CN112236154B - Composition and application thereof - Google Patents
Composition and application thereof Download PDFInfo
- Publication number
- CN112236154B CN112236154B CN201880093354.1A CN201880093354A CN112236154B CN 112236154 B CN112236154 B CN 112236154B CN 201880093354 A CN201880093354 A CN 201880093354A CN 112236154 B CN112236154 B CN 112236154B
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- CN
- China
- Prior art keywords
- composition
- lactobacillus
- lactobacillus acidophilus
- enteric
- bifidobacterium pseudocatenulatum
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 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
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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
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- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- Chemical Kinetics & Catalysis (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
A composition and use thereof is provided, the composition comprising Lactobacillus gasseri and/or its metabolites, lactobacillus acidophilus and/or its metabolites and Bifidobacterium pseudocatenulatum and/or its metabolites. The composition can be used for treating inflammation including ulcerative enteritis and its related diseases.
Description
Technical Field
The application relates to the field of microbial preparations, in particular to a microorganism or a microorganism-related composition and application thereof.
Background
Inflammatory bowel disease (inflammatory bowel disease, IBD) is a chronic inflammatory bowel disease of unknown etiology, which is easily repeated, severely affecting the quality of life of the patient. Modern medicine considers that factors responsible for Inflammatory Bowel Disease (IBD) are genetic, dietary, infectious, autoimmune, psychological factors, environmental, and the like. Inflammatory bowel diseases, including ulcerative enteritis (UC) and Crohn's Disease (CD), are all inflammation-related disorders.
Ulcerative enteritis (ulcerative colitis, UC) is an important disease type of inflammatory bowel disease (inflammatory bowel disease, IBD), the cause of which is unknown, the main lesion is submucosa at colonic mucosa, and it is a chronic intestinal disease. Based on the current research, the etiology of UC is mainly considered to have host genetic susceptibility, intestinal flora and immune response of intestinal mucosa, clinical pathology is manifested by continuous abdominal pain, diarrhea and mucous bloody stool, and the disease is repeated, and the number of patients suffering from UC in China has a remarkable rising trend in recent years.
At present, the clinical drugs for UC mainly comprise salicylic acid drugs, adrenoglucocorticoid drugs and immunosuppressants. All three kinds of medicines can relieve UC to a certain extent, but have defects. The salicylic acid medicine can well inhibit prostaglandin synthesis, remove oxygen free radicals so as to achieve the aim of relieving inflammatory reaction, but can only relieve in a short period, cannot realize radical cure, and the salicylic acid western medicine which is common in clinic for treating UC is mainly sulfasalazine (SASP), and mainly aims at mild, moderate and chronic UC patients. In addition, salicylic acid medicines have a plurality of side effects, such as digestive tract reaction, headache, reticulocyte increase, oligospermia, rash, hepatotoxicity, leukopenia, anemia and the like caused by anaphylaxis, and have antibacterial effects, and are easy to cause flora disturbance and drug resistance enhancement. Adrenoglucocorticoid drugs are the first drug of choice for patients with severe or explosive UC, typical drugs such as betamethasone; however, adrenoglucocorticoid drugs cause side effects such as metabolic disturbance, water retention and the like, and can only be used as emergency drugs and cannot be taken for a long time. Immunosuppressants, such as cyclosporine, may inhibit UC by inhibiting the production of T cell IL-2, affecting the progression of the immune response; however, immunosuppressant treatment has great dependence on drugs, long treatment period, easy nephrotoxicity and secondary infection, and can only be used as an auxiliary treatment means. Therefore, no safe and effective therapeutic drug for inflammation and related diseases, especially ulcerative enteritis, exists at present.
Disclosure of Invention
The application aims to provide a composition and application thereof.
The application adopts the following technical scheme:
In one aspect, the application discloses a composition comprising lactobacillus gasseri and/or a metabolite thereof, lactobacillus acidophilus and/or a metabolite thereof, and bifidobacterium pseudocatenulatum and/or a metabolite thereof.
