WO2024061444A1 - Éponge pour canal vaginal - Google Patents
Éponge pour canal vaginal Download PDFInfo
- Publication number
- WO2024061444A1 WO2024061444A1 PCT/EP2022/076032 EP2022076032W WO2024061444A1 WO 2024061444 A1 WO2024061444 A1 WO 2024061444A1 EP 2022076032 W EP2022076032 W EP 2022076032W WO 2024061444 A1 WO2024061444 A1 WO 2024061444A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sponge
- composition
- growth
- bacteriocin
- vaginal
- Prior art date
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
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- LROWVYNUWKVTCU-STWYSWDKSA-M sodium sorbate Chemical compound [Na+].C\C=C\C=C\C([O-])=O LROWVYNUWKVTCU-STWYSWDKSA-M 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000006150 trypticase soy agar Substances 0.000 description 1
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
- A61K9/0036—Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/164—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/425—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
Definitions
- the present invention relates to a sponge for the vaginal canal, which can be used as a tampon, wherein said sponge recovers the balance of the healthy vaginal microbiota (dominated by Lactobacilli), by selectively inhibiting pathogens (like Candida, S.aureus and others) and preserving Lactobacilli spp.
- Bacterial vaginosis is the most common vaginal infection (inflammation) among women of reproductive age and is associated with devastating health issues preterm births, human immunodeficiency virus, risk of sexually transmitted diseases (STD), risk of human papillomavirus [4, 5].
- General population prevalence of BV is high globally, ranging from 23% to 29% each year [6].
- BV-associated adverse obstetric outcomes ranges from 8% to 51%.
- Bacterial vaginosis appears, when Lactobacilli disappears and microflora is overgrown by Gardnerella vaginalis and resident anaerobic vaginal bac- teria [7].
- Lactobacilli Several species of Lactobacilli dominate the healthy vagina, sup- port a defense system and inhibits fungus (e.g. C. albicans') and pathogenic bacterial growth by competing for nutrients, preventing adhesion, and excreting antimicrobial compounds, like bacteriocins, bacteriocin-like substances (like H2O2) and others [8, 9]. Diminished dominance of Lactobacillus, cause a variety of immunological changes such as the production of pro-inflammatory cytokines/chemokines, greater recruitment of immune cells, and changes to the vaginal lining [10].
- fungus e.g. C. albicans'
- pathogenic bacterial growth by competing for nutrients, preventing adhesion, and excreting antimicrobial compounds, like bacteriocins, bacteriocin-like substances (like H2O2) and others [8, 9]. Diminished dominance of Lactobacillus, cause a variety of immunological changes such as the production of
- a Lactobacilli dominated microbiota is capable of expressing anti-infection protective factors inhibiting yeast/bacteria growth.
- Vaginal microbiota dysbiosis when Lactobacilli spp. are outcompeted by other bacteria species, often is a cause of gynaecological diseases.
- bacterial and fungal infections are favored when the vaginal mi- crobiota is not in balance.
- Vaginal infections affect millions of women each year and these infections often cause vaginal dysbiosis - a misbalance of the vaginal microflora often causing inflammation and/or infection.
- vaginal microbiota are complex ecosystems of more than 200 bacterial species influenced for example by genes, environmental and behav- ioral factors[ll]. Vaginal dysbiosis (or absence of Lactobacilli) and infection are even believed to account of 25-40% of preterm births. Strong deficiency of vaginal Lacto- bacilli are associated with serious reproductive concerns such as miscarriages and hampered in vitro fertilization (IVF) [12]. Furthermore, there is a high (30-40%) prev- alence of abnormal vaginal microbiota in women undergoing IVF [13].
- Lactobacilli are suppressed due to increased pH of the vaginal environment and other factors, resulting in 100-fold decrease in population, which can then be overgrown by pathogens [13, 14].
- An increase in bacteria such as G. vaginalis is associated with menstruation, accompanied by decreased quantities of L. crispatus and other Lactobacilli were observed in healthy women with Lactobacilli dominance over the rest of the cycle [15].
- Lactobacilli restore after menstrua- tion unless the vaginal environment is impaired by other factors such as stress, medi- cation, hormonal contraception, use of menstrual products.
- TSS toxic shock syndrome
- TSS toxic shock syndrome toxin 1
- S.aureus Staphylococcus au- reus bacteria
- S.aureus growth is for example facilitated when the vaginal pH changes and when other unfavourable condi- tions come into play.
- some materials of the tampon may facilitate vaginal colonization or infection more than others [18].
- high absorbency can cause toxic shock syndrome, since particularly short, straight sharp fibres damage the vaginal mucosa and toxin produced by S. aureus is rapidly transferred through the body.
- Toxic shock syndrome can progress rapidly and complications may include shock, renal fail- ure and death.
- Conventional hygienic tampons are made of synthetic materials, polymeric foam layer, cotton or rayon, that during production and bleaching emit dioxin, a health and envi- ronmentally hazardous pesticide [19].
- cotton tampons which usually absorb too much moisture from the vaginal mucosa (causing over-drying of the tissue).
- Fur- thermore they are made up of small and sharp fibres that damage the vaginal mucosa and natural microflora.
- Such tampons can leave small cotton fragments in the vagina together with old blood particles, which can also damage the vaginal pH and cause an infection.
- EP 2 448 536 Al describes a compressed menstrual tampon comprises an elongated rod-shaped body with a filler having an insertion end and a withdrawal end having a withdrawal string.
- the absorbent body with the filler expands as the fluids are ab- sorbed and can be made from viscose, cotton, or cellulose pulp.
- the absorbent body with the filler may also comprise or consist of an absorbent sponge.
- the tampon also includes means to ease the insertion, such as an applicator that conforms to the tam- pon shape, from which the tampon can be expelled.
- WO 1992/013577 Al discloses a tampon or sanitary napkin to be used prophylactically against e.g. vaginal infections. Hence, said disclosure has the aim to prevent vaginal infections by introducing a culture of at least one lactic acid producing bacteria, such as Lactobacilli, into the tampon.
- EP 3 064 072 Al discloses a composition comprising a bacterial culture of an isolated strain of Lactobacillus is used to prevent e.g. Candidiasis.
- said disclosure is not concerned with a porous sponge structure or with the impregnation of the tampon with bacteriocins.
- Lactobacilli when introducing Lactobacilli into a product it is as- sumed that the bacteria support the microflora.
- the vaginal pH- Level is, however, near neutral so that Lactobacilli are not in their preferred environ- ment, which is acidic. Hence, Lactobacilli do not multiply under these conditions and the supportive effect for the microflora is probably marginal.
- WO 2020/003113 Al and US 2021/0121596 Al disclose a tampon made of a porous sponge structure of naturally derived glucomannan. Said tampon is soft and avoids damage to the vaginal mucosa by being moist, soft and deformable.
- One or more of the above objects is achieved by impregnating a porous sponge body with a liquid composition comprising one or more bacteriocin(s).
- This present invention provides a sponge for the vaginal canal comprising a sponge body having a porous sponge structure, as further defined in the claims.
- the porous sponge body forms at least part of a sponge outer surface.
- the porous sponge body is impregnated with a liquid composition comprising one or more bacte- riocin(s).
- the present invention also provides a liquid composition suitable for the vag- inal canal comprising one or more bacteriocin(s) in an amount which promotes the vaginal microflora by inhibiting the growth of one or more pathogen(s).
- said one or more pathogens is selected from S.aureus, Candida spp, Gardnerella vaginalis and combinations thereof.
- the liquid composition is an impregnant of a porous sponge.
