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WO2022100632A1 - Lacticaseibacillus rhamnosus pour prévenir et/ou traiter les maladies causées par un trouble de la flore de l'appareil reproducteur et/ou une perte osseuse - Google Patents

Lacticaseibacillus rhamnosus pour prévenir et/ou traiter les maladies causées par un trouble de la flore de l'appareil reproducteur et/ou une perte osseuse Download PDF

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WO2022100632A1
WO2022100632A1 PCT/CN2021/129909 CN2021129909W WO2022100632A1 WO 2022100632 A1 WO2022100632 A1 WO 2022100632A1 CN 2021129909 W CN2021129909 W CN 2021129909W WO 2022100632 A1 WO2022100632 A1 WO 2022100632A1
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product
vaginitis
lactobacillus rhamnosus
15ph10t
bone loss
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Chinese (zh)
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张笑薇
吕金丽
赵少伟
高蒙玙
邹远强
肖亮
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BGI Shenzhen Co Ltd
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BGI Shenzhen Co Ltd
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING OR TREATMENT THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/123—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt
    • A23C9/1234—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt characterised by using a Lactobacillus sp. other than Lactobacillus Bulgaricus, including Bificlobacterium sp.
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
    • A23L2/385—Concentrates of non-alcoholic beverages
    • A23L2/39—Dry compositions
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • 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
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • 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
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/11—Lactobacillus
    • A23V2400/175—Rhamnosus
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present disclosure relates to the field of biotechnology, in particular to a Lactobacillus rhamnosus for preventing and/or treating diseases caused by genital tract flora disorder and/or bone loss and applications thereof.
  • the female reproductive tract environment is often affected by fluctuations in hormone levels, poor hygiene control, seasonal changes, and even unstable moods, resulting in flora disturbances, which in turn lead to the invasion of pathogenic bacteria and lead to bacterial, mold, virus and other microbial infections.
  • the clinical symptoms of reproductive tract infections are: vaginal itching and burning, abnormal secretions, frequent urination and painful urination, and severe cases can lead to premature birth and cervical cancer.
  • the genital tract microbial infection rate among women of childbearing age in my country is as high as 80%, and the clinical treatment for most patients with bacterial or fungal infections is antibiotics.
  • Antibiotics can reduce the abundance of probiotics while fighting pathogens, which is not conducive to maintaining the homeostasis of reproductive tract flora, thereby increasing the risk of recurrence.
  • pathogens which is not conducive to maintaining the homeostasis of reproductive tract flora
  • Antibiotics can reduce the abundance of probiotics while fighting pathogens, which is not conducive to maintaining the homeostasis of reproductive tract flora, thereby increasing the risk of recurrence.
  • For patients with HPV virus infection there is currently no perfect treatment method. Regular screening and follow-up are mostly used. In severe cases, surgical treatment is performed. Therefore, there is an urgent need to develop a strain or drug that can prevent or treat female reproductive tract infections without affecting the abundance of probiotics in the reproductive tract environment.
  • Osteoporosis is a systemic bone disease characterized by decreased bone mass, impaired bone quality and reduced bone strength, leading to increased brittle bone and susceptibility to fractures.
  • Epidemiological surveys show that osteoporosis has become an important health problem for people over 50 years old in my country, with a prevalence rate of 19.2%, and a low bone mass population of 46.4%.
  • osteoporosis does not directly lead to death in most cases, osteoporosis increases the chance of fracture, which affects the health and independent living ability of patients, and greatly increases the social medical burden.
  • Existing drug treatments, including estrogen replacement therapy, etc. can treat osteoporosis, but have high potential risks and side effects, such as hormonal disorders in the human body.
  • Lactobacillus which mainly produces lactic acid to maintain a lower pH value of the vagina, thereby inhibiting the invasion and growth of pathogenic bacteria
  • Lactobacillus can also synthesize hydrogen peroxide to ensure an anaerobic environment in the vagina to prevent the growth of aerobic bacteria.
  • pathogenic bacteria can infect the reproductive tract, cause inflammation, and form a competitive relationship with Lactobacillus, thereby disrupting the microbial homeostasis of the reproductive tract.
  • supplementation with Lactobacillus to maintain a healthy reproductive tract flora is more effective than antibiotics alone.
  • Existing approaches to prevent and treat osteoporosis include: estrogen replacement therapy, calcitonin, selective estrogen receptor modulators, and bisphosphonates.
  • Drugs used to treat and prevent the development of osteoporosis are divided into two categories.
  • the first category is drugs that inhibit bone resorption, including calcium, vitamin D and active vitamin D, calcitonin, bisphosphonates, estrogens, and isoforms.
  • Flavonoids the second category is bone-promoting drugs, including fluoride, anabolic steroids, parathyroid hormone, and isoflavones.
  • hormone replacement therapy is considered to be the best choice for the treatment of osteoporosis in postmenopausal women, and it is also the most effective treatment method. And hormone replacement therapy cannot be used in patients with breast disease, and those who cannot tolerate its side effects.