The key point of the application is that the research discovers that the combined use of lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum can prevent and treat inflammation and inflammation related diseases, in particular to effectively prevent and treat ulcerative enteritis; research shows that the prevention or treatment and prevention effect mainly comprises two aspects, on one hand, lactobacillus gasseri, lactobacillus acidophilus and pseudosmall chain bifidobacterium are used for improving intestinal microecology in vivo to form an ecological protection barrier formed by beneficial bacteria, so that the prevention and treatment effects of inflammation or inflammation related diseases are achieved; on the other hand, metabolites of lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum are used as probiotic materials to play a role in preventing and treating inflammation or inflammation-related diseases. Thus, an important use of the composition of the application is for the prevention or treatment of inflammation or inflammation-related disorders, in particular for the prevention or treatment of ulcerative colitis or a related disorder thereof.
In addition, in one implementation mode of the application, the composition consisting of the lactobacillus gasseri, the lactobacillus acidophilus and the pseudosmall chain bifidobacterium improves intestinal microecology in vivo through three bacteria to form an ecological protection barrier consisting of beneficial bacteria, thereby having the effects of preventing and treating ulcerative enteritis. It can be understood that the improvement of the microecology has the effects of preventing and treating ulcerative enteritis and other microecology-related diseases such as common enteritis or gastritis and the like; thus, the composition of the present application can be used for preventing or treating inflammation or inflammation-related disorder.
Preferably, the Lactobacillus gasseri is Lactobacillus gasseri TF08-1 with accession number GDMCC 60092, the Lactobacillus acidophilus is Lactobacillus acidophilus AM13-1 with accession number GDMCC 60091, and the Bifidobacterium pseudocatenulatum is Bifidobacterium pseudocatenulatum TM12-14 with accession number GDMCC 60089.
It should be noted that the key point of the present application is that the combination of Lactobacillus gasseri, lactobacillus acidophilus and Bifidobacterium pseudocatenulatum is found to prevent and treat inflammation and inflammation related diseases, while Lactobacillus gasseri TF08-1, lactobacillus acidophilus AM13-1 and Bifidobacterium pseudocatenulatum TM12-14 are three strains with good combination effect found in the course of the present application, so that the three strains are respectively preserved. It is understood that, on the one hand, it is not excluded that other strains of lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum can be used in the inventive concept, achieving effects even exceeding those of the three strains of the application; on the other hand, in the case where there is a low demand for the preventive or therapeutic effect on inflammation or inflammation-related diseases, other strains of lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum may be used.
Preferably, the composition of the application also contains other probiotics and/or prebiotics.
It should be noted that the key point of the composition of the present application is that the combination of lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum can prevent and treat inflammation and inflammation related diseases, and it can be understood that other probiotics or prebiotics can be added without affecting the combined effect of the three of lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum, so that the composition of the present application has more functions or enhances the original efficacy thereof, and the probiotics or prebiotics can be the probiotics or prebiotics reported in the prior study and are not specifically limited herein.
Preferably, in one embodiment of the present application, the prebiotic in the composition of the present application is selected from at least one of fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), xylo-oligosaccharides (XOS), lactulose-oligosaccharides (LACT), soy Oligosaccharides (SOS), inulin (Inulin) and oligosaccharides.
Preferably, the composition of the present application further comprises a substance that helps to maintain the viability of at least one of lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum.
It will be appreciated that in order to maintain the viability of lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum in the composition and to ensure the efficacy thereof, various substances for maintaining the viability of the strain may be added to the composition, and these may be the viability substances reported in the prior studies, and are not particularly limited herein.
Preferably, in one implementation of the present application, the substance that helps to maintain the viability of at least one of lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum is selected from at least one of cysteine, glutathione, butylated hydroxyanisole, dibutylmethyl toluene, tocopherol, bamboo leaf antioxidant, D-isoascorbic acid or its sodium salt, sodium ascorbate, calcium ascorbate, phospholipid, vitamin C and vitamin E.
Preferably, the composition of the present application further comprises a pharmaceutically or food acceptable carrier or adjuvant.
The composition of the present application has an effect of preventing and treating inflammation and inflammation-related diseases, and in one embodiment of the present application, the effect of preventing and treating inflammation and inflammation-related diseases is mainly achieved by eating the composition of the present application. Therefore, the composition can also comprise pharmaceutically or food acceptable carriers or auxiliary materials so as to be convenient for use.
