Sponges for the vaginal canal

Abstract

The present invention is directed to a sponge for the vaginal tract, comprising a sponge body having a porous sponge structure. The sponge structure forms at least a portion of the sponge's outer surface, and the porous sponge structure is impregnated with a liquid composition comprising one or more bacteriocins. The present invention also relates to liquid compositions, particularly gels, suitable for the vaginal tract, comprising one or more bacteriocins in an amount that promotes the vaginal microflora by inhibiting the growth of one or more pathogens. The present invention also relates to a sponge or liquid composition for use in the prevention and / or treatment of intestinal dysbiosis, vulvovaginal candidiasis, and / or bacterial vaginosis.

Description

[Technical Field]

[0001] The present invention relates to a sponge for the vaginal canal that can be used as a tampon, said sponge selectively inhibiting pathogens (Candida, S. aureus, etc.) and retaining Lactobacilli spp, thereby restoring the balance of healthy vaginal flora (Lactobacilli dominance). [Background technology]

[0002] It is estimated that approximately 75% of women suffer from vaginal infections such as candidiasis at some point in their lives, and predisposition may be increased by antibiotic use, feminine hygiene product or douching, humid weather, oral contraceptives, stress, and unknown factors. [1] In approximately 58% of cases, symptoms recur within 12 months. It is estimated that 8–10% of women are susceptible to recurrent vaginal candidiasis (RVVC), experiencing four or more attacks per year. [1] This condition is most commonly caused by C. albicans, but can also be caused by Candida glabrata, Candida tropicalis, and Candida parapsilosis. [2, 3]

[0003] Bacterial vaginosis (BV) is the most common vaginal infection (inflammation) in women of reproductive age and is associated with serious health problems, including preterm birth, risk of human immunodeficiency virus (HIV), sexually transmitted diseases (STDs), and risk of human papillomavirus infection [4, 5]. The incidence of BV in the general population is high worldwide, ranging from 23% to 29% annually [6]. Adverse obstetric outcomes associated with BV range from 8% to 51%. Bacterial vaginosis appears when Lactobacilli are lost and the microflora is overgrown by Gardnerella vaginalis and resident anaerobic vaginal bacteria [7].

[0004] Healthy women have an innate vaginal defense mechanism, and the vaginal microbiota is dominated by Lactobacilli, which regulate immune system cells to prevent infection by external pathogens. Several species of Lactobacilli dominate a healthy vagina, supporting the defense system and inhibiting the growth of fungi (e.g., C. albicans) and pathogenic bacteria by competing for nutrients, preventing adhesion, and excreting antibacterial compounds such as bacteriocins and bacteriocin-like substances (e.g., H2O2) [8, 9]. A decrease in the dominance of Lactobacillus leads to various immunological changes, including the production of proinflammatory cytokines / chemokines, a further increase in immune cells, and changes in the vaginal lining

[10] .

[0005] Lactobacilli-dominated microbiota express anti-infective protective factors that inhibit yeast / bacterial growth. Dysbiosis of the vaginal microbiota, in which Lactobacilli spp. outcompete other bacterial species, is a frequent cause of gynecological diseases. Generally, an imbalance in the vaginal microbiota predisposes women to bacterial and fungal infections. Vaginal infections affect millions of women every year, and these infections often cause vaginal dysbiosis, an imbalance in the vaginal microbiota, leading to inflammation and / or infection. Therefore, microbiota homeostasis is crucial, and microbiota imbalance and damage to the vaginal mucosa must be avoided. The vaginal microbiota is a complex ecosystem consisting of over 200 bacterial species that are influenced by genetic, environmental, and behavioral factors

[11] . Vaginal dysbiosis (or lack of Lactobacilli) and infection are even thought to account for 25–40% of preterm births. A severe deficiency of vaginal Lactobacilli has been associated with serious reproductive problems, including miscarriage and impaired in vitro fertilization (IVF) outcomes.

[12] Furthermore, the incidence of abnormal vaginal flora is high (30–40%) in women undergoing IVF.

[13]

[0006] During menstruation, lactobacilli are inhibited by elevated vaginal pH and other factors, resulting in a 100-fold decrease in their numbers, potentially allowing pathogens to overgrow [13, 14]. Increases in bacteria such as G. vaginalis are associated with menstruation, and decreases in the abundance of L. crispatus and other lactobacilli have been observed in healthy women who are lactobacilli-dominated throughout the remainder of their menstrual cycle

[15] . In healthy women, lactobacilli recover after menstruation unless the vaginal environment is compromised by other factors, such as stress, medication, hormonal contraception, or feminine hygiene product use. This can lead to gut dysbiosis, which can lead to infections such as vulvovaginal candidiasis (VVC) and bacterial vaginosis (BV), and potentially premature birth. Medical treatment with antifungals and antibiotics does not restore the balance of the microbiota, perpetuating the vicious cycle of recurrent disease. Medical treatments are extremely limited, and the inability to prevent frequent recurrences of BV and reduce serious complications such as preterm birth remains a recognized but unresolved problem.

[16] In cases of recurrent candidiasis, treatment options remain elusive, and Candida spp. have become highly resistant.

[17]

[0007] Fungal infections (e.g., vulvovaginal candidiasis), bacterial vaginosis, and aerobic vaginitis are the most common classes. Candidiasis is an infection caused by a yeast (a type of fungus) called Candida. Candida can normally live in the vagina without causing problems. However, Candida can proliferate and cause infection if the vaginal environment is altered in a way that encourages its growth. Changes in hormone levels, medications, or changes in the immune system can affect the environment.

[0008] Furthermore, one of the risks of using tampons is the risk of developing toxic shock syndrome (TSS), which is why some women avoid using tampons. TSS is a rare but life-threatening condition. Up to 99% of cases involve tampon use during menstruation. TSS is caused by toxic shock syndrome toxin 1 (TSST-1), which is produced by Staphylococcus aureus (S. aureus) bacteria, which can naturally form part of the vaginal microbiota. However, rapid proliferation of S. aureus can lead to TSS. For example, changes in vaginal pH and other adverse conditions can promote S. aureus growth. For example, some tampon materials may promote vaginal colonization and infection more than others.

[18] Highly absorbent tampons, especially short, straight, and sharp fibers, can damage the vaginal mucosa, allowing the toxins produced by S. aureus to spread rapidly through the body, potentially causing toxic shock syndrome. In the UK, 40 cases of this condition are diagnosed each year. Toxic shock syndrome can progress rapidly, and complications can include shock, kidney failure, and death.

[0009] Traditional sanitary tampons are made of synthetic materials, polymer foam layers, cotton, or rayon, and during manufacturing and bleaching, they release dioxins, pesticides that are harmful to health and the environment.

[19] Cotton tampons exist, which typically absorb excess moisture from the vaginal mucosa (causing excessive drying of the tissue). Furthermore, they are composed of small, sharp fibers that damage the vaginal mucosa and the natural microflora. Such tampons may leave small cotton fragments in the vagina along with old blood particles, which also lower the vaginal pH and can lead to infection.

[0010] European Patent No. 2 448 536 describes a compressed menstrual tampon, comprising an elongated rod-shaped body with a filler, an insertion end, and a withdrawal end with a withdrawal string. The filler-containing absorbent body expands upon absorption of fluid and can be made from viscose, cotton, or cellulose pulp. The filler-containing absorbent body may also comprise or consist of an absorbent sponge. The tampon also includes a means for facilitating insertion, such as an applicator that conforms to the shape of the tampon and allows the tampon to be expelled. However, this type of menstrual tampon is hard and composed of small, sharp fibers that absorb excessive moisture from the vaginal mucosa and damage the vaginal wall and natural microflora, leaving tiny cotton fibers containing old blood particles in the vagina. This may also disrupt the vaginal pH, leading to infection, or cause discomfort due to its uncomfortable shape.

[0011] WO 1992 / 013577, for example, discloses a tampon or sanitary napkin used to prevent vaginal infections, which is therefore aimed at preventing vaginal infections by introducing into the tampon a culture of at least one lactic acid-producing bacterium, such as Lactobacilli.

[0012] For example, European Patent No. 3 064 072 discloses the use of a composition containing a bacterial culture of an isolated strain of Lactobacillus to prevent candidiasis. However, the disclosure does not relate to the impregnation of porous sponge structures or tampons with bacteriocins. Furthermore, when lactobacilli are incorporated into products, it is assumed that the bacteria will support the microflora. However, during menstruation, the pH level of the vagina is close to neutral, which does not create an acidic environment favorable for lactobacilli. Therefore, lactobacilli do not grow under these conditions, and their supportive effect on the microflora is likely minimal.

[0013] WO 2020 / 003113 and US 2021 / 0121596 disclose a tampon made of a porous sponge structure of naturally derived glucomannan, which is soft, moist, flexible, and deformable to avoid damage to the vaginal mucosa. Summary of the Invention

[0014] An object of the present invention is to provide a sponge for the vaginal canal that does not have one or more of the above-mentioned disadvantages. Another object of the present invention is to provide a sponge for the vaginal canal that does not injure or irritate the vaginal wall, does not damage the mucosa, reduces the possibility of infection, facilitates insertion, prevents excessive absorption of bodily fluids, prevents menstrual leakage, and / or is convenient during use. Yet another object of the present invention is to further improve the sponge for the vaginal canal disclosed in WO 2020 / 003113 or U.S. Patent Application Publication No. 2021 / 0121596 by further supporting the natural homeostasis of the vaginal microflora.

[0015] One or more of the above objects are achieved by impregnating a porous sponge body with a liquid composition comprising one or more bacteriocins.One or more of the above objects are achieved by a liquid composition suitable for the vaginal tract comprising one or more bacteriocins.

[0016] The present invention provides a sponge for the vaginal canal, as further defined in the claims, comprising a sponge body having a porous sponge structure. The porous sponge body forms at least a portion of the sponge's outer surface. The porous sponge body is further impregnated with a liquid composition comprising one or more bacteriocins. The present invention also provides a liquid composition suitable for the vaginal canal, comprising one or more bacteriocins in an amount that promotes the vaginal microflora by inhibiting the growth of one or more pathogens. For example, the one or more pathogens are selected from S. aureus, Candida spp., Gardnerella vaginalis, and combinations thereof. Ideally, the liquid composition is an impregnating agent for the porous sponge.

[0017] In certain embodiments, the one or more bacteriocins are synthetic. For example, the bacteriocins may be synthesized by a bacterial strain such as Lactobacilli. Alternatively, the bacteriocins may be synthesized by E. coli. For example, nisin may be produced by E. coli or Lactobacilli. Alternatively, the bacteriocins may be chemically synthesized. In certain embodiments, the sponge does not contain Lactobacilli.

[0018] In certain embodiments, the sponge is a tampon. For example, the tampon may be a menstrual tampon.

[0019] In certain embodiments, the composition-impregnated sponge body promotes vaginal microflora during menstruation, the follicular phase, the luteal phase, and / or pregnancy.

[0020] In certain embodiments, the composition promotes the vaginal microbiota by inhibiting the growth of pathogens, particularly S. aureus, Candida spp., and / or Gardnerella vaginalis. Ideally, the composition promotes the vaginal microbiota by selectively inhibiting the growth of pathogens. In some embodiments, the composition exhibits at least 10-fold or greater inhibition of one or more pathogens over L. gasseri and / or L. crispatus over an 8-hour period, and particularly, the composition exhibits at least 10-fold or greater, more particularly at least 50-fold, and even more particularly at least 100-fold inhibition of Gardnerella vaginalis over L. gasseri and / or L. crispatus over an 8-hour period. In other words, the vaginal microbiota can be promoted by selectively inhibiting pathogens and inhibiting Lactobacilli by at least 10-fold, at least 50-fold, or at least 100-fold. In particular, Examples 3 and 4 provide evidence that pathogens are selectively inhibited while Lactobacilli are only slightly or not inhibited.

[0021] In certain embodiments, porous sponge structures impregnated with the composition inhibit the growth of S. aureus compared to media alone under the same conditions. The tampon sac method can be used to test the growth of S. aureus, Candida spp., and / or Gardnerella vaginalis. The method is disclosed, for example, in Nonfoux et al. (2018)

[20] and further described in Example 1 herein. In this method, pathogen growth is typically assessed by placing a tampon / sponge in a sterile plastic bag, adding a medium such as BHI broth to the bag, inoculating the medium with the pathogen, and assessing pathogen growth after incubation. A bag containing inoculated media without a tampon / sponge is typically used as a positive control for the method. As used herein, "media only" means that the medium is inoculated with a pathogen, e.g., S. aureus, Candida spp., and / or Gardnerella vaginalis, and the porous sponge structure is absent. Conditions for comparing pathogen growth are otherwise the same, including incubation temperature, incubation time, medium, and inoculum. By performing the tampon sack method, the beneficial effect of the impregnated sponge as a whole can be assessed, since the combination of sponge and impregnation can be compared with the inoculated medium. In some embodiments, growth of S. aureus is inhibited by at least 20-fold, at least 50-fold, or at least 100-fold, or at least 200-fold, or at least 350-fold when tested after 8 hours by the tampon sack method.

[0022] In certain embodiments, a porous sponge structure impregnated with the composition inhibits the growth of Candida spp. compared to medium alone under the same conditions, hi some embodiments, growth is inhibited by at least 30%, or at least 40%, or at least 50%, or at least 60%, or at least 70%, or at least 75% when tested after 8 hours by the tampon sac method.

[0023] In certain embodiments, a porous sponge structure impregnated with the composition inhibits the growth of Gardnerella vaginalis compared to medium alone under the same conditions, hi some embodiments, the growth of Gardnerella vaginalis is inhibited by at least 50 fold, at least 100 fold, or at least 250 fold, or at least 500 fold, or at least 1000 fold, or at least 5000 fold, or at least 10,000 fold, or at least 20,000 fold when tested after 24 hours by the tampon sack method.