  • Selective Estrogen Receptor Modulators These drugs have weak estrogen-like effects in some organs and estrogen antagonistic effects in others. SERMs prevent osteoporosis and also reduce the incidence of cardiovascular disease, breast cancer and endometrial cancer.
  • Such drugs include raloxifene, a non-steroidal benzothiophene, an estrogen agonist that inhibits bone resorption, increases bone density in the spine and hip, and reduces the risk of vertebral fractures by 40% to 50%. %, but the efficacy is worse than that of estrogen, and it is contraindicated in premenopausal women.
  • existing drug treatments can treat osteoporosis, they have high potential risks and side effects, such as hormonal disturbances in the body.
  • the present disclosure is to solve the technical problems of the drugs in the prior art having different degrees of side effects, high recurrence rate or large trauma.
  • Screening out a novel Lactobacillus rhamnosus (Lactobacillus rhamnosus) for preventing and/or treating diseases related to reproductive tract flora disorders (especially referring to female reproductive tract flora disorders in humans) and/or related diseases caused by bone loss rhamnosus) OF44-15Ph10T which can produce secretions such as lactic acid and hydrogen peroxide to inhibit the growth of pathogenic bacteria in reproductive tract infections, for the prevention and/or treatment of reproductive tract flora disorders related diseases, especially to reduce the recurrence rate, toxicity Side effects are small and the effect is long-lasting.
  • the bacteria can inhibit bone loss, thereby treating or improving osteoporosis.
  • one aspect of the present disclosure provides a strain of Lactobacillus rhamnosus OF44-15Ph10T, whose deposit number is GDMCC No: 60406.
  • the present disclosure selects a female reproductive tract probiotic Lactobacillus rhamnosus OF44-15Ph10T from a library of about 30,000 human symbiotic bacteria. On August 24, 2008, it was preserved in the Guangdong Provincial Microbial Culture Collection Center (GDMCC, 5th Floor, Laboratory Building, No. 100, Xianlie Middle Road, Yuexiu District, Guangzhou City, Guangdong Province), and its preservation number is GDMCC No: 60406.
  • GDMCC Guangdong Provincial Microbial Culture Collection Center
  • the Lactobacillus rhamnosus OF44-15Ph10T described in the present disclosure is isolated by using a modified version of PYG medium, and is passaged and preserved in MRS medium after identification. After culturing in MRS medium for 48 hours, the colony of OF44-15Ph10T was white, smooth, round, with neat edges, and the colony diameter was about 1-2 mm. Observed under a microscope at 1000 times, the cells were elongated and rod-shaped, Gram staining was positive, and no spores and flagella were produced.
  • Another aspect of the present disclosure provides the use of the Lactobacillus rhamnosus or its fermentation product or its bacterial suspension or its culture solution in preparing a product for preventing and/or treating genital tract flora disorders related to Disease and/or associated disease caused by bone loss.
  • the Lactobacillus rhamnosus OF44-15Ph10T provided by the present disclosure has been found to have a strong ability to produce L-lactic acid, D-lactic acid and hydrogen peroxide; strong growth ability and high acid and alkali resistance; Antibiotic sensitivity, no risk genes such as plasmids and transfer elements; at the same time, it also shows strong adhesion to human vaginal epithelial cells, and has strong bacteriostatic ability against common vaginal infection pathogens, which can be used for prevention and/or treatment of reproductive tract Microbial infection.
  • Lactobacillus rhamnosus OF44-15Ph10T can effectively reduce bone loss and can be used to prevent and/or treat related diseases caused by osteopenia, such as bone loss. Psoriasis.
  • the disorder associated with a reproductive tract flora disorder comprises a reproductive tract infection.
  • the disease associated with a disorder of the reproductive tract flora is a reproductive tract infection.
  • the reproductive tract infection comprises at least one selected from bacterial vaginosis, fungal vaginitis, trichomonas vaginitis, aerobic vaginitis, senile vaginitis, and viral infection one.
  • the bacteria causing the bacterial vaginosis are common bacteria that cause female genital tract infections, including Escherichia coli (E.coli), Gardnerella vaginalis (BNCC337545), Corynebacterium , Haemophilus, Staphylococcus aureus, Pseudomonas aeruginosa and other Gram-negative anaerobic bacteria.
  • Escherichia coli E.coli
  • Gardnerella vaginalis BNCC337545
  • Corynebacterium Haemophilus
  • Staphylococcus aureus Staphylococcus aureus
  • Pseudomonas aeruginosa and other Gram-negative anaerobic bacteria.
  • the fungal vaginitis-causing mold is a common Candida fungus that causes female genital tract infections, including Candida albicans (Candida albicans SC5314), Candida tropicalis bacteria, Candida parapsilosis, and Candida dublini.
  • the virus causing the genital tract viral infection is a common virus that causes female genital tract infection, including HPV, herpes simplex virus, cytomegalovirus, and the like.
  • the related diseases caused by the bone loss include at least one selected from the group consisting of osteopenia, osteoporosis, and osteoporotic fractures.
