WO2024262189A1 - 細菌の増殖抑制剤、それを含む化粧品、医薬部外品、及び医薬組成物、並びに細菌の増殖抑制方法 - Google Patents

細菌の増殖抑制剤、それを含む化粧品、医薬部外品、及び医薬組成物、並びに細菌の増殖抑制方法 Download PDF

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WO2024262189A1
WO2024262189A1 PCT/JP2024/017716 JP2024017716W WO2024262189A1 WO 2024262189 A1 WO2024262189 A1 WO 2024262189A1 JP 2024017716 W JP2024017716 W JP 2024017716W WO 2024262189 A1 WO2024262189 A1 WO 2024262189A1
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Prior art keywords
bacteria
growth
mass
atopobium
gardnerella
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PCT/JP2024/017716
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English (en)
French (fr)
Japanese (ja)
Inventor
聡史 飯田
雄志 橋爪
マハマドゥ タンジャ
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Toyo Sugar Refining Co Ltd
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Toyo Sugar Refining Co Ltd
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Priority to EP24825598.6A priority Critical patent/EP4732840A1/en
Priority to KR1020257040478A priority patent/KR20260006643A/ko
Priority to JP2025527566A priority patent/JPWO2024262189A1/ja
Priority to CN202480034663.7A priority patent/CN121263191A/zh
Publication of WO2024262189A1 publication Critical patent/WO2024262189A1/ja
Anticipated expiration legal-status Critical
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/602—Glycosides, e.g. rutin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients

Definitions

  • the present disclosure relates to a growth inhibitor for at least one bacterium selected from the group consisting of the genus Gardnerella and the genus Atopobium, a cosmetic product, a quasi-drug, and a pharmaceutical composition containing the same, and a method for inhibiting bacterial growth.
  • Non-Patent Document 1 There are various kinds of bacteria that normally inhabit the vagina of healthy adult women, and the genus Lactobacillus accounts for 75-95% of these.
  • the genus Lactobacillus (Döderlein's bacillus), which normally inhabits the vagina, produces lactic acid and keeps the pH of the vagina at an acidic level of 4.5 or less, preventing the invasion of other germs (Non-Patent Document 1).
  • Non-Patent Document 2 Known Döderlein's bacillus species include Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus jensenii, Lactobacillus casei, Lactobacillus vaginalis, Lactobacillus crispatus, and Lactobacillus iners. Of these, Lactobacillus crispatus and Lactobacillus iners have been reported to be predominant in all four ethnic groups (whites, blacks, Hispanics, and Asians) (Non-Patent Document 2).
  • Vaginitis is a disease concept in which abnormal vaginal discharge is the main complaint, and typical examples include bacterial vaginosis (BV), genital candidiasis, and vaginal trichomoniasis.
  • BV bacterial vaginosis
  • the causative microorganism of genital candidiasis is a fungus of the genus Candida
  • the causative microorganism of vaginal trichomoniasis is the vaginal protozoan Trichomonas vaginalis, but bacterial vaginosis occurs due to the breakdown of the normal flora and is not caused by a specific causative microorganism.
  • bacterial vaginosis In bacterial vaginosis, the number of Döderlein's bacilli is reduced, and various aerobic and/or anaerobic bacteria proliferate abnormally. Although more than half of patients with bacterial vaginosis are asymptomatic, the main symptoms of bacterial vaginosis are foul-smelling vaginal discharge, gray to white vaginal discharge, a burning sensation when urinating, and itching around the vagina, and bacterial vaginosis is thought to increase the risk of pelvic inflammatory disease, miscarriage, premature birth, and postpartum endometritis.
  • overgrowth of aerobic bacteria is known to occur, such as Streptococcus agalactiae, Escherichia coli, and Gardnella vaginalis
  • overgrowth of anaerobic bacteria is known to occur, such as Atopobium spp., Anaerocossus spp., Atopobium vaginae, Peptostreptococcus spp., Finegoldia spp., Micromonas spp., and Peptoniphilus spp.
  • Metronidazole is known as a drug that has a bacterial growth inhibitory effect, mainly targeting Gardnella vaginalis, and is widely used in the treatment of bacterial vaginosis (Non-Patent Document 1).