- the one or more bacteriocin(s) is/are synthesised.
- said bacteriocins may be synthesised in a bacterial strain, such as Lactobacilli.
- bacteriocins may be synthesised by E.coli.
- nisin may be produced by E.collor Lactobacilli.
- said bacteriocins may be synthesised chemically.
- the sponge does not comprise Lactobacilli.
- the sponge is a tampon.
- the tampon may be a menstrual tampon.
- the sponge body impregnated with the composition promotes the vaginal microflora during menstruation, during follicular phase, during luteal phase and/or during pregnancy.
- the composition promotes the vaginal microflora by inhibiting the growth of pathogens, in particular S.aureus, Candida spp and/or Gardnerella vaginalis .
- pathogens in particular S.aureus, Candida spp and/or Gardnerella vaginalis .
- the term 'growth' refers to an increase in number.
- the growth of a pathogen refers to the increase in number of the pathogen in the vaginal canal
- the porous sponge structure impregnated with the composi- tion inhibits the growth of S. aureus compared to medium alone under the same con- ditions.
- the tampon sac method may be used to test the growth of S.aureus, Candida spp. and/or Gardnerella vaginalis. Said method is for example disclosed in Nonfoux et al. (2016) [20] and as further described in Example 1 herein.
- the pathogenic growth is generally assessed by inserting tampons/sponges in sterile plastic bags, adding medium such as BHI broth to the bags, inoculating the medium with a pathogen, and assessing the growth of the pathogen after incubation.
- a bag containing inoculated medium without a tampon/sponge is generally used.
- 'medium alone' means that the medium is inoculated with a pathogen, such as S.aureus, Candida spp and/or Gardnerella vaginalis, and that no porous sponge structure is present. Otherwise the conditions for comparing the growth of the pathogen are the same, such as the temperature of incubation, the length of incubation, the medium, and the inoculation.
- the combination of the sponge and the impregnation can be compared to inoculated medium.
- the 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; tested after 8h by the tampon sac method.
- the porous sponge structure impregnated with the composi- tion inhibits the growth of Candida spp. compared to medium alone under the same conditions.
- the 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%; tested after 8h by the tampon sac method.
- the porous sponge structure impregnated with the composi- tion inhibits the growth of Gardnerella vaginalis compared to medium alone under the same conditions.
- said growth of Gardnerella vaginalis is inhib- ited 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; tested after 24h by the tampon sac method.
- the porous sponge structure impregnated with the composi- tion inhibits the growth of Lactobacilli spp. compared to medium alone under the same conditions. In some embodiments, said growth of Lactobacilli spp. is inhibited by at most 12-fold; tested after 8h by the tampon sac method.
- said one or more bacteriocin(s) is/are selected from Class I, Class II, Class II, and Class IV bacteriocins from Gram-positive bacteria. In some em- bodiments, said one or more bacteriocin(s) is/are selected from Class I and/or Class II bacteriocin from Gram-positive bacteria.
- the one or more bacteriocin(s) is/are a lantibiotic. In some embodiments, the one or more bacteriocin(s) is/are a Type A or B lantibiotic.
- the one or more bacteriocin(s) is a Class II bacteriocin. In some embodiments, the Class II bacteriocin is a one-peptide bacteriocin or a two- peptide bacteriocin. In certain embodiments, the one or more bacteriocin(s) is/are a Class Ila bacteriocin. In some embodiments, the Class Ila bacteriocin is a circular bacteriocin.
- the composition further comprises lactic acid.
- the composition comprises lactic acid in a suitable amount to provide a pH value of said composition from 3.5 to 5.5, or from 3.7 to 5, or from 3.9 to 4.5, or around 4.2, In these embodiments, the lactic acid promotes the natural Lactobacilli of the microbiota by ensuring an acidic pH.
- the porous sponge structure is made of a natural or synthetic fibers. Especially, the porous sponge structure may be made out 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 glucomannan-based sponge material. In some embodiments, the polysaccharide-based material is or comprises glucomannan.
- 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 part of a sponge outer surface; and impregnating said sponge body with a liquid composition comprising one or more bacterioci n(s) to obtain the sponge for the vaginal canal as disclosed herein.
- the present invention also relates to the sponge as disclosed herein or the liquid com- position as disclosed for inhibiting the growth of one or more pathogen(s) associated with a disorder or disease of the vaginal canal.
- Yet another aspect of the present invention provides a sponge for the vaginal canal as disclosed herein for use in preventing or treating dysbiosis. Furthermore, the present invention relates to a sponge for use in preventing or treating vulvovaginal candidiasis, and/or bacterial vaginosis. Moreover, the present invention relates to a sponge for use in preventing toxic shock syndrome.
- liquid composition as described herein for use in preventing or treating dysbiosis is disclosed.
- a liquid composition as described herein for use in preventing or treating vulvovaginal candidiasis, and/or bacterial vaginosis is disclosed.
- a liquid composition as described herein for use in preventing toxic shock syndrome is disclosed.
- the one or more bacteriocin(s) are present at a total concen- tration of the liquid composition of 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).
- the liquid composition is a gel or a lubricant.
- a sponge for the vaginal canal according to the present invention is impregnated with a liquid composition comprising one or more bacteriocins.
- a liquid composition com- prising said one or more bacteriocins is also disclosed.
- the bacteriocins are effective in promoting the 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.
- the bacteriocins are present in an amount so that the vaginal microflora is also promoted by inhibiting Lactobacilli only to a minor degree (see Ex- ample 1).
- a liquid composition comprising one or more bacteriocin(s):
- the vaginal mucosa is not dried, the natural vaginal pH is maintained as much as possible also during menstruation, and the supplied bacteriocins support the vaginal microflora by promoting the microflora and/or inhibiting the growth of pathogens.
- the vaginal pH is near the pH of blood (pH 7) and not acidic.
- the active agent is directly supplied to the vaginal microflora.
- bacteriocins can be supplied, whereas the amount bacteriocins produced by Lactobacilli depends strongly on the environment and thus cannot be controlled during use. The presence of bacteriocins is thus not dependent on the environmental conditions of the Lactobacilli.
- the combination of the porous sponge structure and the impregnation with the liquid composition comprising one or more bacteriocin(s) is particularly advantageous.
- the impregnation of the porous sponge structure ensures that the bacteriocins are supplied throughout the porous sponge structure.
- the liquid composition comprising one or more bac- teriocin(s) is in direct contract with the vaginal microflora ensuring its supportive ef- fects.
- the porous sponge structure is suitable to absorb menstrual fluids.
- Said porous sponge structure is suitable to prevent the occurrence of small fibres and is gentle to the vaginal walls, elastic, and shaped for an easy vaginal insertion.
- the liquid is absorbed where it is formed and safely retained inside the sponge. Since menstrual blood flows into and is retained in the pores of the sponge, the absorption pattern is fundamentally different from the conventional tampons that perform the function when the blood is absorbed by the tampon fabric itself. Menstrual blood accumulated in the pores of sponges is isolated from the vaginal walls, thus maintaining a healthier vaginal pH, where the healthy vaginal pH is more acidic (equal or less than 4.5) than the blood pH (about 7), thus preserving healthy microflora of vagina and reducing risk caused by pathogenic bacteria. This effect is further increased by the presence of one or more bacteriocins, which further inhibit the growth of pathogens and support natural Lactobacilli.
- the sponge structure allows the sponge to be compressed and deformed during use, en- suring convenience, but also function.
