Polyols for use in the prevention and treatment of diseases caused by anaerobic pathogenic microorganisms
Monoanhydrohexitols and dianhydrohexitols like isosorbide are used to inhibit anaerobic bacteria in the oral cavity, preventing infections and systemic diseases by reducing pathogen growth and biofilm formation.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-03-22
- Publication Date
- 2026-03-19
AI Technical Summary
Anaerobic pathogenic microorganisms, particularly obligate anaerobes like Fusobacterium nucleatum and Porphyromonas gingivalis, cause various diseases and symptoms by colonizing low-oxygen environments in the oral cavity and spreading to other body parts, leading to infections and systemic conditions such as periodontitis, cancer, and autoimmune diseases.
The use of monoanhydrohexitols and dianhydrohexitols, such as isosorbide, to inhibit the growth and biofilm formation of these pathogens, thereby preventing and treating associated diseases and symptoms.
Isoorbide effectively reduces the population of anaerobic bacteria, preventing oral infections and systemic diseases by targeting these pathogens in low-oxygen oral environments.
Smart Images
Figure 2026509591000017 
Figure 2026509591000018 
Figure 2026509591000019
Abstract
Description
Technical Field
[0001] The present invention relates to the field of hexitols for use in the prevention and / or treatment of diseases and / or symptoms caused by anaerobic pathogenic microorganisms, and more particularly to monoanhydrohexitols, dianhydrohexitols, or combinations thereof for use in the prevention and / or treatment of such diseases and / or symptoms.
Background Art
[0002] In French Patent No. 1761521, the applicant previously presented a non-therapeutic use of dianhydrohexitols such as isosorbide in oral hygiene that can reduce the occurrence of non-strictly anaerobic oral anaerobic bacterial strains such as Streptococcus mutans, Lactobacillus gasseri, Actinomyces naeslundii, and Actinomyces oris. Therefore, isosorbide has been proposed as a substitute for preservatives in oral care hygiene. [Problems to be Solved by the Invention]
[0003] Recently, a link has been established between the presence of certain anaerobic pathogenic microorganisms in the human oral cavity and several diseases and / or their symptoms. More specifically, anaerobic pathogenic microorganisms are obligate anaerobic pathogenic microorganisms such as Fusobaceterium nucleatum and Porphyromonas gingivalis. They can develop in places in the oral cavity where oxygen is unavailable, such as between teeth and plaque (also known as calculus, which forms on the teeth) or between the gums and teeth. From there, they can cause two types of problems, mainly due to their protease activity. The first is oral infection, leading to periodontal diseases such as periodontitis. The second is ectopic colonization in other parts or organs of the body, because they can enter the bloodstream from the site of infection in the oral cavity. Therefore, they can spread to any organ in the body, such as the brain, heart, and intestines, where they can cause diseases such as cancer, brain inflammation, Alzheimer's disease, premature birth, autoimmune diseases, cardiovascular diseases, diabetes, obesity, insulin resistance, rheumatoid arthritis, inflammatory bowel disease, or respiratory inflammation.
[0004] A method for preventing and / or treating diseases and / or symptoms associated with obligate anaerobic pathogenic microorganisms may include preventing and / or treating oral infections caused by such obligate anaerobic pathogenic microorganisms. This is the object of this patent application. [Brief explanation of the drawing]
[0005] Other features, details, and advantages are shown in the detailed description and drawings below. [Figure 1] The chemical structures of sorbitol, and the monoanhydrohexitol and dianhydrohexitol obtained therefrom, are shown. [Figure 2] The changes in the Fusobacterium nucleatum population under growth conditions with isosorbide content of 2.5%, 5%, and 10% by weight are shown. [Figure 3] This shows the changes in the Fusobacterium nucleatum population under survival conditions with isosorbide content of 2.5%, 5%, and 10% by weight. [Figure 4] The changes in the population of Porphyromonas sp. under growth conditions with isosorbide content of 2.5%, 5%, and 10% by weight are shown. [Figure 5] This shows the changes in the Porphyromonas sp. population under survival conditions with isosorbide content of 2.5%, 5%, and 10% by weight. [Figure 6] The changes in the population of Porphyromonas gingivalis W83 under growth conditions with isosorbide content of 2.5%, 5%, and 10% by weight are shown. [Figure 7] This shows the changes in the Porphyromonas gingivalis W83 population under survival conditions with isosorbide content of 2.5%, 5%, and 10% by weight. [Figure 8] The changes in the population of Porphyromonas gingivalis D141 under growth conditions with isosorbide content of 2.5%, 5%, and 10% by weight are shown. [Figure 9] This shows the changes in the Porphyromonas gingivalis D141 population under survival conditions with isosorbide content of 2.5%, 5%, and 10% by weight. [Figure 10] The changes in the Veillonella parvula population under growth conditions with isosorbide content of 2.5%, 5%, and 10% by weight are shown. [Figure 11] This shows the changes in the Veillonella parvula population under survival conditions with isosorbide content of 2.5%, 5%, and 10% by weight. [Figure 12] The changes in the population of Parvimonas micra under growth conditions with isosorbide content of 2.5%, 5%, and 10% by weight are shown. [Figure 13] This shows the changes in the population of Parvimonas micra under survival conditions with isosorbide content of 2.5%, 5%, and 10% by weight. [Overview of the project]
[0006] The first object of this application is a polyol for use in the prevention and / or treatment of diseases and / or symptoms associated with pathogenic microorganisms in subjects requiring the prevention and / or treatment of diseases and / or symptoms associated with pathogenic microorganisms.
[0007] In one embodiment, the pathogenic microorganism is an anaerobic pathogenic microorganism. In another embodiment, the pathogenic microorganism is an obligate anaerobic pathogenic microorganism.
[0008] In another embodiment, the pathogenic microorganism is a bacterium of the genus Fusobacterium, such as Fusobacterium nucleatum, Fusobacterium necrophorum, or Fusobacterium polymorphum.