  • bacteria of the genus Atopobium are known to be resistant to metronidazole (Patent Document 1), and the effect of metronidazole is therefore insufficient.
  • glyceryl glycoside is a sugar derivative having a structure in which glucose is bound to glycerin, and has traditionally been used as a cosmetic raw material.
  • ⁇ -D-Glucopyranosylglycerol a type of glyceryl glucoside, is non-irritating to the skin and extremely safe. It has also been reported to have antibacterial properties against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus epidermidis, and Corynebacterium minutissimum (Patent Document 2).
  • Patent Document 2 the antibacterial activity is evaluated by inoculating bacteria into ⁇ -D-glucopyranosylglycerol, exposing it for 24 or 48 hours, cultivating the collected sample in a medium, and counting the number of viable bacteria.
  • Patent Document 2 does not disclose how ⁇ -D-glucopyranosylglycerol acts on growing bacteria.
  • ⁇ -D-glucopyranosylglycerol acts on other bacteria, particularly bacteria of the genera Lactobacillus, Gardnerella, and Atopobium.
  • the present inventors have considered that if it were possible to reduce the number of bacteria of the genera Gardnerella and Atopobium without reducing the number of Döderlein's bacilli, it would be preferable in terms of maintaining the health of areas where at least one bacterium selected from the group consisting of Gardnerella and Atopobium is present or suspected to be present, such as the delicate zone, and preventing or treating infections.
  • the present disclosure therefore aims to provide a bacterial growth inhibitor that does not inhibit the growth of Döderlein's bacillus but inhibits the growth of at least one bacterium selected from the group consisting of the genera Gardnerella and Atopobium, a preparation containing the same, and a method for inhibiting bacterial growth.
  • the present inventors have conducted extensive research to solve the above problems, and as a result have found that the above problems can be solved by providing the following configuration, which has led to the completion of the present invention.
  • the present invention relates to, for example, the following [1] to [7].
  • [2] The proliferation inhibitor according to [1], wherein the bacterium is at least one selected from the group consisting of Gardnerella vaginalis and Atopobium vaginae.
  • the proliferation inhibitor according to [1] or [2] which is used as a cleansing agent or an external preparation.
  • a cosmetic or quasi-drug comprising the proliferation inhibitor according to [1] or [2].
  • a bacterial growth inhibitor that does not inhibit the growth of Döderlein's bacillus but inhibits the growth of at least one bacterium selected from the group consisting of the genera Gardnerella and Atopobium, a preparation containing the same, and a method for inhibiting bacterial growth.
  • Glyceryl glucoside is highly safe, as no toxicity has been found in primary skin irritation tests (rabbits), continuous skin irritation tests, skin sensitization tests (guinea pig intradermal maximization method), phototoxicity tests (guinea pigs), photosensitization tests, eye irritation tests (rabbits), mutagenicity tests (in vitro), or human patch tests. Therefore, according to the present disclosure, it is possible to inhibit the growth of at least one bacterium selected from the group consisting of the genus Gardnerella and the genus Atopobium without concerns about safety or side effects.
  • glyceryl glucoside also referred to as GG, refers to a compound in which glycerin is bonded to one or more glucose molecules via ⁇ - or ⁇ -glucoside bond.
  • examples of glyceryl glucoside include compounds represented by formulas (1) to (5). One type of such compound may be used alone, or two or more types may be used.
  • the compound represented by formula (1) is 1-O-( ⁇ - or ⁇ -)D-(mono- or poly-)glucopyranosylglycerol. This compound is also called 1-O-( ⁇ - or ⁇ -)D-dihydroxypropyl (mono- or poly-)glucopyranoside.
  • the carbon atom at the 2-position marked with an asterisk in formula (1) is an asymmetric carbon atom, and optical isomers, that is, a (2R) form and a (2S) form, exist.
  • n is the degree of sugar condensation and is an integer of 1 or more.
  • glyceryl glucosides produced by known methods such as enzymatic methods and organic synthesis methods
  • n is usually an integer of 1 to 6, and most of the compounds are an integer of 1 to 3.
  • the compound represented by formula (2) is 2-O-( ⁇ - or ⁇ -)D-(mono- or poly-)glucopyranosylglycerol. This compound is also called 2-O-( ⁇ - or ⁇ -)D-dihydroxypropyl (mono- or poly-)glucopyranoside.
