WO2008052468A1 - Nouvelle souche de lactobacillus rhamnosus, composition pharmaceutique la contenant et ses utilisations, et procede de preparation associe - Google Patents

Nouvelle souche de lactobacillus rhamnosus, composition pharmaceutique la contenant et ses utilisations, et procede de preparation associe Download PDF

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WO2008052468A1
WO2008052468A1 PCT/CN2007/070962 CN2007070962W WO2008052468A1 WO 2008052468 A1 WO2008052468 A1 WO 2008052468A1 CN 2007070962 W CN2007070962 W CN 2007070962W WO 2008052468 A1 WO2008052468 A1 WO 2008052468A1
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weight
parts
lactobacillus rhamnosus
slr0406
strain
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PCT/CN2007/070962
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Chinese (zh)
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WO2008052468A8 (fr
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Xi Zhu
Jing Liu
Lijun Qiu
Jiafeng Chen
Jiao Chen
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Sine Pharmaceutical Laboratories
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    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12—Antidiarrhoeals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/225—Lactobacillus

Definitions

  • New Lactobacillus strain New Lactobacillus strain, pharmaceutical composition, use thereof, and manufacturing method
  • the present invention relates to a novel Lactobacillus strain of L. rhamn, a process for its preparation, and a novel use for the treatment of antibiotics and chemotherapy-induced diarrhea and related disorders. Background technique
  • antibiotic-associated diarrhea AAD
  • Antibiotics can also damage normal flora while inhibiting or killing pathogenic bacteria, while enterococci or fungi overgrow.
  • Almost all antibiotics can induce AAD, and broad-spectrum penicillins are the most common, followed by clindamycin, cephalosporins, and aminoglycosides.
  • anti-tumor chemotherapy drugs can also cause intestinal flora disorder, leading to diarrhea.
  • Microecological regulator Probiotics are a group of bacteria that promote probiotic effects on the host by increasing the balance of intestinal flora, mainly Lactobacillus, Streptococcus mutans, Bifidobacterium, and the like. These bacteria are the normal flora of the intestines of healthy people.
  • the importance of Lactobacillus in the intestinal flora has been confirmed in many different studies. It has been found that a large oral administration of Lactobacillus rhamnosus to mammals helps to maintain and enhance the health of the animal. After ingestion, Lactobacillus rhamnosus will temporarily colonize the intestinal mucosa and inhibit disease. Growth of bacteria and rotavirus inhibits allergic reactions, thereby reducing the symptoms of diarrhea.
  • the strain of Lactobacillus rhamnosus described in the present invention is named SLR0406, which has been deposited with the China Center for Type Culture Collection in Wuhan on March 17, 2006, and has a deposit number of CCTCC-M206023.
  • the present invention provides a strain of Lactobacillus rhamnosus SLR0406 which survives at 37 ° C for 30-60 days, and the characteristics of sugar fermentation are as follows:
  • the Lactobacillus rhamnosus strain SLR0406 is a live strain or an inactivated strain.
  • the present invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising the Lactobacillus rhamnosus strain SLR0406, a protective agent and a pharmaceutically acceptable carrier according to the present invention.
  • the pharmaceutical composition is selected from the group consisting of oral liquids, tablets, capsules and other oral solid preparations, and lyophilized powder preparations.
  • the content of the Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 is 0.1-99.9 parts by weight, preferably 10-8 parts by weight, more preferably 20 to 70 parts by weight, most preferably 40 to 60 parts by weight;
  • the protective agent is used in an amount of 0.1 to 99.9 parts by weight, preferably 20 to 90 parts by weight, more preferably 30 to 80 parts by weight, most preferably 40 - 60 parts by weight.
  • the protective agent comprises 10 to 20 parts by weight of skim milk powder, 10 to 20 parts by weight of sodium alginate, 10 to 20 parts by weight of isotose, and 6 to 20 parts by weight of starch, sodium glutamate.