- the sponge When the sponge is inserted, the sponge recovers its shape particularly fast due to the sponge structure, the material from which it is made of and its porosity. Softness, flexibility and special shape make it easy to adapt to individual physiology without causing discomfort.
- the sponge is designed to dynamically adopt to women's anatomy during movement so that it is comfortable to wear and effectively absorbs menstrual discharge.
- Figures la, b and c illustrate a sponge for the vaginal canal from the front, side and top without a hollow, respectively, according to one embodiment.
- Figures 2a, b and c illustrate a sponge for the vaginal canal from the front, side, and top with a hollow on the side, respectively, according to another embodiment.
- Figures 3a, b and c illustrate a sponge for the vaginal canal from the front, side and top with a hollow on top, respectively, according to another embodiment.
- Figures 4a, b and c illustrate a sponge from the top, side and top with a hollow on top, respectively, according to another embodiment.
- Figures 5a and 5b schematically illustrate insertion positions of sponges in the vaginal canal according to two different embodiments of the present invention in a vaginal canal.
- Figure 6 illustrates a sponge for the vaginal canal in perspective view according to yet another embodiment.
- Figure 7 illustrates an exemplary package containing the sponge for the vaginal canal of Figure 6.
- Fig. 8a schematically shows a sectional view of the sponge for the vaginal canal of Fig.
- Fig. 8b schematically shows a sectional view of the sponge for the vaginal canal of Fig.
- Bacteriocins can also be effective against yeast.
- bacteriocins are capable of killing bacteria or yeast.
- bacteriocins are generally more effective against bacteria, which do not naturally pro- prise said bacteriocins.
- pathogenic agents such as Candida albicans, S. aureus and/or Gardnerella vaginalis are inhibited from multiplying and thus vaginal infections are reduced. This may also prevent reoccurring infections.
- the composition according to the present invention selectively in- hibits pathogenic bacteria and fungi, such as Candida albicans, S.
- aureus and/or Gard- nerella vaginalis but protects the healthy microflora, such as Lactobacilli spp. In this way, the healthy vaginal microbiota balance is ideally restored and maintained.
- Espe- cially bacteriocins produced by Lactobacilli are preserving natural/vaginal Lactobacilli, but are inhibiting other bacteria and yeast, such as S. aureus, C albicans and/or Gard- nerella vaginalis.
- the one or more bacteriocin(s) are synthesized.
- the skilled person is aware of synthesized bacteriocins, which can be commercially available or can be produced in the laboratory.
- Synthetized bacteriocins may be synthesised chem- ically or in a bacterial strain.
- said bacteriocins may be isolated form said bacterial strain to form part of the liquid composition.
- one or more bacteriocin may be synthesised in Lac- tobacilli and then isolated from said Lactobacilli.
- the one or more bacteriocin(s) has been produced by a bacterial strain.
- bacteriocin(s) are chemically synthesised, the bacteriocin has not been produced by a bacterial strain.
- amino acid sequences of bacteriocins are disclosed in the art and the skilled person is aware of bacteriocin databases such as BAGEL4 (http://bagel4.mol- genrug.nl/) or Bactibase (e.g. http://bactibase.hammamilab.org/main.php), which dis- close the amino acids sequences of bacteriocins.
- products, such as tampons, containing bacteria, e.g. Lactobacilli may comprise naturally derived bacteriocins, wherein the bacteriocins are produced by the Lactobacilli within a product.
- said liquid compo- sition comprises one or more bacteriocin(s).
- the one or more bacteri- ocin(s) is the active agent of the liquid composition.
- the 'active agent' is capable of an activity.
- the composition is a gel or a lubricant.
- the sponge does not comprise Lac- tobacilli.
- the sponge does not comprise bacteria.
- the liquid composition does not comprise bacteria such as Lactobacilli.
- the sponge body impregnated with the composition promotes the vaginal microflora at any stage of the menstrual cycle and/or during pregnancy.
- the liquid composition promotes the vaginal microflora at any stage of the menstrual cycle and/or during pregnancy in some embodiments.
- the sponge body impregnated with the composition or the composition may promote the vaginal microflora during menstruation, during follicular phase, during luteal phase and/or during pregnancy.
- the sponge during menstruation has the particular advantage that the menstrual blood is retained within the pores of the sponge without drying the vaginal mucosa while providing bacteriocins to the natural Lactobacilli of the vaginal canal and thereby inhibit potential pathogens, such as S. aureus, Candida albicans and/or Gardnerella vaginalis.
- the sponge body impregnated with the composition or the liquid composition provide the particular advantage of providing one or more bacterioci n(s) to the vaginal microflora.
- vaginal infections such as vulvovaginal candidiasis or bacterial vaginosis
- vaginal infections may be prevented or treated during follicular phase and luteal phase.
- the sponge is impregnated with a liquid composition comprising the one or more bacteri- ocin(s)
- the sponge is moist and does not dry the vaginal mucosa.
- vaginal infections are recurring.
- the sponge compared to conven- tional tampons, provides the particular advantage of promoting the natural vaginal microbiota with the bacteriocins while not drying the mucosa.
- the sponge is a tampon.
- the tampon is a menstrual tampon.
- the sponge body is impregnated with a liquid com- position comprising one or more bacteriocins.
- 'impregnation' means that the sponge body is soaked with a liquid composition so that the liquid composition is distributed in the sponge body.
- the sponge can be made out of fibers, such as polysaccharide fibres.
- the polysaccharide fibers would be impreg- nated with the liquid composition.
- the pores of the porous sponge structure can absorb menstrual fluids, which is advantageous as the sponge does not dry the vaginal mucosa by retaining the menstrual fluid in the pores.
- the composition promotes the vaginal microflora by inhibiting the growth of one or more pathogens.
- the sponge body im- pregnated with the composition promotes the vaginal microflora by inhibiting the growth of one or more pathogens.
- the composi- tion or the sponge body impregnated with the composition positively influences the microflora.
- the microflora is positively influenced by promoting the health of the microflora.
- the microflora is positively influenced by promoting Lactobacilli spp.
- the composition or the sponge body impregnated with the composition promote a balanced vaginal microflora.
- a balanced vaginal microflora is Lactobacilli spp. dominated.
- the composition or the sponge body impregnated with the composition promotes the dominance of Lactobacilli spp. in the vaginal mi- croflora. Lactobacilli spp. is dominant when the genus Lactobacilli spp. is most abun- dant in the microflora. In turn, no other genus is more abundant than Lactobacilli spp. in the microflora when Lactobacilli spp. is dominant. Ideally, the health of the micro- flora is promoted by the composition or the sponge body impregnated with the com- position.
- the health of the microflora may be promoted by promoting the dominance of Lactobacilli spp. By inhibiting the growth of pathogens, the metabolic activity may be shifted.
- the composition or the sponge body impregnated with the composition inhibits the growth of S. aureus, Candida spp. and/or Gardnerella vaginalis.
- Examples 1 and 2 herein provides data on the inhibition of the growth of S. aureus, Candida spp. and Gardnerella vaginalis specifically.
- the com- position or the sponge body impregnated with the composition promote the vaginal microflora so that a possible disbalance of the vaginal microflora, e.g.
- compositions or the sponge body impregnated with the composition promote the vagi- nal microflora so that a Lactobacilli spp. dominated microflora may be obtained or maintained.
- the porous sponge structure impregnated with the composi- tion inhibits the growth of S. aureus compared to medium alone under the same con- ditions, wherein the growth is inhibited, for example, by at least 20-fold at least 50- fold or at least 100-fold or at least 200-fold or at least 350-fold; tested after 8h by the tampon sac method.