[0009] In another embodiment, the pathogenic microorganism is a bacterium of the genus Porphyromonas, such as the bacterium Porphyromonas gingivalis.
[0010] In another embodiment, the pathogenic microorganism is a bacterium of the genus Veillonella, such as Veillonella parvula, Veillonella dispar, or Veillonella atypica.
[0011] In another embodiment, the pathogenic microorganism is a bacterium of the genus Parvimonas, for example, a bacterium of the species Parvimonas micra.
[0012] In another embodiment, the polyol is a hexitol. In another embodiment, the polyol is a monoanhydrohexitol such as 1,4-sorbitan, 2,5-mannitan, 2,5-iditan, 3,6-sorbitan, or a combination thereof. In another embodiment, the polyol is a dianhydrohexitol such as 1,4-3,6-dianhydrohexitol. In particular, the 1,4-3,6-dianhydrohexitol is isosorbide, isomannide, isoidide, or a combination thereof. In another embodiment, the polyol is isosorbide.
[0013] In yet another aspect, the disease and / or symptom is cancer (e.g., tongue cancer, esophageal cancer, gastric cancer, intestinal cancer, colon cancer, or systemic cancer), brain inflammation, Alzheimer's disease, premature birth, autoimmune disease, cardiovascular disease (e.g., atherosclerosis and / or coronary artery disease), diabetes, obesity, insulin resistance, rheumatoid arthritis, inflammatory bowel disease, or respiratory inflammation.
[0014] In particular, the disease and / or symptom is something in the oral cavity, e.g., oral lichen planus, oral cancer, or periodontal disease (e.g., periodontitis).
[0015] In particular, the symptoms are gingival inflammation, gingival bleeding, gingiva, teeth, and / or jaw pain at rest, gingiva, teeth, and / or jaw pain during chewing, tooth looseness, tooth loss, fever, and bad breath.
[0016] A second object of the present application is a composition containing a polyol for use in the prevention and / or treatment of a disease and / or symptom associated with a pathogenic microorganism in a subject that requires the prevention and / or treatment of a disease and / or symptom associated with a pathogenic microorganism, as described in the first object of the present application.
[0017] In another aspect, the composition is a liquid, gel, compacted powder or loose powder, solid, or film.
[0018] In another aspect, the composition is a toothpaste, toothpaste gel, capsule, soft gel capsule, tablet (e.g., oral care tablet), oral care film, mouthwash, oral spray, or confectionery (e.g., candy).
[0019] In another aspect, the content of the polyol in the composition is at least 0.5% by weight, at least 1% by weight, at least 5% by weight, or at least 10% by weight of the total weight of the composition.
[0020] In another aspect, the composition is rinsed off or left after administration.
[0021] In another embodiment, the composition is applied in or on a dental mold, oral care patch, dental floss, or dental strip.
[0022] In another embodiment, the composition contains less than 1% by weight of dimethyl isosorbide by the total weight of the composition, or does not contain dimethyl isosorbide. [Modes for carrying out the invention]
[0023] polyol The polyol is an alcohol containing at least two alcohol functional groups, i.e., at least two hydroxyl-OH groups. In one embodiment, the polyol contains at least two carbon atoms, at least three carbon atoms, at least four carbon atoms, at least five carbon atoms, or at least six carbon atoms.
[0024] Hexitol Hexitol is a polyol containing six carbon atoms and six alcohol functional groups, such as sorbitol, mannitol, and isitol.
[0025] Anhydrohexitol Anhydrohexitols are hexitols containing at least one heterocyclic ring with an oxygen atom, typically obtained from hexitol by dehydration with a catalyst under acidic conditions. Monoanhydrohexitols are heterocyclic hexitols containing one ring, such as 1,4-sorbitan, 2,5-mannitane, 2,5-iditane, and 3,6-sorbitan. Dianhydrohexitols are heterocyclic hexitols containing two rings, such as 1,4-3,6-dianhydrohexitol, and can be isosorbide, isomannide, or isoidide.
[0026] pathogenic microorganisms A pathogenic microorganism is a bacterium, fungus, or protist that, when it infects a mammal such as a human or animal, causes one or more diseases in that mammal.
[0027] In one embodiment, the pathogenic microorganism is anaerobic.
[0028] Anaerobic microorganisms can be tolerant to the presence of oxygen in their surroundings, in which case they are called non-obligate anaerobes, or they can be completely intolerant to the presence of oxygen in their surroundings, in which case they are called obligate anaerobes. "Tolerance" means that non-obligate anaerobes can grow in media that contain little to no oxygen, such as parts of the human body like the mouth. "Intolerance" means that obligate anaerobes cannot grow at all in such low-oxygen media and, therefore, can only survive in such low-oxygen media for a limited period of time. Obligate anaerobes require oxygen-free media in order to survive and grow for a sufficiently long time.
[0029] In another embodiment, the pathogenic microorganism is obligate anaerobic.
[0030] Those who need it As used herein, the term “subject” means mammals, including, for example, livestock (e.g., cattle, horses, pigs, and sheep) and humans. In one embodiment, the subject is a human. In one embodiment, the subject is female. In one embodiment, the subject is male. In another embodiment, the subject is a dog (e.g., a member of the genus Canis) or a cat (e.g., a member of the genus Feiis or Panthera).
[0031] Compositions containing polyols A composition according to the second purpose of this application may comprise at least one polyol according to the first purpose of this application. Such a composition may be a food, a food ingredient, a nutritional supplement, a cosmetic, a medical food, a vaccine, or a pharmaceutically acceptable composition or formulation, or may be used as an ingredient for the preparation thereof.
[0032] Pharmaceutical composition The compositions according to the second purpose of this application may be used as pharmaceutical compositions or formulations, or in the preparation thereof. Herein, the term “pharmaceutical” is used in a broad sense and includes pharmaceuticals for human use as well as pharmaceuticals for animal use (i.e., veterinary use).
[0033] In one embodiment, the pharmaceutically acceptable composition is a pharmaceutical.
[0034] A pharmaceutical composition may be for therapeutic purposes, and may be essentially curative, palliative, or preventive. A pharmaceutical composition may also be for diagnostic purposes.