  • n is the degree of sugar condensation and is an integer of 1 or more.
  • n is usually an integer between 1 and 6, with most of the compounds being integers between 1 and 3.
  • compounds with n equal to 1 are abundant in GG compositions.
  • n and l in formula (4), and l, m, and n in formula (5) are the degree of sugar condensation, each independently representing an integer of 1 or more, usually an integer of 1 to 6, mostly an integer of 1 to 3, and particularly compounds in which n, m, and l are 1 are abundant in the GG composition.
  • the glucopyranosyl groups may be linked to each other by ⁇ 1-4 bonds, ⁇ 1-4 bonds, ⁇ 1-6 bonds, ⁇ 1-6 bonds, etc.
  • the glyceryl glucoside in the present invention is represented by formula (1) or formula (2), and preferably contains at least one of 1-O-D-glucopyranosylglycerol and 2-O-D-glucopyranosylglycerol, where n is 1, and more specifically, preferably contains at least one selected from 1-O- ⁇ -D-glucopyranosylglycerol, 1-O- ⁇ -D-glucopyranosylglycerol, 2-O- ⁇ -D-glucopyranosylglycerol, and 2-O- ⁇ -D-glucopyranosylglycerol.
  • the glyceryl glucoside in the present invention may be one compound selected from 1-O- ⁇ -D-glucopyranosylglycerol, 1-O- ⁇ -D-glucopyranosylglycerol, 2-O- ⁇ -D-glucopyranosylglycerol, and 2-O- ⁇ -D-glucopyranosylglycerol, or may contain two or more compounds.
  • the glyceryl glucosides of 1-O- ⁇ -D-glucopyranosylglycerol, 1-O- ⁇ -D-glucopyranosylglycerol, 2-O- ⁇ -D-glucopyranosylglycerol, and 2-O- ⁇ -D-glucopyranosylglycerol are glycerin bound to one glucose molecule, but in the present invention, the glyceryl glucoside may be further bound to glucose, i.e., n may be 2 or more, or may be a mixture of a compound where n is 1 and a compound where n is 2 or more.
  • the bonding mode between glucopyranosyl groups is not particularly limited.
  • the wavy lines in formulae (1) to (5) each independently indicate that the hydroxyl group of glycerin may react with the hydroxyl group at position 1 of the ⁇ -D-glucopyranosyl group to form a bond ( ⁇ bond) or may react with the hydroxyl group at position 1 of the ⁇ -D-glucopyranosyl group to form a bond ( ⁇ bond).
  • the glyceryl glucoside is preferably mainly composed of 1-O- ⁇ -D-glucopyranosylglycerol, and more preferably 10-50% by mass of 100% by mass of glyceryl glucoside.
  • Glyceryl glucoside may be used as a composition (also called a GG composition) that further contains, in addition to the compounds represented by formulas (1) to (5), compounds other than the compounds represented by formulas (1) to (5), such as water, and unreacted substances or reaction by-products (impurities) that may be mixed in when preparing the compounds represented by formulas (1) to (5) by organic synthesis.
  • impurities include glycerin and reaction by-products derived therefrom, which are used as raw materials for producing glyceryl glucoside, as well as glucose sources and reaction by-products derived therefrom.
  • examples include alcohols such as ethanol, isopropyl alcohol, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, 1,2-pentanediol, glycerin, diglycerin, and polyglycerin, and sugars such as glucose.
  • the proportion of glycerin remaining in the GG composition is preferably 70% by mass or less, more preferably 50% by mass or less, even more preferably 45% by mass or less, particularly preferably 10% by mass or less, and most preferably 5% by mass or less, based on the total solid content in the GG composition (components excluding water). It is preferable that no glycerin is contained, and it may be 0% by mass based on the total solid content in the GG composition, and is usually 10% by mass or less.
  • the method for producing glyceryl glucoside in the present invention is not particularly limited, and it can be produced by known methods such as an enzymatic method or an organic synthesis method.