  • Another aspect of the present disclosure provides the use of the Lactobacillus rhamnosus or its fermentation product or its bacterial suspension or its culture solution in preparing a product for antibacterial, adhesion to vaginal epithelial cells and/or cervix cells, lactate production, H2O2 production, and/or inhibition of bone loss.
  • the product is a food, a drug, or a nutraceutical.
  • the food can be probiotic yogurt, probiotic tablet, probiotic solid drink and the like.
  • the product is a drug, and the drug is administered at a dose of 10 5 -10 12 CFU/day.
  • a food or health care product in yet another aspect of the present disclosure, includes the Lactobacillus rhamnosus or its fermentation product or its bacterial suspension or its culture solution.
  • the food or health product is selected from the group consisting of products for preventing and/or treating disorders related to reproductive tract flora disorders, preventing and/or treating related diseases caused by bone loss, antibacterial products, At least one of a product of vaginal epithelial cells and/or cervical cells, a lactic acid - producing product, and a H2O2 - producing product.
  • Another aspect of the present disclosure provides a pharmaceutical composition comprising the Lactobacillus rhamnosus or its fermentation product or its bacterial suspension or its culture solution.
  • the pharmaceutical composition is in the form of a single dose, the pharmaceutical composition comprising a daily dose of 105-1012 CFU of the Lactobacillus rhamnosus.
  • the pharmaceutical composition is in a dosage form suitable for topical or oral administration.
  • Another aspect of the present disclosure provides that the above-mentioned Lactobacillus rhamnosus or its fermentation product or its bacterial suspension or its culture solution, the above-mentioned food or health product, and the above-mentioned pharmaceutical composition are used in the prevention and/or treatment of genital tract flora disorder Use in related diseases and/or related diseases caused by bone loss.
  • the disorder associated with a reproductive tract flora disorder comprises a reproductive tract infection.
  • the reproductive tract infection comprises at least one selected from bacterial vaginosis, fungal vaginitis, trichomonas vaginitis, aerobic vaginitis, senile vaginitis, and viral infection one.
  • the related diseases caused by the bone loss include at least one selected from the group consisting of osteopenia, osteoporosis, and osteoporotic fractures.
  • Yet another aspect of the present disclosure provides a method for preventing and/or treating disorders related to reproductive tract flora disorders and/or related diseases caused by bone loss.
  • the method includes:
  • Lactobacillus rhamnosus or its fermentation product or its bacterial suspension or its culture solution (1) above-mentioned Lactobacillus rhamnosus or its fermentation product or its bacterial suspension or its culture solution;
  • the disorder associated with a reproductive tract flora disorder comprises a reproductive tract infection.
  • the reproductive tract infection comprises at least one selected from bacterial vaginosis, fungal vaginitis, trichomonas vaginitis, aerobic vaginitis, senile vaginitis, and viral infection one.
  • the related diseases caused by the bone loss include at least one selected from the group consisting of osteopenia, osteoporosis, and osteoporotic fractures.
  • reproductive tract infection refers to a reproductive tract infection of a female in an animal or a female in a human.
  • Lactobacillus to prevent or treat female genital tract infections, such as the combination of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, which have been recognized and widely commercialized.
  • a probiotic strain for maintaining the health of the female reproductive tract There are many brands of products, including Jarrow Formulas, Blackmores, Renew life and Clinicans.
  • Jarrow Formulas Blackmores
  • Renew life and Clinicans As a probiotic strain for maintaining the health of the female reproductive tract.
  • its strains are not dominant strains of the reproductive tract, and related clinical studies are limited to European and American populations, and there is a lack of efficacy evaluations for Asian populations.
  • antibiotics and suppositories have many disadvantages.
  • antibiotics such as metronidazole, tinidazole, and clindamycin are used to kill invading anaerobic pathogenic bacteria, thereby treating bacterial vaginosis.
  • it also inhibits the growth of the vaginal probiotic Lactobacillus, unable to rebuild a healthy flora structure.
  • Miconazole, clotrimazole and other suppositories are mainly used for fungal vaginitis, and their mechanism of action is to inhibit the sterol synthesis of the fungal cell membrane such as Candida, affect the permeability of the cell membrane, inhibit the growth of fungi, and lead to death.
  • This drug is often used in suppositories, which has certain limitations in use, causing a lot of inconvenience, and improper use can cause secondary infection.
  • the method of oral probiotics intervenes in the intestinal flora to regulate the immune system, and local use to supplement the abundance of lactobacilli in the reproductive tract can make up for the shortcomings of traditional antibiotic treatment, and help the flora to restore its steady state while inhibiting or eliminating pathogenic bacteria. It can greatly improve the cure rate, reduce the recurrence rate, help HPV turn negative, effectively treat or prevent microbial infections in the reproductive tract, and solve a major clinical problem.