[0035] In one embodiment of the present invention, the medicine is for oral administration.
[0036] Pharmaceutically acceptable compositions or supports may be formulations or supports in the form of compressed tablets, tablets, capsules, ointments, suppositories, or creams, foams, gels, lotions, and ointments of oral solutions.
[0037] food In one embodiment, the composition according to the second object of this application is used in food products such as food supplements, beverages, or milk-based powders. Here, the term “food” is used in a broad sense and includes food for human consumption as well as food for animals (i.e., animal feed). In one embodiment, the food is for human consumption.
[0038] Foods may be in the form of a solution or a solid, depending on the mode of use and / or application and / or administration.
[0039] Nutritional supplements The compositions according to the second purpose of this application may take the form of dietary supplements, or may be used by themselves in combination with dietary supplements (also known herein as food supplements). As used herein, the term “dietary supplement” means a product intended for ingestion that contains “nutritional components” intended to add (supplement) nutritional value or health benefits to a diet. “Nutritional components” may include, but are not limited to, one or any combination of the following substances: bacteria, probiotics (e.g., probiotic bacteria), vitamins, minerals, herbs or other plants, amino acids, dietary substances, concentrates, metabolites, components or extracts for human use to supplement a diet by increasing total dietary intake.
[0040] Dietary supplements can be found in many forms, such as tablets, capsules, softgels, gel caps, liquids, or powders. Some dietary supplements may help ensure adequate dietary intake of essential nutrients. Others may help prevent or treat diseases.
[0041] Medical Foods The compositions relating to the second purpose of this application may take the form of medical foods. "Medical foods" means foods that are prescribed to be taken or administered with or without the supervision of a physician and that are intended for a specific dietary regime or condition in which specific nutritional requirements have been established by medical evaluation based on recognized scientific principles.
[0042] cosmetics The compositions according to the second purpose of this application may be in the form of cosmetics such as skincare products, haircare products, makeup products, or hygiene products.
[0043] In one embodiment, the cosmetic is a hygiene product. In particular, the hygiene product may be an oral care tablet, oral care film, mouthwash, oral spray, dental mold, oral care patch, dental floss, or dental strip.
[0044] Specific numbered embodiments of the present invention Embodiment 1. A polyol for use in the prevention and / or treatment of diseases and / or symptoms associated with pathogenic microorganisms in subjects requiring the prevention and / or treatment of diseases and / or symptoms associated with pathogenic microorganisms.
[0045] Embodiment 2. The polyol for use according to Embodiment 1, wherein the pathogenic microorganism is an anaerobic pathogenic microorganism.
[0046] Embodiment 3. The polyol for use according to Embodiment 2, wherein the anaerobic pathogenic microorganism is an obligate anaerobic pathogenic microorganism.
[0047] Embodiment 4. A polyol for use according to any one of Embodiments 1 to 3, wherein the polyol is administered orally.
[0048] Embodiment 5. A polyol for use according to any one of Embodiments 1 to 3, wherein the polyol is administered to the skin, eyes, ears, or genital mucosa of the subject.
[0049] Embodiment 6. The polyol for use according to any one of Embodiments 1 to 5, wherein the pathogenic microorganism is a bacterium of the genus Fusobacterium.
[0050] Embodiment 7. The polyol for use according to Embodiment 6, wherein the bacterium of the genus Fusobacterium is of the species Fusobacterium nucleatum.
[0051] Embodiment 8. The polyol for use according to Embodiment 6, wherein the bacterium of the genus Fusobacterium is of the species Fusobacterium necrophorum.
[0052] Embodiment 9. The polyol for use according to Embodiment 6, wherein the bacterium of the genus Fusobacterium is of the species Fusobacterium polymorphum.
[0053] Embodiment 10. The polyol for use according to any one of Embodiments 1 to 5, wherein the pathogenic microorganism is a bacterium of the genus Porphyromonas.
[0054] Embodiment 11. The polyol for use according to Embodiment 10, wherein the bacterium of the genus Porphyromonas is of the species Porphyromonas gingivalis.
[0055] Embodiment 12. The polyol for use according to any one of Embodiments 1 to 5, wherein the pathogenic microorganism is a bacterium of the genus Veillonella.
[0056] Embodiment 13. The polyol for use according to Embodiment 12, wherein the bacterium of the genus Veillonella is of the species Veillonella parvula.
[0057] Embodiment 14. The polyol for use according to Embodiment 12, wherein the bacterium of the genus Veillonella is of the species Veillonella dispar.
[0058] Embodiment 15. The polyol for use according to Embodiment 12, wherein the bacterium of the genus Veillonella is of the species Veillonella atypica.
[0059] Embodiment 16. The polyol for use according to any one of Embodiments 1 to 5, wherein the pathogenic microorganism is a bacterium of the genus Parvimonas.
[0060] Embodiment 17. The polyol for use according to Embodiment 16, wherein the bacterium of the genus Parvimonas is of the species Parvimonas micra.
[0061] Embodiment 18. A polyol for use according to any one of Embodiments 1 to 17, wherein the polyol is hexitol.
[0062] Embodiment 19. A polyol for use according to any one of Embodiments 1 to 18, wherein the polyol is monoanhydrohexitol.
[0063] Embodiment 20. A polyol for use according to any one of Embodiments 1 to 19, wherein the polyol is selected from 1,4-sorbitan, 2,5-mannitan, 2,5-iditan, 3,6-sorbitan, or a combination thereof.
[0064] Embodiment 21. A polyol for use according to any one of Embodiments 1 to 18, wherein the polyol is dianhydrohexitol.
[0065] Embodiment 22. A polyol for use according to any one of Embodiments 1 to 18 and 21, wherein the polyol is 1,4-3,6-dianehydrohexitol.
[0066] Embodiment 23. A polyol for use according to any one of Embodiments 1 to 18 and 21 to 22, wherein the polyol is selected from isosorbide, isomannide, or isoidide.