- the skilled person is aware of the tampon sac method. Said method has been described e.g. in Nonfoux L, et al. (2016) [7]. In addition, said method was also used in Example 1 herein and further detail is provided. Based on the data disclosed in Example 1, the skilled person is able to test suitable substances and assess the inhibition of a pathogen such as S.
- the liquid composition inhibits the growth of S. aureus compared to medium alone under the same conditions, wherein the growth is inhibited, for example, by at least 20-fold at least 50-fold or at least 100-fold or at least 200-fold or at least 350-fold.
- the porous sponge structure 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 100-fold; tested after 8h by the tampon sac method. In some embodiments, the porous sponge structure 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 200-fold; tested after 8h by the tampon sac method. In some embodiments, the porous sponge structure im- pregnated 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 350-fold; tested after 8h by the tampon sac method.
- the porous sponge structure impregnated with the composi- tion inhibits the growth of Candida spp. compared to medium alone under the same conditions, wherein the growth is inhibited, for example, by at least 30% or at least 40%, or at least 50% or at least 60% or at least 70% or at least 75%; tested after 8h by the tampon sac method.
- the liquid composition inhibits the growth of Candida spp. compared to medium alone under the same con- ditions, wherein the growth is inhibited, for example, by at least 30% or at least 40%, or at least 50% or at least 60% or at least 70% or at least 75%.
- the data of the Examples provide further detail and demonstrates such an inhibition of growth.
- the porous sponge structure impregnated with the composition inhibits the growth of Candida spp. compared to medium alone under the same con- ditions, wherein the growth is inhibited by at least 60 %; tested after 8h by the tampon sac method. In some embodiments, the porous sponge structure impregnated with the composition inhibits the growth of Candida spp. compared to medium alone under the same conditions, wherein the growth is inhibited by at least 70 %; tested after 8h by the tampon sac method. In some embodiments, the porous sponge structure im- pregnated with the composition inhibits the growth of Candida spp.
- the porous sponge structure impregnated with the composition inhibits the growth of Candida spp. compared to medium alone under the same conditions, wherein the growth is, for example, inhibited by at least 50%, or at least 60%, or at least 70%, or at least 80% and or at least 85%; tested after 48h by the tampon sac method.
- the porous sponge structure impregnated with the composi- tion inhibits the growth of Gardnerella vaginalis ⁇ yy at least 50-fold at least 100-fold or at least 250-fold or at least 500-fold; tested after 24h by the tampon sac method.
- the liquid composition inhibits the growth of Candida spp. compared to medium alone under the same conditions, wherein the growth is inhibited, for example, by at least 30% or at least 40%, or at least 50% or at least 60% or at least 70% or at least 75%.
- the data of the Examples provide further detail and demonstrates such an inhibition of growth.
- the porous sponge structure impregnated with the composition inhibits the growth of Gardnerella vaginalis at least 1000-fold tested after 24h by the tampon sac method. In some embodiments, the porous sponge structure impregnated with the composition inhibits the growth of Gardnerella vaginalis at least 5000-fold tested after 24h by the tampon sac method. In some embodiments, the porous sponge structure impregnated with the composition inhibits the growth of Gardnerella vaginalis at least 10000-fold tested after 24h by the tampon sac method. In some embodiments, the porous sponge structure impregnated with the composition inhibits the growth of Gardnerella vaginalis at least 20000-fold tested after 24h by the tampon sac method.
- the porous sponge structure impregnated with the composi- tion inhibits the growth of Lactobacilli spp. compared to medium alone under the same conditions by at most 12-fold; tested after 8h by the tampon sac method.
- An inhibition by at most 12-fold corresponds to a inhibition by at most 1.079 logw.
- the porous sponge structure impregnated with the composition inhibits the growth of Lactobacilli spp. compared to medium alone under the same conditions by at most 20-fold, at most 15-fold, at most 14-fold or at most 13-fold; tested after 8h by the tampon sac method.
- the liquid composition inhibits the growth of Lactobacilli spp. compared to medium alone under the same conditions by at most 12-fold.
- the one or more bacteriocin(s) is/are a bacteriocin from Gram- positive and/or Gram negative bacteria. In some embodiments, the one or more bac- teriocin(s) is/are a bacteriocin from Gram-positive bacteria.
- the one or more bacteriocin(s) is/are selected from Class I, Class II, Class II, and Class IV bacteriocins from Gram-positive bacteria.
- the one or more bacteriocin(s) may be selected from Class I and/or Class II bacteriocin from Gram-positive bacteria.
- the one or more bacteriocin(s) is/are a bacteriocin from Lac- tococcus /act/s and/or Lactobacillus.
- the one or more bacteriocin(s) may be from the Lactobacillales order.
- Lactobacillales order comprises Lacto- bacillus, Leuconostoc, Pediococcus, Lactococcus, Streptococcus, Aerococcus, Carno- bacterium, Enterococcus, Oenococcus, Tetragenococcus, Vagococcus, an Weissella.
- the one or more bacteriocin(s) may be from a bacteriocin Sporolactoba- cillus.
- Bacteriocins originating from Lactobacilli have the particular advantage that said bacteriocins have little inhibiting effect on Lactobacilli but a large effect on other bac- teria.
- the one or more bacterioci n(s) may be a bacteriocin from Lactoba- cillus crispatus and/or Lactobacillus gasseri.
- the one or more bacteriocin(s) is/are a lantibiotic.
- Lantibiotics are a class of polycyclic peptide antibiot- ics that contain the characteristic thioether amino acids lanthionine or methyllanthio- nine, as well as the unsaturated amino acids dehydroalanine, and 2-aminoisobutyric acid. Lantibiotics are produced by a Gram-positive bacteria to attack other Gram-pos- itive bacteria such as S. aureus.
- the one or more bacteriocin(s) may be a Type A or B lantibiotic.
- the lantibiotic may be selected from nisin, lactosin, lacticin, carnocin, cytoly- sin, subtilin, gallidermin, epidermin, mersacidin, actagardine, cinnamycin, duramycin, sublancin and plantaricin.
- the lantibiotic is nisin.
- the nisin may be selected from nisin A, nisin Z, nisin U, nisin Q, and nisin F.
- the nisin is selected from nisin A, nisin Z or a combination thereof.
- the nisin is nisin Z.
- the nisin is nisin A.
- the one or more bacteriocin(s) is a Class II bacteriocin.
- the Class II bacteriocin may be a one-peptide bacteriocin or a two-peptide bacteriocin.
- the Class II bacteriocin is a one-pep- tide bacteriocin.
- said one-peptide bacteriocin may be selected from a pediocin-like bacteri- ocin and/or a nonpediocin-like bacteriocin.
- the one-peptide bacteriocion is a nonpediocin-like bacteriocin.
- the one or more bacteriocin(s) is/are selected from pediocin PAI, leucocin A, sakacin P, curvacin A, mesentericin Y105, carnobacteriocin BM1, car- nobacteriocin B2, enterocin A, pikscicolin 126, bavarian MN, piscicocin Via, lactococcin A, lactococcin B, divergicin 750, lactococcin 972, enterocin B, carnobacteriocin A and crispacin A.
- the one or more bacteriocin(s) is/are selected from lactococcin A, lactococcin B, divergicin 750, lactococcin 972, enterocin B, carnobacte- riocin A and crispacin A. In some embodiments, the one or more bacteriocin(s) is/are crispacin A.
- the one or more bacteriocin(s) is/are a Class Ila bacteriocin, for example, a circular bacteriocin.