  • the inventors of the present disclosure screened out a female reproductive tract probiotic Lactobacillus rhamnosus OF44-15Ph10T from a library of about 30,000 human symbiotic bacteria. It has strong ability to produce L-lactic acid, D-lactic acid and hydrogen peroxide, is sensitive to most antibiotics, has strong growth ability and is highly resistant to acid and alkali, and also shows strong adhesion to human vaginal epithelial cells, and is resistant to common vaginal microbial infections.
  • the pathogenic bacteria Lactobacillus rhamnosus OF44-15Ph10T with strong bacteriostatic ability can be developed as a food, health product, topical or oral drug to prevent, treat or assist in the treatment of female reproductive tract infections.
  • the Lactobacillus rhamnosus in the present disclosure inhibits the growth of pathogenic bacteria of reproductive tract infection by producing secretions such as lactic acid and hydrogen peroxide, and is used for preventing and/or treating reproductive tract infection diseases, especially reducing recurrence rate, toxic and side effects Small, long-lasting potency. Meanwhile, the inventors also found that the Lactobacillus rhamnosus in the present disclosure can effectively reduce bone loss, so the bacteria can also be used to prevent and/or treat related diseases caused by bone loss, such as osteoporosis. Therefore, the existing drugs for the treatment of osteoporosis have large potential risks and large side effects, which may lead to the problem of hormonal disorders in the human body.
  • GDMCC Guangdong Microbial Culture Collection Center
  • Figure 1 Genome map of Lactobacillus rhamnosus OF44-15Ph10T;
  • Figure 2 Annotation results of probiotic function genes of Lactobacillus rhamnosus OF44-15Ph10T;
  • Figure 3A Comparison of Lactobacillus rhamnosus OF44-15Ph10T and commercially available strain L-lactic acid;
  • Figure 3B Comparison of Lactobacillus rhamnosus OF44-15Ph10T and commercially available strain D-lactic acid;
  • GR-1 represents Lactobacillus rhamnosus GR-1
  • OF44 represents Lactobacillus rhamnosus OF44-15Ph10T in the present disclosure
  • Figure 4 Inhibition of growth of E. coli by Lactobacillus rhamnosus OF44-15Ph10T and Lactobacillus rhamnosus GR-1, E.coli in the figure represents E. coli, and OF44 represents rhamnolactide in the present disclosure Bacillus OF44-15Ph10T, GR-1 represents Lactobacillus rhamnosus GR-1;
  • FIG. 5 Lactobacillus rhamnosus OF44-15Ph10T and Lactobacillus rhamnosus GR-1 inhibit the growth of Gardnerella vaginalis, GV in the figure represents Gardnerella, and OF44 represents the present disclosure
  • GR-1 represents Lactobacillus rhamnosus GR-1;
  • Figure 6 The bacterial count of Lactobacillus rhamnosus OF44-15Ph10T in the model group and the probiotic group in Example 9;
  • Figure 7 The bacterial count of Gardnerella in the model group and the probiotic group in Example 9;
  • Fig. 8 Comparison of bone-related indexes of mice in Sham (sham operation) control group, model group and probiotic group in Example 10;
  • Fig. 9 Comparison results of three-dimensional reconstruction images (micro-CT) of bone-related tissues of mice in the Sham (sham operation) control group, the model group and the probiotic group in Example 10.
  • Embodiments of the present disclosure are described in detail below.
  • the embodiments described below are exemplary only for explaining the present disclosure and should not be construed as limiting the present disclosure. If no specific technique or condition is indicated in the examples, the technique or condition described in the literature in the field or the product specification is used.
  • the reagents or instruments used without the manufacturer's indication are conventional products that can be obtained from the market.
  • Example 1 Isolation and identification of Lactobacillus rhamnosus OF44-15Ph10T
  • the isolated sample came from the feces of a healthy female.
  • the feces were collected into sterile sample tubes and brought back to the laboratory for sorting within 1 hour.
  • the collected fresh samples were immediately transferred to the anaerobic operation box, and 0.2 g of the samples were taken in 1 mL of sterile PBS (phosphate buffered saline), fully shaken and mixed, and then applied by gradient dilution.
  • the culture medium was modified PYG medium.
  • the obtained pure cultured strain was cultured to a concentration of about 10 9 CFU/mL, 400 ⁇ L of bacterial liquid was added with 400 ⁇ L of 40% glycerol to make the glycerol concentration reach 20%, and then cryopreserved at -80°C.
  • the vacuum freeze-dried powder of the strain was prepared according to the following operation steps, and was stored in the Guangdong Provincial Microorganism Culture Collection Center GDMCC No: 60406.
  • the ampoule tube and protective agent were sterilized by autoclaving for later use, streaked the bacterial liquid cultured overnight, incubated at 37°C for 24 hours, and performed the following operations after observing that no bacterial contamination was found.
  • the bacterial liquid was collected by centrifugation and washed with sterilized physiological saline, added with 2-3 mL of skimmed milk protective agent, suspended to prepare a bacterial suspension with a colony count of 10 8 to 10 10 /mL, and packed in sterile ampoules, placed in Pre-freeze in -80°C refrigerator for 1-2 hours.