[0067] Embodiment 24. A polyol for use according to any one of Embodiments 1 to 18 and 21 to 23, wherein the polyol is isosorbide.
[0068] Embodiment 25. A polyol for use according to any one of Embodiments 1 to 24, wherein the disease and / or symptoms are cancer, encephalitis, Alzheimer's disease, premature birth, autoimmune disease, cardiovascular disease, diabetes, obesity, insulin resistance, rheumatoid arthritis, inflammatory bowel disease, or respiratory inflammation.
[0069] Embodiment 26. The polyol for use according to Embodiment 25, wherein the cancer is tongue cancer, esophageal cancer, gastric cancer, intestinal cancer, colon cancer, or systemic cancer.
[0070] Embodiment 27. The polyol for use according to Embodiment 25, wherein the cardiovascular disease is atherosclerosis and / or coronary artery disease.
[0071] Embodiment 28. A polyol for use according to any one of Embodiments 1 to 24, wherein the disease and / or symptoms are located in the oral cavity.
[0072] Embodiment 29. The polyol for use according to Embodiment 28, wherein the disease and / or symptoms are oral lichen planus, oral cancer, or periodontal disease.
[0073] Embodiment 30. The polyol for use according to Embodiment 29, wherein the periodontal disease is periodontitis.
[0074] Embodiment 31. The polyol for use according to Embodiment 28, wherein the symptoms are gingival inflammation, gingival bleeding, pain of the gums, teeth, and / or jaw at rest, pain of the gums, teeth, and / or jaw during chewing, tooth loosening, tooth loss, fever, and bad breath.
[0075] Embodiment 32. A polyol for use according to any one of Embodiments 1 to 31, wherein the polyol slows or inhibits the growth of the pathogenic microorganism.
[0076] Embodiment 33. A polyol for use according to any one of Embodiments 1 to 32, wherein the polyol slows and / or reduces the formation of a biofilm formed by the pathogenic microorganism.
[0077] Embodiment 34. The polyol for use according to Embodiment 33, wherein the biofilm is formed in the oral cavity.
[0078] Embodiment 35. A polyol for use according to any one of Embodiments 1 to 34, wherein the polyol is applied during conditions for the proliferation of a pathogen and / or during conditions for the survival of a pathogen.
[0079] Embodiment 36. The polyol for use according to Embodiment 35, wherein the conditions for the proliferation of the pathogen correspond to a period after food intake, such as after a meal, and the conditions for the survival of the pathogen correspond to a state in which nutrients are not available to the target.
[0080] Embodiment 37. A polyol for use according to any one of Embodiments 1 to 36, wherein the polyol is administered at least once a day, at least twice a day, at least three times a day, or at least four times a day.
[0081] Embodiment 38. A polyol for use according to any one of Embodiments 1 to 37, wherein the polyol is administered for at least 30 seconds, at least 1 minute, at least 2 minutes, at least 3 minutes, at least 5 minutes, at least 10 minutes, at least 30 minutes, at least 1 hour, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours.
[0082] Embodiment 39. A composition comprising a polyol for use in the prevention and / or treatment of diseases and / or symptoms related to pathogenic microorganisms, in subjects requiring the prevention and / or treatment of diseases and / or symptoms related to pathogenic microorganisms, as described in Embodiments 1 to 38.
[0083] Embodiment 40. The composition according to Embodiment 39, which is a liquid, gel, compacted powder or loose powder, solid or film.
[0084] Embodiment 41. The composition according to Embodiment 39 or 40, wherein the composition is toothpaste, toothpaste gel, capsules, softgel capsules, tablets (e.g., oral care tablets), oral care films, mouthwash, oral spray, or confectionery (e.g., candy).
[0085] Embodiment 42. The composition according to any one of Embodiments 39 to 41, wherein the content of the polyol in the composition is at least 0.5% by weight, at least 1% by weight, at least 5% by weight, or at least 10% by weight of the total weight of the composition.
[0086] Embodiment 43. The composition according to any one of Embodiments 39 to 42, wherein the composition is washed away or left standing after administration.
[0087] Embodiment 44. The composition according to any one of Embodiments 39 to 43, wherein the composition is applied in or on a dental mold, oral care patch, dental floss, or dental strip.
[0088] Embodiment 45. The composition according to any one of Embodiments 39 to 44, wherein the composition contains less than 1% by weight of dimethyl isosorbide by the total weight of the composition, or does not contain dimethyl isosorbide.
[0089] Embodiment 46. Use of polyols for the prevention and / or treatment of diseases and / or symptoms associated with pathogenic microorganisms in subjects requiring the prevention and / or treatment of diseases and / or symptoms associated with pathogenic microorganisms.
[0090] Embodiment 47. The use described in Embodiment 46, wherein the pathogenic microorganism is an anaerobic pathogenic microorganism.
[0091] Embodiment 48. The use described in Embodiment 47, wherein the anaerobic pathogenic microorganism is an obligate anaerobic pathogenic microorganism.
[0092] Embodiment 49. The use according to any one of Embodiments 46 to 48, wherein the polyol is administered orally.
[0093] Embodiment 50. The use according to any one of Embodiments 46 to 48, wherein the polyol is administered to the skin, eyes, ears, or genital mucosa of the subject.
[0094] Embodiment 51. The use according to any one of Embodiments 46 to 50, wherein the pathogenic microorganism is a bacterium of the genus Fusobacterium.
[0095] Embodiment 52. The use according to Embodiment 51, wherein the bacterium of the genus Fusobacterium is of the species Fusobacterium nucleatum.
[0096] Embodiment 53. The use according to Embodiment 51, wherein the bacterium of the genus Fusobacterium is of the species Fusobacterium necrophorum.
[0097] Embodiment 54. The use according to Embodiment 51, wherein the bacterium of the genus Fusobacterium is of the species Fusobacterium polymorphum.
[0098] Embodiment 55. The use according to any one of Embodiments 46 to 50, wherein the pathogenic microorganism is a bacterium of the genus Porphyromonas.
