RU2286799C1 - Method for preventing inflammatory diseases of female genital organs - Google Patents

Abstract

FIELD: medicine, obstetrics, gynecology.

SUBSTANCE: the present innovation deals with hygienic products applied for preventing inflammatory diseases of genital organs and could be used as antibacterial filler for female hygienic panty shield and/or tampon for daily usage. The suggested innovation has the tendency to solve the problem in developing efficient filler for female hygienic panty shield and/or tampon for daily usage to prevent inflammatory diseases of genital organs being of the following advantages: absolute intoxicity, prophylactic action in case of potential development of inflammatory process in female genital tract, antibacterial effect, selective action upon microflora of female genital organs at keeping the number of viable useful lactobacilli, steady action upon mucosa and skin of genital organs due to viscosity and high fluidity of gel composition, form-resistance of gel composition along with its transparency and absence of fragrance, no formation of antibioticoresistant strains of microorganisms at daily applications of panty shields or tampons. The purpose mentioned should be achieved due to the fact that the filler in the composition of panty shield or tampon contains about 0.5-1%-chitosan hydrochloride aqueous solution for medicinal indication ("M" mark) at molecular weight ranged 300-700 kDa, at degree of deacetylation being 89-98% at the following ratio of components/1000 ml composition: dry chitosan hydrochloride 5-10 g, distilled water - the rest. For normalizing vaginal biocenosis 10 applications will be sufficient.

EFFECT: higher efficiency of prophylaxis.

1 ex, 1 tbl

Description

The invention relates to medicine, namely to obstetrics and gynecology, in particular to hygiene products used for the prevention of inflammatory diseases of the genital organs, and can be used as an antibacterial filler for feminine sanitary napkins or tampons for every day.

Known antibacterial composition for local treatment of bacterial vaginosis based on a 3.5% gel form of chitosan ascorbate containing metronidazole at a dose of 2 mg in 1 ml [1]. The gel base of chitosan in the form of a 3.5% concentration is convenient for insertion into the vagina on a tampon in the treatment of inflammatory diseases of the internal genital organs of a woman. However, the presence of the antibacterial drug metronidazole in the gel composition of the pad or swab cannot be used to prevent inflammatory diseases, even if subtherapeutic doses of the antibiotic are used. The restriction is associated with the need for prolonged (daily) use of a sanitary pad or tampon and the danger of developing antibiotic-resistant microbial strains.

Known methods of using 2-8% chitosan gel as an anti-inflammatory agent in the field of dentistry in the treatment of deep caries as a medical pad [2] and in the treatment of destructive forms of periodontitis as chitosan-containing paste when it is introduced into the transapical region of the tooth [3].

However, the authors did not set the task of obtaining an antibacterial filler for a feminine sanitary pad or tampon for every day that did not contain antibacterial agents.

Known composition on a candle or gel basis for the normalization of the internal microflora of the body with antimicrobial and anti-inflammatory effects, including a dry lyophilized mass of live lactobacilli, miramistin and water [4]. However, chitosan was not used by the authors as a gel base for feminine sanitary napkins or tampons for every day in order to prevent inflammatory diseases. In addition, the composition of the gel filler does not have the properties of preserving the lactobacillary microflora, which is mandatory for normal biocenosis of vaginal tissues, includes an antibiotic that can cause the formation of resistant microbial strains with prolonged use.

As the polymers used to treat diseases of the female genital organs, the Sangvikol collagen sponge is used after tissue treatment (cervical pseudo-erosion) with a plasma-chemical nitric oxide gas stream [5]. In the composition of the filler for feminine sanitary napkins, the collagen polymer or chitosan was not used. In addition, daily use of protein preparations in the excipient is undesirable, since it can lead to tissue sensitization and the development of a hypersensitivity reaction in them.

Closest to the claimed composition in terms of features are:

1. Biological composition for the treatment of wounds "Collachitis", containing, as well as the claimed invention, chitosan, as well as antiseptic preparations of synthetic origin. The design can be made in the form of a film or sponge, which are biodegradable agents [6];

2. A dressing for the treatment of wounds in the form of a film containing, like the claimed invention, chitosan, an organic acid, an antimicrobial or antiseptic preparation [7];

3. Hydrocolloid application coating containing, as well as the claimed invention, chitosan, organic acid and water [8].

All these technical solutions are associated with the closure and treatment of wound defects, made in the form of a sponge or film and were not offered as a filler for feminine sanitary napkins or tampons. In addition, the technical (mechanical) introduction of these compositions in the form of a film or sponge into a woven or non-woven material with its uniform distribution is difficult.