  • the "Standard Operating Procedure of Freeze Dryer" freeze-dry in freeze-drier for 8-20h until freeze-drying.
  • the obtained isolated strains were cultured in liquid PYG medium for 24 hours, 1 mL of bacterial liquid was taken and centrifuged at 10,000 r/min for 5 minutes, the bacteria were collected, and genomic DNA was extracted. Using genomic DNA as a template, 16S rDNA universal primers were used for PCR amplification.
  • the amplification system was: 10 ⁇ PCR buffer, 3 ⁇ L; dNTP, 2.5 ⁇ L; 27F(5'-AGAGTTTGATCATGGCTCAG-3', as shown in SEQ ID NO:1 shown), 0.5 ⁇ L; 1492R (5′-TAGGGTTACCTTGTTACGACTT-3′, shown in SEQ ID NO: 2), 0.5 ⁇ L; Taq enzyme, 0.3 ⁇ L; template, 1 ⁇ L; ddH 2 O, 18.2 ⁇ L.
  • PCR amplification conditions were: pre-denaturation at 95°C for 4 min, followed by 30 cycles of denaturation at 95°C for 30s, annealing at 57°C for 40s, and extension at 72°C for 1 min for 30s.
  • the obtained 16S rDNA amplification product was detected by electrophoresis, purified, and sequenced at 3730 to obtain a 16S rDNA sequence with a length of 1200 bp (SEQ ID NO: 3). This sequence was analyzed by blast in genebank, and the identification result of OF44-15Ph10T was obtained as Lactobacillus rhamnosus.
  • the 16S rDNA sequence of Lactobacillus rhamnosus OF44-15Ph10T is as follows:
  • Example 2 Genome sequencing, species classification and functional gene analysis of Lactobacillus rhamnosus OF44-15Ph10T
  • the whole genome sequence was compared and analyzed using Checkm software, and the closest species information to the genome was found to be Firmicutes-Bacillus-Lactobacillus-Lactobacillus-Lactobacillus-Lactobacillus rhamnosus species , the number of annotated genomes is 31, the number of annotated markers is 586, the completeness of the genome is 99.46%, and the degree of contamination is 0.
  • Lactic acid synthesis and Peroxide hydrogen production from the prokaryoties database of KEGG.
  • a separate database is established for all enzymes related to short-chain fatty acid synthesis.
  • Use blastx to align the whole gene sequences of OF44-15Ph10T with these databases select the annotation results with e-value greater than or equal to 0.01 and identity greater than or equal to 60, the gene copy number of the enzyme in the relevant pathway is indicated by the shade of color, and the gene is annotated to the gene. It proves that the strain has this function, and the higher the number of gene copies, the stronger the function ( Figure 2).
  • the genome is not annotated with antibiotic resistance genes, virulence factors, plasmids, transfer elements, bacteriophages and viruses, which proves that the strain can be used safely. .
  • the bioactive substances of OF44-15Ph10T were mainly examined for L-lactic acid content, D-lactic acid content, and hydrogen peroxide production in metabolites.
  • the strain OF44-15Ph10T was inoculated into MRS medium and cultured at 37°C for 24h under aerobic and anaerobic conditions, respectively.
  • L-lactic acid and D-lactic acid content were measured with L-Lactic Acid (L-Lactate) Assay Kit and D-Lactic Acid (D-Lactate) Assay Kit (purchased from Megazyme Inc. US) according to standard operating manual.
  • the hydrogen peroxide content was measured with a hydrogen peroxide assay kit (colorimetric method) (purchased from Nanjing Jiancheng Bioengineering Institute) according to the standard operation manual.
  • the present disclosure selects commercially available Lactobacillus rhamnosus GR-1 as a control test, the experimental method is the same as above, and the results show that under anaerobic conditions, L-lactic acid of Lactobacillus rhamnosus GR-1 and The yields of D-lactic acid were 5.59 g/L and 0.45 g/L, respectively. In contrast, the yields of L-lactic acid and D-lactic acid of OF44-15Ph10T were higher than those of the control strains. The results are shown in Figures 3A and 3B.
  • Example 4 Identification of the ability of Lactobacillus rhamnosus OF44-15Ph10T to inhibit reproductive tract infection pathogens
  • E.coli represents the bacterial solution added to the MRS liquid medium
  • OF44 represents the bacterial solution added to the supernatant of OF44-15Ph10T
  • GR-1 represents the bacterial solution added to Lactobacillus rhamnosus GR- 1
  • GV represents the bacterial solution added to the MRS liquid medium
  • OF44 represents the bacterial solution added to the supernatant of OF44-15Ph10T
  • GR-1 represents the bacterial solution added to the upper layer of Lactobacillus rhamnosus GR-1
  • the overnight cultured OF44-15Ph10T and Lactobacillus rhamnosus GR-1 were inoculated into 1.5 mL of MRS medium, and then 100 uL of overnight cultured SC5314 (concentration of 10 5 CFU) was inoculated into OF44-
  • the mixed bacterial solution was obtained from 15Ph10T and Lactobacillus rhamnosus GR-1 bacterial solution, and cultured at 37°C for 24h under aerobic conditions.
