable of surpassing the disadvantages of previously known compositions and capable of simultaneous release of active ingredients to accelerate the onset of action of the drug.

The technical result consists in increasing the antimicrobial and antifungal activity of the claimed composition in the shell.

The technical result is achieved by the fact that the composition for the prevention of fungal diseases in the form of an oily suspension, coated with a shell, includes unrefined black cumin oil containing 50% linoleic acid belonging to the family of omega-6 polyunsaturated fatty acids, magnesium caprylate, essential oil of cinnamon bark, CO2 - extract of cloves, essential oil of tea tree food, essential oil of garlic and filler in the following ratio of components, wt. %:

Unrefined black cumin oil 29.7-44.7; Magnesium caprylate 5.8-8.8; Cinnamon essential oil 0.6-0.9; CO2 extract of clove 0.48-0.72; Edible tea tree essential oil 0.17-0.26; Garlic essential oil 0.12-0.18; Filler rest.

The mass of the shell of one capsule is 324-396 mg, and the shell consists of a suture soft gelatin shell containing gelatin, a humectant, and an enteric shell containing Collicut MAE 100P, a humectant, an anti-caking agent, a thickener and dyes, while the masses of the shells are equal.

The mass of the suture soft soluble shell can be equal to 180 ± 10% with the following ratio of components, mg in one capsule:

Gelatin 144.0; Humectant agent 36.0;

The humectant component may contain equal portions of D-sorbitol and glycerin.

The mass of the enteric coating can be 180 mg ± 10% in one capsule with the following ratio of components:

Collicut MAE 100R 68.95; Humectant agent 45.0; Anti-caking agent 42.62; Thickener 18.95; Dye 4.48.

The enteric coating may contain propylene glycol as a humectant, talc as an anti-caking agent, and polyvinylpyrrolidone as a thickener.

The enteric coating may contain titanium dioxide, iron oxide red, iron oxide black, and iron oxide yellow as a colorant.

The proposed ratios and the mass of the shell allow for targeted delivery of the composition.

Suggested ratio of components found

experimentally and is optimal. Going beyond the lower limit of the ratios of the main component and additives leads to a decrease in antifungal activity, and an increase in the components is impractical, since it reduces the quality of some indicators and leads to overspending of raw materials.

The invention is illustrated with tables and photographs.

Table 1 shows specific examples of the invention, Table 2 shows the specific composition of the shell, Table 3 shows the dynamics of the microbial landscape of the colon before and after taking capsules, Table 4 shows the dynamics of indicators before and after taking capsules.

Figures 1-12 show data on the antimicrobial and antifungal activity of the composition.

FIG. 1 shows a check of the effect of the mixture "Example No. 1" on the growth of fungi of the genus Candida sp. The zone of inhibition was 40 ± 5 mm.

FIG. 2 - checking the effect of the mixture "Example No. 2" on the growth of fungi of the genus Candida sp. The zone of inhibition was 43 ± 2.5 mm.

FIG. 3 - checking the effect of the mixture "Example No. 3" on the growth of fungi of the genus Candida sp. The zone of inhibition was 43 ± 2.5 mm.

FIG. 4 - check the effect of the mixture "Example No. 1" on the growth of fungi of the genus Aspergillus niger. The zone of inhibition was 27 ± 2 mm.

FIG. 5 - check the effect of the mixture "Example No. 2" on the growth of fungi of the genus Aspergillus niger. The zone of inhibition was 27 ± 3 mm.

FIG. 6 - check the effect of the mixture "Example No. 3" on the growth of fungi of the genus Aspergillus niger. The zone of inhibition was 27 ± 5 mm.

FIG. 7 - check the effect of the mixture "Example No. 1" on the growth of the yeast Saccharomyces cerevisiae. The zone of inhibition was 41 ± 6.5 mm.

FIG. 8 - test the effect of the mixture "Example 2" on the growth of the yeast Saccharomyces cerevisiae. The zone of inhibition was 41 ± 7.5 mm.

FIG. 9 - check the effect of the mixture "Example No. 3" on the growth of the yeast Saccharomyces cerevisiae. The zone of inhibition was 41 ± 7.5 mm.

FIG. 10 - check the effect of the mixture "Example No. 1" on the growth of bacteria Escherichia coli. The zone of inhibition was 60 ± 10 mm.

FIG. 11 - check the effect of the mixture "Example No. 2" on the growth of bacteria Escherichia coli. The zone of inhibition was 60 ± 12 mm.

Fig - check the effect of the mixture "Example No. 3" on the growth of bacteria Escherichia coli. The zone of inhibition was 60 ± 22 mm.

Implementation of the invention

To obtain a composition, first liquid and then dry components are added to black cumin oil with constant stirring in a strictly defined sequence. The mixture is stirred and homogenized to obtain a uniform suspension.

Was investigated the antimicrobial and antifungal activity of the claimed composition for the prevention of fungal diseases against Escherichia coli, Saccharomyces cerevisiae, Aspergillus niger, Candida sp.

The invention is illustrated by examples in tables and figures.