[0024] In certain embodiments, a porous sponge structure impregnated with the composition inhibits the growth of Lactobacilli spp. compared to medium alone under the same conditions, hi some embodiments, the growth of the Lactobacilli spp. is inhibited by up to 12-fold when tested after 8 hours by the tampon sac method.

[0025] In certain embodiments, the one or more bacteriocins are selected from Class I, Class II, Class II, and Class IV bacteriocins from Gram-positive bacteria, hi some embodiments, the one or more bacteriocins are selected from Class I and / or Class II bacteriocins from Gram-positive bacteria.

[0026] In certain embodiments, the one or more bacteriocins are lantibiotics, hi some embodiments, the one or more bacteriocins are type A or type B lantibiotics.

[0027] In certain embodiments, the one or more bacteriocins are Class II bacteriocins. In some embodiments, the Class II bacteriocin is a one-peptide bacteriocin or a two-peptide bacteriocin.

[0028] In certain embodiments, the one or more bacteriocins are Class IIa bacteriocins. In some embodiments, the Class IIa bacteriocin is a cyclic bacteriocin.

[0029] In certain embodiments, the composition further comprises lactic acid. In some embodiments, the composition comprises lactic acid in an amount appropriate to achieve a pH value of the composition of 3.5 to 5.5, or 3.7 to 5, or 3.9 to 4.5, or about 4.2. In these embodiments, the lactic acid promotes natural Lactobacillus flora by ensuring an acidic pH.

[0030] In certain embodiments, the porous sponge structure is made of natural or synthetic fibers. In particular, the porous sponge structure may be made of natural fibers. In some embodiments, the porous sponge structure is made of a natural polysaccharide-based sponge material. In some embodiments, the natural polysaccharide-based sponge material is a glucomannan-based sponge material. In some embodiments, the polysaccharide-based material comprises glucomannan. In some embodiments, the polysaccharide-based material is glucomannan.

[0031] In another aspect, the present invention provides a method of manufacturing a sponge for the vaginal canal as disclosed herein, the method comprising the steps of providing a sponge for the vaginal canal comprising a sponge body having a porous sponge structure, the porous sponge structure forming at least a part of the sponge exterior surface; and impregnating the sponge body with a liquid composition comprising one or more bacteriocins to obtain a sponge for the vaginal canal as disclosed herein.

[0032] The present invention also relates to a sponge as disclosed herein or a liquid composition as disclosed herein for inhibiting the growth of one or more pathogens associated with disorders or diseases of the vaginal tract.

[0033] Yet another aspect of the present invention provides a sponge for the vaginal tract as disclosed herein for use in the prevention or treatment of intestinal dysbiosis. Further, the present invention relates to a sponge for use in the prevention or treatment of vulvovaginal candidiasis and / or bacterial vaginosis. Furthermore, the present invention relates to a sponge for use in the prevention of toxic shock syndrome.

[0034] Further disclosed are liquid compositions described herein for use in the prevention or treatment of intestinal dysbiosis. Further disclosed are liquid compositions described herein for use in the prevention or treatment of vulvovaginal candidiasis and / or bacterial vaginosis. Additionally disclosed are liquid compositions described herein for use in the prevention of toxic shock syndrome.

[0035] In certain embodiments, the liquid composition contains a fixed amount of the one or more bacteriocins. A fixed amount has the advantage that the amount of bacteriocin available in the vaginal canal does not fluctuate. In comparison, for example, when Lactobacilli are incorporated into a sponge, the Lactobacilli may vary in bacteriocin composition and concentration. In addition, under unfavorable conditions, Lactobacilli may significantly reduce the amount of bacteriocin produced, potentially rendering the amount of bacteriocin ineffective. Therefore, impregnating a sponge with a fixed amount of bacteriocin has the advantage that the amount of bacteriocin is always the same, thereby making the technical effect reproducible. Because the amount of bacteriocin is fixed, the amount of bacteriocin is not affected by the microenvironment.

[0036] In some embodiments, the one or more bacteriocins are present in a total concentration in the liquid composition of between 0.0001% (v / v) and 0.005% (v / v), between 0.0002% (v / v) and 0.002% (v / v), between 0.0004% (v / v) and 0.001% (v / v), between 0.0005% (v / v) and 0.0014% (v / v), between 0.0001% (v / v) and 0.0005% (v / v), or between 0.0014% (v / v) and 0.008% (v / v).

[0037] In certain embodiments, the liquid composition is a solution. In these embodiments, the liquid composition is a liquid solution. Generally, a solution is a homogeneous mixture of two or more substances. In this case, one or more bacteriocins and possible other ingredients are homogeneously mixed to provide a liquid solution.

[0038] In certain embodiments, the liquid composition is a gel or lubricant. As known in the art, a gel is a thick, clear liquid composition. Lubricants for the vaginal tract are also known in the art, and lubricants are typically water- or oil-based. In some embodiments, the gel further comprises a polysaccharide, such as glucomannan, pectin, inulin, or a combination thereof. Ideally, the gel further comprises glucomannan. In some embodiments, the lubricant further comprises glucomannan. In particular, Example 4 provides evidence that a gel further comprising glucomannan promotes the growth of Lactobacilli while selectively inhibiting pathogens. A gel or lubricant further comprising glucomannan has the added advantage that glucomannan has a prebiotic effect on vaginal Lactobacilli, thereby further enhancing the effectiveness of one or more bacteriocins. In other words, glucomannan provides "nutrition" for natural Lactobacilli, thereby promoting natural Lactobacilli. Additionally, glucomannan helps maintain an acidic pH. Therefore, glucomannan further supports the inhibition of, for example, G. vaginalis, which is inhibited by an acidic pH. Thus, natural flora is promoted, and / or pathogens such as G. vaginalis are inhibited by glucomannan. At the same time, one or more bacteriocins specifically inhibit pathogenic bacteria and fungi, such as S. aureus and Candida. Thus, in these embodiments, support of natural lactobacilli by glucomannan and inhibition of pathogens by one or more bacteriocins are simultaneously achieved.

[0039] The sponge for vaginal tract according to the present invention is impregnated with a liquid composition comprising one or more bacteriocins. Liquid compositions comprising one or more bacteriocins are also disclosed. The bacteriocins are effective in promoting vaginal microflora by inhibiting the growth of pathogens such as S. aureus, Candida albicans, and / or Gardnerella vaginalis, as shown in Examples 1 and 2. At the same time, the bacteriocins are present in an amount such that vaginal microflora is also promoted by slightly inhibiting Lactobacilli (see Example 1).

[0040] Liquid compositions containing one or more bacteriocins offer several advantages: they prevent vaginal mucosa from drying out, maintain the natural vaginal pH as much as possible during menstruation, and provide bacteriocins that support the vaginal microbiota by promoting the microbiota and / or inhibiting the growth of pathogens. Furthermore, providing bacteriocins directly instead of providing bacteria such as Lactobacilli is advantageous because the production and release of bacteriocins by Lactobacilli depends on optimal growth conditions for Lactobacilli, which require an acidic environment. However, during menstruation, the vaginal pH is close to the pH of blood (pH 7) and is not acidic. Various studies have demonstrated a 100-fold decrease in Lactobacilli during menstruation. Meanwhile, pathogenic bacteria such as Gardnerella vaginalis increase by 4 logs during menstruation in healthy women [21, 23]. Therefore, by impregnating a sponge with bacteriocin or by applying a liquid composition containing one or more bacteriocins, the active agent can be directly supplied to the vaginal microflora.Furthermore, although a specified amount of bacteriocin can be supplied, the amount of bacteriocin produced by Lactobacilli is highly dependent on the environment, and therefore cannot be controlled during use.Therefore, the presence of bacteriocin does not depend on the environmental conditions of Lactobacilli.

[0041] The combination of a porous sponge structure and impregnation with a liquid composition containing one or more bacteriocins is particularly advantageous. Impregnation of the porous sponge structure ensures that the bacteriocins are distributed throughout the porous sponge structure. Because the porous sponge structure forms at least a portion of the outer surface of the sponge, the liquid composition containing one or more bacteriocins comes into direct contact with the vaginal microflora, ensuring its supportive effect. Furthermore, the porous sponge structure is suitable for absorbing menstrual fluid. The porous sponge structure is suitable for preventing the generation of small fibers, is gentle on the vaginal wall, is elastic, and has a shape that allows for easy insertion into the vagina.

[0042] Thanks to the shape and structure of the sponge, fluid is absorbed where it is formed and safely retained within the sponge. Because menstrual blood flows into and is retained within the sponge's pores, the absorption pattern is fundamentally different from traditional tampons, which function when blood is absorbed by the tampon fabric itself. Accumulating menstrual blood in the sponge's pores is isolated from the vaginal wall, thus maintaining a healthier vaginal pH. A healthy vaginal pH is more acidic (below 4.5) than blood's pH (approximately 7), thus preserving a healthy vaginal microflora and reducing the risk of infection caused by pathogenic bacteria. This effect is further enhanced by the presence of one or more bacteriocins, which further inhibit pathogen growth and support natural lactobacilli. The sponge structure allows the sponge to compress and deform during use, ensuring functionality as well as convenience.

[0043] Once inserted, the sponge regains its shape particularly quickly due to its structure, the material from which it is made, and its porosity. Its softness, flexibility, and special shape allow it to easily adapt to individual physiology without causing discomfort. The sponge is designed to dynamically adapt to the female anatomy during movement, and is therefore comfortable to wear and effectively absorbs menstrual secretions. [Brief explanation of the drawings]

[0044] Further objects, principles, and features of the present invention will become apparent from the following description of exemplary embodiments of the present invention, taken in conjunction with the accompanying drawings. However, it should be understood that these embodiments are not intended to limit the scope of the present invention, but are merely intended to illustrate exemplary implementations. The drawings are as follows: [Figure 1] 1a, 1b, and 1c show front, side, and top views of a solid vaginal canal sponge according to one embodiment. [Figure 2] 2a, b and c show front, side and top views of another embodiment of a sponge for the vaginal canal with a hollow lateral portion. [Figure 3] 3a, b and c show front, side and top views of another embodiment of a sponge for the vaginal canal with a hollow top. [Figure 4] FIG. 3c shows top, side and top views of a sponge for the vaginal canal with a hollow top according to another embodiment. [Figure 5] 5a, b are schematic illustrations of insertion positions of sponges within the vaginal canal according to two different embodiments of the present invention. [Figure 6] FIG. 6 shows a sponge for the vaginal canal in a perspective view, according to yet another embodiment. [Figure 7] FIG. 7 shows an exemplary package containing the vaginal sponge of FIG. [Figure 8a] 8a is a schematic cross-sectional view of the sponge for the vaginal canal of FIG. 6 taken along line AA shown in FIG. [Figure 8b] 8b is a schematic cross-sectional view of the sponge for the vaginal canal of FIG. 6 taken along line BB shown in FIG. [Figure 9] FIG. 9 shows experimental data regarding the inhibitory effects of exemplary solutions and gels against G. vaginalis. [Figure 10] FIG. 10 shows experimental data regarding the effects of exemplary solutions on L. gasseri. [Figure 11a]FIG. 11a shows experimental data regarding the effect of exemplary gels on L. crispatus. [Figure 11b] FIG. 11b shows experimental data regarding the efficacy of exemplary gels against L. crispatus and G. vaginalis. DETAILED DESCRIPTION OF THE INVENTION

[0045] Before describing the preferred embodiments of the present invention in detail with reference to the drawings, it should be noted that identical elements are represented by the same numbers in all the drawings.

[0046] It should be understood that numerous specific details have been provided to provide a thorough and understandable description of exemplary embodiments of the present invention. However, the detailed description of embodiments of the present invention does not limit the practice of the present invention, and it will be apparent to those skilled in the art that the present invention can be practiced without such specific instructions. Well-known techniques, procedures, and components have not been described in detail so as to avoid misleading examples of practicing the present invention. Furthermore, this description should not be considered as limiting the presented examples, but only as schemes of their implementation. Equivalent features or modifications of features of the present invention are considered to be within the scope of the present invention.

[0047] Generally, bacteriocins are antimicrobial peptides produced by different bacteria, thereby inhibiting the growth of other bacteria. Bacteriocins can also be effective against yeast. Generally, bacteriocins can kill bacteria or yeast. In particular, bacteriocins are generally more effective against bacteria that do not naturally produce said bacteriocins. By specifically retaining and thereby supporting natural Lactobacilli in the vaginal flora using bacteriocins, the growth of potentially pathogenic agents such as Candida albicans, S. aureus, and / or Gardnerella vaginalis is inhibited, thereby reducing vaginal infections. This may also prevent recurrence of infections. Ideally, compositions according to the present invention selectively inhibit pathogenic bacteria and fungi such as Candida albicans, S. aureus, and / or Gardnerella vaginalis, while protecting healthy microflora such as Lactobacilli spp. In this way, the balance of a healthy vaginal flora is ideally restored and maintained. In particular, bacteriocins produced by Lactobacilli preserve native / vaginal Lactobacilli but inhibit other bacteria and yeasts such as S. aureus, C. albicans, and / or Gardnerella vaginalis.

[0048] In certain embodiments, one or more bacteriocins are synthesized. Those skilled in the art are aware of synthetic bacteriocins that are commercially available or can be produced in a laboratory. Synthetic bacteriocins may be chemically synthesized or synthesized within a bacterial strain. If the bacteriocin is synthesized within a bacterial strain, the bacteriocin can be isolated from the bacterial strain to form part of the liquid composition. For example, one or more bacteriocins can be synthesized within Lactobacilli and then isolated from the Lactobacilli. In certain embodiments, the one or more bacteriocins are produced by the bacterial strain. If the bacteriocin is chemically synthesized, the bacteriocin is not produced by the bacterial strain. Furthermore, the amino acid sequences of bacteriocins are disclosed in the art, and those skilled in the art are aware of bacteriocin databases such as BAGEL4 (http: / / bagel4.molgenrug.nl / ) and Bactibase (e.g., http: / / bactibase.hammamilab.org / main.php), which publish the amino acid sequences of bacteriocins. Furthermore, products such as tampons that contain bacteria, e.g., Lactobacilli, may contain naturally occurring bacteriocins, where the bacteriocin is produced by the Lactobacilli within the product.