The content of crosslinking agents in the proposed compositions in the form of epichlorohydrin or glutaraldehyde is undesirable in view of their high toxicity (tissue, cell poison). For the treatment of wounds, the authors of [7, 8] achieve a decrease in the adhesion force to the wound surface and the adsorption force of less than 400%, while using filler for a sanitary pad or tampon requires high adhesion and sorption ability to the mucous membrane and skin of the external genital organs.

The filler for a sanitary pad or tampon for every day should be easily flowing, highly adhesive to the mucous membrane or skin, have a high sorption capacity, be transparent and not degrade the aesthetic characteristics of the product, have antibacterial properties against pathogenic residual microflora of the vagina and external genital organs , do not contain antibiotics, maintain the lactobacillary microflora of the vagina, be a non-toxic composition, it is easy to dose in small doses when turned on composition napkin or tampon, be stable in storage, does not have odor.

The well-known Russian analogue of "Femina-Mixorb" LLC "BioSorb", Novosibirsk, intended for the treatment and prevention of gynecological inflammatory diseases, as a laying for every day, for use by a woman on critical days. This design is a cellulose-viscose strip containing carbon-mineral sorbent SUMS-1 as a filler. Along with the high ability of such a filler to absorb moisture, nonspecific antibacterial and anti-inflammatory effects, the filler has no analgesic effect, selective antimicrobial effect, the safety of lactobacilli, adhesion to the mucous membranes, biocompatibility with vaginal tissues. There is moderate cytotoxicity due to contact of the vaginal biological fluid with dry filler granules. In addition, when using dry granules of a carbon mineral sorbent (filler), the problem arises of introducing this material into the vagina as part of a tampon.

The foreign analogue “New Shin Kui Pao” (China) is known, which is intended for painful menstruation, antibacterial and fungal leucorrhoea, to improve blood circulation in the pelvis, blood supply, restore the vaginal microflora, eliminate itching of the vagina and external genital organs, and inflammation of the external genitalia organs. Herbal extracts are used as filler. Along with the low ability of the filler to absorb moisture, moderate anti-inflammatory, antibacterial and analgesic effects, the filler only partially retains lactobacillary microflora, does not have the ability to adhere to the mucous membranes of the genital tract, has a grassy odor, stains the pad with plant dyes. The filler does not have a stable form during storage, does not have biocompatibility with tissues of the female genital tract, has moderate cytotoxicity, and the shelf life is limited due to the presence of plant materials.

Foreign analogues “ALLWAYS”, “LIBRESSE”, “CAREFREE”, “INCOGNITO”, “Amelia Super Soft”, “Amelia Super Dry”, “OLA” are used as everyday hygiene products, like sanitary napkins for absorbing biological liquids. The cellulose-viscose base of the pad contains a filler, which is Granulate Airlight - pressed cellulose. Along with high gel stability and high moisture intake, the filler has no analgesic, anti-inflammatory, antibacterial effects, vaginal lactobacilli, adhesion to the mucous membranes of the genital tract, biocompatibility with biological fluid of the vagina.

The invention is aimed at solving the problem of creating an effective filler for feminine sanitary pads or tampons for every day with the aim of preventing inflammatory diseases of the external genital organs and has the following advantages:

- absolute non-toxicity;

- preventive action in case of the possible development of the inflammatory process of the female genital tract, antibacterial effect;

- selective effect on the microflora of the female genital organs while maintaining the number of viable beneficial lactobacilli;

- uniform effect on the mucous membranes and skin of the external genital organs due to the viscosity and high fluidity of the gel composition;

- shape stability of the gel composition;

- transparency and lack of composition odor;

- the absence of the formation of antibiotic-resistant strains of microorganisms with daily applications of a pad or tampon.