  • a commercially available product containing glyceryl glucoside can be purchased and used, for example, "COSARTE-2G (registered trademark) (manufactured by Toyo Sugar Refining Co., Ltd.)" or "C-mo 2G (manufactured by Toyo Sugar Refining Co., Ltd.)” can be used.
  • COSARTE-2G contains glyceryl glucoside at approximately 66 to 78% by mass and glycerin at approximately 10% by mass or less in 100% by mass of "COSARTE-2G".
  • C-mo 2G has a glyceryl glucoside content of approximately 30 to 38 mass% and a glycerin content of approximately 36 to 44 mass% in 100 mass% of "C-mo 2G".
  • Glyceryl glucoside has good water solubility, so it can be dissolved or dispersed uniformly even when added to water or preparations with a high moisture content.
  • glyceryl glucoside has a high moisturizing effect and is low in irritation to the skin, so it can be used preferably in sensitive areas such as delicate zones.
  • a growth inhibitor in one embodiment of the present invention contains glyceryl glucoside and inhibits the growth of at least one bacterium selected from the group consisting of the genera Gardnerella and Atopobium.
  • the amount of glyceryl glucoside contained in the growth inhibitor is not particularly limited.
  • the lower limit of the amount of glyceryl glucoside contained in the growth inhibitor can be, for example, 20 mass%, 25 mass%, 30 mass%, 40 mass%, 45 mass%, 50 mass%, 60 mass%, 70 mass%, or 80 mass%.
  • the upper limit of the amount of glyceryl glucoside contained in the growth inhibitor can be, for example, 100 mass%, 99 mass%, 98 mass%, 95 mass%, 90 mass%, or 85 mass%.
  • the range of the amount of glyceryl glucoside contained in the growth inhibitor can be set to any range that combines the lower limit and the upper limit, for example, 25 to 100 mass%, 30 to 90 mass%, or 60 to 80 mass%. From the viewpoint of the growth inhibitory effect, the amount of glyceryl glucoside contained in the growth inhibitor is preferably 20 mass% or more, and more preferably 30 mass% or more.
  • the growth inhibitor may contain glycerin, diglycerin, glucose, water, and other ingredients as necessary.
  • Examples of bacteria of the Gardnerella genus include Gardnerella vaginalis, and examples of bacteria of the Atopobium genus include Atopobium vaginae (Fannyhessea vaginae), Atopobium rimae, Atopobium parvulum, Atopobium fossor, Atopobium minutum, and Atopobium deltae. Since these are the main bacteria that overgrow in bacterial vaginosis, it is preferable that the bacterium is at least one selected from the group consisting of Gardnerella vaginalis and Atopobium vaginae.
  • the method for evaluating the effect of inhibiting the growth of the bacteria is not particularly limited, and any known method can be used. For example, if the degree of growth of bacteria cultured with the addition of a test substance is lower than the degree of growth of bacteria cultured without the addition of the test substance under the same culture conditions, the test substance can be evaluated as having an effect of inhibiting the growth of bacteria.
  • the test substance when the number of bacteria cultured without adding the test substance is taken as 100%, if the number of bacteria cultured with the test substance added is less than 100%, the test substance can be evaluated as having an effect of inhibiting bacterial growth.
  • the number of bacteria cultured with the test substance added is preferably 90% or less, more preferably 80% or less, even more preferably 70% or less, and particularly preferably 60% or less of the number of bacteria cultured without adding the test substance.
  • the bacteria used are preferably growing bacteria, more preferably bacteria in the logarithmic growth phase.
  • the method for measuring the number of bacteria is not particularly limited, and known methods can be used.
  • the number of bacteria may be measured by a direct detection method for counting the number of bacteria, such as counting with a bacteria counting chamber, culturing on an agar plate and counting colonies, or culturing on an agar plate and observing the presence and size of growth inhibition zones formed, or by an indirect method for quantitatively detecting various indicators due to the presence of bacteria, such as measuring turbidity (absorbance) using a spectrophotometer, measuring the weight of bacterial bodies, or measuring bacterial components or biochemical activity. Because of simplicity, the bacterial count is preferably measured by an indirect method, more preferably turbidity measurement using a spectrophotometer.