[0049] With respect to liquid compositions suitable for the vaginal tract, the liquid composition comprises one or more bacteriocins. In particular, the one or more bacteriocins are active agents of the liquid composition. As known in the art, an "active agent" can have an activity. In some embodiments, the composition is a gel or a lubricant.

[0050] In certain embodiments of the present invention, the sponge does not contain Lactobacilli. In some embodiments, the sponge does not contain bacteria. In some embodiments, the liquid composition does not contain bacteria such as Lactobacilli. In certain embodiments, a sponge body impregnated with the composition promotes vaginal microflora during any stage of the menstrual cycle and / or pregnancy. Similarly, in some embodiments, a liquid composition promotes vaginal microflora during any stage of the menstrual cycle and / or pregnancy. Specifically, a sponge body impregnated with the composition or the composition may promote vaginal microflora during menstruation, the follicular phase, the luteal phase, and / or pregnancy. Using a sponge during menstruation has the particular advantage that menstrual blood is retained within the pores of the sponge without drying out the vaginal mucosa, and bacteriocins are provided to natural Lactobacilli in the vaginal tract, thereby inhibiting potential pathogens such as S. aureus, Candida albicans, and / or Gardnerella vaginalis. During the follicular and luteal phases, a sponge body impregnated with the composition or liquid composition provides the particular advantage of providing one or more bacteriocins to the vaginal microflora. In particular, recurrent vaginal infections, such as vulvovaginal candidiasis or bacterial vaginosis, can be prevented or treated during the follicular and luteal phases. Because the sponge is impregnated with a liquid composition containing one or more bacteriocins, the sponge is moisturizing and does not dry out the vaginal mucosa. Vaginal infections are particularly common during pregnancy. Therefore, compared with conventional tampons, the sponge offers the specific advantage of promoting natural vaginal flora with bacteriocins without drying out the mucosa.

[0051] In certain embodiments, the sponge is a tampon. In some embodiments, the tampon is a menstrual tampon.

[0052] According to the present invention, the sponge body is impregnated with a liquid composition containing one or more bacteriocins. As used herein, "impregnated" means that the sponge body is saturated with the liquid composition and dispersed within the sponge body. For example, the sponge can be made from fibers such as polysaccharide fibers. In this case, the polysaccharide fibers are impregnated with the liquid composition. During use, the pores of the porous sponge structure can absorb menstrual fluid, which is advantageous because the sponge does not dry out the vaginal mucosa by retaining menstrual fluid within the pores.

[0053] In certain embodiments, the composition promotes the vaginal microbiota by inhibiting the growth of one or more pathogens. In some embodiments, the sponge body impregnated with the composition promotes the vaginal microbiota by inhibiting the growth of one or more pathogens. By promoting the vaginal microbiota, the composition or the sponge body impregnated with the composition has a positive effect on the microbiota. For example, the microbiota is positively affected by promoting the health of the microbiota. For example, the microbiota is positively affected by promoting Lactobacilli spp. Ideally, the composition or the sponge body impregnated with the composition promotes a balanced vaginal microbiota. A balanced vaginal microbiota is dominated by Lactobacilli spp. Ideally, the composition or the sponge body impregnated with the composition promotes the dominance of Lactobacilli spp. in the vaginal microbiota. Lactobacilli spp. are dominant when the genus Lactobacilli spp. is most abundant in the microbiota. Then, when Lactobacilli spp. predominate, there will be no genera more abundant than Lactobacilli spp. in the microbiome. Ideally, the health of the microbiome is promoted by the composition or a sponge body impregnated with the composition. Specifically, the health of the microbiome can be promoted by promoting the dominance of Lactobacilli spp. Inhibiting the growth of pathogens can shift metabolic activity. For example, the composition or a sponge body impregnated with the composition inhibits the growth of S. aureus, Candida spp., and / or Gardnerella vaginalis. Examples 1 and 2 provide data specifically regarding the inhibition of the growth of S. aureus, Candida spp., and Gardnerella vaginalis. Advantageously, the composition or a sponge body impregnated with the composition promotes the vaginal microbiome, thereby overcoming imbalances in the vaginal microbiome that may occur, for example, in vulvovaginal candidiasis and bacterial vaginosis.More advantageously, the composition or a sponge body impregnated with the composition promotes vaginal microflora, whereby a Lactobacilli spp.-dominated microflora can be obtained or maintained.

[0054] In certain embodiments, a porous sponge structure impregnated with the composition inhibits the growth of S. aureus compared to medium alone under the same conditions, with growth being inhibited by at least 20-fold, at least 50-fold, or at least 100-fold, or at least 200-fold, or at least 350-fold when tested after 8 hours, for example, by the tampon sack method. Those skilled in the art are aware of the tampon sack method. This method is described, for example, in Nonfoux L, et al. (2018) [7]. Additionally, this method is also used in Example 1 herein, where further details are provided. Based on the data disclosed in Example 1, those skilled in the art can test appropriate substances to evaluate inhibition of pathogens such as S. aureus, Candida spp., and / or Gardnerella vaginalis. Similarly, in some embodiments, a liquid composition inhibits the growth of S. aureus compared to medium alone under the same conditions, with growth being inhibited by, for example, at least 20-fold, at least 50-fold, or at least 100-fold, or at least 200-fold, or at least 350-fold.

[0055] In some embodiments, a porous sponge structure impregnated with the composition inhibits the growth of S. aureus compared to medium alone under the same conditions, wherein growth is inhibited by at least 100-fold when tested after 8 hours by the tampon sack method. In some embodiments, a porous sponge structure impregnated with the composition inhibits the growth of S. aureus compared to medium alone under the same conditions, wherein growth is inhibited by at least 200-fold when tested after 8 hours by the tampon sack method. In some embodiments, a porous sponge structure impregnated with the composition inhibits the growth of S. aureus compared to medium alone under the same conditions, wherein growth is inhibited by at least 350-fold when tested after 8 hours by the tampon sack method.

[0056] In certain embodiments, a porous sponge structure impregnated with the composition inhibits the growth of Candida spp. compared to medium alone under the same conditions, where growth is inhibited by at least 30%, or at least 40%, or at least 50%, or at least 60%, or at least 70%, or at least 75% when tested after 8 hours, for example, by the tampon sack method. Similarly, in some embodiments, a liquid composition inhibits the growth of Candida spp. compared to medium alone under the same conditions, where growth is inhibited by, for example, at least 30%, or at least 40%, or at least 50%, or at least 60%, or at least 70%, or at least 75%. Additionally, data in the Examples provide further details and demonstrate such growth inhibition. In some embodiments, a porous sponge structure impregnated with the composition inhibits the growth of Candida spp. compared to medium alone under the same conditions, where growth is inhibited by at least 60% when tested after 8 hours by the tampon sack method. In some embodiments, a porous sponge structure impregnated with the composition inhibits the growth of Candida spp. compared to medium alone under the same conditions, wherein growth is inhibited by at least 70% when tested after 8 hours by the tampon sack method. In some embodiments, a porous sponge structure impregnated with the composition inhibits the growth of Candida spp. compared to medium alone under the same conditions, wherein growth is inhibited by at least 80% when tested after 8 hours by the tampon sack method. In certain embodiments, a porous sponge structure impregnated with the composition inhibits the growth of Candida spp. compared to medium alone under the same conditions, wherein growth is inhibited by at least 50%, or at least 60%, or at least 70%, or at least 80%, and / or at least 85% when tested after 48 hours by, for example, the tampon sack method.

[0057] In certain embodiments, porous sponge structures impregnated with the composition inhibit the growth of Gardnerella vaginalis by at least 50-fold, at least 100-fold, or at least 250-fold, or at least 500-fold when tested after 24 hours by the tampon sack method. Similarly, in some embodiments, the liquid composition inhibits the growth of Candida spp. compared to medium alone under the same conditions, with growth being inhibited by, for example, at least 30%, or at least 40%, or at least 50%, or at least 60%, or at least 70%, or at least 75%. Additionally, data in the Examples provide further details and demonstrate such growth inhibition. In some embodiments, porous sponge structures impregnated with the composition inhibit the growth of Gardnerella vaginalis by at least 1000-fold when tested after 24 hours by the tampon sack method. In some embodiments, porous sponge structures impregnated with the composition inhibit the growth of Gardnerella vaginalis by at least 5000-fold when tested after 24 hours by the tampon sack method. In some embodiments, a porous sponge structure impregnated with the composition inhibits the growth of Gardnerella vaginalis by at least 10,000 fold when tested after 24 hours by the tampon sack method. In some embodiments, a porous sponge structure impregnated with the composition inhibits the growth of Gardnerella vaginalis by at least 20,000 fold when tested after 24 hours by the tampon sack method.

[0058] In certain embodiments, the porous sponge structure impregnated with the composition inhibits the growth of Lactobacilli spp. by up to 12-fold when tested after 8 hours by the tampon sac method compared to medium alone under the same conditions. The up to 12-fold inhibition is up to 1,079 log 10In some embodiments, a porous sponge structure impregnated with the composition inhibits the growth of Lactobacilli spp. by up to 20-fold, up to 15-fold, up to 14-fold, or up to 13-fold when tested after 8 hours by the tampon sack method compared to medium alone under the same conditions. Similarly, in some embodiments, a liquid composition inhibits the growth of Lactobacilli spp. by up to 12-fold compared to medium alone under the same conditions.

[0059] In certain embodiments, the one or more bacteriocins are bacteriocins from Gram-positive and / or Gram-negative bacteria, hi some embodiments, the one or more bacteriocins are bacteriocins from Gram-positive bacteria.

[0060] In some embodiments, the one or more bacteriocins are selected from Class I, Class II, Class II, and Class IV bacteriocins from Gram-positive bacteria. For example, the one or more bacteriocins may be selected from Class I and / or Class II bacteriocins from Gram-positive bacteria.

[0061] In certain embodiments, the one or more bacteriocins are derived from Lactococcus lactis and / or Lactobacillus. Furthermore, the one or more bacteriocins may be derived from the order Lactobacillales. Specifically, the order Lactobacillales includes Lactobacillus, Leuconostoc, Pediococcus, Lactococcus, Streptococcus, Aerococcus, Carnobacterium, Enterococcus, Oenococcus, Tetragenococcus, Vagococcus, and Weissella. Alternatively, the one or more bacteriocins may be derived from the bacteriocin Sporolactobacillus. Bacteriocins derived from Lactobacilli have the particular advantage of having little inhibitory effect on Lactobacilli but a greater inhibitory effect on other bacteria. For example, the one or more bacteriocins may be bacteriocins derived from Lactobacillus crispatus and / or Lactobacillus gasseri. In some embodiments, the one or more bacteriocins are lantibiotics. Lantibiotics are a class of polycyclic peptide antibiotics containing the characteristic thioether amino acids lanthionine or methyllanthionine, as well as the unsaturated amino acids dehydroalanine and 2-aminoisobutyric acid. Lantibiotics are produced by Gram-positive bacteria and attack other Gram-positive bacteria, such as S. aureus.

[0062] In particular, the one or more bacteriocins may be a type A or B lantibiotic. For example, the lantibiotic may be selected from nisin, lactocin, lacticin, carnosine, cytolysin, subtilin, gallidermin, epidermin, mersacidin, actagardine, cinnamycin, duramycin, sublancin, and plantaricin. In certain embodiments, the lantibiotic is nisin. In some embodiments, the one or more bacteriocins include nisin. In embodiments in which the one or more bacteriocins is nisin, the nisin may be selected from nisin A, nisin Z, nisin U, nisin Q, and nisin F. In some embodiments, the nisin is selected from nisin A, nisin Z, or a combination thereof. Ideally, the nisin is nisin Z. Alternatively, the nisin is nisin A. In some embodiments, the composition comprises one bacteriocin. The one bacteriocin may be nisin, e.g., nisin A or nisin Z. Ideally, the composition has an acidic pH, e.g., a pH of 3.5 to 5.5. In particular embodiments, the composition comprises one bacteriocin that is nisin and lactic acid in an amount such that the pH of the composition is 3.5 to 5.5, or 3.7 to 5, or 3.9 to 4.5, or about 4.2.

[0063] In certain embodiments, the one or more bacteriocins are Class II bacteriocins. In these embodiments, the Class II bacteriocin may be a one-peptide bacteriocin or a two-peptide bacteriocin. In some embodiments, the Class II bacteriocin is a one-peptide bacteriocin. In embodiments where the one or more bacteriocins are one-peptide bacteriocins, the one-peptide bacteriocin may be selected from a pediocin-like bacteriocin and / or a non-pediocin-like bacteriocin. In some embodiments, the one-peptide bacteriocin is a non-pediocin-like bacteriocin.

[0064] In certain embodiments, the one or more bacteriocins are selected from pediocin PA1, leucocin A, sakacin P, curvacin A, mesentericin Y105, carnobacteriocin BM1, carnobacteriocin B2, enterocin A, picxicolin 126, bavaricin MN, picicoccin V1a, lactococcin A, lactococcin B, divergicin 750, lactococcin 972, enterocin B, carnobacteriocin A, and crispasin A. In some embodiments, the one or more bacteriocins are selected from lactococcin A, lactococcin B, divergicin 750, lactococcin 972, enterocin B, carnobacteriocin A, and crispasin A. In some embodiments, the one or more bacteriocins are crispasin A.