[0099] Embodiment 56. The use according to Embodiment 55, wherein the bacterium of the genus Porphyromonas is of the species Porphyromonas gingivalis.
[0100] Embodiment 57. The use according to any one of Embodiments 46 to 50, wherein the pathogenic microorganism is a bacterium of the genus Veillonella.
[0101] Embodiment 58. The use described in Embodiment 57, wherein the bacterium of the genus Veillonella is of the species Veillonella parvula.
[0102] Embodiment 59. The use described in Embodiment 57, wherein the bacterium of the genus Veillonella is of the species Veillonella dispar.
[0103] Embodiment 60. The use described in Embodiment 57, wherein the bacterium of the genus Veillonella is of the species Veillonella atypica.
[0104] Embodiment 61. The use according to any one of Embodiments 46 to 50, wherein the pathogenic microorganism is a bacterium of the genus Parvimonas.
[0105] Embodiment 62. The use according to Embodiment 61, wherein the bacterium of the genus Parvimonas is of the species Parvimonas micra.
[0106] Embodiment 63. The use according to any one of Embodiments 46 to 62, wherein the polyol is hexitol.
[0107] Embodiment 64. The use according to any one of Embodiments 46 to 63, wherein the polyol is monoanhydrohexitol.
[0108] Embodiment 65. The use according to any one of Embodiments 46 to 64, wherein the polyol is selected from 1,4-sorbitan, 2,5-mannitane, 2,5-iditane, 3,6-sorbitan, or a combination thereof.
[0109] Embodiment 66. The use according to any one of Embodiments 46 to 63, wherein the polyol is dianhydrohexitol.
[0110] Embodiment 67. The use according to any one of Embodiments 46 to 63 and 66, wherein the polyol is 1,4-3,6-dianehydrohexitol.
[0111] Embodiment 68. The use according to any one of Embodiments 46-63 and 66-67, wherein the polyol is selected from isosorbide, isomannide, or isoidide.
[0112] Embodiment 69. The use according to any one of Embodiments 46-63 and 66-68, wherein the polyol is isosorbide.
[0113] Embodiment 70. The use according to any one of Embodiments 46 to 69, wherein the disease and / or symptoms are cancer, encephalitis, Alzheimer's disease, premature birth, autoimmune disease, cardiovascular disease, diabetes, obesity, insulin resistance, rheumatoid arthritis, inflammatory bowel disease, or respiratory inflammation.
[0114] Embodiment 71. The use according to Embodiment 70, wherein the cancer is tongue cancer, esophageal cancer, gastric cancer, intestinal cancer, colon cancer, or systemic cancer.
[0115] Embodiment 72. The use according to Embodiment 70, wherein the cardiovascular disease is atherosclerosis and / or coronary artery disease.
[0116] Embodiment 73. The use according to any one of Embodiments 46 to 69, wherein the disease and / or symptoms are located in the oral cavity.
[0117] Embodiment 74. The use according to Embodiment 73, wherein the disease and / or symptoms are oral lichen planus, oral cancer, or periodontal disease.
[0118] Embodiment 75. The use described in Embodiment 74, wherein the periodontal disease is periodontitis.
[0119] Embodiment 76. The use described in Embodiment 73, wherein the symptoms are inflammation of the gums, bleeding of the gums, pain of the gums, teeth, and / or jaw at rest, pain of the gums, teeth, and / or jaw during chewing, loose teeth, tooth loss, fever, and bad breath.
[0120] Embodiment 77. The use according to any one of Embodiments 46 to 76, wherein the polyol slows or inhibits the growth of the pathogenic microorganism.
[0121] Embodiment 78. The use of the polyol according to any one of Embodiments 46 to 76, wherein the polyol slows and / or reduces the formation of a biofilm formed by the pathogenic microorganism.
[0122] Embodiment 79. The use described in Embodiment 78, wherein the biofilm is formed in the oral cavity.
[0123] Embodiment 80. The use according to any one of Embodiments 46 to 79, wherein the polyol is applied during conditions for the proliferation of pathogens and / or during conditions for the survival of pathogens.
[0124] Embodiment 81. The use described in Embodiment 80, wherein the conditions for the proliferation of the pathogen correspond to the period after food intake, such as after a meal, and the conditions for the survival of the pathogen correspond to a state in which nutrients are not available to the target.
[0125] Embodiment 82. The use according to any one of Embodiments 46 to 81, wherein the polyol is administered at least once a day, at least twice a day, at least three times a day, or at least four times a day.
[0126] Embodiment 83. The use according to any one of Embodiments 46 to 82, wherein the polyol is administered for at least 30 seconds, at least 1 minute, at least 2 minutes, at least 3 minutes, at least 5 minutes, at least 10 minutes, at least 30 minutes, at least 1 hour, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours.
[0127] Embodiment 84. A method for preventing and / or treating a disease and / or symptom associated with a pathogenic microorganism in a subject requiring prevention and / or treatment of such a disease and / or symptom, comprising administering an effective amount of any one of Embodiments 39 to 45.
[0128] Embodiment 85. The method according to Embodiment 84, wherein the pathogenic microorganism is an anaerobic pathogenic microorganism.
[0129] Embodiment 86. The method according to Embodiment 85, wherein the anaerobic pathogenic microorganism is an obligate anaerobic pathogenic microorganism.
[0130] Embodiment 87. The method according to any one of Embodiments 84 to 86, wherein the polyol is administered orally.
[0131] Embodiment 88. The method according to any one of Embodiments 84 to 86, wherein the polyol is administered to the skin, eyes, ears, or genital mucosa of the subject.
[0132] Embodiment 89. The method according to any one of Embodiments 84 to 88, wherein the pathogenic microorganism is a bacterium of the genus Fusobacterium.
[0133] Embodiment 90. The method according to Embodiment 89, wherein the bacterium of the genus Fusobacterium is of the species Fusobacterium nucleatum.
[0134] Embodiment 91. The method according to Embodiment 89, wherein the bacterium of the genus Fusobacterium is of the species Fusobacterium necrophorum.