Preferably, the pharmaceutically or food acceptable carrier or adjuvant is at least one selected from glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, gelatin, albumin, water and physiological saline.
The application also discloses application of the composition in preparing foods, health care products, food additives or medicines for treating or preventing inflammation or inflammation-related diseases.
It will be appreciated that the composition of the present application has an effect of preventing and treating inflammation and inflammation-related diseases, and for convenience of use, the composition of the present application may be formulated into various foods, health products, food additives or medicines.
Preferably, the composition of the present application can be used for preparing foods, health products, food additives or medicines for treating or preventing ulcerative enteritis or related diseases thereof.
In a further aspect, the application discloses the use of a composition of the application in the manufacture of a food, nutraceutical, food additive or pharmaceutical product for controlling weight loss in a mammal.
Wherein, the weight of the mammal is reduced, especially the weight of the mammal is reduced due to inflammation.
Preferably, the inflammation is ulcerative enteritis, i.e. controlling weight loss in a mammal due to ulcerative enteritis.
In a further aspect, the application discloses the use of a composition of the application in the manufacture of a food, nutraceutical, food additive or pharmaceutical product for reducing the disease activity index of a mammal.
In a further aspect, the application discloses the use of a composition of the application in the manufacture of a food, health product, food additive or pharmaceutical product for ameliorating intestinal lesions in a mammal.
The composition can prevent and treat inflammation and inflammation-related diseases, and is characterized by controlling the weight loss caused by the inflammation and the inflammation-related diseases, reducing the disease activity index caused by the inflammation and the inflammation-related diseases and improving the intestinal lesions of mammals; thus, the composition of the present application may also be used alone in the preparation of a food, nutraceutical, food additive or pharmaceutical product for controlling weight loss, decreasing the disease activity index or ameliorating intestinal lesions in a mammal.
In a further aspect, the application discloses methods of treating or preventing inflammation or inflammation-related disorder using the compositions of the application.
In yet another aspect, the application discloses methods of controlling weight loss in a mammal using the compositions of the application.
In yet another aspect, the application discloses methods of reducing the disease activity index of a mammal using the compositions of the application.
In yet another aspect, the application discloses a method of ameliorating intestinal lesions in a mammal using the composition of the application.
In the above methods, the composition of the present application is mainly used for treating or preventing inflammation or inflammation-related diseases, controlling weight loss of mammals, reducing the disease activity index of mammals or improving intestinal lesions of mammals.
In a further aspect of the application, a food product is disclosed comprising the composition of the application.
Preferably, the food product is a lactic acid drink or a soy milk drink. The food product of the present application is an edible product in any form in a broad sense, and is not limited to a lactic acid drink or a soybean milk drink, and may be, for example, a fermented food product or an animal feed.
The food of the present application has the effects of treating or preventing inflammation or inflammation-related disorder, controlling weight loss in mammals, reducing the index of activity of diseases in mammals, and improving intestinal lesions in mammals, because of the composition of the present application. It will be appreciated that the food product of the present application, which is critical to the inclusion of the composition of the present application, is not specifically limited herein as to the particular form of the food product, such as solids, liquids, etc., and may be varied depending on the food product or use requirements. In one implementation mode of the application, the composition is mainly prepared into common lactic acid beverage or soybean milk beverage so as to be convenient for drinking; of course, solid foods such as milk chips and cheese bars may be produced, and are not particularly limited herein.
The amount of active bacteria or intake of lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum in the food of the present application is not particularly limited, and may be flexibly selected according to actual conditions in practical applications. Taking Lactobacillus gasseri TF08-1, lactobacillus acidophilus AM13-1 and Bifidobacterium pseudocatenulatum TM12-14 as examples, the study of the application shows that the daily intake of the composition of Lactobacillus gasseri TF08-1, lactobacillus acidophilus AM13-1 and Bifidobacterium pseudocatenulatum TM12-14 with the concentration of 10 9 cfu/mL is 0.2mL, has good therapeutic effect on ulcerative enteritis, and the active bacterial dose can be used as the reference dosage or reference intake of food, health care products, food additives or medicines.
The application also discloses a health-care product, which contains the composition.
The health care product of the application has the effects of treating or preventing inflammation or inflammation related diseases, controlling the weight reduction of mammals, reducing the activity index of the mammals and improving intestinal tract diseases of the mammals because of containing the composition of the application.