  • the protective agent contains 12 to 18 parts by weight of skim milk powder, 12 to 18 parts by weight of isolactose, 10 to 16 parts by weight of starch, glutamic acid 0.05 to 1.5 parts by weight of sodium, 0.05 to 0.15 parts by weight of vitamin C-sodium, more preferably 14 to 16 parts by weight of the skim milk powder, 14 to 16 parts by weight of the isoflavone, 12 to 14 parts by weight of the starch, glutamic acid Sodium 0.5 ⁇ 1.0 parts by weight, vitamin C-sodium 0.1 ⁇ 0.12 parts by weight.
  • the present invention also provides a method of preparing the lyophilized powder formulation of the present invention, the method comprising:
  • step (b) placing the medium obtained in the step (a) in a fermentor, inoculating the Lactobacillus rhamnosus strain SLR0406 CCTCC-M206030, and fermenting;
  • step (e) adding an excipient to the lyophilized powder obtained in the step (d), and sieving to obtain a lyophilized powder preparation.
  • the present invention also provides the use of the Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 for the treatment of antibiotics and chemotherapy-induced diarrhea and related disorders, particularly intestinal flora disorders, hepatopathy adjuvant therapy, and reduction of blood ammonia concentration.
  • the related condition comprises acute diarrhea, chronic diarrhea, irritable bowel syndrome and constipation.
  • Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 of the present invention can be preserved for a long time, and can effectively treat diarrhea and related symptoms caused by antibiotics and chemotherapy drugs, especially intestinal flora disorders.
  • Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 of the present invention was obtained by the following method:
  • the culture characteristics and bacterial morphology of the Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 of the present invention are as follows:
  • the optimum growth temperature is 37 ° C ⁇ 40 ° C
  • the optimum pH value is 5.5 ⁇ 7.0
  • the milky white colonies grow on the MRS medium for 48 hours
  • the rounded bulge of the colony is smooth
  • Gram Positive staining no spores, no sandwich, no flagella
  • the bacteria are short rods at both ends, spherical, single or double.
  • the Lactobacillus rhamnosus strain SLR0406 of the present invention can survive at 37 ° C for at least 30 days, for example 30-60 days, 30-50, 30-40 days.
  • Lactobacillus rhamnosus SLR0406 CCTCC-M206023 and the commercially available Lactobacillus rhamnosus (purchased from the Beijing General Microbiology Center) according to the present invention were carried out according to the kit instructions using API 50CHL kit (purchased from BioMerieux, Lyon, France). The fermentation method was measured and the results were as follows:
  • the Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 of the present invention can be administered in a conventional dosage form in the art.
  • the above-mentioned Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 can be prepared into oral liquids, tablets, capsules and other oral solid preparations, as well as lyophilized powder preparations and the like.
  • the Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 can be formulated into a lyophilized powder preparation.
  • the present invention also provides a lyophilized powder preparation comprising the Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 freeze-dried powder and a protective agent.
  • the content of the Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 is conventional as long as the desired effect can be obtained.
  • the Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 is used in an amount of 0.1 to 99.9 parts by weight, preferably 10 to 80 parts by weight, more preferably 20 to 70 parts by weight, most preferably 40 to 60 parts by weight.
  • the protective agent is a conventional protective agent in the art.
  • the protective agent comprises 10 to 20 parts by weight of skim milk powder, 10 to 20 parts by weight of sodium alginate, 10 to 20 parts by weight of isolose, and 6 to 20 parts by weight of starch, sodium glutamate. 0.01 part by weight, vitamin C-sodium 0.01 to 0.2 parts by weight.
  • the protective agent contains 12 to 18 parts by weight of skim milk powder, 12 to 18 parts by weight of isolactose, 10 to 16 parts by weight of starch, and 0.05 to 1.5 parts by weight of sodium glutamate, vitamin C. - Sodium 0.05 ⁇ 0.15 parts by weight.
  • the skim milk powder containing 14 to 16 parts by weight, the isoflavone 14 to 16 parts by weight, the starch 12 to 14 parts by weight, the sodium glutamate 0.5 to 1.0 part by weight, the vitamin C- Sodium 0.1-0.12 parts by weight.