  • the use of the proliferation inhibitor of the present invention is not particularly limited, but since the proliferation inhibitor has a high effect of inhibiting the proliferation of at least one bacterium selected from the group consisting of the genera Gardnerella and Atopobium, it can be administered to a living body once or multiple times, for example, for the purpose of maintaining the health of delicate areas, etc. and/or for the purpose of preventing or treating infectious diseases.
  • the proliferation inhibitor is useful for preventing or improving a disease or symptom involving at least one bacterium selected from the group consisting of the genus Gardnerella and the genus Atopobium, and contributes to preventing or improving the onset and progression of, for example, bacterial vaginosis, urinary tract infection, endometritis, acute salpingitis, postoperative infection, amniotic fluid infection, infertility, premature birth, and neonatal sepsis.
  • the disease or symptom is preferably bacterial vaginosis.
  • the dosage of the growth inhibitor may be appropriately selected depending on the type or severity of the disease or symptom associated with at least one bacterium selected from the group consisting of the genus Gardnerella and the genus Atopobium, the route of administration, etc.
  • the administration period of the growth inhibitor may be appropriately selected depending on the type or severity of the disease or symptom involving at least one bacterium selected from the group consisting of the genus Gardnerella and the genus Atopobium, the administration route, etc. From the viewpoint of the growth inhibitory effect, the administration period is preferably 3 to 80 days, more preferably 7 to 60 days.
  • the route of administration of the proliferation inhibitor is not particularly limited, and any known route of administration may be used, and the proliferation inhibitor may be administered orally or parenterally. Because of ease of administration, the proliferation inhibitor is preferably administered parenterally, and more preferably administered externally. When the proliferation inhibitor is orally administered, it may be used as a medicine or as a food or drink. From the viewpoint of the effect of inhibiting bacterial proliferation, the proliferation inhibitor is preferably used as a cleansing agent or an external preparation.
  • the target area for the cleanser or topical agent is an area where at least one bacterium selected from the group consisting of the genus Gardnerella and the genus Atopobium is present or suspected to be present, and is preferably the female or male intimate area, more preferably the female intimate area, and even more preferably the vagina.
  • the female intimate area means the vulva, vagina, and the skin surrounding them
  • the male intimate area means the penis, testicles, and the skin surrounding them.
  • An external preparation means a preparation that is applied directly to the surface of the skin, mucous membrane, etc., and may be any of a pharmaceutical composition, a quasi-drug, or a cosmetic.
  • a pharmaceutical composition a pharmaceutical composition, a quasi-drug, or a cosmetic.
  • the properties and dosage form of the external preparation may be in the form of a solid, semi-solid, liquid, emulsion, cream, gel, mousse, spray, or a two-component system that uses a mixture of these.
  • a cleanser refers to a preparation for cleaning the skin, mucous membranes, etc., and may be any of a pharmaceutical composition, a quasi-drug, or a cosmetic. There are no limitations on the properties and formulation of the cleanser, which may be in a solid, semi-solid, liquid, emulsion, cream, gel, mousse, spray form, or a two-component form in which these are mixed.
  • the cleanser may be a cleanser that contains a surfactant and is usually foamed before use (e.g., soap, body wash), or a cleanser that is filled into a cleaner and sprayed onto the area to be cleaned.
  • a cleanser that contains a surfactant and is usually foamed before use (e.g., soap, body wash), or a cleanser that is filled into a cleaner and sprayed onto the area to be cleaned.
  • the wash is preferably a vaginal wash.
  • the vaginal wash is filled, for example, in a container (vaginal wash device) equipped with a nozzle that can be inserted into the vagina, and sprayed into the vagina to wash away residual blood and/or secretions remaining inside or outside the vagina.
  • the proliferation inhibitor may be administered to a living body as it is, or may be administered as a preparation in which an effective amount of the proliferation inhibitor is mixed with a pharma- ceutically acceptable carrier.
  • the dosage form of the preparation is not particularly limited, and may be any of a drug, a quasi-drug, and a cosmetic.
  • one aspect of the present invention is a cosmetic or a quasi-drug that contains the proliferation inhibitor.
  • a further aspect of the present invention is a pharmaceutical composition that contains the proliferation inhibitor.