  • the mixed bacterial solution was diluted and spread on PDA solid medium (purchased from Huankai Microorganism Technology Co., Ltd.) and cultured at 37°C for 24 h, and the colonies were counted.
  • PDA solid medium purchased from Huankai Microorganism Technology Co., Ltd.
  • the count results showed that the OF44-15Ph10T group was 9.4x10 4 CFU/mL, the SC5314 group was 8.6x10 5 CFU/mL, and the GR-1 group was 1.2x10 5 CFU/mL.
  • the results showed that OF44-15Ph10T and Lactobacillus rhamnosus GR-1 could inhibit the growth of Candida albicans, and OF44-15Ph10T had better inhibitory effect than GR-1.
  • antibiotic Inhibition zone diameter (cm) antibiotic Inhibition zone diameter (cm) Ampicillin 3 Ceftriaxone 2 Bacitracin 0 Vancomycin 0 penicillin 3.6 oxacillin 1.4 kanamycin 1.5 amoxicillin 3 tetracycline 2.6 Azithromycin 2 guaracillin 3.5 Clindamycin 2.2 erythromycin 2.7 Gentamicin 1.4 Chloramphenicol 2.7
  • Example 6 Tolerance of Lactobacillus rhamnosus OF44-15Ph10T to acids and bile salts
  • MRS mediums of pH 2, pH 3, pH 4, pH 4.5 and pH 7 were prepared respectively, and 100 ⁇ L of OF44-15Ph10T bacterial liquid with a concentration of 8.5E+09 overnight culture was inoculated into MRS medium of different pH, and cultured at 37°C After 24h, the bacterial liquid was counted by plate coating.
  • the results showed that OF44-15Ph10T could not only survive but also grow under the conditions of pH 2, pH 3, pH 4, pH 4.5 and pH 7 (Table 4).
  • MRS medium containing 0.05%, 0.1%, 0.2% and 0.3% bile salts was prepared respectively, and 100 ⁇ L of OF44-15Ph10T bacterial liquid with a concentration of 8.5E+09 overnight culture was inoculated into MRS medium with different bile salt contents, 37 After culturing at °C for 24 h, the bacterial liquid was counted by plate coating. The results showed that OF44-15Ph10T could not only survive but also grow under the conditions of 0.05%, 0.1%, 0.2%, and 0.3% bile salts (Table 5).
  • Lactobacillus rhamnosus OF44-15Ph10T of the present disclosure has strong tolerance to acids and bile salts.
  • Example 7 Evaluation of the colonization ability of Lactobacillus rhamnosus OF44-15Ph10T
  • the OF44-15Ph10T bacterial liquid cultured overnight was divided into 10 mL in a 15 mL test tube, the uppermost bacterial liquid was taken, and the absorbance at OD600 was measured with a UV spectrophotometer. Let stand at room temperature for 30min, then take the uppermost bacterial liquid, and measure the absorbance value at OD600 with an ultraviolet spectrophotometer. The absorbance values before and after were compared, and the larger the difference, the stronger the self-aggregation ability. OF44-15Ph10T showed better self-aggregation ability (Table 6).
  • the six-well culture plate was taken out, the bacterial suspension was discarded, and the monolayer was washed 5 times with sterilized PBS buffer to remove unadhered bacteria, and then fixed with anhydrous methanol for 20 min.
  • the above cell slides fixed with anhydrous methanol were taken for Gram staining. After drying, the cells were observed and counted under a microscope, and the number of bacteria adhered to 100 cells in 20 random fields of view was calculated, and the average adhesion of each cell was calculated to be 34.59 ⁇ 4.63.
  • the present disclosure selects commercially widely used strains: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC-14 and marketed medicinal strain Lactobacillus delbrueckii as control experiments.
  • the experimental methods are the same as above, and the results show that each Hela cells adhered on average to 13.43 ⁇ 7.07 GR-1, 17.48 ⁇ 4.24 RC-14 and 25.23 ⁇ 2.12 Lactobacillus delbrueckii, indicating that the adhesion ability of OF44-15Ph10T to human cervical cancer cell Hela was higher than that of the two strains commercial strains.
  • VK2E6/E7 cells purchased from Beijing Beina Chuanglian Institute of Biotechnology
  • dilute the cells with 1640 complete culture medium without double antibody and count them on a hemocytometer (see below for the method) to make the cell concentration
  • drop 1 mL into a cell culture dish (12 or 6-well plate) and incubate at 37° C. in a 5% CO 2 -95% air incubator until complete differentiation.
  • the present disclosure selects commercially widely used strains: Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC-14 and marketed medicinal strain Lactobacillus delbrueckii as control experiments.
  • the experimental methods are the same as above, and the results show that each The average number of VK2E6/E7 cells adhered to 27.4 ⁇ 8.11 GR-1, 14.5 ⁇ 4.63 RC-14 and 22.24 ⁇ 9.26 L.