The research data are shown in Table 1. The test cultures used: Escherichia coli bacteria, Candida sp. Fungi, Aspergillus niger fungi, Saccharomyces cerevisiae yeast. Nutrient media for cultivation: Escherichia coli - GRM, Candida sp., Saccharomyces cerevisiae - Sabouraud's medium, Aspergillus niger - wort agar. The volume of the test culture is 100 μl, the volume of the object introduced into the wells is 100 μl. According to the prescription, we prepared media that were optimal for test cultures. Sterilized by autoclaving. In Petri dishes, set on tables with a strictly horizontal surface, the same amount of molten culture medium in the amount of 30 ml was poured into each dish. The agar plates were dried in a thermostat or in a laminar flow hood, slightly opening the lids of the plates. Test cultures of E. coli, Candida sp., Asp. niger, the Saccharomyces yeast was inoculated by the surface method, 100 μl of the suspension in each Petri dish, taking the cell suspension with a pipette with a sterile tip and transferring it to the surface of an agar plate. With a sterile spatula, rubbed the drop in a circular motion from the center to the edges of the agar plate, without touching the walls of the plate, until a slight feeling of friction, dried the plates. Then, discs were cut from the agar plate with a sterile cork drill 12 mm in diameter. The discs were removed from the plate with sterile forceps, and a 100 μL dose of the liquid containing the test drug was introduced into the holes. After adding the liquid to the wells, the dishes were carefully, avoiding splashing liquid from the well, transferred to a thermostat and cultured at the optimum temperature for each test culture for 48 hours. Then, measurements were made of the growth inhibition zone (mm) (from the border of the studied substrate to the border of no action ("radius")).

The research data are shown in Figures 1-12. The presented photographs confirm that the proposed composition prevents the growth of yeast fungi, pathogenic bacteria and enhances the colonization of a friendly bacterial flora.

The composition of the shell is shown in Table 2. The capsule disintegration tests were carried out. The tests were carried out in two stages. For testing, 18 capsule samples were taken, one was placed in each tube, and 6 plastic guide discs were inserted into glass tubes. The use of discs is necessary to prevent the capsules from floating. The collecting basket was placed in a vessel with a liquid medium at a temperature of 37 ° C. At the first stage, a 0.1 M hydrochloric acid solution was used as a liquid medium. The capsule stability time in an acidic medium was 1 hour. The capsules did not disintegrate and did not show signs of cracking or softening. In the second step, the acid was replaced with phosphate buffered saline with a pH of 6.8. In buffered solution, the capsules disintegrated after 38 minutes. For comparison, there were capsules of dietary supplements "Kandigon Immunohels". In the second phase of the test, the capsules in phosphate buffered saline disintegrated after 11 minutes.

Tests have shown that the shell allows delivery of the composition into the intestine.

Also, studies of the microbial landscape were carried out in 10 volunteers (male 1 - people, female - 9 people). Based on the clinical and laboratory-instrumental studies carried out, the following diseases were revealed in the volunteers:

1. Fatty hepatosis - 6 people.

2. Obesity - 6 people.

3. Pancreatitis - 4 people.

4. Hypothyroidism - 4 people.

5. Chr. gastritis, duodenal ulcer - 8 people.

6. ZhKB, KhBKh - 4 people.

7. SRK-4 people.

8. Resected stomach - 1 person.

All subjects showed disturbances in the intestinal microbiota from minimal to pronounced changes.

After a course of recovery, including the use of capsules for 45 days, various degrees of changes in the intestinal microflora were revealed: a decrease in the number of normal symbionts (bifidobacteria, lactobacilli, Escherichia coli (Lac +), the presence of pathogenic microbes (Klebsiella pneumoniae, fungi of the genus Candida albikans). microbiota recovery was noted in 90% of cases (9 people) .The dynamics of the microbial landscape of the colon is presented in Table 3.

Dynamics of local intestinal syndrome: stool disturbance from constipation to relaxation, flatulence, rumbling and transfusion, pains of various localization and of a different nature, the presence of mucus on the feces were noted in 100% of cases (10 people); against the background of ongoing therapy, these complaints disappeared completely in 8 volunteers (80%), decreased in 2 (20%). The dynamics of indicators before taking the drug and after taking the drug is shown in Table 5.

The invention makes it possible to expand the arsenal of drugs that contribute to the prevention of fungal infections.

Composition for the prevention of fungal diseases

Claims (12)

1. Capsule for the prevention of fungal diseases, active against Escherichia coli, Candida sp., Aspergillus niger, Saccharomyces cerevisiae, consisting of a shell and an enclosed composition in the form of an oily suspension, including unrefined black cumin oil containing 50% of linoleic acid related to omega-6 family of polyunsaturated fatty acids, magnesium caprylate, cinnamon bark essential oil, _{clove CO 2} extract, edible tea tree essential oil, garlic essential oil and filler in the following ratio, wt%: unrefined black cumin oil 29.7-44.7 magnesium caprylate 5.8-8.8 essential oil of cinnamon bark 0.6-0.9 CO _{2 -} clove extract 0.48-0.72 edible tea tree essential oil 0.17-0.26 essential oil of garlic 0.12-0.18 filler rest, in this case, the mass of the shell of one capsule is 324-396 mg, and the shell consists of a suture soft gelatin shell containing gelatin, a water-retaining agent, and an enteric shell containing Collicut MAE 100P, a water-retaining agent, an anti-caking agent, a thickener and dyes, while the masses are equal. 2. A capsule according to claim 1, characterized in that the mass of the suture soft soluble shell is 180 mg ± 10% with the following ratio of components, mg in one capsule: gelatin 144.0 humectant 36.0. 3. A capsule according to claim 2, characterized in that the water-retaining component contains D-sorbitol and glycerin in equal parts. 4. A capsule according to claim 1, characterized in that the mass of the enteric coating is 180 mg ± 10% in one capsule with the following ratio of components: Collicut MAE 100R 68.95 humectant 45.0 anti-caking agent 42.62 thickener 18.95 dye 4.48. 5. A capsule according to claim 4, characterized in that the enteric coating contains propylene glycol as a humectant. 6. A capsule according to claim 4, characterized in that it contains talc as an anti-caking agent. 7. A capsule according to claim 4, characterized in that it contains polyvinylpyrrolidone as a thickener. 8. A capsule according to claim 4, characterized in that it contains titanium dioxide, iron oxide red, iron oxide black, iron oxide yellow.

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