- the circular bacterioncin is selected from gassericin A, reutericin A, butyrivibricin A, lactocyclicin Q, circularin A, leucocyclicin Q, amylocyclin A, carnocyclin A, uberolysin A, AS-48, and garvicin ML, preferably wherein the circular bacteriocin is gassericin A.
- the composition comprises one, two or three bacterioci n(s). In some embodiments, the composition comprises one or two bacteriocin(s).
- the composition may comprise one Class I and one Class II bacteriocin.
- An exemplary Class I bacteriocin may be nisin and an exemplary Class II bacteriocin may be a one-peptide bacteriocin, such as crispacin A.
- the composition may comprise one Class I and one circular bacteriocin.
- An exemplary Class I bacteriocin may be nisin and an exemplary circular bacteriocin may be gassericin A.
- the composition further comprises lactic acid.
- the composition may comprise lactic acid in a suitable amount to provide a pH value of said composition from 3.5 to 5.5.
- the composition may also comprise lactic acid in a suitable amount to provide a pH value of said composition from 3.7 to 5.
- the composition may comprise lactic acid in a suitable amount to provide a pH value of said composition from 3.9 to 4.5.
- the composition may comprise lactic acid in a suitable amount to provide a pH value of said composition of about 4.2.
- the lactic acid may be synthesised or may stem from natural sources such as lactic acid bacteria.
- the skilled person is able to determine a suitable concentra- tion of bacterioci n(s) by using the tampon sac method as disclosed in Example 1 and 2.
- the one or more bacterioci n(s) are present at a total con- centration of the liquid composition from 0.000001% (v/v) to 5% (v/v).
- the total concentration of said one or more bacteriocin(s) may be present in the com- position from 0.00001% to 2% of the liquid composition.
- the total concentration of said one or more bacteriocin(s) may also be present in the composition from 0.00005% to 1% of the liquid composition.
- the total concentration of said one or more bacteriocin(s) may be present in the composition from 0.0001% to 0.5% of the liquid composition.
- the total concentration of said one or more bacteri- ocin(s), such as crispacin A may be present in the composition from 0.0005% to 0.25% of the liquid composition.
- the one or more bacteriocin(s) may be present at a total concentration of the liquid composition from 0.0001 % (v/v) to 0.005 % (v/v).
- the one or more bacteriocin(s), such as gassericin A may be present at a total concentration of the liquid composition from 0.0002 % (v/v) to 0.0020 % (v/v).
- the one or more bacteriocin(s), such as nisin Z are present at a total concentration of the liquid composition from 0.0005 % (v/v) to 0.0014 % (v/v).
- the one or more bacteriocin(s), such as curvacin A may be present at a total concentration of the liquid composition from 0.0001 % (v/v) to 0.0005% (v/v).
- the one or more bacteriocin(s), such as lacticin may be present at a total concentration of the liquid composition from 0.0014 % (v/v) to 0.008% (v/v).
- the sponge is moist.
- the sponge is slightly wet and not dry.
- the sponge is impregnated with a liquid composition and thus moist.
- Said moist sponge is soft and gentle to vaginal epithelial cells of the mucous membrane, which keeps the mucosal lining moist and healthy. By being soft and thereby easily deformable, the sponge is also comfortable to use.
- the composition may further comprise one or more excipients.
- excipients are benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, boric acid, sodium propionate, sorbic acid, propylene glycol, potassium lactate, calcium ac- etate, calcium chloride, sodium sorbate, sodium benzoate, sodium chloride, sodium formate, sodium propionate, ethylenediaminetetraacetic acid (EDTA), sodium lactate, organic and inorganic salts and acids, like sorbic acid, ascorbic acid, propionic acid, and/or fumaric acid.
- These excipients preserve the bacterioci n(s) in the composition.
- These excipients also preserve the sponge. Excipients thus have the advantage that the bacteriocins are stabilized and the sponge material is preserved.
- the composition may further comprise sodium chloride and EDTA.
- the buffer solution may also comprise GPB (Gelatin Phosphate Buffer), sodium phosphate buffer, Tris-glycine and Tris-tricine, octanol phosphate, sodium citrate com- bined with sodium diacetate (BSCSD), EDTA, sodium sulphate, sodium phosphate, so- dium acetate and sodium citrate, EGTA (ethylene glycol-bis(p-aminoethyl ether).
- the composition may also comprise benzalkonium chloride, benzethonium chloride, ben- zoic acid, benzyl alcohol, boric acid, sodium propionate, sorbic acid, propylene glycol, potassium lactate, calcium acetate, and/or calcium chloride.
- the compo- sition may also comprise the following components at a concentration 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.
- Exemplary embodiments of a sponge for the vaginal canal 10, as depicted in Figures 1 to 4, include an absorbent sponge body 12 comprising a porous sponge structure 14.
- the material of the sponge structure 14 may be a plant-derived material that can easily deform and readily reform to a non-deformed, or partially deformed state.
- Such material can be produced from Amorphophallus konjac (Konjac plant) plant root pow- der by production of glucomannan and subsequently processing it by a specific method in order to obtain the sponge structure, or it can be made from other naturally occur- ring polysaccharides, such as starch, cellulose, chitosan, chitin, and their mixtures, without limitation.
- the porous sponge structure is made of a natural polysaccha- ride-based sponge material.
- Said natural polysaccharide-based sponge material may be glucomannan-based sponge material.
- the sponge is made out of completely natural-occurring materials, such as glucomannan. Due to its biolog- ical origin, glucomannan-based sponge and all its additives are biodegradable and de- compose naturally in nature. In these embodiments, the sponge fully biodegradable thus friendly to the environment. In these embodiments, the sponge biodegrades within 30-90 days in natural environment (depending on environment, the moisture level and microorganisms quantity, species).
- Glucomannan further improves the effect of the one or more bacteriocin(s), as Glucomannan such has a prebiotic effect on the vaginal Lactobacilli. Hence, the natural microbiota is promoted by the glucomannan. At the same time, the one or more bacteriocins specifically inhibit pathogenic bacteria and fungi, such as S. aureus and Candida. Hence, supporting the natural Lactobacilli by glucomannan and inhibiting pathogens by one or more bacteriocin(s) is simultane- ously achieved.
- glucomannan is a substance used in food industry, also in medicine for wound dressing which, together with vaginal Lactobacteria, inhibits the growth of bac- teria such as Staphylococcus aureus and S. typhimurium.
- the sponge may not contain toxic chemicals and the resulting final product may be biocompatible with the human body, i.e. ensures protection of natural vaginal microflora and healthy intimate hy- giene.
- Glucomannan is hydrophilic and, thanks to its unique molecular structure, at- tracts water molecules, so the sponge walls are always moist and come in contact with the vaginal walls with a molecular barrier of liquid - protecting extremely sensitive vaginal walls.
- the porous sponge structure makes up for at least 70% or at least 80% or at least 90% or at least 95% or at least 97% or at least 99% by volume of the sponge body.
- the porous sponge structure forms at least part of a sponge outer surface. This ensures that the impregnation with the liquid composition comprising the one or more bacteriocins is in direct contact with the vaginal microflora.
- the one or more bacteriocin(s) can support the natural Lactobacilli by inhibiting potential pathogens such as S.aureus and/or Candida.
- 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 outer surface.
- the porous sponge structure forms 100% of the sponge outer surface. This embodiment is particularly advantageous, as the surface of the sponge and the vaginal microflora are in maximal contact.
- the sponge comprises the sponge body having an insertion end and a withdrawal end.