  • the amount of the protective agent is conventional.
  • the protective agent is used in an amount of from 0.1 to 99.9 parts by weight, preferably from 20 to 90 parts by weight, more preferably from 30 to 80 parts by weight, most preferably from 40 to 60 parts by weight.
  • a pharmaceutically acceptable carrier may also be included.
  • the pharmaceutically acceptable carrier is conventional in the art and may be, for example, a pharmaceutically acceptable filler, excipient, flavoring or the like.
  • the invention also provides a preparation method of the above lyophilized powder preparation, the method comprising the following steps:
  • step (b) placing the medium obtained in step (a) in a fermentor to inoculate a strain of Lactobacillus rhamnosus SLR0406 CCTCC-M206023, and fermented;
  • the medium comprises a nitrogen source, a carbon source, and a special ingredient.
  • the nitrogen source is selected from the group consisting of skim milk powder, peptone, tryptone, ammonium salt, beef extract, and/or plant mash;
  • the carbon source is selected from the group consisting of glucose, lactose, isolose, and half. Lactose, glycerol, sorbitol, trehalose and/or maltose; the specific ingredients are selected from the group consisting of yeast powder, tomato juice, kimchi juice, cysteine and/or earth temperature 80.
  • the step of preparing the medium and performing the sterilization is conventional in the art, and those skilled in the art can directly obtain how to prepare the medium and perform sterilization by reading the present invention in combination with its expertise.
  • the step of preparing the medium and performing the sterilization comprises fully dissolving the skim milk powder, the glucose and the yeast extract in water, adjusting the pH to 6.5 to 7.5, and placing the obtained aqueous solution in the pressure cooker. Sterilize at 100-200 °C for 5-6 minutes, then cool to 37 ⁇ 38 °C.
  • the step of inoculating the Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 and performing the fermentation comprises: placing the product obtained in the step (a) in a fermentor and inoculating under aseptic conditions 5 30% by volume (based on the volume of the product obtained in the step (a)) of the Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023, and then passed at 37 to 38 ° C under a can pressure of 0.3 0.6 kg / cm 2 Fermented into sterile air for 12 hours to 24 hours.
  • the step of lyophilizing to obtain a lyophilized powder is conventional in the art, and those skilled in the art can directly know how to carry out cold according to the description of the present invention and its expert knowledge. Freeze to dry.
  • the step of lyophilizing to obtain a lyophilized powder comprises: adding 5-30% by weight of a protective agent to the slime by weight of the obtained slime, and performing freeze-drying to obtain a frozen Dry powder.
  • the amounts of the skim milk powder, the glucose, and the yeast extract are not particularly limited as long as a medium capable of forming the inoculated strain of Lactobacillus rhamnosus SLR0406 CCTCC-M206023 is formed.
  • the skimmed milk powder is used in an amount of 5 to 15 kg, preferably 6 to 10 kg, more preferably 7 to 9 kg.
  • the glucose is used in an amount of from 0.5 to 5 kg, preferably from 1 to 3 kg, more preferably from 1.2 to 2 kg, and most preferably from 1.3 to 1.8 kg.
  • the yeast extract is used in an amount of from 0.5 to 5 kg, preferably from 0.6 to 3 kg, more preferably from 0.7 to 2 kg, most preferably from 0.8 to 1.5 kg.
  • the sterilization time is preferably 6 to 40 minutes, more preferably 7 to 20 minutes, and most preferably 8 to 15 minutes.
  • the amount of Lactobacillus rhamnosus strain SLR0406 CCTCC-M206030 is preferably 6-20% by volume, more preferably 7-15% by volume, most preferably 8-12% by volume.
  • the internal pressure of the fermenter is preferably 0.4 - 0.5 kg / cm 2 .
  • the freeze-drying is preferably carried out at -50 ° C to 30 ° C, more preferably at -40 ° C to 10 ° C.