[0065] In certain embodiments, the one or more bacteriocins are Class IIa bacteriocins, e.g., cyclic bacteriocins. In some embodiments, the cyclic bacteriocin is selected from gassericin A, reutericin A, butyrivibricin A, lactocyclin Q, circularin A, leucocyclin Q, amylocyclin A, carnocyclin A, uberolysin A, AS-48, and garvicin ML; preferably, the cyclic bacteriocin is gassericin A.

[0066] In certain embodiments, the composition comprises one, two, or three bacteriocins. In some embodiments, the composition comprises one or two bacteriocins. For example, the composition can comprise one Class I bacteriocin and one Class II bacteriocin. An exemplary Class I bacteriocin can be nisin, and an exemplary Class II bacteriocin can be a one-peptide bacteriocin, such as crispasin A. In another example, the composition can comprise one Class I bacteriocin and one cyclic bacteriocin. An exemplary Class I bacteriocin can be nisin, and an exemplary cyclic bacteriocin can be gassericin A.

[0067] In certain embodiments, the composition may have a pH value of 3.5 to 5.5. In certain embodiments, the composition may have a pH value of 3.7 to 5. The composition may have a pH value of 3.9 to 4.5. The composition may have a pH value of about 4.2. In certain embodiments, the composition further comprises lactic acid. For example, the composition may comprise an amount of lactic acid suitable to adjust the pH value of the composition to 3.5 to 5.5. The composition may also comprise an amount of lactic acid suitable to adjust the pH value of the composition to 3.7 to 5. Alternatively, the composition may comprise an amount of lactic acid suitable to adjust the pH value of the composition to 3.9 to 4.5. In some embodiments, the composition may comprise an amount of lactic acid suitable to adjust the pH value of the composition to about 4.2. Lactic acid may be synthetic or derived from natural sources, such as lactic acid bacteria.

[0068] In certain embodiments, one skilled in the art can determine the appropriate concentration of bacteriocins by using the tampon sack method disclosed in Examples 1 and 2. In certain embodiments, the one or more bacteriocins are present in a total concentration of the liquid composition of 0.000001% (v / v) to 5% (v / v). Alternatively, the one or more bacteriocins may be present in a total concentration of 0.00001% to 2% of the liquid composition. The one or more bacteriocins may be present in a total concentration of 0.00005% to 1% of the liquid composition. For example, the one or more bacteriocins may be present in a total concentration of 0.0001% to 0.5% of the liquid composition. Alternatively, the one or more bacteriocins, such as crispasin A, may be present in a total concentration of 0.0005% to 0.25% of the liquid composition. In particular, the one or more bacteriocins may be present at a total concentration in the liquid composition of between 0.0001% (v / v) and 0.005% (v / v). Ideally, the one or more bacteriocins, such as gassericin A, may be present at a total concentration in the liquid composition of between 0.0002% (v / v) and 0.0020% (v / v). In some embodiments, the one or more bacteriocins, such as nisin Z, are present at a total concentration in the liquid composition of between 0.0005% (v / v) and 0.0014% (v / v). In some embodiments, the one or more bacteriocins, such as nisin A, are present at a total concentration in the liquid composition of between 0.0005% (v / v) and 0.0014% (v / v). In certain embodiments, the one or more bacteriocins, such as nisin A and / or Z, are present in a total concentration of the liquid composition between 0.0006% (v / v) and 0.0013% (v / v). In certain embodiments, the one or more bacteriocins, such as nisin A and / or Z, are present in a total concentration of the liquid composition between 0.0007% (v / v) and 0.0012% (v / v). In certain embodiments, the one or more bacteriocins, such as nisin A and / or Z, are present in a total concentration of the liquid composition between 0.0008% (v / v) and 0.0011% (v / v). In certain embodiments, the one or more bacteriocins, such as nisin A and / or Z, are present in a total concentration of the liquid composition between 0.0009% (v / v) and 0.0010% (v / v).Alternatively, the one or more bacteriocins, such as curvacin A, may be present in a total concentration of the liquid composition of from 0.0001% (v / v) to 0.0005% (v / v). Alternatively, the one or more bacteriocins, such as lacticin, may be present in a total concentration of the liquid composition of from 0.0014% (v / v) to 0.008% (v / v).

[0069] In certain embodiments, the sponge is moist. In these embodiments, the sponge is slightly moist and not dry. The sponge is impregnated with a liquid composition and is therefore moist. The moist sponge is soft and gentle on vaginal mucosal epithelial cells, keeping the mucosal lining moist and healthy. The sponge is soft and therefore easily deformable, making it comfortable to use.

[0070] The composition may further comprise one or more excipients. Exemplary excipients are benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, boric acid, sodium propionate, sorbic acid, propylene glycol, potassium lactate, calcium acetate, calcium chloride, sodium sorbate, sodium benzoate, sodium chloride, sodium formate, sodium propionate, ethylenediaminetetraacetic acid (EDTA), sodium lactate, organic and inorganic salts and acids, such as sorbic acid, ascorbic acid, propionic acid, and / or fumaric acid. These excipients retain the bacteriocin in the composition. These excipients also retain the sponge. Thus, excipients have the advantage of stabilizing the bacteriocin and preserving the sponge material.

[0071] Those skilled in the art will also recognize suitable buffer solutions for the composition. For example, the composition may further contain sodium chloride and EDTA. Alternatively, the buffer solution may also contain GPB (gelatin phosphate buffer), sodium phosphate buffer, Tris-glycine and Tris-glycine, octanol phosphate, sodium citrate and sodium diacetate (BSCSD), EDTA, sodium sulfate, sodium phosphate, sodium acetate, and sodium citrate, EGTA (ethylene glycol bis(β-aminoethyl ether)). The composition may also contain benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, boric acid, sodium propionate, sorbic acid, propylene glycol, potassium lactate, calcium acetate, and / or calcium chloride. For example, the composition may also contain the following ingredients in concentrations of 0.01-0.02% v / v benzalkonium chloride, 0.01-0.02% v / v benzethonium chloride, 0.1-0.2% v / v benzoic acid, 5-10% v / v sodium propionate, and / or 0.05-0.2% v / v sorbic acid.

[0072] An exemplary embodiment of a sponge 10 for the vaginal canal, as illustrated in Figures 1-4, includes an absorbent sponge body 12 with a porous sponge structure 14. The material of the sponge structure 14 may be a plant-derived material that can be easily deformed and easily reformed into an undeformed or partially deformed state. Such a material can be manufactured by producing glucomannan from powder of the roots of the Amorphophallus konjac plant, followed by processing in a specific manner to obtain a sponge structure, or can be made from other naturally occurring polysaccharides, such as, but not limited to, starch, cellulose, chitosan, chitin, and mixtures thereof.

[0073] In certain embodiments, the porous sponge structure is made of a natural polysaccharide-based sponge material. The natural polysaccharide-based sponge material may be a glucomannan-based sponge material. In certain embodiments, the sponge is made from a completely naturally occurring material, such as glucomannan. Due to its biological origin, the glucomannan-based sponge and all of its additives are biodegradable and decompose naturally in nature. In these embodiments, the sponge is completely biodegradable and therefore environmentally friendly. In these embodiments, the sponge biodegrades in the natural environment within 30 to 90 days (depending on the environment, moisture level, and microbial abundance and species). Glucomannan has a prebiotic effect on vaginal Lactobacilli, thereby further enhancing the effectiveness of one or more bacteriocins. In other words, glucomannan provides "nutrition" for natural Lactobacilli, thereby promoting their growth. Additionally, glucomannan helps maintain an acidic pH. Thus, glucomannan further aids in the inhibition of, for example, G. vaginalis, which is inhibited by an acidic pH. Thus, the natural flora is promoted and / or pathogens such as G. vaginalis are inhibited by the glucomannan. At the same time, the one or more bacteriocins specifically inhibit pathogenic bacteria and fungi such as S. aureus and Candida. Thus, in these embodiments, the support of natural Lactobacilli by the glucomannan and the inhibition of pathogens by the one or more bacteriocins are simultaneously achieved.

[0074] Glucomannan is commonly used in the food industry and in pharmaceutical wound dressings, inhibiting the growth of bacteria such as Staphylococcus aureus and S. typhimurium, as well as vaginal Lactobacteria. The sponge contains no toxic chemicals, and the resulting final product is biocompatible with the human body, ensuring the protection of the natural vaginal microflora and healthy intimate hygiene. Because glucomannan is hydrophilic and its unique molecular structure attracts water molecules, the sponge wall remains moist and provides a molecular barrier to fluid contact with the vaginal wall, protecting the extremely sensitive vaginal wall.

[0075] In certain embodiments, the porous sponge structure occupies at least 70%, or at least 80%, or at least 90%, or at least 95%, or at least 97%, or at least 99% of the volume of the sponge body. In particular, the porous sponge structure may occupy the entire sponge body. The sponge body may be composed entirely of glucomannan.

[0076] According to the present invention, the porous sponge structure forms at least a portion of the sponge's outer surface. This ensures that the impregnation of the liquid composition containing one or more bacteriocins is in direct contact with the vaginal microflora. This has the advantage that the one or more bacteriocins can support natural Lactobacilli by inhibiting potential pathogens such as S. aureus and / or Candida. In some embodiments, the sponge structure forms at least 30%, or at least 40%, or at least 50%, or at least 60%, or at least 70%, or at least 80%, or at least 90% of the sponge's outer surface. In some embodiments, the porous sponge structure forms 100% of the sponge's outer surface. This embodiment is particularly advantageous because it maximizes contact between the sponge's surface and the vaginal microflora.

[0077] In certain embodiments, the sponge comprises a sponge body having an insertion end and a withdrawal end. In some embodiments, the sponge comprises a removal facilitation portion for facilitating removal of the sponge body from a person's vaginal canal, the removal facilitation portion being connected to the sponge body and extending from the withdrawal end of the sponge body. Additionally, the sponge can be placed into the vaginal canal by an applicator.

[0078] In some embodiments, the sponge structure is exposed in at least some area of ​​the body exterior surface located at or near the insertion end of the sponge body. In some embodiments, the body exterior surface has a fluid-trapping recess formed at least in part by the exposed portion of the sponge structure. In these embodiments, the fluid-trapping recess may be located closer to the insertion end than to the withdrawal end of the sponge body.

[0079] In certain embodiments, the sponge body comprises a fluid-impermeable layer covering the sponge structure in some areas of the body exterior surface, hi these embodiments, the fluid-impermeable layer may be made of a non-porous glucomannan-based material.

[0080] 1a-4c, the sponge body 12 also includes a liquid-impermeable layer 16 (i.e., a fluid-impermeable layer, shown hatched in the drawings) that at least partially covers the sponge structure 14 and that retains moisture within the sponge body 12 until use and prevents liquid from leaking out of the sponge body 12 during use. The liquid-impermeable layer 16 covers more than half, half, or less than half of the outer surface of the sponge structure 14 in certain embodiments.

[0081] The sponge may also have an outer fluid impermeable layer that keeps fluid within the sponge even when the sponge is deformed during use, i.e., prevents fluid from leaking out when a person moves and the sponge material is squeezed, flexed, and similarly deformed.

[0082] In certain embodiments, the liquid-impermeable layer (i.e., fluid-impermeable layer) 16 is a non-absorbent, non-porous layer having a thickness of, for example, 0.01 mm to 2 mm. For example, the liquid-impermeable layer may be 0.01 mm. It should be understood that the indicated thickness range of the liquid-impermeable layer 16 is merely exemplary and is not intended to limit the scope of the present invention. For example, the liquid-impermeable layer 16 may have a thickness of only a few tenths of a millimeter in other embodiments. The liquid-impermeable layer 16 may be made of a glucomannan-based material. The liquid-impermeable layer 16 may be formed directly on the sponge structure 14 after the sponge structure 14 is manufactured. Polysaccharides other than glucomannan (e.g., agar, xanthan gum, carrageenan, or starch) may be used as a base for manufacturing the liquid-impermeable layer 16 in alternative embodiments. However, it should be understood that the present invention is not limited to the use of polysaccharide materials for the liquid impermeable layer 16, but that latex or similar polymeric or resinous materials may be used instead.

[0083] In embodiments omitting the liquid-impermeable layer 16, the sponge body 12 may be formed entirely by the sponge structure 14. Thus, the sponge structure 14 may occupy up to 100% of the volume of the sponge body 12. In embodiments having the liquid-impermeable layer 16, the sponge structure 14 may, for example, occupy 90% or more of the volume of the sponge body 12. The remaining volume of the sponge body 12 may be formed by the liquid-impermeable layer 16. In certain embodiments, the sponge structure 14 occupies at least 95% or at least 97% of the volume of the sponge body 12.

[0084] The sponge may also include an applicator to facilitate insertion and a cord, string, or ring to facilitate removal, although it can be used without an applicator.

[0085] In certain embodiments, the sponge body 12 has an insertion end 18, a withdrawal end 20, and a body exterior surface 22. The insertion end is the leading end of the sponge body when it is pushed into a person's vaginal canal, and the withdrawal end is the trailing end of the sponge body during insertion of the sponge body. The body exterior surface 22 is defined by the outer surface of the sponge body 12. If the sponge structure 14 has one or more exposed portions (i.e., portions exposed to the outside of the sponge body 12), these exposed portions form at least a part of the body exterior surface 22. If a liquid-impermeable layer 16 is present and covers at least a part of the sponge structure 14, the liquid-impermeable layer 16 forms at least a part of the body exterior surface 22. The extension of the sponge body 12 from the insertion end 18 to the withdrawal end 20 defines the longitudinal extension (or direction) of the sponge body 12. The longitudinal extension is indicated by dashed line 24 in some figures.

[0086] In certain embodiments, the sponge body has a length dimension in a direction from the withdrawal end toward the insertion end, and the fluid-impermeable layer continuously covers the sponge structure in an area of ​​the body exterior extending from the withdrawal end over at least one-quarter, or at least one-third, or at least half of the length of the sponge body.