  • the content of glyceryl glucoside in the preparation can be appropriately set depending on the form and/or application of the preparation, but from the viewpoint of the effect of inhibiting bacterial growth, examples of the content include 0.002 mass% or more, 0.003 mass% or more, 0.004 mass% or more, 0.005 mass% or more, 0.006 mass% or more, 30 mass% or less, 29 mass% or less, 28 mass% or less, 27 mass% or less, 26 mass% or less, 25 mass% or less, 24 mass% or less, 23 mass% or less, 22 mass% or less, 21 mass% or less, and 20 mass% or less.
  • the cosmetic or quasi-drug is preferably a cosmetic or quasi-drug for the delicate zone, and more preferably a cream, ointment, gel, or lotion for the delicate zone.
  • the cosmetic or quasi-drug may contain, as necessary, ingredients that are usually used in cosmetics, skin preparations for external use that are pharmaceuticals, or cleansing agents, such as fats and oils, waxes, hydrocarbon oils, ester oils, higher alcohols, silicone oils, moisturizing agents, surfactants, water-soluble polymers, thickeners, powders, skin protective agents, whitening agents, wrinkle improving agents, anti-aging agents, plant extracts, preservatives, anti-inflammatory agents, pH adjusters, sequestering agents, antioxidants, stabilizers, fragrances, colorants, pigments, etc., within the scope of not impairing the effects of the present invention. These ingredients may be used alone or in combination of two or more.
  • the cosmetic or quasi-drug may also contain probiotics such as Doderlein's bacillus.
  • the pharmaceutical composition is preferably for treating or preventing a disease involving Gardnerella vaginalis or Atopobium vaginae.
  • a disease involving Gardnerella vaginalis or Atopobium vaginae.
  • the disease include bacterial vaginosis, urinary tract infection, endometritis, acute salpingitis, postoperative infection, amniotic fluid infection, infertility, premature birth, and neonatal sepsis, with bacterial vaginosis being preferred.
  • the dosage form of the pharmaceutical composition is not particularly limited, and may be a solid preparation such as a powder, granules, tablets, or capsules; or a liquid preparation such as a solution, suspension, or emulsion.
  • the pharmaceutical composition is preferably a pharmaceutical composition for the delicate area, more preferably a vaginal suppository or a cream, ointment, gel, or lotion to be applied to the skin or mucous membrane of the delicate area, and even more preferably a vaginal suppository or a cream, ointment, gel, or lotion to be applied to the skin or mucous membrane of a female delicate area.
  • Vaginal suppositories are external preparations to be applied inside the vagina, and may be in any form such as tablets, capsules, ointments, gels, etc., and may be inserted into the vagina using an applicator.
  • the pharmaceutical composition may contain antibiotics, antifungals, germicides, local anesthetics, antihistamines, antipruritics, preservatives, pH adjusters, excipients, binders, disintegrants, lubricants, stabilizers, solubilizers, suspending agents, isotonicity agents, buffers, antioxidants, probiotics such as Doderlein's bacillus, etc. These components may be used alone or in combination of two or more.
  • antibiotics examples include metronidazole, clindamycin, secnidazole, chloramphenicol, and nifrateral.
  • Antifungal agents include, for example, fluconazole, butoconazole, clotrimazole, miconazole, and tioconazole.
  • germicidal disinfectants include benzalkonium chloride, benzethonium chloride, povidone iodine, and isopropyl methylphenol.
  • Local anesthetics include, for example, lidocaine, xylocaine, dibucaine, and ethyl aminobenzoate.
  • antihistamines examples include diphenhydramine, cetidine, doxepin, and hydroxyzine.
  • An example of an antipruritic agent is crotamiton.
  • the formulation can be manufactured by adding the growth inhibitor according to a method generally used for these formulations.
  • the growth inhibitor may be added at the beginning of the manufacturing process of the formulation, or at the middle or end of the manufacturing process, and the method of addition may be selected from among mixing, kneading, dissolving, immersion, scattering, spraying, coating, etc., as appropriate depending on the form of the formulation.
  • One aspect of the present invention is a method for inhibiting the growth of at least one bacterium selected from the group consisting of the genera Gardnerella and Atopobium, comprising the step of administering glyceryl glucoside to a subject.
  • the method of administering glyceryl glucoside to a subject is not particularly limited, and any suitable means can be used depending on the subject.