In a further aspect of the application, a food additive is disclosed comprising the composition of the application.
The composition of the present application can be consumed in combination with a usual food material. For example, cereals including rice, flour, miscellaneous cereals, potatoes including potatoes, sweet potatoes, etc.; animal foods including meat, poultry, fish, milk, eggs, and the like; legumes and products thereof, including soybeans and other dried legumes; vegetables and fruits including fresh beans, rhizomes, leaf vegetables, solanaceous fruits, etc.; pure heat energy foods including animal and vegetable oils, starches, edible sugars, alcoholic beverages, and the like; therefore, the composition of the application can be independently used as a food additive or a modulator to be added into various food materials for direct eating, thereby having the effect of treating or preventing inflammation and related diseases.
In a further aspect of the application, a pharmaceutical product comprising a composition of the application is disclosed.
Preferably, the pharmaceutical product is a tablet, granule, powder, enteric, solution or suspension.
The medicine of the present application has the therapeutic or prophylactic effect on inflammation and diseases related to inflammation, because of containing the composition of the present application; the medicine of the present application may be the composition of the present application alone or in combination with other inflammation medicine, so long as the activities of the medicine and the medicine are not affected. It will be appreciated that the pharmaceutical product of the present application may take a variety of existing dosage forms, provided that the activity of each strain in the composition is not affected. In the medicine of the present application, the medicine may further include common supplementary material, such as stabilizer, wetting agent, emulsifier, adhesive, isotonizing agent, etc.
The medicine of the application can be administered in any form of oral liquid, tablet, injection, orally disintegrating tablet, freeze-dried powder preparation or enteric-coated preparation. Enteric-coated dosage forms, such as capsules or enteric-coated tablets, are preferred so that the active ingredient of the pharmaceutical product, i.e., the microorganism, can pass smoothly through the stomach without being destroyed by gastric acid. More preferably, the pharmaceutical product of the present application may be formulated into enteric-coated tablets for oral use.
The enteric-coated dosage form of the present application refers to a pharmaceutical dosage form which does not disintegrate in gastric juice but is capable of disintegrating and absorbing in intestinal juice, and enteric-coated dosage forms include capsules and enteric-coated tablets. Wherein the capsule is formed by encapsulating a powdered drug in a capsule shell which is allowed to be used by a conventional drug; the enteric-coated tablet is prepared by coating a layer of enteric-coated coating outside the common tablet medicine. The "enteric coating" of the present application is abbreviated as "enteric coating" and includes all coatings which are allowed to be applied by conventional drugs and which are not degraded by gastric acid but are sufficiently decomposed in the small intestine and rapidly released from the drug of the present application. For example, the enteric coating of the present application can be maintained in a synthetic gastric acid such as HCl solution at ph=1 for more than 2 hours at 36-38 ℃ and preferably disintegrated in a synthetic intestinal fluid such as buffer at ph=7.0 within 1.0 hours.
Preferably, in the enteric coated tablet of the present application, the thickness of the enteric coating is 5 to 100. Mu.m, and desirably 20 to 80. Mu.m. The casing ingredients are selected from conventional materials known in the art.
The active bacterial content of each strain of the probiotic composition in the medicament of the application, or the medicament amount is not particularly limited, and in practical application, the active bacterial content can be flexibly selected according to the health condition of the administration object. However, the study of the application shows that the daily intake of 0.2mL of the probiotic composition with the concentration of 10 9 cfu/mL of Lactobacillus gasseri TF08-1, lactobacillus acidophilus AM13-1 and Bifidobacterium pseudocatenulatum TM12-14 has good treatment effect on ulcerative enteritis, and the dosage can be used as the reference of the content of active bacteria in medicines or the dosage of administration.
The application has the beneficial effects that:
the composition provided by the application has good treatment and prevention effects on inflammation, particularly ulcerative enteritis and related diseases thereof by combining lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum, and provides a novel safe, effective, low-toxic and side-effect composition which is not easy to generate resistance for the treatment and prevention of inflammation and related diseases thereof.