[0087] The sponge body 12 may have an insertion end 18, a withdrawal end 20, and a body exterior surface 22. The insertion end is the leading end of the sponge body when it is pushed into a person's vaginal canal, and the withdrawal end is the trailing end of the sponge body during insertion of the sponge body. The body exterior surface 22 is defined by the outer surface of the sponge body 12. If the sponge structure 14 has one or more exposed portions (i.e., portions exposed to the outside of the sponge body 12), these exposed portions form at least part of the body exterior surface 22. If a liquid-impermeable layer 16 is present and covers at least a portion of the sponge structure 14, the liquid-impermeable layer 16 forms at least part of the body exterior surface 22. The extension of the sponge body 12 from the insertion end 18 to the withdrawal end 20 defines the longitudinal extension (or direction) of the sponge body 12. The longitudinal extension is indicated by dashed line 24 in some figures.

[0088] When viewed in the longitudinal direction 24 from the withdrawal end 20 to the insertion end 18, the sponge body 12 has a lower portion 25, a central portion 26, and an upper portion 28, in that order. The sponge body has opposing major surfaces 30, 32 that extend between the withdrawal end and the insertion end 18, 20, respectively. Major surface 30 is the back surface of the sponge body 12, and major surface 32 is the front surface. When considering insertion of the sponge body 12 into a human vagina 34 in its intended, appropriate insertion position, as shown in Figures 5a and 5b, major surface 30 faces substantially downward, away from the wearer's uterus 36, and major surface 32 faces substantially upward, toward the uterus 36. In the embodiment shown in Figures 1a-5b, major surface 30 is convex in the longitudinal direction 24 along substantially the entire length of the sponge body 12. Major surface 32 is generally formed with a lesser degree of convexity in the longitudinal direction 24 than major surface 30. In some embodiments (see, for example, Figures 2b, 3b, 4b, 5a, 5b), the major surface 32 may be formed with substantially no curvature when viewed in the longitudinal direction 24, or may be formed with a concave surface along at least a portion of the longitudinal length of the sponge body 12.

[0089] When viewed in a cross-sectional profile (i.e., transverse cross-section), major surface 30 is convex, while major surface 32 is generally less convex than major surface 30, or has no convexity at all. The non-convexity situation covers both a substantially linear extension of major surface 32 in the transverse cross-section, or a profile of major surface 32 having one or more concave portions. When viewed in a cross-section perpendicular to longitudinal direction 24, sponge body 12 has an irregular, rotationally asymmetric shape. This irregular cross-sectional shape of the sponge body may extend continuously over a majority of the longitudinal length of sponge body 12, for example, over more than 50%, or over 60%, or over 70%, or over 80%, or over 90% of the sponge body 12. In certain embodiments, sponge body 12 may also comprise an outer reinforcing casing (not shown in the drawings) that reinforces the structure of sponge body 12 and helps maintain the desired shape.

[0090] Exemplary approximate sizes of the sponge body 12 may be as follows: Size 1: Length 4.0~4.5cm; Width 1.5~2.0cm; Thickness approx. 1.0cm Size 2: Length 4.5cm; Width 3.6cm; Thickness 1.9cm Size 3: Length 5.8cm; Width 4.5cm; Thickness 2.3cm Size 4: Length 6.0cm; Width 3.9cm; Thickness 2.2cm

[0091] In some embodiments, the sponge 10 comprises a removal facilitator 38, such as a thread, ring, or string. The removal facilitator 38 is coupled to the sponge body 12 and extends from the withdrawal end 20 in a manner known per se. The removal facilitator 38 is attached to the sponge body 12 at two ends, approximately at the central portion 26, or the upper portion 28, or the lower portion 25, on opposite sides of the sponge body 12, thereby forming a U-shaped loop extending from one side of the sponge body 12 to the other and allowing for a gap to be formed between at least the lower portion 25 of the sponge body 12 and the gripping portion of the removal facilitator 38. The removal facilitator 38 can also be formed as a single element that penetrates the sponge body 12 anywhere, such as at the upper, central, or lower portions 28, 26, 25 of the sponge body 12.

[0092] In some embodiments, the sponge body 12 has an irregular shape resembling an oval or other smooth shape. The sponge body 12 may be generally wider near its insertion end 18 and then wider near its withdrawal end 20. The aforementioned flat profile, in which the width (designated W in FIG. 1a) of the sponge body 12 is greater than its height or thickness (designated H in FIG. 1b) over at least a majority of its longitudinal length, mimics the natural biological shape of the vaginal canal (https: / / i.pinimg.com / originals / d9 / d1 / 3b / d9d13b90a7d2c5ba6e5314f2c8b3258f.jpg) and helps provide a comfortable experience for the user. This is related to the fact that using a solid-shaped device that exerts pressure on the anterior and posterior regions of the vagina (where many nerve endings are concentrated) can cause additional pain or discomfort for the user. As can be seen from Figures 1a, 2a, 3a and 4a, the upper portion 28 is usually wider than the lower portion 25. When inserted into the vagina, the upper portion 28 of the sponge body 12 is located closer to the source of menstrual fluid than the lower portion 25 (see Figures 5a and 5b). The wider width of the upper portion 28 can improve the absorbency of menstrual fluid in the sponge structure 14, while the lower portion 28, despite its narrower width, can efficiently retain accumulated fluid and ensure high wearing comfort.

[0093] In the embodiment of Figures 2a-5b, the sponge body 12 is formed with hollows 40 having a generally concave absorbent surface 42 where the sponge structure 14 is exposed to the outside of the sponge body 12. If present, the liquid impermeable layer 16 does not cover the sponge structure 14 at the absorbent surface 42. The hollows 40 may also be referred to as fluid-acquisition depressions or pockets. The surface area of ​​the absorbent surface 42 is at least 1.5 cm in certain embodiments. 2 or at least 2.0 cm 2 The hollow portion 40 may have a shape that is concave in all directions, for example resembling a bowl shape.

[0094] In certain embodiments of the present invention, the liquid-impermeable layer 16 may cover the entire outer body surface 22 of the sponge body 12 up to the periphery of said hollow portion 40. In other embodiments of the present invention, the liquid-impermeable layer 16 may cover the sponge structure 14 only up to a certain distance from the periphery of the hollow portion 40, so that the sponge structure 14 remains uncoated by the liquid-impermeable layer 16 (i.e. exposed to the outside of the sponge body 12) not only within the area of ​​the hollow portion 40 but also outside the hollow portion 40 in the region between the liquid-impermeable layer 16 and the periphery of the hollow portion 40.

[0095] The hollow portion 40 is designed for easier fluid accumulation at the cervix and for faster liquid absorption to prevent blood stagnation at the cervix. The surface 42 comprises part of the sponge structure 14 material of the sponge body 12 and is generally concave in shape, such as a scoop, hollow hemisphere, oval, or other shape. While the absorbent surface 42 is said to be generally concave in shape, it should be understood that one or more subportions of the absorbent surface 42 that form part of the overall area of ​​the absorbent surface 42 may nevertheless have a planar or convex shape. In other words, the absorbent surface 42 generally forms a concave depression or pocket, but may also be comprised of concave and non-concave portions. The hollow portion 40 may be formed on the main surface 32 at a longitudinal position closer to the insertion end 18 than to the withdrawal end 20 (as shown by way of example in Figures 2a to 2c and 5a and 5b), or may be formed in the region of the insertion end 18 (as shown by way of example in Figures 3a to 3c and 4a to 4c).

[0096] The sponge body 12 has at least three states: a fully expanded, undeformed state; a deformed state in which it is compressed to occupy the smallest possible volume; and an at least partially deformed state in which the sponge body 12 fills the entire vaginal cavity by partially deforming the vaginal cavity wall at the contact site. In this way, the volume of liquid absorbed by the sponge body 12 is increased while at the same time ensuring conformity to the vagina. The reversible deformation of the sponge body 12 ensures continuous conformity to the vagina whether the user is at rest or moving. When the force from the vaginal wall is no longer acting on the sponge body 12, the deformed sponge body 12 returns to its original shape or partially to its original shape.

[0097] As can be seen from Figures 6, 7 and 8b, the absorbent surface 42 defined by the hollow portion 40 has a concavely curved shape in both the width and height directions of the sponge body 12 (the width and height, or thickness, dimensions lie in a plane perpendicular to the longitudinal direction 24). On the side of the main surface 32, the hollow portion 40 forms a deeper neck than on the side of the main surface 30. Thus, the hollow portion 40 cuts out a relatively larger portion from the main surface 32 than from the main surface 30.

[0098] In certain embodiments, the sponge body 12 substantially maintains its shape and volume in a non-deformed (i.e., at rest) state over a wide range of moistening levels of the material of the sponge structure. In at least some embodiments, it may be envisioned that the material of the sponge structure 14 should be relatively dry rather than moist, in order to enable the sponge 10 to be stored for extended periods of time without deterioration, even when hermetically packed in a package. Accordingly, in certain embodiments, a capsule or other suitable container (e.g., a sachet) is included in the package along with the sponge 10, the capsule or container containing a predetermined amount of water or another liquid substance used to moisten the sponge body 12 prior to use.

[0099] An embodiment of the present invention also includes a waterproof package 44 (FIG. 7) for the sponge 10. The package 44 is designed as a pouch in the example shown in FIG. 7 and is configured to maintain the sterility and moisture of the body 12 of the sponge 10. It should be understood that many different configurations of the pouch are possible, and many other designs of the waterproof package 44 other than a pouch are also possible, so long as the waterproof package 44 is capable of maintaining a moist and sterile environment for the tampon 10. The sponge body 12 of the embodiment shown in FIGS. 6 and 7 has only the sponge structure 14 and does not have the liquid-impermeable layer 16. The package 44 also includes a schematically illustrated capsule 46 containing a quantity of water that can be used, for example, by a user to moisten the sponge body 12 before insertion into a human vagina.

[0100] The present invention also relates to a sponge or a liquid composition disclosed herein for inhibiting the growth of one or more pathogens associated with disorders or diseases of the vaginal tract caused by one or more pathogens, such as bacteria and fungi, including, but not limited to, dysbiosis, bacterial vaginosis, toxic shock syndrome, and vulvovaginal candidiasis.

[0101] For example, the vaginal sponge disclosed herein is used for the prevention or treatment of vaginal dysbiosis. The liquid composition suitable for the vaginal tract disclosed herein is used for the prevention or treatment of dysbiosis. Dysbiosis (also known as dysbiosis) is characterized as a disruption of the homeostasis of the microbiota caused by an imbalance in the microbiota, a change in its functional composition and metabolic activity, or a shift in its local distribution. Such dysbiosis can lead to vulvovaginal candidiasis, bacterial vaginosis, and toxic shock syndrome. The present invention also relates to the vaginal sponge disclosed herein for use in the prevention or treatment of vulvovaginal candidiasis. The present invention also relates to the liquid composition disclosed herein for use in the prevention or treatment of vulvovaginal candidiasis. Vulvovaginal candidiasis can be caused by Candida albicans, Candida glabrata, Candida kefyr, Candida krusei, Candida parapsilosis, and / or Candida tropicalis. For example, vulvovaginal candidiasis may be caused by Candida albicans. In some embodiments, the vulvovaginal candidiasis is prevented or treated in pregnant women. In some embodiments, the vulvovaginal candidiasis is prevented or treated in menstruating women. The present invention also relates to a sponge for the vaginal tract disclosed herein for use in preventing or treating bacterial vaginosis. The present invention also relates to a liquid composition disclosed herein for use in preventing or treating bacterial vaginosis. Bacterial vaginosis may be caused by Gardnerella vaginalis, Prevotella, Peptostreptococcus, Bacteroides spp., Leptotrichia spp., and / or Sneathia spp. In some embodiments, the bacterial vaginosis is prevented or treated in pregnant women. In some embodiments, the bacterial vaginosis is prevented or treated in menstruating women. The present invention also relates to a sponge for the vaginal tract or a liquid composition disclosed herein for use in preventing toxic shock syndrome.Toxic shock syndrome can be caused by S. aureus. In some embodiments, the toxic shock syndrome is prevented in pregnant women. In some embodiments, the toxic shock syndrome is prevented in menstruating women.

[0102] In certain embodiments of the uses disclosed herein, the liquid composition inhibits the growth of pathogens such as S. aureus, Candida spp., and / or Gardnerella vaginalis. In some embodiments, the liquid composition selectively inhibits the growth of one or more pathogens. In these embodiments, the growth of one or more pathogens is inhibited potently, such as by at least 10-fold, at least 100-fold, or at least 1000-fold. In certain embodiments, the liquid composition exhibits at least 10-fold or greater inhibition of one or more pathogens over L. gasseri and / or L. crispatus over an 8-hour period. This is supported by Examples 3 and 4 of the accompanying invention. In particular, the liquid composition may exhibit at least 10-fold or greater inhibition of Gardnerella vaginalis over L. gasseri and / or L. crispatus over an 8-hour period. For example, the inhibition may be at least 50-fold, at least 60-fold, at least 70-fold, at least 80-fold, at least 100-fold, at least 500-fold, or at least 1000-fold.

[0103] The sponge and / or liquid composition for the vaginal tract according to the present invention advantageously protects the vaginal microflora, particularly preventing pathogenic infections during menstruation. As further defined in the claims, the combination of a porous sponge structure impregnated with a liquid composition containing one or more bacteriocins advantageously preserves the vagina's natural defense mechanisms, thus strengthening natural defenses during menstruation. As demonstrated in Examples 1 and 2, tampons according to the present invention selectively inhibit the growth of S. aureus, Candida albicans, and / or Gardnerella vaginalis. Thus, the liquid composition prevents the growth of pathogens, thereby preventing, for example, vulvovaginal candidiasis and / or toxic shock syndrome. In doing so, sponges according to the present invention can also be used for a longer period of time than conventional tampons. Due to their inhibitory effect on pathogens, sponges according to the present invention can also be used for a longer period of time than sponges that do not contain a liquid composition containing one or more bacteriocins. For example, sponges according to the present invention can be used for up to 12 hours.