  • Parenteral administration is preferred as the administration method, and external application to the skin or mucosa is more preferred.
  • External application to the skin or mucosa may be, for example, a simple application method, layering therapy, occlusive therapy, moist therapy, etc.
  • the target site to which glyceryl glucoside is administered is a site where at least one bacterium selected from the group consisting of the genus Gardnerella and the genus Atopobium is present or suspected to be present, preferably the female or male intimate area, more preferably the female intimate area, and even more preferably the vagina.
  • One aspect of the present invention is a therapeutic or preventive agent for a disease involving Gardnerella vaginalis or Atopobium vaginae, which contains glyceryl glucoside.
  • One aspect of the present invention is glyceryl glucoside for use as a therapeutic or preventive agent for diseases involving Gardnerella vaginalis or Atopobium vaginae.
  • One aspect of the present invention is the use of glyceryl glucoside to inhibit the growth of at least one bacterium selected from the group consisting of the genera Gardnerella and Atopobium.
  • One aspect of the present invention is the use of glyceryl glucoside in the manufacture of a growth inhibitor for at least one bacterium selected from the group consisting of the genera Gardnerella and Atopobium.
  • One aspect of the present invention is a method for treating or preventing a disease involving Gardnerella vaginalis or Atopobium vaginae, comprising administering to a subject an effective amount of glyceryl glucoside.
  • Example 1 Growth test using Gardnerella vaginalis, Atopobium vaginae and Doderlein's bacillus (Test substance)
  • C-mo 2G manufactured by Toyo Sugar Refining Co., Ltd.
  • penicillin-streptomycin manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., No. 168-23191
  • sterilized water was used.
  • Bacteria and culture medium The bacteria and media used were those shown in Table 1, and cultured under the conditions shown in Table 1.
  • the GAM semi-fluid upper layer medium used was No. 05424 manufactured by Nissui Pharmaceutical Co., Ltd. The number of days for which the bacteria growth was visually confirmed in the control was determined.
  • C-mo 2G was added to the medium at final concentrations of 0.5%, 1.0%, and 2.0%.
  • penicillin-streptomycin was added to Lactobacillus crispatus at a final concentration of 10%, Lactobacillus iners at a final concentration of 1%, Gardnerella vaginalis at a final concentration of 1%, and Atopobium vaginae at a final concentration of 10%.
  • glyceryl glucoside does not inhibit the growth of the Doderlein bacillus bacteria Lactobacillus crispatus and Lactobacillus iners, but inhibits the growth of Gardnerella vaginalis and Atopobium vaginae.
  • Propionibacterium acnes JCM 6425 was used as a representative strain of Propionibacterium acnes.
  • the Propionibacterium acnes strain was placed in a GAM liquid medium, which was then placed in an Anaeropack at 35° C. and pre-cultured under anaerobic conditions.
  • Staphylococcus aureus Staphylococcus aureus (NBRC 13276) was used as a representative strain of Staphylococcus aureus.
  • the Staphylococcus aureus strain was placed in a BHI liquid medium and pre-cultured at 37°C.
  • GAM agar plate medium and BHI agar plate medium were prepared.
  • the pre-cultured Propionibacterium acnes strain, Propionibacterium dental caries strain, and Staphylococcus aureus strain in the logarithmic growth phase were suspended in liquid medium to a concentration of 1 x 107 cells/mL, and 50 ⁇ L of this suspension was smeared on each agar plate medium with a Conlarge stick.
  • Each test substance was sterilized by filtration using a membrane filter, and 50 ⁇ L of the substance was soaked into a sterilized paper disk.
  • the paper disk was aseptically placed on an agar plate medium and cultured for 48 hours under conditions suitable for each bacterial strain. The effect of inhibiting bacterial growth was judged based on the presence and size of a growth inhibition zone around the paper disc.
  • Glyceryl glucoside did not show any zones of inhibition for Propionibacterium acnes, Streptococcus mutans, or Staphylococcus aureus. In other words, it was revealed that glyceryl glucoside does not inhibit the growth of Propionibacterium acnes, Streptococcus mutans, or Staphylococcus aureus. The results with glycerin, which was used as a control, were similar to those of glyceryl glucoside.

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