This task is achieved due to the fact that the filler in the composition of the pad or tampon contains a 0.5-1% aqueous solution of medical chitosan hydrochloride (grade "M") with a molecular weight of 300-700 kDa, a degree of deacetylation of 89-98% with a ratio of components on 1000 ml of the composition:

- dry chitosan hydrochloride - 5-10 g

- distilled water - the rest

In order to identify the antibacterial action of the filler for feminine sanitary napkins or tampons, nutrient media were used in the cultivation of microorganisms (MPA and 0.7% nutrient agar, 2% and 0.7% bifidum agar), samples of chitosan gels, clinical microorganism strains: Escherichia coli, Enterococcus faecalis, Candida albicans and the reference strain of Staphylococcus aureus 209 P, lactobacilli, which are part of the official preparation “Lactobacterin dry”, dyes, ethyl alcohol 96%.

Antimicrobial properties were tested on the following samples of chitosan gels:

- Sample No. 1 - 0.5% aqueous solution of chitosan ascorbate (molecular weight 700 kDa, degree of deacetylation of 98%)

- Sample No. 2 - 0.5% aqueous solution of chitosan ascorbate (molecular weight 250 kDa, degree of deacetylation of 87%)

- Sample No. 3 - 0.5% aqueous solution of chitosan hydrochloride (molecular weight 100 kDa, degree of deacetylation of 87%)

- Sample No. 4 - 0.5% aqueous solution of chitosan hydrochloride (molecular weight 70 kDa, degree of deacetylation of 87%)

- Sample No. 5 - 0.625% solution of ascorbic acid

- Sample No. 6 - 0.5% aqueous solution of chitosan hydrochloride (molecular weight 300 kDa, degree of deacetylation of 89%)

- Sample No. 7 - 1% aqueous solution of chitosan hydrochloride (molecular weight 300 kDa, degree of deacetylation of 89%)

- Sample No. 8 - 0.5% aqueous solution of chitosan hydrochloride (molecular weight 700 kDa, degree of deacetylation of 98%)

- Sample No. 9 - 1% aqueous solution of chitosan hydrochloride (molecular weight 700 kDa, degree of deacetylation of 98%)

Antimicrobial analysis is as follows

In sterile Petri dishes under aseptic conditions, MPA is poured in a volume of 15 ml. After the medium has solidified, a 0.7% nutrient agar is poured in a volume of 4 ml with 0.1 ml of a suspension of one of the microorganism cultures taken in the experiment at a concentration corresponding to the turbidity standard 10 ⁹ . For the cultivation of lactobacilli, bifidum agar was selected, respectively 2% 15 ml and 0.7% 4 ml. In the first series of experiments, 1 cm diameter wells were punched with a sterile puncher in two-layer agar, into which 0.1 ml of gel samples were introduced into the well using an automatic micropipette. In the second series of experiments, gel samples in the form of droplets with a volume of 0.01 ml are applied onto the surface of a two-layer agar using an automatic micropipette. To control the sterility of the gel samples, two-layer agar is used without suspension of microorganisms. The results are evaluated after 24 and 48 hours of cultivation in a thermostat at a temperature of 37 ° C. The results of experiments with lactobacilli are evaluated after 72 hours of cultivation in desiccators at a temperature of 37 ° C.

The research results showed:

Sample No. 1.

When the sample was introduced into the wells, uniform continuous growth of S.aureus 209 P (intensity ++++), E.faecalis (intensity +++) and E. coli (intensity ++++) was observed over the entire surface of the agar, except for 1- 2 mm around the periphery of the holes. When applying the sample to the surface of the agar against the background of uniform continuous growth of S.aureus 209 P (intensity ++++), E.faecalis (intensity +++) and E. coli (intensity ++++) directly under the applied gel, the following were noted: lack of growth of S.aureus 209 P and E.faecalis, meager growth (intensity +) of E. coli. After 48 hours, the results are unchanged. In the experiment with C. albicans, when the sample was introduced into the wells against the background of uniform continuous growth on the cup surface (intensity +++), more intensive growth (++++) of microorganisms was observed along the periphery of the hole (zones 28, 29 and 29 mm in diameter, including hole diameter). When a sample was applied to the agar surface against a background of uniform continuous growth (+++ intensity), moderate inhibition of microorganism growth (+) was observed directly under the applied gel; a growth intensification zone (++++) of 2-3 mm width was observed around the periphery. After 48 hours, the results are unchanged. In experiments with lactobacilli in both cases, continuous growth was observed over the entire surface with intensity (++++).