  • the excipient is preferably starch or pregelatinized starch.
  • Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 of the present invention is simple to use, for example, can be administered orally.
  • Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 of the present invention can be preserved for a long time, and can effectively treat diarrhea and related symptoms caused by antibiotics and chemotherapy drugs.
  • the invention is described in detail below with reference to the embodiments, which are intended to be illustrative only and not to limit the scope of the invention.
  • Example 1 Preparation of Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023
  • Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 was prepared as follows:
  • Lactobacillus rhamnosus strain SLR0406 CCTCC-M206023 was prepared in the same manner as in Example 1, except that the storage temperatures of the step (a) were 4 ° C, 25 ° C, 40 ° C and 45 ° C, respectively.
  • Example 6 Preparation of lyophilized powder capsules
  • skim milk powder New Zealand imported skim milk powder
  • glucose 8 kg
  • the inoculation amount of 10% by volume (based on the volume of the above-mentioned sterile product) in the above-mentioned aseptic product was inoculated to Lactobacillus rhamnosus SLR0406 CCTCC-M206023 obtained in Example 1, and cultured under aerobic conditions at 37 ° C. After cooling for an hour, centrifuge 3 kg of bacteria.
  • skim milk powder New Zealand imported skim milk powder
  • glucose 8 kg
  • Lactobacillus rhamnosus SLR0406 CCTCC-M206023 obtained in Example 2 was inoculated in the above aseptic product in an amount of 10% by volume (based on the volume of the above-mentioned sterile product), and cultured under aerobic conditions at 37 ° C. After cooling for an hour, centrifuge 3 kg of bacteria.
  • Protective agent formula skimmed milk powder (New Zealand imported skim milk powder) 2 kg, 2.5 kg of isolactose, sodium glutamate (Guangzhou MSG Food Factory) 0.4 kg, vitamin C-sodium (Jiangsu Jingjiang Pharmaceutical Factory) 0.05 kg, the above components dissolved It is sterilized in 12 kg of water and sterilized at 121 °C for 15 minutes.
  • Example 8 Preparation of lyophilized powder capsules
  • skim milk powder New Zealand imported skim milk powder
  • glucose Shanghai Sugar Sugar Factory
  • yeast powder OXOID ⁇ TD
  • the sodium oxide solution adjusted the pH to 7.0.
  • the resulting aqueous solution was sterilized in an autoclave at 121 °C for 10 minutes to obtain a sterile product.
  • Lactobacillus rhamnosus SLR0406 CCTCC-M206023 obtained in Example 3 was inoculated in the above aseptic product in an amount of 10% by volume (based on the volume of the above-mentioned sterile product), and cultured under aerobic conditions at 37 ° C. After cooling for an hour, centrifuge 3 kg of bacteria.
  • skim milk powder New Zealand imported skim milk powder
  • glucose Shanghai Sugar Sugar Factory
  • yeast powder OXOID ⁇ TD
  • the sodium oxide solution adjusted the pH to 7.0.
  • the resulting aqueous solution was sterilized in an autoclave at 121 °C for 10 minutes to obtain a sterile product.
  • Lactobacillus rhamnosus SLR0406 CCTCC-M206023 obtained in Example 4 was inoculated in the above aseptic product in an amount of 10% by volume (based on the volume of the above-mentioned sterile product), and cultured under aerobic conditions at 37 ° C. After cooling for an hour, centrifuge 3 kg of bacteria.
  • Protective agent formula skimmed milk powder (New Zealand imported skim milk powder) 2 kg, 2.5 kg of isolactose, sodium glutamate (Guangzhou MSG Food Factory) 0.4 kg, vitamin C-sodium (Jiangsu Jingjiang Pharmaceutical Factory) 0.05 kg, the above components dissolved It is sterilized in 12 kg of water and sterilized at 121 °C for 15 minutes.