Drawings
FIG. 1 is a graph showing the change in body weight of mice in Control group, model group, VSL # group, and probiotic composition treatment group in examples of the present application;
FIG. 2 is a plot of the DAI index of Control, model, VSL #, and probiotic composition treated mice in the examples of the present application.
The lactobacillus gasseri TF08-1 is preserved in the microorganism strain collection center of Guangdong province at 10-13 days of 2016, the address of the preservation unit is five buildings of experiments conducted by microorganisms of No. 100 province in martyr of Guangzhou province of Guangdong province in China, and the preservation number is GDMCC 60092.
Lactobacillus acidophilus AM13-1 was deposited at the microorganism strain collection of Guangdong province at 10 and 13 days of 2016, and the deposit was found in the five-story building of the microorganism institute, road 100, guangzhou City martyr, guangdong province, china, with a deposit number of GDMCC 60091.
The pseudocatenulate bifidobacterium TM12-14 was deposited at the microorganism strain collection center of Guangdong province at 10-13 of 2016, and the deposit unit was five buildings of experiments conducted by microorganisms of No. 100 in martyr of Guangzhou province of Guangdong province, china, and the deposit number was GDMCC 60089.
Detailed Description
With the intensive research of intestinal microecology, the pathogenesis of ulcerative enteritis is closely related to the composition of intestinal microorganisms, and the unbalance of intestinal bacteria is closely related to the inflammatory reaction of intestinal mucosa, wherein the excessive proliferation of harmful bacteria can trigger the inflammatory reaction, thereby inducing the pathogenesis of ulcerative enteritis. There are a large number of beneficial bacteria in the healthy human intestinal tract, which constitute the first biological barrier of the intestinal tract.
Based on the above studies and findings, the present application has been developed and proposed a novel composition comprising lactobacillus gasseri and/or a metabolite thereof, lactobacillus acidophilus and/or a metabolite thereof, and bifidobacterium pseudocatenulatum and/or a metabolite thereof. The composition of the application not only has the functions of treating and preventing ulcerative enteritis, but also has the same effects on other diseases related to microecology, such as common enteritis or gastritis, etc.; thus, the composition of the present application can be used for preventing or treating inflammation or inflammation-related disorder.
In one implementation mode of the application, the composition consisting of the Lactobacillus gasseri TF08-1 with the preservation number of GDMCC 60092, the Lactobacillus acidophilus AM13-1 with the preservation number of GDMCC 60091 and the Bifidobacterium pseudocatenulatum TM12-14 with the preservation number of GDMCC60089 has better curative effect on ulcerative enteritis than the VSL # 3 composite probiotic produced by the company ALFASIGMA, and can be used for preparing foods, health products, food additives or medicines for treating or preventing inflammation and related diseases.
The application is further illustrated by the following examples. The following examples are merely illustrative of the present application and should not be construed as limiting the application.
Example 1
In this example, a sodium dextran sulfate (abbreviated DSS) induced ulcerative enteritis mouse model with a molecular weight of 36000-50000 is taken as a study object, and the therapeutic effects of Lactobacillus gasseri (Lactobacillus gasseri) TF08-1, lactobacillus acidophilus (Lactobacillus acidophilus) AM13-1 and Bifidobacterium pseudocatenulatum (Bifidobacterium pseudocatenulatum) TM12-14 probiotic compositions on ulcerative enteritis are studied. The method comprises the following steps:
1. Materials and methods
1. Strain culture and identification
1.1 Lactobacillus gasseri TF08-1
Lactobacillus gasseri TF08-1 was isolated using PYG medium at 37deg.C under anaerobic conditions. TF08-1 was cultured in PYG medium for 2 days in white, low-bulge, nearly circular, edge-wave colonies with diameters of about 1-2mm, and the microscopic morphology of the cells was rod-shaped, gram-positive, and sporefree and flagellum-free. The strain is deposited in the microorganism strain collection of Guangdong province with the deposit number of GDMCC 60092.
The specific isolation and identification steps of the lactobacillus gasseri TF08-1 are as follows:
1.1.1 sample collection
The isolated sample was from a fecal sample of a16 year old healthy female volunteer living in Shenzhen city, guangdong. And the diet and physical condition of the volunteer were recorded in detail.