[0104] While numerous features and advantages have been described above, together with details and characteristics of the structure of the present invention, this description is provided as an illustrative embodiment of the invention. Changes may be made in details, particularly in matters of form, size, and arrangement of materials, without departing from the principles of the invention in accordance with the broadest understood terms used in the claims.

[0105] The present invention can be further illustrated by the following embodiments: 1. A sponge for the vaginal canal, comprising: A sponge body having a porous structure, said porous sponge structure forming at least a part of the sponge outer surface. Equipped with The sponge body is impregnated with a liquid composition comprising one or more bacteriocins. sponge. 2. The sponge of embodiment 1, wherein said porous sponge structure is made of a polysaccharide-based material comprising glucomannan. 3. The sponge according to embodiment 1 or 2, wherein the sponge does not contain Lactobacilli, in particular the sponge is bacteria-free. 4. A sponge according to any one of embodiments 1 to 3, wherein the liquid composition comprises a fixed amount of the one or more bacteriocins. 5. The sponge of any one of embodiments 1 to 4, wherein the sponge is wettable. 6. The sponge of any one of embodiments 1 to 5, wherein the one or more bacteriocins are synthetic, for example, synthesized within a bacterial strain. 4. The sponge of any one of embodiments 1 to 3, wherein the polysaccharide-based material is glucomannan. 5. The sponge of any one of embodiments 1 to 4, wherein the sponge is a tampon. 6. The sponge of any one of embodiments 1 to 5, wherein the sponge body impregnated with the composition promotes vaginal microbiota during menstruation, the follicular phase, the luteal phase, and / or pregnancy. 7. A sponge according to any one of embodiments 1 to 6, wherein the sponge body impregnated with the composition promotes the vaginal microbiota by inhibiting the growth of pathogens, in particular S. aureus, Candida spp. and / or Gardnerella vaginalis, more particularly, the composition promotes the vaginal microbiota by selectively inhibiting the growth of said pathogens, and even more particularly, the composition promotes the vaginal microbiota by not selectively inhibiting the growth of Lactobacilli. 8. The sponge of embodiment 7, wherein the sponge body impregnated with the composition inhibits the growth of S. aureus compared to medium alone under the same conditions, wherein the growth is inhibited by at least 20-fold, or at least 50-fold, or at least 100-fold, or at least 200-fold, or at least 350-fold when tested after 8 hours by the tampon sac method. 9. A sponge according to embodiment 7 or 8, wherein the sponge body impregnated with the composition inhibits the growth of Candida spp. compared to medium alone under the same conditions, the growth being inhibited by, for example, at least 30%, or at least 40%, or at least 50%, or at least 60%, or at least 70%, or at least 75% after 8 hours when tested by the tampon sac method, and by 85% after 48 hours. 10. A sponge according to any one of embodiments 7 to 9, wherein the porous sponge structure impregnated with the composition inhibits the growth of Gardnerella vaginalis compared to medium alone under the same conditions, the growth being inhibited by at least 50 times, at least 100 times, or at least 250 times, or at least 500 times, or at least 1000 times, or at least 5000 times, or at least 10000 times, or at least 20000 times when tested after 24 hours by the tampon sack method. 11. A sponge according to any one of embodiments 1 to 10, wherein the sponge body impregnated with the composition inhibits the growth of Lactobacilli spp. by up to 12 times when tested after 8 hours by the tampon sack method compared to medium alone under the same conditions. 12. The sponge of any one of embodiments 1 to 11, wherein the one or more bacteriocins are selected from Class I, Class II, Class II, and Class IV bacteriocins from Gram-positive bacteria, e.g., the one or more bacteriocins are selected from Class I and / or Class II bacteriocins from Gram-positive bacteria. 13. The sponge of any one of embodiments 1 to 12, wherein the one or more bacteriocins are lantibiotics, for example, type A or type B lantibiotics. 14. The sponge of any one of embodiments 1 to 13, wherein the one or more bacteriocins are class II bacteriocins, the class II bacteriocin being, for example, a one-peptide bacteriocin or a two-peptide bacteriocin. 15. The sponge of any one of embodiments 1 to 14, wherein the one or more bacteriocins are class IIa bacteriocins, for example, class IIa bacteriocins, which are cyclic bacteriocins. 16. A sponge described in any one of embodiments 1 to 15, wherein the composition further comprises lactic acid, for example, in an amount such that the pH of the composition is 3.5 to 5.5, or 3.7 to 5, or 3.9 to 4.5, or about 4.2. 17. A sponge described in any one of embodiments 1 to 16, wherein the liquid composition comprises an effective amount of one or more bacteriocins, in particular, said effective amount inhibits the growth of Gardnerella vaginalis, S. aureus, and / or Candida spp., more particularly, said effective amount selectively inhibits the growth of Gardnerella vaginalis, S. aureus, and / or Candida spp. 18. A sponge described in any one of embodiments 1 to 17, wherein the liquid composition comprises one bacteriocin. 19. The sponge of any one of embodiments 1 to 18, wherein the one or more bacteriocins comprise nisin. 20. The sponge of embodiment 19, wherein the nisin is nisin A and / or nisin Z. 21. A sponge according to any one of embodiments 1 to 20, wherein the liquid composition comprises one bacteriocin, which is nisin, in particular nisin A or nisin Z. 22. A method for producing a sponge, comprising: providing a sponge body having a porous sponge structure, said porous sponge structure forming at least a portion of an outer sponge surface; impregnating said porous sponge structure with a liquid composition comprising one or more bacteriocins to obtain a sponge according to any one of embodiments 1 to 21; A method comprising: 23. A liquid composition suitable for the vaginal tract, comprising one or more bacteriocins in an amount that promotes the vaginal microflora by inhibiting the growth of one or more pathogens. 24. The liquid composition of embodiment 23, wherein the composition has a pH value of 3.5 to 5.5. 25. A liquid composition according to embodiment 23 or 24, wherein the composition does not contain Lactobacilli, in particular the composition does not contain bacteria. 26. A liquid composition according to any one of embodiments 23 to 25, wherein the one or more bacteriocins comprise nisin. 27. A liquid composition according to any one of embodiments 23 to 26, wherein the liquid composition is an impregnating agent for a porous sponge. 28. A liquid composition according to any one of embodiments 23 to 27, wherein the liquid composition comprises a fixed amount of the one or more bacteriocins. 29. A liquid composition according to any one of embodiments 23 to 28, wherein the liquid composition comprises one bacteriocin. 30. The liquid composition of any one of embodiments 23 to 29, wherein the one or more bacteriocins comprises nisin. 31. The liquid composition according to embodiment 30, wherein the nisin is nisin A and / or nisin Z. 32. A liquid composition according to any one of embodiments 23 to 31, wherein the liquid composition comprises one bacteriocin, which is nisin, in particular nisin A or nisin Z. 33. A liquid composition according to any one of embodiments 23 to 32, wherein the one or more pathogens are selected from S. aureus, Candida spp, Gardnerella vaginalis, and combinations thereof. 34. The one or more bacteriocins are 0.0001% (v / v) to 0.005% (v / v), 0.0002% (v / v) to 0.002% (v / v), 0.0004% (v / v) to 0.001% (v / v), 0.0005% (v / v) to 0.0014% (v / v), 0.0001% (v / v) to 0.0005% (v / v), or 0.0014% (v / v) to 0.008% (v / v). 34. The liquid composition of any one of embodiments 23 to 33, wherein the one or more bacteriocins are present at a total concentration in the liquid composition of from 0.0006% (v / v) to 0.0013, 0.0007% (v / v) to 0.0012%, 0.0008% (v / v) to 0.0011%, or 0.0009% (v / v) to 0.0010%. 35. A liquid composition according to any one of embodiments 23 to 34, wherein the liquid composition selectively inhibits the growth of one or more pathogens. 36. A liquid composition according to any one of embodiments 23 to 35, wherein the liquid composition exhibits at least 10-fold or greater inhibition of one or more pathogens over L. gasseri and / or L. crispatus over a period of 8 hours, and in particular, the liquid composition exhibits at least 10-fold or greater, more particularly at least 50-fold, and even more particularly at least 100-fold inhibition of Gardnerella vaginalis over L. gasseri and / or L. crispatus over a period of 8 hours. 37. The liquid composition of any one of embodiments 23 to 36, wherein the one or more bacteriocins are further defined in any one of embodiments 12 to 15. 38. A liquid composition according to any one of embodiments 23 to 37, wherein the composition is a gel, a solution, or a lubricant, in particular, the composition is a gel. 39. A liquid composition according to any one of embodiments 23 to 38, wherein the liquid composition is a gel, and the gel further comprises a polysaccharide, in particular, the polysaccharide is glucomannan. 40. A liquid composition according to any one of embodiments 23 to 39, wherein the composition further comprises lactic acid, for example, in an amount such that the pH of the composition is 3.5 to 5.5, or 3.7 to 5, or 3.9 to 4.5, or about 4.2. 41. A liquid composition according to any one of embodiments 23 to 40, wherein the composition inhibits the growth of one or more pathogens during menstruation, the follicular phase, the luteal phase, and / or pregnancy. 42. A sponge according to any one of embodiments 1 to 21 or a liquid composition according to any one of embodiments 23 to 41 for inhibiting the growth of one or more pathogens associated with disorders or diseases of the vaginal tract. 43. A sponge according to any one of embodiments 1 to 21 or a liquid composition according to any one of embodiments 23 to 41 for use in the prevention or treatment of intestinal dysbiosis. 44. A sponge according to any one of embodiments 1 to 21 or a liquid composition according to any one of embodiments 23 to 41 for use in the prevention or treatment of vulvovaginal candidiasis. 45. A sponge according to any one of embodiments 1 to 21 or a liquid composition according to any one of embodiments 23 to 41 for use in the prevention or treatment of bacterial vaginosis. 46. ​​A sponge according to any one of embodiments 1 to 21 or a liquid composition according to any one of embodiments 23 to 41 for use in the prevention of toxic shock syndrome. [Example]

[0106] The following examples are intended to further illustrate, but not limit, the present invention. The examples illustrate technical features, and the present invention also relates to combinations of technical features presented in this section.

[0107] Example 1 - Bacteriocin-impregnated porous sponge inhibits the growth of S. aureus and Candida albicans

[0108] The purpose of this example was to determine the effect of test substances on the growth of yeast or bacterial cultures. Specifically, the effect of various substances was tested for inhibition against pathogenic bacteria in order to identify substances beneficial for impregnation of porous sponge tampons.

[0109] method The fungistatic effect of menstrual sponges against Candida albicans ATCC10231 was evaluated. Furthermore, the antibacterial effect of menstrual sponges against S. aureus and Lactobacillus crispatus was evaluated. The tampon sack method, as described in Nonfoux L, et al. (2018) [7], was used. Briefly, a wet konjac sponge (glucomannan) sample (regular size with an absorbency of 6-9 ml) was inserted into a 532 ml sterile plastic bag containing 10 ml of brain heart infusion (BHI) broth for experiments with Candida spp. ATCC10231 or Lactobacillus crispatus. For experiments with S. aureus, a wet konjac sponge (glucomannan) sample was inserted into a 532 ml sterile plastic bag containing 10 ml of BHI broth infused with sheep's blood (BHI and sheep's blood were mixed at a 1:1 ratio). The solution contained 10 ml of BHI broth. 5The pouches were inoculated with CFU / ml of Candida spp., ATCC10231, Lactobacillus crispatus, and S. aureus (e.g., S. aureus ST20140321). Excess air introduced during insertion of the product into the pouch was removed by manual deflating, and the pouch was then sealed. One pouch containing inoculated BHI broth without a sponge served as a positive control. The pouches were incubated vertically at 37°C with shaking (approximately 200 rpm) for 8 or 48 hours. At the end of the incubation period, 4 mL of solution was withdrawn from the plastic pouch. A tampon was kneaded inside the pouch for 5 seconds, and the liquid was squeezed out by compressing the tampon and collected for bacterial quantification as follows: The number of yeast / bacteria in the solution was estimated by standard spread-plate techniques using trypticase soy agar. Colonies were counted after 8, 24, and 48 hours of incubation at 30°C in an aerobic atmosphere.

[0110] result Various different types of potentially beneficial substances were tested to determine the selective inhibition of pathogenic bacteria or yeast. Surprisingly, bacteriocins were identified as being highly beneficial for inhibiting pathogens, while not inhibiting Lactobacilli. Natamycin is a known antifungal compound / drug used, for example, to treat fungal infections around the eyes. Therefore, natamycin is expected to exhibit fungistatic effects even in the tampon-sack method. When natamycin derived from Streptomyces species was tested for the inhibition of Candida albicans using the tampon-sack method, natamycin showed no inhibitory effect (data not shown).

[0111] Similarly, polylysine has been reported to have antibacterial effects against yeast, fungi, and bacteria. However, when tested using the tampon sack method, the antibacterial effect against S. aureus was not detected. Specifically, the growth of S. aureus was reduced by 1.0 × 10 7 to 2.3 x 10 8Therefore, although polylysine was expected to have an inhibitory effect on S. aureus, polylysine did not inhibit the growth of S. aureus.

