RU2848598C1 - Suppository from oil extract from calendula flowers for the treatment of bacterial vaginosis and method for treating bacterial vaginosis with its help - Google Patents

Abstract

FIELD: pharmaceutical industry.

SUBSTANCE: group of inventions relates to the remedy for the treatment of bacterial vaginosis and a method for treating bacterial vaginosis. Remedy for the treatment of bacterial vaginosis, which is a pressed suppository consisting of a mixture of calendula flower oil extract and cocoa butter, the composition of which is selected in the following ratio, wt.%: calendula flower oil extract - 14.29, cocoa butter - 85.71. Method for treating bacterial vaginosis characterised by the introduction of the above-described suppositories into the vagina, in a course of 7 days, 1 suppository per night.

EFFECT: treatment of bacterial vaginosis, convenient for use in women, has a long-term therapeutic effect, and can also be used to treat pregnant women in the first trimester.

2 cl, 2 tbl

Description

The invention relates to medicine, namely to obstetrics and gynecology, and can be used for sanitizing the mucous membrane and restoring the vaginal biocenosis in cases of vaginosis in gynecological practice, including in obstetrics - for correcting vaginal dysbiosis in pregnant women, including in the first trimester.

Treatment of vaginal dysbiotic conditions in women of reproductive age is an important aspect of outpatient obstetrics and gynecology. The quality of the prescribed treatment affects a woman's sex life, quality of life, and reproductive health.

According to global statistics, bacterial vaginosis is one of the leading vaginal diseases. Its prevalence among women ranges from 12% to 80% of examined women. This disease mainly affects women of reproductive age [Kira E.F. Bacterial vaginosis. Moscow: MIA, 2012; 472. 2nd ed., corr., suppl.; Kaufman R., Faro S., Brown D. Benign diseases of the vulva and vagina. Transl. from English. Moscow: BINOM, 2009; 544.; Gynecology: National Guidelines. Ed. by Savelyeva G.M., Sukhikh G.T., Serov V.N., Radzinsky V.E., Manukhin I.B. Moscow: GEOTAR-Media, 2017; 1008; 2nd ed.]: from 80% to 87% of those who experience pathological vaginal discharge, and from 37% to 40% of pregnant women [Skin diseases. Sexually transmitted infections. Russian Society of Dermatovenerologists, Venereologists and Cosmetologists. Federal clinical guidelines. Dermatovenerology 2015; 5th ed., revised and enlarged. - M.: Delovoy Express, 2016; 768.; Diagnostics and treatment of diseases accompanied by pathological discharge from the genital tract of women. Clinical guidelines. M. 2014; B.i. 50 p.; Efimov B.A., Tyutyunnik V.L. Bacterial vaginosis: a modern look at the problem. RMJ. 2008; 16(1): 18-22.]. Although this disease is not life-threatening, it is a risk factor for pregnancy complications such as spontaneous abortion, intra-amniotic infection, premature rupture of membranes, and preterm labor. Women with bacterial vaginosis may develop endometritis and sepsis after cesarean section. Currently, bacterial vaginosis is considered one of the causes of infectious complications after gynecological surgeries and abortions, inflammatory diseases of the pelvic organs, peritonitis, and pelvic abscesses during the insertion of intrauterine contraceptives [Gomberg M.A. Bacterial vaginosis and new infections associated with it. Russian Bulletin of Obstetrician-Gynecologist. 2010; 2: 28-31.]. Chronic bacterial vaginosis is also associated with the risk of developing cervical neoplasia and increased susceptibility to sexually transmitted infections, especially HIV and genital herpes [Moodley P., Connolly C., Sturm A.W. Interrelationships among human immunodeficiency virus type 1 infection, bacterial vaginosis, trichomoniasis, and the presence of yeasts. J Infect Dis 2002; 185: 69-73].

The success of treatment depends not only on the selection of rational antibacterial and anti-inflammatory therapy regimens, but also on the state of the vaginal microflora.

While the effectiveness of traditional antibiotics is generally unquestionable, their use during pregnancy requires special consideration. Potential risks to the fetus and the mother's health must be considered.

A method for treating pregnant women with colpitis of non-specific etiology is known as the main method of local therapy, as well as for genital candidiasis using the cream "Malavtilin", which contains natural oils of macadamia, jojoba, aloe vera gel, hyaluronic acid of plant origin, extracts of eleutherococcus, calendula, horse chestnut, chamomile, juniper essential oil, and also a solution of "Malavit" from 3 to 5% is added to the cream as an ingredient (GOST R 52343-2005; developer: NPO Adeleid LLC, Chelyabinsk. [Electronic resource], https://vk.com/topic-13664154_21804606 (published: 12/18/2009).

The closest analogue is a product for vaginal douching during the phase of restoration of vaginal microflora after treatment of bacterial vaginosis (RU 2486911, publication: 2013.07.10), candidal colpitis (thrush), characterized by the fact that it is a powder containing sodium acetate, lactose and dry extract of calendula (Calendula officinalis) with the following content of components, wt.%: sodium acetate 61.5 lactose 37.5 dry extract of calendula (Calendula officinalis) 1.0.