  • Example 8 Rat toxicity test of Lactobacillus rhamnosus OF44-15Ph10T
  • the rats selected in this example are SD female rats, 7 weeks old, body weight 250g ⁇ 50g, the rat rearing environment is SPF grade, and the experimental animals are divided into 6 groups, which are respectively 3 groups of gavage groups and 3 groups of vaginal irrigation groups. Wash group. Each group of 10 animals, a total of 60 animals, were fed with a standard diet.
  • Oral gavage group divided into 3 groups, gavaged with different doses, each rat was orally gavaged with 0.5 mL of fresh bacterial solution (concentrations were 1 ⁇ 10 5 , 1 ⁇ 10 9 , 1 ⁇ 10 12 CFU/mL, respectively), Once a day for 3 consecutive days, from the first day of gavage to the seventh day, the rats were all healthy and survived and gained weight.
  • Vaginal lavage group divided into 3 groups, the vagina was lavaged with different doses, each rat was lavaged with 0.2 mL of fresh bacterial solution (concentrations were 1 ⁇ 10 5 , 1 ⁇ 10 9 , 1 ⁇ 10 12 CFU/mL, respectively ) once a day for 3 consecutive days. From the lavage on the first day to the seventh day, the rats were all healthy and survived and gained weight.
  • Example 9 The ability of Lactobacillus rhamnosus OF44-15Ph10T to treat genital tract infection in rats
  • the rat model selected in this example is a rat model infected with Gardnerella genitalium, SD female rats, 7 weeks old, body weight 250g ⁇ 250g, the rat rearing environment is SPF grade, and the experimental animals are divided into 2 groups groups, the model group and the probiotic group, respectively. Each group of 10 animals, a total of 20 animals, were fed with a standard diet.
  • Adaptation period Rats were fed a standard diet for 7 days. Three days before modeling, 0.5 mg ⁇ -estradiol-3-benzoate was subcutaneously injected to keep the rat estrus phenomenon. Before modeling, observe and record whether the rat vagina is red, swollen and discharge, whether there is erythema and particulate phenotype; modeling period: use overnight cultured Gardnerella vaginalis (purchased from Beijing Beina Chuanglian Institute of Biotechnology) (PBS bacterial solution) rinse the rat vagina once a day for 3 consecutive days.
  • Gardnerella vaginalis purchasedd from Beijing Beina Chuanglian Institute of Biotechnology
  • Observation period 3 days after the intervention, observe and record whether the rat vagina is red, swollen and discharge, and whether there is erythema and particulate phenotype. While observing the rat phenotype each time, the vaginal washing fluid of the rat was taken, and quantitative PCR was used to detect the clearance of Gardnerella and the colonization of Lactobacillus gasseri
  • Example 10 The effect of Lactobacillus rhamnosus OF44-15Ph10T on the bone loss model in mice
  • Bone loss model adopts C57BL/6 female mice (purchased from Guangdong Provincial Medical Experimental Animal Center), 8 weeks old, body weight 20 ⁇ 2g, and can eat and drink freely in SPF environment. Randomly divided into 3 groups with 9 to 10 animals in each group.
  • mice The first group of 9 mice was the Sham (sham operation) control group. Sham operation was performed, only the skin was incised and then sutured. During the experiment, the medium containing the target strain (OF44-15Ph10T) was fed, and the feeding amount and body weight were proportional;
  • the second group of 10 mice was used as the experimental group.
  • the osteoporosis model was induced by the removal of ovarian organs.
  • the target strain was given a saturated suspension by gavage, and the feeding amount was proportional to the body weight;
  • the third group of 10 mice was the negative control group, and the osteoporosis model was induced by the removal of ovarian organs.
  • mice were sacrificed after the experiment, and the changes in bone-related indexes were detected by micro-CT (shown in Table 9 and Figure 8), and three-dimensional reconstructed images of the tissues were established ( Figure 9).

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Abstract

Lacticaseibacillus rhamnosus pour prévenir et/ou traiter les maladies causées par le trouble de la flore de l'appareil reproducteur et/ou la perte osseuse et une application associée. Le Lacticaseibacillus rhamnosus en question est l'OF44-15Ph10T, et son numéro de dépôt est le GDMCC n°60406. La souche est capable de produire des sécrétions telles que l'acide lactique et le peroxyde d'hydrogène pour inhiber la croissance des bactéries pathogènes de l'infection de l'appareil reproducteur, et est utilisée pour prévenir et/ou traiter la maladie de l'infection de l'appareil reproducteur. La souche peut également inhiber la perte osseuse de façon à traiter et à améliorer l'ostéoporose.