[0112] In contrast, bacteriocins reliably inhibited pathogen growth. Specifically, impregnation of tampons with a liquid composition containing nisin and lactic acid at a pH of approximately 4.2 was tested. The composition reliably inhibited C. albicans after 8, 24, or 48 hours of incubation using the tampon sack method. Specifically, C. albicans growth was assessed in four individual cultures, and after 8 hours, it was reduced by 78%, 75%, 76%, and 73%. Furthermore, after 24 hours, C. albicans growth was reduced by 32%, 35%, 39%, and 28%, respectively. Furthermore, after 48 hours, C. albicans growth was reduced by 83%, 84%, and 87%, respectively. In summary, approximately 75% reduction was observed after 8 hours, approximately 30% reduction after 24 hours, and approximately 85% reduction after 48 hours. The percentages indicate the number of viable cells (colonies) compared to control cells grown without a menstrual sponge. The viability of the control cells corresponds to 100%.

[0113] In addition, the bacteriocin also effectively inhibited S. aureus. After 8 hours, the colony counts were detected as follows: [Table 1]

[0114] On average, the composition inhibited S. aureus by 2.6 logs 10 It was inhibited.

[0115] To confirm that the compositions do not inhibit vaginal Lactobacilli, they were also tested for inhibition against Lactobacillus crispatus: [Table 2]

[0116] On average, the composition slightly inhibited Lactobacillus crispatus, i.e., 10.95-fold, which is 1.04 log 10 is equivalent to

[0117] In summary, the tested bacteriocins potently inhibited the growth of Candida albicans and S. aureus, while Lactobacilli were inhibited only to a small extent. Thus, impregnating a tampon with a liquid composition containing one or more bacteriocins effectively inhibited Candida albicans and S. aureus. In contrast, other test substances previously reported to have antibacterial or antifungal effects did not have this effect.

[0118] Example 2 Bacteriocin-impregnated porous sponges are free of bacteria and inhibit the growth of Gardnerella vaginalis

[0119] The purpose of this example is to confirm that the impregnated porous sponge is free of bacteria. Separately, this example tests for inhibition of the growth of Gardnerella vaginalis.

[0120] Materials and Methods Bacterial strain: Gardnerella vaginalis ATCC49145.

[0121] Liquid culture medium and incubation method: Sterile BHI (brain heart infusion, Liofilchem, ref. 620008) solution supplemented with 1% D-glucose and 2% horse serum (Thermofisher Scientific, Oxoid, ref. SR0035). The inoculated medium was incubated in a 50 ml conical centrifuge tube (Thermofisher Scientific, Nunc) at 37°C in a vertical position without shaking. The tube was gently swirled several times during incubation. This method is considered equivalent to the tampon sac method.

[0122] Solid culture medium: sterilized chocolate agar and Vitox plates (Thermofisher Scientific, Oxoid, ref. PO5090A). Plates were incubated for 43 hours at 37°C in a 5% CO2 atmosphere provided by CO2 Gen 2.5L (Thermofisher Scientific, Oxoid, ref. CD0025A).

[0123] a) Bacteriocin-impregnated porous sponges are free of bacteria While other commercially available products may contain bacteriocins produced by bacteria within the product, the present invention relates to a porous sponge impregnated with a liquid composition comprising a bacteriocin, and ideally, the porous sponge is free of bacteria.

[0124] To confirm the absence of bacteria such as Lactobacilli in the porous sponges, three porous sponges (wet konjac sponges made from glucomannan) were incubated in a growth medium and tested for potential bacterial growth by counting potential colony-forming units (CFU). The sponges tested were impregnated with a liquid composition containing nisin and lactic acid at a pH value of about 4.2.

[0125] Specifically, three sponges were inserted into separate 50 ml sterile tubes. 10 ml of liquid culture medium was added to each tube. The control tube contained medium alone. After 24 hours of incubation at 37°C, the sponges were compressed several times using a sterile pipette tip. 200 μl of medium was removed from each tube and spread onto a culture plate. The plate was then evaluated. This method is considered equivalent to the tampon sac method.

[0126] All plates were found to be free of microbial colonies. Therefore, the sponges tested were not bacteriologically contaminated. It can therefore be concluded that the porous sponges tested were free of bacteria.

[0127] b) Bacteriocin-impregnated porous sponges inhibit the growth of Gardnerella vaginalis As Gardnerella vaginalis is the most common cause of bacterial vaginosis, the inventors also tested the inhibitory effect of the porous sponge on inhibiting the growth of Gardnerella vaginalis.

[0128] Two independent experiments (A and B) were performed. Each experiment compared bacterial growth with and without a sponge. A porous sponge (a moist konjac sponge made from glucomannan impregnated with a liquid composition containing nisin and lactic acid with a pH value of approximately 4.2) was inserted into the bottom of a 50 ml conical centrifuge tube. G. vaginalis ATCC49145 was retrieved from frozen storage, streaked onto a plate, and incubated. The optical density OD 600 The bacteria were suspended in liquid medium at a density of 0.12 (Tests A and B). Densities 100-fold and 10-fold lower did not result in adequate bacterial growth during preliminary testing.

[0129] 15 ml of the bacterial suspension was poured onto the sponge and 15 ml into the control tube. A serological pipette was used to wet the sponge evenly.

[0130] The tubes were either loosely screwed (A) or tightly screwed (B) in a 5% CO2 atmosphere and incubated at 37°C for 24 hours (Tests A and B). Because of the known slow growth rate of G. vaginalis, 8 hours of incubation was not considered for evaluation (Janulaitiene, 2018, Figure B in S2 File). After 24 hours of incubation, the sponge was compressed 10 times in the tube using the barrel of a sterile syringe. The OD of the suspension was measured. 600 0.5 ml of culture medium was removed from each tube and serial 10-fold dilutions of the culture were made in sterile PBS. -7100 μl of the suspension at the relevant dilution was plated in duplicate. Colonies were counted manually on plates suitable for reading. This count was used to calculate the colony-forming units per milliliter (CFU / ml) of the undiluted liquid culture. The bacterial growth inhibition factor was calculated by dividing the CFU / ml of the culture without the sponge by the CFU / ml of the sponge-incubated culture.

[0131] result: [Table 3]

[0132] [Table 4]

[0133] In these tests, the OD of the culture without the sponge 600 demonstrated sufficient growth potential of the starter G. vaginalis suspension. The tubes with sponges showed an OD 600 In conclusion, the growth of G. vaginalis ATCC 49145 was reduced by 3.6 × 10 when the porous sponge was impregnated with the liquid composition containing bacteriocin. 4 times 2.6 x 10 6 was inhibited 2-fold.

[0134] Example 3 - Solutions containing bacteriocins have an inhibitory effect on Gardnerella vaginalis.

[0135] The purpose of this example is to test the inhibitory effect of a composition containing a bacteriocin against Garnerella vaginalis, the main cause of bacterial vaginosis.

[0136] Materials and Methods In this example, a liquid solution containing nisin (also referred to as "Avodes solution") was tested. Additionally, the composition contained lactic acid with a pH value of approximately 4.2. The bacterial strain used in this example was Gardnerella vaginalis ATCC49145. The culture medium was liquid BHI (brain heart infusion) solution (Liofilchem) supplemented with horse serum (Thermofisher Scientific, Oxoid). Sterile chocolate agar (Thermofisher Scientific, Oxoid) was used as the solid medium. All experiments were performed at 37°C under anaerobic conditions provided by a CO2Gen 2.5 (Thermofisher Scientific, Oxoid) to mimic the conditions in the vaginal tract as closely as possible.

[0137] Ten ml of liquid medium was mixed with 6 ml of Avodes solution in a sterile glass tube. Each tube contained 4–6 × 10 cells at a final concentration. 5 Controls were (i) sterile glass tubes containing 10 ml of liquid medium without bacteria (negative control), (ii) tubes containing 10 ml of liquid medium containing bacteria at a final concentration of 4–6 × 10 CFU / ml. 5 (iii) a sterile glass tube containing 10 ml of liquid medium inoculated with CFU / ml of G. vaginalis (positive control), and (iv) a sterile 10 ml glass tube containing 6 ml of solution (solution control). After 8 and 24 hours of incubation, 100 μl of medium was removed from each tube, diluted (if necessary), and spread onto a culture plate. The results were evaluated after 48 hours of incubation. The provided solutions were sterile (no microbial colonies were present on the negative control plate).

[0138] [Table 5]

[0139] result This experiment shows that "Avodes Solution" had a significant inhibitory effect on the bacterial growth of Gardnerella vaginalis, even after incubation in growth medium at 37°C for several hours. The solution control showed an approximately 50-fold increase in CFU count after 8 hours, while the "Avodes Solution" reduced CFU count by approximately 2-fold after 8 hours. After 24 hours of incubation, the effect was even more dramatic: the solution control showed an approximately 7230-fold increase in CFU count after 24 hours, while the "Avodes Solution" showed only an approximately 22-fold increase in CFU count after 24 hours. The coefficient of inhibition of bacterial growth was 1.02 x 10 after 8 hours. 2 , and 3.18 × 10 after 24 hours. 4 This becomes:

[0140] These are very encouraging results, demonstrating that compositions containing bacteriocins effectively inhibit the growth of Gardnerella vaginalis, a major cause of bacterial vaginosis. Because Gardnerella vaginalis is often present in small numbers in the vaginal microbiota, compositions containing bacteriocins such as nisin are expected to effectively keep the number of Gardnerella vaginalis bacteria low and / or reduce the number of Gardnerella vaginalis bacteria. Importantly, this exemplary solution can strongly inhibit Gardnerella vaginalis while only slightly inhibiting bacteria that promote vaginal flora, such as Lactobacillus crispatus or Lactobacillus gasseri (see also the following examples).

[0141] Example 4 - Solutions and gels containing bacteriocins have a strong inhibitory effect on Gardnerella vaginalis and only a weak inhibitory effect on Lactobacillus spp.

[0142] The purpose of this example was to test the inhibitory effects of solutions and gels containing bacteriocins against Gardnerella vaginalis and Lactobacillus spp. Gardnerella vaginalis is the primary cause of bacterial vaginosis, so a strong inhibitory effect would be advantageous. In contrast, Lactobacillus spp. support the vaginal flora, so it would be advantageous if Lactobacillus spp. were not inhibited or only slightly inhibited. The potential selective effect of the solutions and gels was also tested.

[0143] Materials and Methods In this example, a liquid solution containing nisin was tested (also referred to as "Avodes solution"). Additionally, in this example, a gel containing nisin was tested (also referred to as "Avodes gel"). Avodes gel further contained glucomannan. Additionally, both compositions (solution and gel) contained lactic acid with a pH value of about 4.2. The bacterial strains used in this example were Gardnerella vaginalis ATCC49145, Lactobacillus crispatus DSM20584, and Lactobacillus gasseri DSM20243.

[0144] Culture conditions: Gardnerella vaginalis was grown using BHI (brain heart infusion, Sigma-Aldrich) supplemented with 1% D-glucose and 2% horse serum (Thermofisher Scientific, Oxoid). The inoculated medium was incubated in a sterile 15 ml conical centrifuge tube in a vertical position at 37°C without shaking. To determine CFU counts, plates were incubated on chocolate agar with Vitox plates (Thermofisher Scientific, Oxoid) using CO2Gen™ Compact Sachets (Thermofisher Scientific, Oxoid). Lactobacillus crispatus and Lactobacillus gasseri were grown in MRS broth containing Tween 80 (Biolife). The inoculated cultures were incubated in sterile 15 ml conical centrifuge tubes at 37°C in a vertical position without shaking and grown on MRS agar medium containing Tween 80 (Biolife) using CO2Gen™ Compact Sachets (Thermofisher Scientific, Oxoid).

[0145] 0.5 ml of Avodes solution and 0.5 ml of Avodes gel were separately diluted with 1 ml of MRS or 1 ml of BHI culture medium in a 24-well plate and incubated at 37°C for 24 hours. Controls contained the respective medium alone. 200 μl of medium was removed from each well and spread onto the culture plate. The plate was evaluated after incubation.

[0146] To evaluate the effect on G. vaginalis inhibition, two independent tests (Test A, Test B) were performed using Avodes solution and one test using Avodes gel, which were then compared with the respective media and a control containing sodium lactate and lactic acid, maintaining a pH of 4.2. One mL of Avodes solution was transferred to a 24-well plate and mixed with 1 mL of G. vaginalis inoculum in BHI broth supplemented with 1% D-glucose and 2% horse serum, to a final concentration of 10. 5CFU / ml. Plates were incubated at 37°C for 8 and 24 hours with CO2Gen™ Compact Sachets to maintain anaerobic conditions. After incubation, serial 10-fold dilutions of the culture in sterile PBS were plated on chocolate agar at 10 -9 The plates were prepared twice. Colonies were counted manually on plates suitable for reading. This count was used to calculate the colony-forming units per milliliter (CFU / ml) of the undiluted liquid culture. result: [Table 6]

[0147] These results demonstrate that the compositions (solution or gel) significantly inhibit the growth of Gardnerella vaginalis. Thus, these results further support the data from the previous examples. In addition, the data demonstrate that the inhibitory effect was 2.01 x 10 after 8 hours. 4 times, and after 24 hours it is 3.29 × 10 5 The gels are even more advantageous because they are even more effective than the nisin gels. This demonstrates that the nisin-containing gels particularly potently inhibit the growth of Gardnerella vaginalis. The data reflected in the table above are also shown in Figure 9.

[0148] [Table 7]

[0149] Evaluation of growth inhibition of L. gasseri To evaluate the effect on L. gasseri inhibition, two independent tests (Test A, Test B) were performed using Avodes solution and one test using Avodes gel, which were then compared with the respective media and a control containing sodium lactate and lactic acid, maintaining a pH of 4.2. 1 mL of Avodes solution was transferred to a 24-well plate and mixed with 1 mL of L. gasseri inoculum in MRS broth to a final concentration of 10.5 CFU / ml. Plates were incubated at 37°C for 8 and 24 hours with CO2Gen™ Compact Sachets to maintain anaerobic conditions. After incubation, serial 10-fold dilutions of the culture in sterile PBS were plated on chocolate agar at 10 -9 The plates were prepared twice. Colonies were counted manually on plates suitable for reading. This count was used to calculate the colony-forming units per milliliter (CFU / ml) of the undiluted liquid culture. result: [Table 8]

[0150] This data indicates that Lactobacilli, such as L. gasseri, are only very slightly inhibited by Avodes Solution. For example, it is particularly advantageous that the solution only slightly inhibits Lactobacilli, while very strongly inhibiting Gardnerella vaginalis, because L. gasseri supports a healthy vaginal microbiota. This selective inhibition is surprising and unexpected.