A disadvantage of known methods is the use of calendula extract, as well as auxiliary substances, which can cause allergic reactions, and are also contraindicated in the first trimester of pregnancy.

However, calendula extract is less effective than the oil extract from calendula flowers.

In addition, douching with an aqueous solution does not have a long-term effect due to the rapid flow of the product out.

The objective of the invention is to eliminate the above mentioned disadvantages and increase the effectiveness of treatment.

The technical result is ease of use for women, a long-term therapeutic effect, and the possibility of treating pregnant women in the first trimester.

The said technical result is achieved due to the fact that the claimed remedy is for the treatment of bacterial vaginosis, which is a pressed suppository made from mixed oil extract from calendula flowers and cocoa butter, the composition of which is selected in the ratio, wt. %:

Oil extract from calendula flowers - 14.29,

Cocoa butter - 85.71.

A method for treating bacterial vaginosis is also claimed, characterized by the introduction of the above suppositories into the vagina in a course of 7 days, 1 suppository at night.

Implementation of the invention

The claimed remedy for the treatment of bacterial vaginosis is a pressed suppository made from mixed oil extract from calendula flowers and cocoa butter, the composition of which is selected in the following ratio, wt. %:

Oil extract from calendula flowers - 14.29,

Cocoa butter - 85.71.

The active ingredient is an oil extract from calendula flowers, and cocoa butter is an auxiliary substance.

Cocoa butter is a solid, yellowish-beige vegetable fat extracted from the cocoa bean. Its melting point is between 32-33°C. This melting point allows cocoa butter to be used in the manufacture of gynecological and urological suppositories.

Studies have shown that cocoa butter is neutral and does not react with calendula flower oil extract, making it ideal as an excipient.

The production of the claimed vaginal suppositories can be carried out, for example, by the method of manual molding (rolling out).

Example.

To prepare a suppository of the stated composition from an oil extract of calendula flowers and cocoa butter, a dough-like suppository mass was prepared in mortars.

Ground cocoa butter in a volume of 85.71% of the total mass (for example, grated or ground in a blender) is placed in a mortar and an oil extract from calendula flowers is added in a volume of 14.29% of the total mass.

The ingredients are first mixed without applying pressure to the pestle until a coarse mixture is obtained. Then, the mixture is pressed with a pestle until a homogeneous, non-sticky "dough" is formed, pulling away from the sides of the mortar and pestle.

The prepared suppository mass is compressed into a "ball" using a sheet of parchment paper. It is then transferred to the glass plate of a pill machine covered with parchment paper, and a board is used to shape it into a cylindrical rod or bar.

The length of the bar (rod) is determined by a pill knife, on which a certain number of divisions are counted, usually equal to twice the required number of suppositories.

The edges of the bar (rod) must be limited by equal planes parallel to each other.

The pill block (rod) is placed on the pill machine's cutter and pressed lightly with a small board, creating notches. The pill block (rod) is then cut into individual doses using a blade or scalpel along the notches (marks).

Examples:

For a 3.5 g suppository, the proportion of oil extract from calendula flowers is 0.5 g, and cocoa butter is 3.0 g.

For a 2.5 g suppository, the proportion of oil extract from calendula flowers is 0.36 g, and cocoa butter is 2.14 g.

For a 5.0 g suppository, the proportion of oil extract from calendula flowers is 0.71 g, and cocoa butter is 4.29 g.

The cut surface of the bar (rod) should be uniform. A "marbled" texture indicates poor mixing. Such a mixture should be remixed.

Using a pill machine board, spherical suppositories are rolled out from each dose (portion).

The finished suppositories should be of uniform size and shape. The resulting suppositories are packaged.

Spherical suppositories are rolled out of each part and packaged.

The finished suppositories should be of the same size and shape.

The oil extract from the flowers of calendula officinalis is obtained in two ways: by the infusion method (maceration), when the inflorescences of calendula officinalis flowers are infused for some time in vegetable (sunflower or olive) oil.

The method for treating bacterial vaginosis based on the obtained suppositories is carried out by introducing the above suppositories into the vagina in a course of 7 days, 1 suppository at night.

Clearly, each treatment should be based on the woman's individual health and the progress of her pregnancy. In these situations, alternative methods, such as the use of natural remedies, are becoming increasingly relevant. One such example is calendula flower oil extract, a powerful natural remedy with numerous healing properties. It has a wide range of applications in the treatment of gastrointestinal tract diseases, ENT conditions, chronic oral diseases, and urogenital problems. Thanks to its ability to restore the microbiota and enhance the regeneration of damaged tissue, calendula flower oil extract can become an indispensable element in the comprehensive treatment of bacterial vaginosis and other inflammatory gynecological conditions.

In our study, we analyzed the gynecological health of women who presented to our outpatient clinic with complaints of abnormal vaginal discharge and treated the patients' symptoms with vaginal suppositories prepared with an oil extract and calendula. Treatment outcomes were assessed based on clinical progression and laboratory testing of vaginal and cervical discharge.