[0135] Embodiment 92. The method according to Embodiment 89, wherein the bacterium of the genus Fusobacterium is of the species Fusobacterium polymorphum.
[0136] Embodiment 93. The method according to any one of Embodiments 84 to 88, wherein the pathogenic microorganism is a bacterium of the genus Porphyromonas.
[0137] Embodiment 94. The method according to Embodiment 93, wherein the bacterium of the genus Porphyromonas is of the species Porphyromonas gingivalis.
[0138] Embodiment 95. The method according to any one of Embodiments 84 to 88, wherein the pathogenic microorganism is a bacterium of the genus Veillonella.
[0139] Embodiment 96. The method according to Embodiment 95, wherein the bacterium of the genus Veillonella is of the species Veillonella parvula.
[0140] Embodiment 97. The method according to Embodiment 95, wherein the bacterium of the genus Veillonella is of the species Veillonella dispar.
[0141] Embodiment 98. The method according to Embodiment 95, wherein the bacterium of the genus Veillonella is of the species Veillonella atypica.
[0142] Embodiment 99. The method according to any one of Embodiments 84 to 88, wherein the pathogenic microorganism is a bacterium of the genus Parvimonas.
[0143] Embodiment 100. The method according to Embodiment 99, wherein the bacterium of the genus Parvimonas is of the species Parvimonas micra.
[0144] Embodiment 101. The method according to any one of Embodiments 84 to 100, wherein the polyol is hexitol.
[0145] Embodiment 102. The use according to any one of Embodiments 84 to 101, wherein the polyol is monoanhydrohexitol.
[0146] Embodiment 103. The method according to any one of Embodiments 84 to 102, wherein the polyol is selected from 1,4-sorbitan, 2,5-mannitane, 2,5-iditane, 3,6-sorbitan, or a combination thereof.
[0147] Embodiment 104. The method according to any one of Embodiments 84 to 101, wherein the polyol is dianhydrohexitol.
[0148] Embodiment 105. The method according to any one of Embodiments 84 to 101 and 104, wherein the polyol is 1,4-3,6-dianehydrohexitol.
[0149] Embodiment 106. The method according to any one of Embodiments 84-101 and 104-105, wherein the polyol is selected from isosorbide, isomannide, or isoidide.
[0150] Embodiment 107. The method according to any one of Embodiments 84-101 and 104-106, wherein the polyol is isosorbide.
[0151] Embodiment 108. The method according to any one of Embodiments 84 to 107, wherein the disease and / or symptoms are cancer, encephalitis, Alzheimer's disease, premature birth, autoimmune disease, cardiovascular disease, diabetes, obesity, insulin resistance, rheumatoid arthritis, inflammatory bowel disease, or respiratory inflammation.
[0152] Embodiment 109. The method according to Embodiment 108, wherein the cancer is tongue cancer, esophageal cancer, gastric cancer, intestinal cancer, colon cancer, or systemic cancer.
[0153] Embodiment 110. The method according to Embodiment 108, wherein the cardiovascular disease is atherosclerosis and / or coronary artery disease.
[0154] Embodiment 111. The method according to any one of Embodiments 84 to 107, wherein the disease and / or symptoms are located in the oral cavity.
[0155] Embodiment 112. The method according to Embodiment 111, wherein the disease and / or symptoms are oral lichen planus, oral cancer, or periodontal disease.
[0156] Embodiment 113. The method according to Embodiment 112, wherein the periodontal disease is periodontitis.
[0157] Embodiment 114. The method according to Embodiment 111, wherein the symptoms are inflammation of the gums, bleeding of the gums, pain of the gums, teeth, and / or jaw at rest, pain of the gums, teeth, and / or jaw during chewing, loose teeth, tooth loss, fever, and bad breath.
[0158] Embodiment 115. The method according to any one of Embodiments 84 to 114, wherein the polyol slows or inhibits the growth of the pathogenic microorganism.
[0159] Embodiment 116. The method according to any one of Embodiments 84 to 114, wherein the polyol slows and / or reduces the formation of a biofilm formed by the pathogenic microorganism.
[0160] Embodiment 117. The method according to Embodiment 116, wherein the biofilm is formed in the oral cavity.
[0161] Embodiment 118. The method according to any one of Embodiments 84 to 117, wherein the polyol is applied during the conditions for the proliferation of the pathogen and / or during the conditions for the survival of the pathogen.
[0162] Embodiment 119. The method according to Embodiment 118, wherein the conditions for the proliferation of the pathogen correspond to the period after food intake, such as after a meal, and the conditions for the survival of the pathogen correspond to a state in which nutrients are not available to the target.
[0163] Embodiment 120. The method according to any one of Embodiments 84 to 119, wherein the polyol is administered at least once a day, at least twice a day, at least three times a day, or at least four times a day.
[0164] Embodiment 121. The method according to any one of Embodiments 84 to 120, wherein the polyol is administered for at least 30 seconds, at least 1 minute, at least 2 minutes, at least 3 minutes, at least 5 minutes, at least 10 minutes, at least 30 minutes, at least 1 hour, at least 4 hours, at least 6 hours, at least 8 hours, at least 12 hours, at least 16 hours, at least 20 hours, or at least 24 hours. [Examples]
[0165] Example 1: In vitro test using Fusobacterium nucleatum. The growth of bacterial populations of the strain Fusobacterium nucleatum under two different conditions was simultaneously measured in culture broth without isosorbide (i.e., "control culture") and in culture broth containing isosorbide at concentrations of 2.5% by weight, 5% by weight, and 10% by weight. The isosorbide used was Beaute by Roquette® PO500, sold by the applicant, which is a liquid pure isosorbide containing 99%+ isosorbide.
[0166] The experiment consisted of inoculating a pre-culture of the bacteria to be tested, prepared 24 or 48 hours prior to inoculation, into a culture broth. For each experiment, the culture broth was boiled at 100°C for 20 minutes immediately before inoculation to remove oxygen.