Thus, this gel sample has a bactericidal effect on gram-positive cocci and a bacteriostatic effect on gram-negative bacilli and yeast-like fungi of the genus Candida. Moreover, this sample stimulates the growth of yeast-like fungi of the genus Candida along the periphery of the zone of bacteriostatic action. The sample does not have a visible antimicrobial effect on lactobacilli.

Sample No. 2.

When the sample was introduced into the wells, uniform continuous growth of S.aureus 209 P (intensity ++++), E.faecalis (intensity +++) and E.coli (intensity ++++) over the entire agar surface was observed. When applying the sample to the surface of the agar against the background of uniform continuous growth of S.aureus 209 P (intensity ++++), E.faecalis (intensity +++) and E. coli (intensity ++++) directly under the applied gel, the following were noted: poor growth of S.aureus 209 P (intensity +), E.faecalis (intensity +), E. coli (intensity ++). After 48 hours, the results are unchanged. In the experiment with C. albicans, when the sample was introduced into the wells against the background of uniform continuous growth (intensity +++), more intensive growth (++++) of microorganisms was observed along the periphery (zones 27, 28, and 29 mm in diameter, including the diameter of the hole ) When the sample was applied to the surface of the agar against a background of uniform continuous growth (+++ intensity), growth inhibition of microorganisms (++) was observed directly under the applied gel; an intensification zone (++++) of 2-3 mm growth was observed along the periphery. After 48 hours, the results are unchanged. In experiments with lactobacilli in both cases, continuous growth was observed over the entire surface with an intensity of ++++.

Thus, this gel sample has a bacteriostatic effect on the studied cultures of microorganisms, more pronounced in relation to gram-positive cocci. Moreover, this sample stimulates the growth of yeast-like fungi of the genus Candida along the periphery of the zone of bacteriostatic action. A decrease in the inhibitory effect on the studied microorganisms is associated with a decrease in the molecular weight of chitosan in the gel composition. The sample does not have a visible antimicrobial effect on lactobacilli.

Sample No. 3.

When the sample was introduced into the wells, continuous uniform growth of S.aureus 209 P (intensity ++++), E.faecalis (intensity +++), E.coli (intensity ++++) and C. albicans (intensity ++ +) over the entire surface of the agar. Growth intensification of C. albicans was not observed. When applying the sample to the surface of the agar against the background of continuous uniform growth of S.aureus 209 P (intensity ++++) and E.faecalis (intensity +++), directly under the applied gel, there was a scanty growth of S.aureus 209 P (intensity + ) and E.faecalis (intensity +). In experiments with E. coli and C. albicans. - continuous uniform growth (intensity ++++ and +++, respectively). After 48 hours, the results are unchanged. In experiments with lactobacilli in both cases, continuous growth was observed over the entire surface with an intensity of ++++.

Thus, this gel sample has a bacteriostatic effect on gram-positive cocci and does not stimulate the growth of yeast-like fungi of the genus Candida. The sample does not have a visible antimicrobial effect on lactobacilli.

Sample No. 4.

When the sample was introduced into the wells, continuous uniform growth of S.aureus 209 P (intensity ++++), E.faecalis (intensity +++), E.coli (intensity ++++) and C. albicans (intensity ++ +) over the entire surface of the agar. Growth intensification of C. albicans was not observed. When applying the sample to the surface of the agar against the background of continuous uniform growth of S.aureus 209 P (intensity ++++) directly under the applied gel, it was noted: meager growth (intensity ++). In experiments with E. faecalis, E. coli, and C. albicans, continuous uniform growth (intensity +++, ++++, and +++, respectively).

After 48 hours, the results are unchanged. In experiments with lactobacilli in both cases, continuous growth was observed over the entire surface with an intensity of ++++. Thus, this gel sample has a bacteriostatic effect on S.aureus 209 P and does not stimulate the growth of yeast-like fungi of the genus Candida. A progressive decrease in the inhibitory effect on the studied microorganisms is associated with a decrease in the molecular weight of chitosan in the gel. The sample does not have a visible antimicrobial effect on lactobacilli.

Sample No. 5.