  • Example 10 Preparation of lyophilized powder capsules
  • Lactobacillus rhamnosus SLR0406 CCTCC-M206023 obtained in Example 5 was inoculated in the above-mentioned aseptic product in an amount of 10% by volume (based on the volume of the above-mentioned sterile product), and cultured under aerobic conditions at 37 ° C. After cooling for an hour, centrifuge 3 kg of bacteria.
  • Protective agent formula skimmed milk powder (New Zealand imported skim milk powder) 2 kg, 2.5 kg of isolactose, sodium glutamate (Guangzhou MSG Food Factory) 0.4 kg, vitamin C-sodium (Jiangsu Jingjiang Pharmaceutical Factory) 0.05 kg, the above components dissolved It is sterilized in 12 kg of water and sterilized at 121 °C for 15 minutes.
  • Example 1 1-15 Preparation of live bacteria tablets
  • Example 16 Acute toxicity test
  • Wistar rats and beagle dogs were selected as subjects, and the toxicity of the live bacteria tablets obtained in Examples 11 to 15 was examined.
  • Six Wistar rats (male and female) and 10 beagle dogs (female and half) were selected.
  • 10 Wistar rats (male and female) plus 2 beagle dogs (male and female) were divided into 1 group (experiment group 1 to 5), and 10 Wistar rats alone (male and female) were divided into one group (control group). )
  • the 500 mg tablets prepared in Examples 11 to 15 were dispersed in 12.5 ml of sterile physiological saline and diluted into a suspension, and the experimental group 1 to 5 was administered once at a standard of 2 g tablet/kg body weight. The reaction of the animals was observed and observed continuously for 14 days. The general indicators (animal appearance, behavior, excretion, etc.) of the experimental group and the control group were normal, and there was no significant difference in body weight, and no poisoning and death occurred.
  • Example 17 Acute toxicity test
  • mice Sixty Kunming mice were selected and divided into 10 groups (experimental group 1 5 and control group).
  • the 500 mg tablets obtained in Examples 11 to 15 were dispersed in 12.5 ml of sterile physiological saline to prepare a suspension, and the resulting suspension was intraperitoneally injected into the animals of the experimental group 1-5, 0.5 ml each.
  • the control group was intraperitoneally injected with 0.5 ml of normal saline.
  • the response of the animals was observed and observed continuously for 14 days.
  • the general indicators (animal appearance, behavior, excretion, etc.) of the experimental group and the control group were normal, and there was no significant difference in body weight, and no poisoning and death occurred.
  • Example 18 Long-term toxicity test
  • Example 16-18 show that the preparation prepared by the Lactobacillus rhamnosus SLR0406 CCTCC-M206023 of the present invention has no acute toxicity and accumulation toxicity to Wistar rats, Kunming mice and beagle dogs, and can be safely taken.
  • Example 19
  • the control group was 10.
  • the antibiotic ampicillin sodium was used as a model drug, and the model group was modeled by drinking water + gavage. Ampicillin sodium was administered at a dose of 300 mg / day. The treatment time for ampicillin sodium was 3 days, and stool changes were observed and recorded.
  • Diarrhea was determined by the presence of loose stools (with or without stains on the filter paper).
  • mice treated with the antibiotic ampicillin sodium as above were equally divided into 6 groups (experiment group 1 5 and control).
  • the tablets obtained in Examples 1 to 15 were orally administered to the experimental group 1 to 5 at a dose of 10 8 CFU per day, and the natural recovery group was administered with physiological saline without a live bacteria.
  • the mice were sacrificed for 7 days, and the mice were sacrificed on the eighth day and dissected under aseptic conditions.
  • the intestinal samples of each mouse were cultured and counted for viable counts. Quantitative analysis of intestinal flora after 1 week of treatment in each group of experimental mice (log value)
  • mice were diarrhea after continuous administration of antibiotics. After that, the products of the present invention were continuously administered. Compared with the natural recovery group, the symptoms of the diarrhea in the test group were significantly improved, and the number of intestinal probiotics recovered rapidly. To normal level.