- the sponge comprises a removal facilitator for facilitating removal of the sponge body from a human vaginal canal, the removal facilitator connected to the sponge body and extending from the withdrawal end of the sponge body. Additionally, the sponge may be placed into the vaginal canal by an applicator.
- the sponge structure is exposed at least in a region of the body outer surface that is located at or near the insertion end of the sponge body.
- the body outer surface has a fluid capture depression formed at least partially by an exposed portion of the sponge structure. In these embodiments, the fluid capture depression may be located closer to the insertion end than to the with- drawal end of the sponge body.
- the sponge body comprises a fluid impervious layer covering the sponge structure in a partial area of the body outer surface.
- the fluid impervious layer may be made of a non-porous, glucomannan-based material.
- the sponge body 12 also includes a liquid im- permeable layer 16 (i.e. fluid impervious layer; hatched in the drawings) which at least partially covers the sponge structure 14 to retain the moisture in the sponge body 12 until its use and prevent leakage of liquid from the sponge body 12 during its use.
- the liquid impermeable layer 16 covers in certain embodiments more than half, half or less than half of the outer surface of the sponge structure 14.
- the sponge also may have an outer fluid-impervious layer that provides fluid retention in the sponge even when its deformed during use, i.e. prevents leakage of fluid as the person moves causing squeezing, bending and similar deformation of the sponge ma- terial.
- the liquid impermeable layer (i.e. fluid impervious layer) 16 is a non-absorbent, non-porous layer having a thickness, e.g., from 0,01mm to 2 mm.
- the liquid impermeable layer may be 0,01 mm.
- the indicated thickness range of the liquid impermeable layer 16 is merely exem- plary and not intended to be limiting to the scope of the invention.
- the liquid impermeable layer 16 may have in other embodiments a thickness of only a few tenths of a millimeter.
- the liquid impermeable layer 16 may be made of a glucoman- nan-based material.
- the sponge body 12 may be formed entirely by the sponge structure 14.
- the sponge structure 14 may thus make up for up to 100% by volume of the sponge body 12.
- the sponge structure 14 may make up for, e.g., 90% or more by volume of the sponge body 12.
- the remainder of the volume of the sponge body 12 may be formed by the liquid impermeable layer 16.
- the sponge structure 14 makes up for at least 95% or at least 97% by volume of the sponge body 12.
- the sponge also may include an applicator for easy insertion and a cord, string or ring for convenient removal, but it can also be used without an applicator.
- the sponge body 12 has an insertion end 18, a withdrawal end 20 and a body outer surface 22.
- the insertion end is the leading end of the sponge body as the sponge body is shoved into a human vaginal canal
- the withdrawal end is the trailing end of the sponge body during insertion of the sponge body.
- the body outer surface 22 is defined by the outer surface of the sponge body 12. Where the sponge structure 14 has one or more exposed portions (i.e. exposed to the outside of the sponge body 12), these exposed portions form at least part of the body outer surface 22.
- the liquid impermeable layer 16 forms at least part of the body outer surface 22.
- the extension of the sponge body 12 from the insertion end 18 to the withdrawal end 20 defines a longitudinal extension (or direction) of the sponge body 12.
- the longitudinal extension is illustrated by a dashed line 24 in some of the Figures.
- the sponge body has a length dimension in a direction from the withdrawal end to the insertion end, wherein the fluid impervious layer covers the sponge structure continuously in a region of the body outer surface that extends from the withdrawal end over at least one fourth or at least one third or at least one half of the length of the sponge body.
- the sponge body 12 may have an insertion end 18, a withdrawal end 20 and a body outer surface 22.
- the insertion end is the leading end of the sponge body as the sponge body is shoved into a human vaginal canal
- the withdrawal end is the trailing end of the sponge body during insertion of the sponge body.
- the body outer surface 22 is defined by the outer surface of the sponge body 12. Where the sponge structure 14 has one or more exposed portions (i.e. exposed to the outside of the sponge body 12), these exposed portions form at least part of the body outer surface 22. Where the liquid impermeable layer 16 is present and covers at least part of the sponge structure 14, the liquid impermeable layer 16 forms at least part of the body outer surface 22.
- the extension of the sponge body 12 from the insertion end 18 to the withdrawal end 20 defines a longitudinal extension (or direction) of the sponge body 12. The longitudinal extension is illustrated by a dashed line 24 in some of the Figures.
- 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 opposite main faces 30, 32 each ex- tending between the withdrawal and insertion ends 18, 20.
- the main face 30 is a rear face of the sponge body 12 and the main face 32 is a front face, considering an in- tended, proper insertion position of the sponge body 12 in a human vagina 34, in which insertion position the main face 30 faces substantially downward and away from a uterus 36 of the wearer and the main face 32 faces substantially upward and toward the uterus 36, as shown in Figs. 5a and 5b.
- the main face 30 has convexity in the longitudinal direction 24 over essentially the entire longitudinal length of the sponge body 12.
- the main face 32 is generally formed with a smaller degree of convexity in the longitudinal direction 24 than the main face 30.
- the main face 32 when viewed in the longitudinal direction 24, may be formed with substantially no curvation or with concavity in at least a part of the longitudinal length of the sponge body 12.
- the main face 30 When viewed in cross-sectional profile (i.e. in a transverse plane), the main face 30 has convexity, with the main face 32 generally having a smaller degree of convexity than the main face 30 or no convexity at all.
- the situation of no convexity covers both a substantially straight extension of the main face 32 in the transverse plane or a profile of the main face 32 having one or more concavely shaped portions.
- the sponge body 12 Viewed in a cross-section orthogonal to the longitudinal direction 24, the sponge body 12 thus has an irregular, rotationally asymmetrical shape.
- This irregular cross-sectional shape of the sponge body may extend continuously over a major part of the longitudinal length of the sponge body 12, e.g., more than 50% or more than 60% or more than 70% or more than 80% or more than 90% of the length of the sponge body 12.
- the sponge body 12 may also comprise an outer reinforcing casing (not shown in the drawing), which reinforces the structure of the sponge body 12 and helps maintain the desired shape.
- Exemplary approximate sizes of the sponge body 12 may be as follows: Size 1: length 4.0-4.5 cm; width 1.5-2.0 cm; thickness ca. 1.0 cm
- Size 2 length 4.5 cm; width 3.6 cm; thickness 1.9 cm
- Size 3 length 5.8 cm; width 4.5 cm; thickness 2.3 cm
- Size 4 length 6.0 cm; width 3.9 cm; thickness 2.2 cm
- 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 conventionally known per se.
- the removal facilitator 38 may be attached at two ends to the sponge body 12 approxi- mately in the central portion 26 or the upper portion 28 or the lower portion 25, on opposite sides of the sponge body 12 so as to form a U-shaped loop that extends from one lateral side of the sponge body 12 to the other and forms the possibility of a gap between at least the lower portion 25 of the sponge body 12 and a gripping part of the removal facilitator 38.
- the removal facilitator 38 can also be formed as a single element that is pierced through the sponge body 12 at any location, such as the upper, central or lower portions 28, 26, 25 of the sponge body 12.
- the sponge body 12 is irregular in shape, similar to an oval, or any other sleek shape.
- the sponge body 12 may be generally wider near its insertion end 18 then near its withdrawal end 20.
- the mentioned flattened profile according to which the width of the sponge body 12 (designated W in Fig. la) is larger than its height, or thickness (designated H in Fig. lb) over at least a major part of the longitu- dinal length of the sponge body 12, serves to reproduce the natural biological vaginal canal form (https://i.
- the upper portion 28 is generally formed with a larger width than the lower portion 25.