There was continuous uniform growth of S. aureus 209 P, E. faecalis and E. coli (intensity ++++, +++ and ++++, respectively) over the entire surface of the agar, regardless of the method of application of the sample. After 48 hours, the growth pattern is maintained. In the experiment with C. albicans, when the sample was introduced into the wells after 24 hours against the background of uniform continuous growth (+++ intensity), growth intensification zones (++++) with blurred borders (approximately 33-34 mm in diameter, including the diameter of the hole) were noted ) After 48 hours, an increase in the diameter of the zones was recorded (up to 37, 38 and 39 mm), their boundaries became clearer (prolongation of the stimulating effect of ascorbic acid). When the sample was applied to the surface of the agar, fuzzy growth intensification (++++) was observed in the center of the cup and more meager growth (+++) along the periphery. In experiments with lactobacilli in both cases, continuous growth was observed over the entire surface with an intensity of ++++.

Thus, ascorbic acid stimulates the growth of yeast fungi of the genus Candida and does not have a visible effect on other studied cultures.

Sample No. 6.

When the sample was applied to the agar surface after 24 hours against the background of continuous growth of E. coli (intensity ++++), immediately below the applied gel, a decrease in the growth intensity to ++ was observed, after 48 hours to +++ (i.e., a weak bacteriostatic effect). Against the background of continuous growth of S.aureus 209 P (intensity ++++) after 24 hours, zones of lack of growth were observed directly under the applied gel, after 48 hours, single colonies were observed (i.e., a pronounced bacteriostatic effect is preserved). Against the background of continuous growth of E. faecalis (intensity +++), after 24 hours there is a lack of growth, after 48 hours the picture is unchanged (i.e., the bactericidal effect remains). Against the background of continuous growth of C. albicans (intensity ++++), after 24 hours immediately below the applied gel, a decrease in growth intensity to +++ was observed, after 48 hours, continuous uniform growth with intensity ++++ (i.e., a weak short bacteriostatic effect). In experiments with lactobacilli in both cases, continuous growth was observed over the entire surface with an intensity of ++++.

Thus, this gel sample has a pronounced antimicrobial effect on gram-positive cocci and a weak bacteriostatic effect on E. coli and yeast-like fungi of the genus Candida. The sample does not have a visible antimicrobial effect on lactobacilli.

Sample No. 7.

When applying the sample to the surface of the agar after 24 hours against the background of continuous growth of E. coli (intensity ++++) immediately under the applied gel, there was a lack of growth; after 48 hours, the picture is unchanged (i.e., the bactericidal effect remains). Against the background of continuous growth of S.aureus 209 P (intensity ++++) after 24 hours, zones of lack of growth were observed directly under the applied gel, after 48 hours, the picture was unchanged (i.e., the bactericidal effect directly under the applied gel was preserved). Against the background of continuous growth of E. faecalis (intensity +++) after 24 hours, there is no growth, after 48 hours the picture is unchanged (i.e., the bactericidal effect remains). Against the background of continuous growth of C. albicans (intensity ++++), after 24 hours there was a decrease in growth intensity to ++, after 48 hours - the picture was unchanged (i.e., the bacteriostatic effect remains). In experiments with lactobacilli in both cases, continuous growth was observed over the entire surface with an intensity of ++++. Thus, this gel sample has a bactericidal effect on gram-positive cocci and E. coli and a bacteriostatic effect on yeast-like fungi of the genus Candida. The increased antimicrobial activity is associated with an increase in the concentration of chitosan. The sample does not have a visible antimicrobial effect on lactobacilli.

Sample No. 8.

When a sample was introduced into the wells, uniform continuous growth of S.aureus 209 P (intensity ++++), E.faecalis (intensity +++), E.coli (intensity ++++) and C. albicans (intensity ++ +) over the entire surface of the agar with the exception of the zone of 1-2 mm along the periphery of the hole. After 48 hours, the results are unchanged. When applying the sample to the agar surface after 24 hours against a background of continuous growth of E. coli (intensity ++++), S.aureus 209 P (intensity ++++) and E.faecalis (intensity +++) directly under the applied gel there was a lack of growth, after 48 hours - the picture is unchanged (i.e., the bactericidal effect remains). Against the background of continuous growth of C. albicans (intensity +++), a decrease in growth intensity (4-5 small colonies) was noted immediately after the applied gel after 24 hours, the picture was unchanged after 48 hours (i.e., the bacteriostatic effect remains).

In experiments with lactobacilli in both cases, continuous growth was observed over the entire surface with an intensity of ++++.