To study the vaginal microbiome, a microscopic examination of female genital discharge stained with Gram stain (hereinafter referred to as smear analysis) was used. The study included 10 patients with characteristic complaints and symptoms of dysbiosis, who underwent smear analysis.

Microscopic examination was performed on women up to 12 weeks of pregnancy who were diagnosed with bacterial vaginosis, vaginitis, and/or cervicitis based on the detection of "clue cells" and complaints of abnormal, foul-smelling vaginal discharge. Clinical and laboratory confirmation of vaginitis and/or cervicitis was obtained in 4 women (40%), who, based on microscopic examination of their smears, demonstrated a decrease in normal (gram-positive) flora and an increase in opportunistic (gram-negative) flora, along with an increased white blood cell count. The study results are presented in Table 1.

Table 1. Results of microscopic examination of samples of discharge from female genital organs.

Patient number Leukocytes in a smear of discharge from the cervical canal, quantity in the field of view. Leukocytes in a smear of vaginal discharge, number per field of view. Key cells Microflora 1 25-30 25-30 - Gr- bacilli, abundant seeding 2 a large number 10-15 - Mixed microflora, abundant seeding of Gr+, Gr- 3 25-30 3-5 - Rods Gr+, single 4 a large number single - Gr- bacilli, abundant seeding 5 6-8 0-1 + Gr- bacilli, abundant seeding 6 0-1 0-1 + Sticks Gr- 7 a large number single + Gr- bacilli, abundant seeding 8 1-2 0-2 + Sticks Gr- 9 0-1 1-3 + Sticks Gr- 10 0-2 2-4 + Sticks Gr-

All women underwent a course (one suppository per night for 7 days) of treatment with vaginal suppositories containing an extract of oil extract from calendula flowers made from 3.0 g of cocoa butter and 0.5 g of oil extract from calendula flowers.

Following this, a repeat clinical laboratory study was conducted according to the 14th pharmacopoeia, which showed a significant increase in gram-positive flora and a decrease in the content of gram-negative flora.

For example, key cells disappeared in 100% of cases.

Improvements in laboratory parameters and the disappearance of clinical symptoms (reduced discharge, odor, discomfort, etc.) were observed. Three out of four (75%) women diagnosed with vaginitis and/or cervicitis showed a change from gram-negative (Gr-) to gram-positive (Gr+) flora after treatment, along with a decrease in the leukocyte count in the smear (Table 2), underscoring the effectiveness of vaginal suppositories with calendula flower oil extract and its selective antimicrobial and anti-inflammatory effects.

Table 2. Results of microscopic examination of female genital discharge before and after treatment.

Patient number Leukocytes in the cervical canal discharge, quantity per field of view. Leukocytes in vaginal discharge, number per field of view. Key cells Microflora to after to after to after to after 1 25-30 single 25-30 single - - Sticks abundantly Gr- Rods Gr+, moderate 2 Large quantity single 10-15 20-30 - - Mixed, abundant Gr+- Mixed, abundant Gr+- 3 25-30 3-5 3-5 6-8 + - Rods Gr+, units Rods Gr+, moderate 4 Large quantity Large quantity single single + - Gr- sticks, abundant Rods Gr+, abundant 5 6-8 6-8 0-1 8-10 + - Sticks Gr- Sticks abundantly Gr+ 6. 0-1 3-5 0-1 6-8 + - Gr- sticks, abundant Gr+ sticks 7. Large quantity single single single + - Sticks Gr- Gr+ sticks 8 1-2 4-6 0-2 6-8 + - Sticks Gr- Gr+ sticks 9 0-1 6-8 1-3 10-12 + - Sticks Gr- Gr+ sticks 10 0-2 4-6 2-4 8-10 + - Sticks Gr- Gr+ sticks

Thus, this study demonstrates the possibility of using suppositories based on an oil extract from calendula flowers in correcting the vaginal microbiota and improving the condition of women with dysbiosis, opening up new prospects for its use in gynecological practice, as well as the possibility of using this drug to correct the vaginal microbiocenosis, especially in pregnant women in the early stages of pregnancy.

All pregnant women who completed the 7-day course of treatment noted the ease of use of suppositories.

For comparison, women with gynecological conditions diagnosed with bacterial vaginosis, vaginitis, and/or cervicitis were also tested. This control group of 12 women, independent of the first group, also underwent a 7-day course of nighttime douching, but with pure calendula flower extract oil.

Following the course, women reported discomfort and inconvenience with this method (douching). They were required to use a pad at night, but it often failed to absorb all the oil, which stained their underwear, further increasing the discomfort. Furthermore, only three out of 12 women reported a positive effect from this method.

Thus, the use of a suppository form based on an oil extract from calendula flowers provides a long-term therapeutic effect.

Claims (3)

1. A remedy for the treatment of bacterial vaginosis, which is a pressed suppository made from mixed oil extract from calendula flowers and cocoa butter, the composition of which is selected in the ratio, wt.%: Oil extract from calendula flowers 14.29 Cocoa butter 85.71 2. A method for treating bacterial vaginosis, characterized by the introduction of suppositories according to paragraph 1 into the vagina, in a course of 7 days, 1 suppository at night.