- the sponge body 12 is located with its upper portion 28 closer to the origin of the menstrual fluids than with its lower portion 25 (cf. Figs.
- the greater width of the upper portion 28 can thus en- hance the absorption of the menstrual fluids in the sponge structure 14, whereas the lower portion 28 can efficiently retain the accumulated fluids in spite of its reduced width whilst ensuring high wearing comfort.
- the sponge body 12 is formed with a hollow (recessed portion) 40 exhibiting a generally concavely shaped absorption surface 42 at which 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 absorption surface 42.
- the hollow 40 may also be referred to as a fluid capture depression or pocket.
- the surface area of the absorption surface 42 is in certain em- bodiments at least 1.5 cm 2 or at least 2.0 cm 2 .
- the hollow 40 may be concavely shaped in all directions, resembling, e.g., a bowl shape or the like.
- the liquid impermeable layer 16 may cover the entire body outer surface 22 of the sponge body 12 up to the perimetrical edge of said hollow 40. In other embodiments of the invention, the liquid impermeable layer 16 may wrap the sponge structure 14 only up to a distance from the perimetrical edge of the hollow 40, so that the sponge structure 14 remains uncoated by the liquid im- permeable layer 16 (i.e. exposed to the outside of the sponge body 12) not only within the area of the hollow 40 but also outside the hollow 40 in the region between the liquid impermeable layer 16 and the perimetrical edge of the hollow 40.
- the hollow 40 is designed for cervix and easier fluid accumulation, and for faster fluid uptake to prevent blood stagnation at the cervix.
- the surface 42 comprises a portion of the material of the sponge structure 14 of the sponge body 12 and is generally concave in shape, such as in the form of a scoop, a hollow half-sphere, an oval, or any other form.
- the absorption surface 42 is said to be generally concavely shaped, it is to be understood that one or more sub-portions of the absorption surface 42 forming a part of the entire area of the absorption surface 42 may nevertheless have a plane or even convex shape.
- the absorption surface 42 may be comprised of con- cave and non-concave surface portions.
- the hollow 40 may be formed on the main face 32 at a longitudinal position closer to the insertion end 18 than to the withdrawal end 20 (as shown exemplarily in Figs. 2a-c and Figs. 5a, 5b), or may be formed in the region of the insertion end 18 (as shown exemplarily in Figs. 3a-c and 4a-c).
- the sponge body 12 comprises at least a non-deformed state when it is fully expanded, a deformed state when it is compressed to occupy the smallest possible volume, and a partially deformed state in which the sponge body 12 fills the entire vaginal cavity by partially deforming the vaginal cavity walls at the contact site.
- the volume of fluids absorbed by the sponge body 12 is increased, while ensuring conven- ient vaginal adaptation.
- Reversible deformations of the sponge body 12 ensure that the adaptation to the vagina will take place continuously, while the user is both at rest and during movement.
- the deformed sponge body 12 recovers its original or partially original shape.
- the absorption surface 42 defined by the hollow 40 has a concavely curved shape both in the width direction and the height direction of the sponge body 12 (the width and height, or thickness, dimensions are in a plane perpendicular to the longitudinal direction 24).
- the hollow 40 forms a deeper neck than on the side of the main face 30.
- the hollow 40 thus cuts out a relatively larger portion from the main face 32 than from the main face 30.
- the sponge body 12 substantially maintains its shape and volume in a non-deformed (i.e. quiescent) state over a broad range of levels of hu- midification of the material of the sponge structure.
- the material of the sponge structure 14 should rather be relatively dryer than moister.
- Certain embodiments therefore include in package a capsule or other suitable container (e.g., a sachet) together with the sponge 10, the capsule or container containing a predetermined amount of water or another liquid substance to be used for moisturizing the sponge body 12 before use.
- Embodiments of the present invention also comprise a waterproof package 44 (Fig. 7) for said sponge 10.
- the package 44 is designed as a pouch in the example case shown in Figure 7 and is configured to retain sterility and moisture of the body 12 of the sponge 10. It is to be understood that many different configurations of the pouch are conceivable and likewise many other designs of the waterproof package 44 than a pouch are conceivable, so long as the package 44 can retain a moist and sterile envi- ronment for the tampon 10.
- the sponge body 12 of the embodiment shown in Figs. 6 and 7 has only the sponge structure 14, but no liquid impermeable layer 16.
- Also included in the package 44 is a schematically depicted capsule 46 containing an amount of, e.g., water which that the user can use to moisturize the sponge body 12 prior to its insertion into a human vagina.
- the present invention also relates to a sponge as disclosed herein or a liquid compo- sition as disclosed herein for inhibiting the growth of one or more pathogen(s) associ- ated with a disorder or disease of the vaginal canal.
- Disorders or diseases of the vaginal canal are caused by one or more pathogen(s) such as bacteria and fungi.
- Disorder or diseases include but are not limited to dysbiosis, bacterial vaginosis, toxic shock syn- drome and vulvovaginal candidiasis.
- the sponge for the vaginal canal as disclosed herein is used for preventing or treating vaginal dysbiosis.
- the liquid composition suitable for the vaginal canal as disclosed herein is used for preventing or treating dysbiosis.
- Dysbiosis also called dysbacteriosis
- Such dysbiosis may lead to vulvo- vaginal candidiasis, bacterial vaginosis and toxic shock syndrome.
- the present -U - invention also relates to a sponge for the vaginal canal as disclosed herein for use in preventing or treating vulvovaginal candidiasis.
- the present invention also relates to a liquid composition as disclosed herein for use in preventing or treating vulvovaginal candidiasis.
- the vulvovaginal candidiasis may be caused by Candida albicans, Candida giabrata, Candida kefyr, Candida krusei, Candida parapsiiosis, and/or Candida tropi- ca/is.
- vulvovaginal candidiasis may be caused by Candida albicans.
- said vulvovaginal candidiasis is prevented or treated in pregnant women.
- said vulvovaginal candidiasis is prevented or treated in menstruating women.
- the present invention also relates to a sponge for the vaginal canal as disclosed herein for use in preventing or treating bacterial vaginosis.
- the present invention is also concerned with a liquid composition as disclosed herein for use in preventing or treating bacterial vaginosis.
- Bacterial vaginosis may be caused by Gardnerella vaginalis, Prevoteiia, Peptostreptococcus, Bacteroides spp., Leptotrichia spp. and/or Sneathia spp.
- said bacterial vaginosis is prevented or treated in pregnant women.
- said bacterial vaginosis is pre- vented or treated in menstruating women.
- the present invention also relates to a sponge for the vaginal canal or a liquid composition as disclosed herein for use in preventing toxic shock syndrome.
- Toxic shock syndrome may be caused by S.aureus.
- said toxic shock syndrome is prevented in pregnant women.
- said toxic shock syndrome is prevented in menstruating women.
- the liquid composition inhibits the growth of pathogens, such as S.aureus, Candida spp. and/or Gardnerella vaginalis.
- the sponge for the vaginal canal and/or the liquid composition according to the present invention advantageously protect the vaginal microflora and prevents pathogenic in- fection in particular during menstruation.
- the combination of the porous sponge struc- ture impregnated with a liquid composition comprising one or more bacteriocin(s), as further defined in the claims, is advantageous as it preserves the vaginal natural de- fence mechanisms and thus strengthens the natural defence during menstruation.
- the tampon according to the present invention selectively inhibits the growth of S.aureus, Candida albicans, and/or Gardnerella vaginalis.
- the liquid composition prevents pathogen growth and thus prevents e.g.