Thus, this gel sample has a bactericidal effect on gram-positive cocci and E. coli and a pronounced bacteriostatic effect on yeast-like fungi of the genus Candida. Enhanced antimicrobial activity is associated with an increase in the molecular weight of chitosan. The sample does not have a visible antimicrobial effect on lactobacilli.

Sample No. 9.

When a sample was introduced into the wells, uniform continuous growth of S.aureus 209 P (intensity ++++), E.faecalis (intensity +++), E.coli (intensity ++++) and C. albicans (intensity ++ +) over the entire surface of the agar with the exception of the zone of 1-2 mm along the periphery of the hole. After 48 hours, the results are unchanged. When the sample is applied to the agar surface after 24 hours against a background of continuous growth of E. coli (intensity ++++), S.aureus 209 P (intensity ++++), E.faecalis (intensity +++) and C. albicans (intensity +++) immediately under the applied gel, there was a lack of growth, after 48 hours - the picture was unchanged (i.e., the bactericidal effect remains). In experiments with lactobacilli in both cases, continuous growth was observed over the entire surface with an intensity of ++++.

Thus, this gel sample has a bactericidal effect on the studied cultures. The increased antimicrobial activity is associated with an increase in the concentration of chitosan. The sample does not have a visible antimicrobial effect on lactobacilli.

Based on the research, the following is stated:

1. Chitosan 0.5-1% gels that do not contain official antibacterial agents have, depending on the molecular weight of chitosan, a bactericidal or bacteriostatic effect on gram-positive cocci (S.aureus 209 P and E.faecalis), and a weaker bacteriostatic effect gram-negative bacilli (E. coli) and yeast-like fungi of the genus Candida, manifested in gels with a molecular mass of chitosan of at least 300 kDa. With an increase in molecular weight, the antibacterial effect of the gel increases. Chitosan hydrochloride with a molecular weight of 700 kDa at a concentration of 1% has a bactericidal effect on all of the above cultures.

2. Gels that do not contain official antibacterial agents do not have an antimicrobial effect on lactobacilli, the main representatives of the normal microflora of the vagina of women of childbearing age. Ascorbic acid stimulates the growth of yeast-like fungi of the genus Candida outside the zone of bacteriostatic action of chitosan in connection with its dissociation from the polymer. The filler does not have a stimulating effect on the growth of yeast-like fungi of the genus Candida.

3. The filler for laying or tampon is stable during storage for two years, retains a gel consistency, is odorless, and transparent.

Clinical studies of an antibacterial filler in a feminine sanitary pad and tampon were performed on 7 women. The average age of the patients was 27.5 years. All patients before starting the prophylactic course with the proposed pads repeatedly underwent a course of antibiotic therapy for vaginitis and bacterial vaginosis. Five patients had a history of chronic salpingoophoritis, one patient after total hysterectomy.

It is known that 80% of patients with vaginosis have a relapse of the disease within 9 months after treatment [9]. This is largely due to a large number of factors affecting the species composition of the vaginal flora. Predisposing factors leading to the development of vaginosis and vaginitis include: the use of antibiotics, the prolonged use of intrauterine contraceptives, previously transferred or concomitant inflammatory diseases of the genital organs, hormonal status disorders, changes in the state of local immunity, exposure to small doses of ionizing radiation, stressful effects on the body, dysbiosis in the digestive system [9]. The vaginal microecosystem is very dynamic, a distinctive feature of which is strict estrogen dependence [10]. With a decrease in estrogenic effect, the amount of glycogen contained in the stratified squamous epithelium of the vagina, which is a necessary substrate for indigenous lactic acid flora, is reduced. This leads to a decrease in the number of Dederlein sticks in the vagina, the pH of the vaginal secretion rises, colonization resistance decreases, and favorable conditions are created for the activation of conditionally pathogenic microflora, which causes a pathological process in the vagina.

The development of bacterial vaginosis and vaginitis requires the use of antibiotics, which often leads to the development of antibiotic-resistant strains, as well as an even deeper violation of vaginal microecology. It is also known that after the use of antibiotics of the anti-anaerobic spectrum of action, on the one hand, the number of such vaginal opportunistic microorganisms as E. coli, Enterococcus spp. and others, and on the other hand, the deficiency of indigenous lacto- and bifidoflora is maintained, and in some cases exacerbated, [9].