[0167] The "growth conditions" consisted of culturing in a nutrient-rich Brain Heart culture medium supplemented with 2 g / L cysteine hydrochloride and 10% horse blood, suitable for black pigment anaerobic bacteria. The "survival conditions" consisted of non-nutrient RC broth, i.e., a boiled meat medium supplemented with 2 g / L cysteine.
[0168] For each experiment, 10 mL of the final volume of culture broth was placed in a test tube. Each test tube was covered with a paraffin stopper to maintain anaerobic conditions, and the test tubes were placed in an anaerobic jar. The incubation times were 0, 6, 24, and 48 hours. At each incubation time, 0.1 mL of cultured medium was sampled and diluted with 0.9 mL of RC broth (10 -1 (Dilution), 10 -5 Serial dilutions were performed until the dilution was complete. Each 0.1 mL volume of dilution was plated onto cysteine-treated Columbian agar (with 10% horse blood added for black pigment anaerobic bacteria) and incubated in an anaerobic chamber for 5 days. Then, counting was performed by plate counting. The number of viable cells was counted and recorded as LogCFU.mL-1 It was expressed as follows.
[0169] The results under the propagation conditions are shown in Table 1 and Figure 2 in the appendix.
[0170] [Table 1]
[0171] Isosorbide was observed to initially stimulate the growth of Fusobacterium nucleatum within 6 hours, then act as a biocide at all three isosorbide concentrations within 24 hours, and finally remain a biocide even after 48 hours.
[0172] The results under survival conditions are shown in Table 2 and Figure 3 in the appendix.
[0173] [Table 2]
[0174] Isosorbide was observed not to be metabolized by Fusonucleatum bacteria; therefore, it is not a carbon source for this strain. Compared to controls, isosorbide slightly accelerated the decay of Fusobacterium nucleatum.
[0175] Example 2: In vitro test using Porphyromonas sp. The growth of bacterial populations of the strain Porphyromonas sp. under two different conditions was measured according to the same protocol as for Fusobacterium nucleatum in Example 1.
[0176] The results under the propagation conditions are shown in Table 3 and Figure 4 in the appendix.
[0177] [Table 3]
[0178] Isosorbide at concentrations of 2.5% and 5% by weight initially slowed the growth of Porphyromonas sp. compared to the control at 6 and 24 hours, but then stimulated growth compared to the control at 48 hours. Isosorbide at a concentration of 10% by weight acted as a biocide as early as 6 to 48 hours.
[0179] The results under survival conditions are shown in Table 4 and Figure 5 in the appendix.
[0180] [Table 4]
[0181] Isosorbide was observed not to be metabolized by Porphyromonas sp. Compared to the control, isosorbide slightly accelerated the decay of Porphyromonas sp.
[0182] Example 3: In vitro test using Porphyromonas gingivalis W83. The growth of the bacterial population of Porphyromonas gingivalis strain W83 under two different conditions was measured according to the same protocol as for Fusobacterium nucleatum in Example 1.
[0183] The results under the propagation conditions are shown in Table 5 and Figure 6 in the appendix.
[0184] [Table 5]
[0185] Isosorbide was observed to act as a biocide at concentrations of 2.5, 5, and 10% by weight.
[0186] The results under survival conditions are shown in Table 6 and Figure 7 in the Appendix.
[0187] [Table 6]
[0188] Isosorbide was observed not to be metabolized by Porphyromonas gingivalis W83. It is not a carbon source for this strain. Compared to controls, isosorbide significantly accelerated the decay of Porphyromonas gingivalis W83.
[0189] Example 4: In vitro test using Porphyromonas gingivalis D141. The growth of bacterial populations of Porphyromonas gingivalis strain D141 under two different conditions was measured according to the same protocol as for Fusobacterium nucleatum in Example 1.
[0190] The results under the propagation conditions are shown in Table 7 and Figure 8 in the appendix.
[0191] [Table 7]
[0192] Isosorbide was observed to promote the decay of Porphyromonas gingivalis D141 at 5% and 10% by weight.
[0193] The results under survival conditions are shown in Table 8 and Figure 9 in the Appendix.
[0194] [Table 8]
[0195] Isosorbide was observed not to be metabolized by Porphyromonas gingivalis D141. It is not a carbon source for this strain. Compared to controls, isosorbide did not promote the decay of Porphyromonas gingivalis D141.
[0196] Example 5: In vitro test using Veillonella parvula. The growth of bacterial populations of the strain Veillonella parvula under two different conditions was measured according to the same protocol as for Fusobacterium nucleatum in Example 1.
[0197] The results under the propagation conditions are shown in Table 9 and Figure 10 in the appendix.
[0198] [Table 9]
[0199] Isosorbide was observed to act as a biocide against Veillonella parvula at a concentration of 10% by weight.
[0200] The results under survival conditions are shown in Table 10 and Figure 11 in the appendix.
[0201] [Table 10]
[0202] Isosorbide was observed not to be metabolized by Veillonella parvula. It is not a carbon source for this strain. Compared to the control, the attenuation of Veillonella parvula by isosorbide is approximately the same as that of the control.
[0203] Example 6: In vitro test using Parvimonas micra. The growth of bacterial populations of the strain Parvimonas micra under two different conditions was measured according to the same protocol as for Fusobacterium nucleatum in Example 1.
[0204] The results under the propagation conditions are shown in Table 11 and Figure 12 in the appendix.
[0205] [Table 11]
[0206] Isosorbide initially inhibited growth within 6 hours at all three concentrations tested, but then allowed growth to recover within 24 hours. Ultimately, it acted as a biocide at concentrations of 2.5, 5, and 10% by weight, and it was observed that the higher the concentration of isosorbide, the greater the biocide effect.
[0207] The results under survival conditions are shown in Table 12 and Figure 13 in the appendix.
[0208] [Table 12]
[0209] Isosorbide was observed not to be metabolized by Parvimonas micra. It is not a carbon source for this strain. Compared to the control, the decay of Veillonella parvula at 6 hours with isosorbide was slightly lower than that of the control, reaching the same level after 24 hours.