PCT/CN2021/129909 2020-11-10 2021-11-10 Lacticaseibacillus rhamnosus pour prévenir et/ou traiter les maladies causées par un trouble de la flore de l'appareil reproducteur et/ou une perte osseuse Ceased WO2022100632A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117535207A (zh) * 2024-01-04 2024-02-09 四川厌氧生物科技有限责任公司 一种格氏乳杆菌及其应用
CN118726136A (zh) * 2024-06-06 2024-10-01 科为生物(镇江)有限公司 一株可调节生殖道微生态和修复生殖道黏膜屏障损伤的鼠李糖乳酪杆菌bb520及其应用

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112760247B (zh) * 2020-11-10 2022-10-25 深圳华大生命科学研究院 用于预防和/或治疗生殖道菌群紊乱和/或骨质流失引起的疾病的鼠李糖乳杆菌
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7063836B2 (en) * 2002-01-08 2006-06-20 Garner Bryan E Compositions and methods for inhibiting pathogenic growth
CN103889241A (zh) * 2011-10-18 2014-06-25 雀巢产品技术援助有限公司 用于促进健康的骨生长和/或用于预防和/或治疗骨疾病的组合物
CN108004188A (zh) * 2018-01-11 2018-05-08 广东龙创基药业有限公司 一种鼠李糖乳杆菌及其用于制备阴道抑菌药物的应用
EP3318262A2 (fr) * 2016-11-03 2018-05-09 Cell Biotech Co., Ltd. Composition pour prévenir ou traiter une maladie osseuse, l'obésité et des maladies métaboliques lipidiques
CN110016442A (zh) * 2019-02-21 2019-07-16 河北一然生物科技有限公司 鼠李糖乳杆菌及其复合菌粉在防治阴道炎制品中的应用
CN112760247A (zh) * 2020-11-10 2021-05-07 深圳华大生命科学研究院 用于预防和/或治疗生殖道菌群紊乱和/或骨质流失引起的疾病的鼠李糖乳杆菌

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102009037089A1 (de) * 2009-08-11 2011-03-03 Heller, Knut J., Prof. Dr. Zusammensetzung mit Stämmen von Lactobazillus fermentum
AU2015227075A1 (en) * 2014-03-06 2016-09-22 Ohio State Innovation Foundation Probiotic formulations and methods for use
CN110122877B (zh) * 2018-02-09 2022-12-23 深圳华大基因农业控股有限公司 鼠李糖乳杆菌及其用途
CN110172420B (zh) * 2019-05-15 2022-03-01 福建省农业科学院农业工程技术研究所 一株鼠李糖乳杆菌及其应用
CN111647525B (zh) * 2020-05-18 2022-08-05 深圳华大基因农业控股有限公司 复合益生菌、菌剂及其在制备防治白色念珠菌性阴道炎菌剂中的应用

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7063836B2 (en) * 2002-01-08 2006-06-20 Garner Bryan E Compositions and methods for inhibiting pathogenic growth
CN103889241A (zh) * 2011-10-18 2014-06-25 雀巢产品技术援助有限公司 用于促进健康的骨生长和/或用于预防和/或治疗骨疾病的组合物
EP3318262A2 (fr) * 2016-11-03 2018-05-09 Cell Biotech Co., Ltd. Composition pour prévenir ou traiter une maladie osseuse, l'obésité et des maladies métaboliques lipidiques
CN108004188A (zh) * 2018-01-11 2018-05-08 广东龙创基药业有限公司 一种鼠李糖乳杆菌及其用于制备阴道抑菌药物的应用
CN110016442A (zh) * 2019-02-21 2019-07-16 河北一然生物科技有限公司 鼠李糖乳杆菌及其复合菌粉在防治阴道炎制品中的应用
CN112760247A (zh) * 2020-11-10 2021-05-07 深圳华大生命科学研究院 用于预防和/或治疗生殖道菌群紊乱和/或骨质流失引起的疾病的鼠李糖乳杆菌

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEN, CHEN: "The Effect and Mechanism Research of Intestinal Probiotics on Osteoporosis", CHINESE DOCTORAL DISSERTATIONS FULL-TEXT DATABASE, 1 May 2018 (2018-05-01), pages 1 - 108, XP055929847 *
DADARWAL DINESH; PALMER COLIN; GRIEBEL PHILIP: "Mucosal immunity of the postpartum bovine genital tract", THERIOGENOLOGY, vol. 104, 1 January 1900 (1900-01-01), US , pages 62 - 71, XP085228023, ISSN: 0093-691X, DOI: 10.1016/j.theriogenology.2017.08.010 *
ZHONG YAN , INGE TARNOW , SUI LONG: "Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 for Treatment and Prevention of Vaginal Infections", JOURNAL OF INTERNATIONAL OBSTETRICS AND GYNECOLOGY, vol. 40, no. 5, 15 October 2013 (2013-10-15), pages 428 - 431, XP055929843, ISSN: 1674-1870 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117535207A (zh) * 2024-01-04 2024-02-09 四川厌氧生物科技有限责任公司 一种格氏乳杆菌及其应用
CN118726136A (zh) * 2024-06-06 2024-10-01 科为生物(镇江)有限公司 一株可调节生殖道微生态和修复生殖道黏膜屏障损伤的鼠李糖乳酪杆菌bb520及其应用

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