Before the preventive course, subjective and objective signs of the disease were absent.

Gynecological examination (examination in the mirrors), bacteriological examination (microscopy of vaginal smears with preliminary staining according to Gram, bacteriological examination of vaginal microflora with determination of sensitivity to antibiotics by the disk method) were used as criteria for the effectiveness of preventive treatment before treatment, on days 5, 10 and after a month after the course.

All patients underwent signs of inflammation of the vaginal mucosa during gynecological examination. Discharges of milky color, in a small amount.

When examining a vaginal smear, an intermediate type of biocenosis was found in all patients (according to the classification of E.F. Kira and S.V. Cherkasov). In the smear, a moderate or reduced number of lactobacilli, gram-positive cocci and gram-negative bacilli. In a moderate amount, leukocytes, monocytes, epithelial cells were found.

In a bacteriological study, Bacteroides fragilis was found in 43% of patients, Echerichia coli in 29%, Staphilococcus aureus in 14%, and Fusobacterium nucleatum in 14%. When determining the sensitivity to antibiotics, antibiotic resistance to erythromycin was detected in 43%, metronidazole in 29%, clindamycin in 14% of patients, ofloxacin in 14% of patients. These drugs are widely used in gynecological practice both as monotherapy and as part of some complex preparations.

Patients are treated as follows: in a manipulation room, 1% chitosan hydrochloride gel in an amount of 5 ml is administered vaginally on a tampon and a pad containing this gel in an amount of 5 ml is dispensed for application to the external genitalia. The tampon and pad were left for 6 hours.

The gel is easily applied to the swab and pad, is well absorbed and does not spread over the surface. During storage, the organoleptic properties of the gel did not change. The gel has a transparent, slightly straw color, slightly opalescent, odorless. You can store the gel at room temperature in a dark place.

During treatment, the composition of the vaginal secretion changes significantly. The number of lactobacilli is increasing, there is no gram-negative microflora, the number of leukocytes is 1-2 in the field of view, single epithelial cells. The composition of vaginal secretion in dynamics is presented in the table.

Characterization of vaginal contents in the dynamics of the prophylactic course of treatment (%)

Table The composition of the vaginal secretion Before treatment 5 days of treatment 10 days of treatment 1 month after treatment Epithelial cells one hundred 86 fourteen 29th Single epithelial cells - fourteen 86 71 Leukocytes are single in s / sp. - fourteen 86 71 White blood cells more than 10 in n / a one hundred 86 fourteen 29th Dederlein sticks over 150 in p / sp. - 29th one hundred 86 Moderate number of Dederlein sticks. one hundred 71 - fourteen

As can be seen from the table, already on the 5th day of treatment the number of smears with a single content of leukocytes and epithelial cells increased by 14%, with the content of Dederlein sticks - by 29%.

On the 10th day of treatment in all patients, the vaginal secretion corresponded to the normocenosis. The number of smears with a single content of epithelial cells and leukocytes increased by 86%, with a large number of Dederlein sticks (more than 150 in n / a) 100%.

When studying the growth of cultures on nutrient media, it was found that one patient with the growth of Staphilococcus aureus before treatment showed an increase in normal microflora after treatment, in the remaining patients the microflora spectrum did not change, since these representatives are components of normal vaginal microflora. This indicates the selectivity of the effect of the gel on the vaginal microflora, since the number of opportunistic microflora decreases, the content of lactic acid bacteria that maintain colonization resistance increases. The spectrum of antibiotic resistance has not changed.

Thus, 10 applications are sufficient to achieve a stable normalization of the vaginal biocenosis.

A month after the course, the number of vaginal smears with a single content of epithelial cells and leukocytes decreased by 15%, in one patient in a vaginal secret, Dederlein sticks were in moderation. In the remaining patients, the obtained positive effect was persistent and remained unchanged.

Since the proposed gel does not contain antibacterial drugs and its use does not change the spectrum of antibiotic resistance, the filler can be used daily as part of a feminine sanitary pad and swab in order to maintain vaginal normocenosis. This is especially true for women with risk factors for the development of vaginosis and vaginitis. The use of these pads immediately after menstruation is also recommended, since during this period the estrogenic effect is significantly reduced, the vaginal environment is shifted to the alkaline side.