- the sponge according to the present invention may also be in use for a longer amount of time than a conventional tampon.
- the sponge according to the present invention may also be in use for a longer amount of time than a sponge not comprising a liquid composition comprising one or more bacteriocin(s), due to the inhibitory effect on pathogens.
- the sponge according to the present invention may be used for up to 12 hours.
- Example 1 A porous sponge impregnated with bacteriocins inhibits S.aureus and Candida albicans growth
- the bags were incubated vertically at 37°C shaking (around 200 rpm) for 8 h or 48 hours.
- Four mL of the solution was sampled from the plastic bag at the end of the incubation time.
- the tampons were kneaded in the bag for 5 seconds, and the liquid was squeezed out by compressing the tampon and collected for quantification of bacteria as described as follows.
- the number of yeast/bacteria in the solutions was estimated by standard spread plate technique using trypticase soy agar. Colonies were counted after 8h, 24h and 48h of incubation at 30°C in aerobic atmosphere.
- bacteriocins were identified to be exceptionally beneficial to inhibit pathogens, while not inhibiting Lactobacilli.
- Natamycin is a known antifungal chemical compound/medication used to treat fungal infection e.g. around the eye.
- natamycin would also show a fungistatic effect in the tampon sac method.
- natamycin did not show an inhibitory effect (data not shown).
- polylysine has an antimicrobial effect against yeast, fungi and bacteria.
- said antimicrobial effect against S. aureus could however not be detected.
- the growth of S.aureus was induced from 1.0 x 10 7 to 2.3 x 10 8 and not inhibited at all.
- polylysine did not inhibit the growth of S.aureus.
- bacteriocins reliably inhibited the growth of pathogens.
- the impregnation of the tampon with a liquid composition comprising nisin and lactic acid at a pH value of around 4.2 was tested.
- Said composition reliably inhibited C. albicans for 8, 24 or 48 hours of incubation using the tampon sac method.
- the growth of C. albicans was assessed in four individual cultures and it was reduced by 78%, 75%, 76% and 73% after 8 hours.
- the growth of C. albicans was reduced by 32%, 35%, 39% and 28%, after 24 hours, respectively.
- C.aibicans was reduced by 83%, 84% and 87% after 48 hours, respectively.
- a reduction by around 75% after 8 hours could be observed; a reduction by around 30% after 24 hours could be observed; a reduction by around 85% after 48 hours could be observed.
- Percentages indicate the number of live cells (colony count) compared to control cells grown without menstrual sponge. The viability of control cells is equivalent to 100%.
- composition inhibited Lactobacillus crispatus only to a minor degree, i.e. by 10.95 fold, which corresponds to 1.04 logio-
- Example 2 A porous sponge impregnated with bacteriocins does not comprise bacte- ria and inhibits Gardnerella vaglna/is growth
- Bacterial strain Gardnerella vaginalis ATCC 49145.
- Liquid culture medium and incubation method sterile BHI (Brain-heart infusion, Li- ofilchem, ref. 620008) solution supplemented with 1% D-glucose and 2% horse serum (Thermofisher Scientific, Oxoid, ref. SR0035).
- the inoculated medium was incubated in 50ml conical centrifugal tubes (Thermofisher Scientific, Nunc) in vertical position at 37°C without shaking. The tubes were gently swirled for several times during the in- cubation. This method is considered equivalent to the tampon sac method.
- Solid culture medium sterile Chocolate Agar with Vitox plates (Thermofisher Scientific, Oxoid, ref. P05090A). Plates were incubated for 43 hours at 37°C in 5% CO2 atmos- phere provided by CO2 Gen 2.5L (Thermofisher Scientific, Oxoid, ref. CD0025A).
- the porous sponge impregnated with bacteriocins does not comprise bacteria While other products on the market may comprise bacteriocins, which are produced by bacteria within said product, the present invention in concerned with a porous sponge impregnated with a liquid composition comprising bacteriocins. Ideally, said porous sponge is free of bacteria.
- porous sponge is free of bacteria, such as Lactobacilli
- three porous sponges (moist konjac sponges made out of glucomannan) were incubated in growth medium and potential bacterial growth was tested by counting potential colony forming units (CFUs).
- CFUs colony forming units
- the tested sponges were impregnated with a liquid composition com- prising nisin and lactic acid at a pH value of around 4.2.
- a porous sponge impregnated with bacteriocins inhibits Gardnerella vaginalis growth As Gardnerella vaginalis ⁇ s the most common cause of bacterial vaginosis, the inventors also tested the inhibitory effect of the porous sponge on the inhibition of growth of Gardnerella vaginalis. Two independent tests (A, B) were carried out. Each test compared the bacterial growth with and without the sponge.
- the porous sponge (moist konjac sponges made out of glucomannan impregnated with a liquid composition comprising nisin and lactic acid at a pH value of around 4.2) was inserted into the bottom of 50ml conical centrif- ugal tube.
- G. vaginalis ATCC 49145 was recovered from frozen storage by streaking and incubating it on the plate, and suspended in liquid medium at the optical density of ODeoo 0.12 (tests A, B). 100-fold and 10-fold lower densities failed to provide ade- quate bacterial growth during pre-testing.
- the Vaginal Microenvironment The Physiologic Role of Lac- tobacilli. Front Med (Lausanne). 2018 Jun 13;5: 181 D. Eschenbach et al. Influence of the Normal Menstrual Cycle on Vaginal Tissue, Dis- charge, and Microflora. Clinical Infectious Diseases, Volume 30, Issue 6, June 2000, Pages 901-907 S. Srinivasan et al. Temporal Variability of Human Vaginal Bacteria and Relationship with Bacterial Vaginosis. PLoS One. 2010; 5(4): el0197 C. Bradshaw, J.D. Sobel Current Treatment of Bacterial Vaginosis— Limitations and Need for Innovation. J Infect Dis.
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Abstract
La présente invention concerne une éponge pour canal vaginal comprenant un corps spongieux dont la structure est poreuse. La structure de l'éponge forme au moins une partie de la surface externe de l'éponge et la structure poreuse de l'éponge est imprégnée d'une composition liquide comprenant une ou plusieurs bactériocines. L'invention concerne également une composition liquide adaptée au canal vaginal, comprenant une ou plusieurs bactériocines en quantité suffisante pour favoriser la microflore vaginale en inhibant la croissance d'un ou de plusieurs agents pathogènes. L'invention concerne en outre une telle éponge ou une telle composition liquide à utiliser pour prévenir et/ou traiter la dysbiose, la candidose vulvovaginale et/ou la vaginose bactérienne.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/EP2022/076032 WO2024061444A1 (fr) | 2022-09-20 | 2022-09-20 | Éponge pour canal vaginal |
PCT/EP2023/075734 WO2024061867A1 (fr) | 2022-09-20 | 2023-09-19 | Eponge pour canal vaginal |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/EP2022/076032 WO2024061444A1 (fr) | 2022-09-20 | 2022-09-20 | Éponge pour canal vaginal |
Publications (1)
Publication Number | Publication Date |
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WO2024061444A1 true WO2024061444A1 (fr) | 2024-03-28 |
Family
ID=83978895
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2022/076032 WO2024061444A1 (fr) | 2022-09-20 | 2022-09-20 | Éponge pour canal vaginal |
PCT/EP2023/075734 WO2024061867A1 (fr) | 2022-09-20 | 2023-09-19 | Eponge pour canal vaginal |
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PCT/EP2023/075734 WO2024061867A1 (fr) | 2022-09-20 | 2023-09-19 | Eponge pour canal vaginal |
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