  • Example 20 Storage stability
  • Example 1 The Lactobacillus rhamnosus obtained in Example 1 (ie, SLR0406 CCTCC-M206023), the fermentation broth was stored at 37 ° C, and the number of viable cells was measured on days 5, 10, 30, and 40, respectively. , the results are as follows: Storage days (d) 0 5 10 30 40
  • the Lactobacillus rhamnosus obtained by the present invention can be stably stored at least for 30 days at 37 °C. Further, by storing the Lactobacillus rhamnosus obtained in Example 1 on the 60th day, the number of viable cells viable was also about 100.

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Abstract

L'invention concerne une souche de Lactobacillus rhamnosus SLR0406 pouvant subsister pendant 30 à 60 jours à 37°. L'invention concerne une composition pharmaceutique contenant cette souche de Lactobacillus rhamnosus SLR0406. La souche SLR0406 CCTCC-M206023 selon l'invention peut être conservée pendant une longue durée et peut être utilisée efficacement dans le traitement de la diarrhée et d'autres symptômes connexes causés par les antibiotiques et les médicaments chimiothérapeutiques.
PCT/CN2007/070962 2006-11-01 2007-10-26 Nouvelle souche de lactobacillus rhamnosus, composition pharmaceutique la contenant et ses utilisations, et procede de preparation associe WO2008052468A1 (fr)

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CN200610117825.7 2006-11-01
CN2006101178257A CN101173228B (zh) 2006-11-01 2006-11-01 新的乳酸杆菌菌株、药物组合物及其用途、以及制造方法

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CN108103128A (zh) * 2017-12-01 2018-06-01 安佑生物科技集团股份有限公司 一种用于治疗仔猪腹泻的乳酸菌素的制备方法
CN110584118A (zh) * 2019-09-24 2019-12-20 上海儿童营养中心有限公司海南分公司 一种婴幼儿用益生菌粉的制备方法
CN111743875A (zh) * 2019-09-17 2020-10-09 河南金百合生物科技股份有限公司 一种丁酸梭菌微囊化活菌制剂的制备方法
CN112063547A (zh) * 2020-08-14 2020-12-11 润盈生物工程（上海）有限公司 一种格氏乳杆菌lg-g12高密度发酵及提高菌粉质量的方法
CN114128882A (zh) * 2020-09-03 2022-03-04 香港科技大学深圳研究院 具有润肠通便的苁蓉益生咀嚼片及其制备方法和应用
CN114672441A (zh) * 2022-05-05 2022-06-28 华中农业大学 一种乳酸菌组合物及其应用
CN115025133A (zh) * 2022-06-14 2022-09-09 山东省农业科学院 一种乳酸菌口服液及其在缓解和治疗腹泻中的应用

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CN111743875A (zh) * 2019-09-17 2020-10-09 河南金百合生物科技股份有限公司 一种丁酸梭菌微囊化活菌制剂的制备方法
CN111743875B (zh) * 2019-09-17 2022-07-29 河南金百合生物科技股份有限公司 一种丁酸梭菌微囊化活菌制剂的制备方法
CN110584118A (zh) * 2019-09-24 2019-12-20 上海儿童营养中心有限公司海南分公司 一种婴幼儿用益生菌粉的制备方法
CN112063547A (zh) * 2020-08-14 2020-12-11 润盈生物工程（上海）有限公司 一种格氏乳杆菌lg-g12高密度发酵及提高菌粉质量的方法
CN114128882A (zh) * 2020-09-03 2022-03-04 香港科技大学深圳研究院 具有润肠通便的苁蓉益生咀嚼片及其制备方法和应用
CN114672441A (zh) * 2022-05-05 2022-06-28 华中农业大学 一种乳酸菌组合物及其应用
CN115025133A (zh) * 2022-06-14 2022-09-09 山东省农业科学院 一种乳酸菌口服液及其在缓解和治疗腹泻中的应用
CN115025133B (zh) * 2022-06-14 2023-08-04 山东省农业科学院 一种乳酸菌口服液及其在缓解和治疗腹泻中的应用

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