During the prophylactic course, none of the patients had any complications (allergic reactions, the development of the inflammatory process). This gel is safe to use due to its good biocompatibility and biodegradability.

Clinical example: Patient E., 23 years old, had suffered from bacterial vaginosis for 4 years, and had repeatedly undergone antibiotic treatment both per os and per vaginum. In this case, the therapeutic effect persisted on average 2-3 months.

The patient was periodically disturbed by copious discharge from the genital tract of a mucous nature, with an unpleasant smell of “rotten fish”, intensifying after intercourse, washing. From the anamnesis it is known that the patient has chronic salpingoophoritis from 16 years. Menstruation as oligomenorrhea, dysmenorrhea. Last menstruation 7 days ago. A month ago, she was treated with vaginal suppositories containing an antibiotic for bacterial vaginosis.

Gynecological examination showed no signs of inflammation, milky discharge, moderate.

When studying the composition of the vaginal secretion, an intermediate type of normocenosis was found. In the smear - epithelial cells more than 10 in the field of view, leukocytes - 12 in the field of view, gram-negative rods in a small amount, Dederlein sticks - up to 40 in the field of view.

Bacteriological examination revealed the growth of Bacteroides fragilis, in a concentration acceptable in the vagina. In the study of antibiotic sensitivity, resistance to metronidazole was found.

The treatment is carried out as follows: a tampon containing 5 ml of 1% chitosan hydrochloride and a pad soaked with 5 ml of the same gel are administered daily in the treatment room for application to the external genitalia. The tampon and pad are left for 6 hours.

The composition of the vaginal secretion changed on the 5th day of treatment: the number of Dederlein sticks increased in the smear - 100 in s / sp, leukocytes to 5 in s / sp, epithelial cells 3-4 in s / sp, there were no gram-negative sticks.

When studying the vaginal composition on the 10th day after treatment, the microscopic picture of the smear corresponded to the normocenosis. In the smear, an abundant number of Dederlein sticks (more than 150 in n / a), white blood cells, epithelial cells are single, there were no gram-negative rods.

When studying culture growth on a nutrient medium, a less intensive growth of Bacteroides fragilis (+) was established, sensitivity to antibacterial drugs did not change, antibiotic resistance only to metronidazole remained.

A month after undergoing a preventive course, with a gynecological examination, there are no signs of inflammation of the vaginal mucosa. Discharges of milky color in a small amount. In a vaginal smear of Dederlein rods more than 150 in n / a., There were no gram-negative rods, leukocytes, single epithelial cells.

Thus, a promising sample of a gel filler for a feminine sanitary pad or tampon for every day was isolated - a 0.5-1% aqueous solution of chitosan hydrochloride with a molecular weight of 300-700 kDa and a degree of deacetylation of at least 89%, which has an antibacterial effect with prolonging properties, high fluidity and dosage, preservation of the lactobacillary microflora of the vagina, dimensional stability, transparency of the gel and lack of smell, not causing the formation of antibiotic resistance during daily application .

Information sources

1. RF patent No. 2236851, BIPM No. 27, 2004

2. RF patent No. 2228164, BIPM No. 13, 2004

3. RF patent No. 2229858, BIPM No. 16, 2004.

4. RF patent No. 2212889, BIPM No. 27, 2003

5. RF patent No. 2217150, BIPM No. 33, 2003.

6. RF patent No. 2108114, BIPM No. 10, 1998.

7. RF patent No. 2219954, BIPM No. 36, 2003.

8. RF patent No. 2219955, BIPM No. 36, 2003.

9. Korshunov V.M., Volodin N.N., Efimov B.A. et al. Microecology of the vagina. Correction of microflora in vaginal dysbiosis. Moscow. - 1999.- P.1-15.

10. Sidorova I.S., Vorobev A.A., Borovkova E.I. Microbiocenosis of the genital tract of women of reproductive age. J. Obstetrics and Gynecology, 2005. - No. 2, S.7-9.

Claims (1)

A method for the prevention of inflammatory diseases of the female genital organs by using a sanitary pad and / or tampon for every day containing a filler, characterized in that the filler is 0.5-1% chitosan hydrochloride hydrogel of molecular weight 300-700 kDa and a degree of deacetylation of at least 89 %, in a volume of 5 ml.