[0151] Evaluation of growth inhibition of L. crispatus To evaluate the effect on L. crispatus, two independent tests (Test A, Test B) were performed with Avodes solution and one test with Avodes gel, which were then compared to a control containing medium and sodium lactate and lactic acid, maintaining a pH of 4.2. 1 mL of Avodes solution was transferred to a 24-well plate and mixed with 1 mL of L. gasseri inoculum in MRS broth to a final concentration of 10. 5 CFU / ml. Plates were incubated at 37°C for 8 and 24 hours with CO2Gen™ Compact Sachets to maintain anaerobic conditions. After incubation, serial 10-fold dilutions of the culture in sterile PBS were plated on chocolate agar at 10 -9The plates were prepared twice. Colonies were counted manually on plates suitable for reading. This count was used to calculate the colony-forming units per milliliter (CFU / ml) of the undiluted liquid culture. result: [Table 9] [Table 10]

[0152] This data further supports the finding that not only L. gasseri but also L. crispatus is very slightly or not at all inhibited by the bacteriocin-containing composition. Notably, the gel inhibited both Lactobacilli tested either not at all or very slightly. In summary, the data demonstrate that the composition (solution or gel) selectively inhibits bacteria: the composition potently inhibits Gardnerella vaginalis and only very slightly inhibits Lactobacilli. Additionally, the gel promoted the growth of L. crispatus by at least 1 log unit, i.e., at least 10-fold. This selective inhibition is expected to support the natural microflora of the vaginal tract. Due to its potent effect, this selective inhibition is also expected to prevent bacterial vaginosis, candidiasis, and / or intestinal dysbiosis. Due to its potent effect, this selective inhibition is also expected to treat bacterial vaginosis, candidiasis, and / or intestinal dysbiosis.

[0153] References 1. J. Yano, JD Sobel et al. Current patient perspectives of vulvovaginal candidiasis: incidence, symptoms, management and posttreatment outcomes. 2019 Mar 29;19(1):48. doi: 10.1186 / s12905-019-0748-8. 2. F. Bernardis et al. Candida vaginitis: virulence, host response and vaccine prospects. Med Mycol. 2018 Apr 1;56(suppl_1):26-31.doi: 10.1093 / mmy / myx139. 3. J.D. Sobel Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol. 1998 Feb;178(2):203-11.doi: 10.1016 / s0002-9378(98)80001-x. 4. E. Gillet et al. Bacterial vaginosis is associated with uterine cervical human papillomavirus infection: a meta-analysis. BMC Infect Dis. 2011; 11: 10. doi: 10.1186 / 1471-2334-11-10, https: / / www.ncbi.nlm.nih.gov / pmc / articles / PMC3023697 / 5. F.M.T. Lewis et al. Vaginal Microbiome and Its Relationship to Behavior, Sexual Health, and Sexually Transmitted Diseases. Obstet Gynecol. Author manuscript; available in PMC 2019 Sep 13. doi: 10.1097 / AOG.0000000000001932 6. K. Peebles et al. High Global Burden and Costs of Bacterial Vaginosis: A Systematic Review and Meta-Analysis. Sex Transm Dis. 2019 May;46(5):304-311. doi: 10.1097 / OLQ.0000000000000972. 7. J. D. Sobel Bacterial vaginosis. Annu Rev Med. 2000;51:349-56.doi: 10.1146 / annurev.med.51.1.349. 8. M. Petrova et al. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Front Physiol. 2015; 6: 81.doi: 10.3389 / fphys.2015.00081 9. J. Kaewsrichan et al. Selection and identification of anaerobic lactobacilli producing inhibitory compounds against vaginal pathogens. FEMS Immunol Med Microbiol. 2006 Oct;48(1):75-83.doi: 10.1111 / j.1574-695X.2006.00124.x. 10. J. Garza et al. Cytokine profiles and Lactobacillus species presence in prie-menopausal subjects with genital Mycoplasma genitalium or Ureaplasma urealyticum colonization. Womens Health (Lond). 2021; 17: 17455065211009181. doi: 10.1177 / 17455065211009181 11. W.Mendling. Vaginal Microbiota Adv Exp Med Biol . 2016;902:83-93. doi: 10.1007 / 978-3-319-31248-4_6. 12. A. Kiecka. Can Lactobacillus spp. be a Factor Reducing the Risk of Miscarriage? Pol J Microbiol. 2021 Dec; 70(4): 431-446; Eckert LO et. al. Relationship of vaginal bacteria and inflammation with conception and early pregnancy loss following in vitro fertilization. Infect Dis Obstet Gynecol. (2003) 11:11-7. 13. Amabebe E, Anumba DOC. The Vaginal Microenvironment: The Physiologic Role of Lactobacilli. Front Med (Lausanne). 2018 Jun 13;5:181 14. D. Eschenbach et al. Influence of the Normal Menstrual Cycle on Vaginal Tissue, Discharge, and Microflora. Clinical Infectious Diseases, Volume 30, Issue 6, June 2000, Pages 901-907 15. S. Srinivasan et al. Temporal Variability of Human Vaginal Bacteria and Relationship with Bacterial Vaginosis. PLoS One. 2010; 5(4): e10197 16. C. Bradshaw, J.D. Sobel Current Treatment of Bacterial Vaginosis-Limitations and Need for Innovation. J Infect Dis. 2016 Aug 15; 214(Suppl 1): S14-S20. doi: 10.1093 / infdis / jiw159 17. J. Sobel Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol. 2016 Jan;214(1):15-21. doi: 10.1016 / j.ajog.2015.06.067. Epub 2015 Jul 9. 18. Vostral, SL, 2011. Rely and Toxic Shock Syndrome: A Technological Health Crisis Yale J. Biol. Med. 84, 447- 459 19. Nicole, W., 2014. A Question for Women’s Health: Chemicals in Feminine Lubricants, Environmental Health Perspect 122, A70-75 20. Nonfoux L, et al. Impact of Currently Marketed Tampons and Menstrual Cups on Staphylococcus aureus Growth and Toxic Shock Syndrome Toxin 1 Production In Vitro. Appl Environ Microbiol. 2018 May 31;84(12):e00351-18 21. S. Srinivasan et al. Temporal Variability of Human Vaginal Bacteria and Relationship with Bacterial Vaginosis. PLoS One. 2010; 5(4): e10197 22. Janulaitiene M, Gegzna V, Baranauskiene L, Bulavaite A, Simanavicius M, Pleckaityte M. Phenotypic characterization of Gardnerella vaginalis subgroups suggests differences in their virulence potential. PLoS One. 2018 Jul 12;13(7):e0200625. doi: 10.1371 / journal.pone.0200625. eCollection 2018. 23. J. Sobel et al. Conventional oral and secondary high dose vaginal metroni-dazole therapy for recurrent bacterial vaginosis: clinical outcomes, im-pacts of sex and menses. Infect Drug Resist. 2019; 12: 2297-2307. Published online 2019 Jul 24.

Claims

1. 1. A sponge for the vaginal canal, comprising: A sponge body having a porous structure, said porous sponge structure forming at least a part of the sponge outer surface. Equipped with the porous sponge structure is made of a polysaccharide-based material, including glucomannan; the sponge is free of bacteria; The sponge body is impregnated with a liquid composition comprising one or more bacteriocins. sponge.

2. The sponge of claim 1 , wherein the liquid composition comprises a fixed amount of the one or more bacteriocins.

3. 3. The sponge of claim 1 or 2, wherein the sponge is wettable.

4. 4. The sponge of claim 1, wherein the polysaccharide-based material is glucomannan.

5. The sponge of claim 1 , wherein the sponge is a tampon.

6. 6. The sponge of any one of claims 1 to 5, wherein the sponge body impregnated with the composition promotes vaginal microflora during menstruation, the follicular phase, the luteal phase, and / or pregnancy.

7. 7. The sponge of any one of claims 1 to 6, wherein the sponge body impregnated with the composition promotes the vaginal microflora by inhibiting the growth of pathogens, in particular S. aureus, Candida spp., and / or Gardnerella vaginalis, more particularly wherein the growth of the pathogens is inhibited at least 10 times more than the growth of L. gasseri and / or L. crispatus over a period of 8 hours.

8. 8. The sponge of claim 7, wherein the porous sponge structure impregnated with the composition inhibits the growth of Gardnerella vaginalis compared to medium alone under the same conditions, the growth being inhibited by at least 50 fold, at least 100 fold, or at least 250 fold, or at least 500 fold, or at least 1000 fold, or at least 5000 fold, or at least 10000 fold, or at least 20000 fold when tested after 24 hours by the tampon sack method.

9. 9. The sponge of any one of claims 1 to 8, wherein the sponge body impregnated with the composition inhibits the growth of Lactobacillus spp. by up to 12 fold when tested after 8 hours by the tampon sack method compared to medium alone under the same conditions.

10. 10. The sponge of any one of claims 1 to 9, wherein the liquid composition comprises an effective amount of one or more bacteriocins, in particular, said effective amount inhibiting the growth of Gardnerella vaginalis, S. aureus, and / or Candida spp.

11. 11. The sponge of claim 1, wherein the one or more bacteriocins are selected from Class I, Class II, Class II, and Class IV bacteriocins from Gram-positive bacteria, e.g., the one or more bacteriocins are selected from Class I and / or Class II bacteriocins from Gram-positive bacteria.

12. 12. The sponge of claim 1, wherein the liquid composition comprises one bacteriocin.

13. 13. The sponge of any one of claims 1 to 12, wherein the one or more bacteriocins comprise nisin.

14. 14. The sponge of claim 13, wherein the nisin is nisin A and / or nisin Z.

15. 15. The sponge of any one of claims 1 to 14, wherein the liquid composition comprises one bacteriocin, which is nisin, in particular nisin A or nisin Z.

16. 16. The sponge of any one of claims 1 to 15, wherein the composition further comprises lactic acid, for example in an amount such that the pH of the composition is 3.5 to 5.5, or 3.7 to 5, or 3.9 to 4.5, or about 4.

2.

17. 1. A method of making a sponge, comprising: providing a sponge body having a porous sponge structure, said porous sponge structure forming at least a portion of an outer sponge surface; impregnating the porous sponge structure with a liquid composition comprising one or more bacteriocins to obtain a sponge according to any one of claims 1 to 16; A method comprising:

18. 1. A liquid composition suitable for the vaginal tract comprising one or more bacteriocins in an amount that promotes the vaginal microflora by inhibiting the growth of one or more pathogens, the composition has a pH value of 3.5 to 5.5; The composition is free of bacteria, the one or more bacteriocins include nisin; liquid composition.

19. 20. The liquid composition of claim 18, wherein the composition is an impregnating agent for a porous sponge.

20. 20. The liquid composition of claim 18 or 19, wherein the composition comprises a fixed amount of the one or more bacteriocins.

21. 21. The liquid composition of any one of claims 18 to 20, wherein the liquid composition comprises one bacteriocin.

22. 22. The liquid composition of claim 21 , wherein the one bacteriocin is nisin, in particular nisin A or nisin Z.

23. 23. The liquid composition of any one of claims 18 to 22, wherein the one or more pathogens are selected from S. aureus, Candida spp, Gardnerella vaginalis, and combinations thereof.

24. The one or more bacteriocins may be present in an amount of from 0.0001% (v / v) to 0.005% (v / v), from 0.0002% (v / v) to 0.002% (v / v), from 0.0004% (v / v) to 0.001% (v / v), from 0.0005% (v / v) to 0.0014% (v / v), from 0.0001% (v / v) to 0.0005% (v / v), or from 0.0014% (v / v) to 0.008% (v / v).

24. A liquid composition according to any one of claims 18 to 23, wherein the one or more bacteriocins are present at a total concentration in the liquid composition of from 0.0006% (v / v) to 0.0013, 0.0007% (v / v) to 0.0012%, 0.0008% (v / v) to 0.0011%, or 0.0009% (v / v) to 0.0010%.

25. 25. The liquid composition according to any one of claims 18 to 24, wherein the liquid composition is a gel, a solution or a lubricant, in particular the composition is a gel.

26. 26. The liquid composition of any one of claims 18 to 25, wherein the liquid composition is a gel, and the gel further comprises glucomannan.

27. 27. The liquid composition of any one of claims 18 to 26, wherein the composition further comprises lactic acid, for example, in an amount such that the pH of the composition is 3.5 to 5.5, or 3.7 to 5, or 3.9 to 4.5, or about 4.

2.

28. 27. The liquid composition of any one of claims 18 to 26, wherein the composition inhibits the growth of one or more pathogens during menstruation, the follicular phase, the luteal phase, and / or pregnancy.

29. 28. A sponge according to any one of claims 1 to 16 or a liquid composition according to any one of claims 18 to 27 for inhibiting the growth of one or more pathogens associated with disorders or diseases of the vaginal tract.

30. 28. A sponge according to any one of claims 1 to 16 or a liquid composition according to any one of claims 18 to 27 for use in the prevention or treatment of intestinal dysbiosis.

31. 28. A sponge according to any one of claims 1 to 16 or a liquid composition according to any one of claims 18 to 27 for use in the prevention or treatment of vulvovaginal candidiasis and / or bacterial vaginosis.

32. 28. A sponge according to any one of claims 1 to 16 or a liquid composition according to any one of claims 18 to 27 for use in the prevention of toxic shock syndrome.

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