[0210] Example 7: In vitro study using Streptococcus oralis. The growth of the bacterial population of the strain Streptococcus oralis under growth conditions was measured according to the same protocol as for Fusobacterium nucleatum in Example 1. The results under growth conditions are shown in Table 13 below.
[0211] [Table 13]
[0212] Therefore, it was observed that isosorbide at concentrations of 2.5–10% by weight did not alter the growth of this bacterial strain.
[0213] Example 8: In vitro test using Streptococcus sanguinis. The growth of bacterial populations of the strain Streptococcus sanguinis under growth conditions was measured according to the same protocol as for Fusobacterium nucleatum in Example 1. The results under growth conditions are shown in Table 14 below.
[0214] [Table 14]
[0215] Therefore, it was observed that isosorbide at concentrations of 2.5–10% by weight did not alter the growth of this bacterial strain.
[0216] Example 9: In vitro test using Lactobacillus plantarum. The growth of the bacterial population of the strain Lactobacillus plantarum under growth conditions was measured according to the same protocol as for Fusobacterium nucleatum in Example 1. The results under growth conditions are shown in Table 15 below.
[0217] [Table 15]
[0218] Therefore, it was observed that isosorbide at concentrations of 2.5–10% by weight did not alter the growth of this bacterial strain.
[0219] Example 10: In vitro test using Lactobacillus gasseri. The growth of the bacterial population of the strain Lactobacillus gasseri under growth conditions was measured according to the same protocol as for Fusobacterium nucleatum in Example 1. The results under growth conditions are shown in Table 16 below.
[0220] [Table 16]
[0221] Therefore, it was observed that isosorbide at concentrations of 2.5–10% by weight did not alter the growth of this bacterial strain.
[0222] List of References Patent Documents For any purpose, the following patent documents are cited. -Patent Document 1: French Patent No. 1761521, "Use of dianhydrohexitol in oral and dental care to reduce the development of bacterial strains."
Claims
1. Polyols for use in the prevention and / or treatment of diseases and / or symptoms associated with pathogenic microorganisms in subjects requiring the prevention and / or treatment of diseases and / or symptoms associated with pathogenic microorganisms.
2. The polyol for use according to claim 1, wherein the pathogenic microorganism is an anaerobic pathogenic microorganism.
3. The polyol for use according to claim 2, wherein the anaerobic pathogenic microorganism is an obligate anaerobic pathogenic microorganism.
4. The polyol for use according to any one of claims 1 to 3, wherein the pathogenic microorganism is a bacterium of the genus Fusobacterium, such as Fusobacterium nucleatum, Fusobacterium necrophorum, or Fusobacterium polymorphum.
5. The polyol for use according to any one of claims 1 to 3, wherein the pathogenic microorganism is a bacterium of the genus Porphyromonas, such as a bacterium of the species Porphyromonas gingivalis.
6. The polyol for use according to any one of claims 1 to 3, wherein the pathogenic microorganism is a bacterium of the genus Veillonella, such as Veillonella parvula, Veillonella dispar, or Veillonella atica.
7. The polyol for use according to any one of claims 1 to 3, wherein the pathogenic microorganism is a bacterium of the genus Parvimonas, such as a bacterium of the species Parvimonas micro.
8. The polyol for use according to any one of claims 1 to 7, wherein the polyol is hexitol.
9. The polyol for use according to any one of claims 1 to 8, wherein the polyol is a monoanhydrohexitol such as 1,4-sorbitan, 2,5-mannitan, 2,5-iditan, 3,6-sorbitan, or a combination thereof.
10. The polyol for use according to any one of claims 1 to 8, wherein the polyol is a dianhydrohexitol such as 1,4-3,6-dianhydrohexitol, or isosorbide, isomannide, isoidide, or a combination thereof.
11. The polyol for use according to any one of claims 1 to 8 and 10, wherein the polyol is isosorbide.
12. The polyol for use according to any one of claims 1 to 11, wherein the disease and / or symptoms are cancer such as tongue cancer, esophageal cancer, stomach cancer, intestinal cancer, colon cancer, or systemic cancer, encephalitis, Alzheimer's disease, premature birth, autoimmune disease, cardiovascular disease such as atherosclerosis and / or coronary artery disease, diabetes, obesity, insulin resistance, rheumatoid arthritis, inflammatory bowel disease, or respiratory inflammation.
13. The polyol for use according to any one of claims 1 to 12, wherein the disease and / or symptoms are located in the oral cavity, such as oral lichen planus, oral cancer, or periodontal disease such as periodontitis.
14. The polyol for use according to claim 13, wherein the symptoms are inflammation of the gums, bleeding of the gums, pain of the gums, teeth, and / or jaw at rest, pain of the gums, teeth, and / or jaw during chewing, loosening of teeth, tooth loss, fever, and bad breath.
15. A composition comprising a polyol for use in the prevention and / or treatment of diseases and / or symptoms related to pathogenic microorganisms, in subjects requiring the prevention and / or treatment of diseases and / or symptoms related to pathogenic microorganisms, as described in claims 1 to 14.
16. The composition according to claim 15, wherein the composition is a liquid, gel, compacted powder or loose powder, solid or film.
17. The composition according to claim 15 or 16, wherein the composition is a toothpaste, toothpaste gel, capsule, softgel capsule, oral care tablet or other tablet, oral care film, mouthwash, oral spray, or confectionery such as candy.
18. The composition according to any one of claims 15 to 17, wherein the content of the polyol in the composition is at least 0.5% by weight, at least 1% by weight, at least 5% by weight, or at least 10% by weight of the total weight of the composition.
19. The composition according to any one of claims 15 to 18, wherein the composition is washed away or left standing after administration.
20. The composition according to any one of claims 15 to 19, wherein the composition is applied in or on a dental mold, oral care patch, dental floss, or dental strip.
21. The composition according to any one of claims 15 to 20, wherein the composition contains less than 1% by weight of dimethyl isosorbide of the total weight of the composition, or does not contain dimethyl isosorbide.