1.1.2 Isolation culture of strains
Preparing a separation culture medium in advance, wherein the culture medium is PYG culture medium purchased from the CycloKai microorganism science and technology company, and comprises the following specific components: 5g of peptone, 5g of pancreatic casein, 10g of yeast powder, 5g of beef extract, 5g of glucose, 0.5g of K 2HPO4 2g,Tween 80 1mL,Cysteine-HCl·H2 O, 0.25g of sodium sulfide, 5mg of heme, 1 mu L of vitamin K 1, 40mL of inorganic salt solution, 1mg of resazurin, 950mL of distilled water, pH of 6.8-7.0 and sterilization at 115 ℃ for 25min. The solid medium was added to 1.5% agar and poured into an anaerobic box. Each 1L of the inorganic salt solution contains CaCl2·2H2O 0.25g,MgSO4·7H2O 0.5g,K2HPO41g,KH2PO4 1g,NaHCO3 10g,NaCl 2g.
The collected fresh fecal sample was transferred to an anaerobic tank, 0.2g of fecal was suspended in 1mL of sterile phosphate buffer (abbreviated as PBS), thoroughly mixed, then subjected to gradient dilution, 100 μl of the diluted solution was subjected to plate coating, anaerobic culture was performed at 37 ℃ for 3-4 days, and the anaerobic gas composition was N 2∶CO2∶H2 = 90:5:5. And (3) selecting a single colony after the colony grows out of the flat plate, streaking and purifying to obtain a pure culture strain, and then carrying out identification and functional verification.
1.1.3 Identification of 16S rDNA of Strain
The isolated strains were subjected to 16S rDNA identification to determine species classification information for the strains. Culturing the obtained isolated strain in liquid PYG culture medium for 24h, centrifuging 1mL of bacterial liquid for 5min at 10000r/min, collecting bacterial cells, extracting genome DNA of the strain, amplifying 16S rDNA by taking the genome DNA as a template, and using a general primer of the 16S rDNA.
The PCR amplification system of the 16S rDNA is as follows: 10 XPCR buffer 3. Mu. L, dNTP 2.5.5. Mu.L, upstream primer 27F 0.5. Mu.L, downstream primer 1494r0.5. Mu. L, taq enzyme 0.3. Mu.L, template 1. Mu. L, ddH 2 O18.2. Mu.L.
The amplification conditions of 16S rDNA were: pre-denatured at 95 ℃ for 4min, then enter 30 cycles: denaturation at 95℃for 30s, annealing at 57℃for 40s, extension at 72℃for 1min 30s.
The PCR amplified product of 16S rDNA was purified, 3730 sequenced to obtain the 16S rDNA sequence of the strain, and then the NCBI database was aligned.
The upstream and downstream primers of the 16S rDNA universal primer of the test are respectively shown as SEQ ID NO.1 and SEQ ID NO. 2. The 16S rDNA sequence of the isolated strain TF08-1 has the sequence shown in SEQ ID NO. 3. NCBI blast comparison shows that the TF08-1 strain isolated in this example has the highest homology with Lactobacillus gasseri and the similarity is 99.9%, so that TF08-1 is judged to be Lactobacillus gasseri, named Lactobacillus gasseri TF08-1, and is preserved.
SEQ ID NO.1：5’-AGAGTTTGATCATGGCTCAG-3’
SEQ ID NO.2：5’-TAGGGTTACCTTGTTACGACTT-3’
1.2 Lactobacillus acidophilus AM13-1
Lactobacillus acidophilus AM13-1 was isolated using PYG medium at 37℃anaerobic conditions. The bacterial colony of AM13-1 cultured in PYG culture medium for 2 days is white, convex, viscous, opaque, round, regular in edge and about 2-3mm in diameter, and the bacterial colony has a microscopic morphology of rod shape, is gram positive, and does not produce spores and flagella. The strain is deposited in the microorganism strain collection of Guangdong province with the deposit number of GDMCC 60091.
The specific isolation and identification steps of lactobacillus acidophilus AM13-1 are as follows:
1.2.1 isolation culture
The isolated sample was from a fecal sample of a healthy male in Shenzhen, and Lactobacillus acidophilus AM13-1 was isolated as follows:
(1) Transferring the sample into an anaerobic box, taking about 0.2g of the sample to suspend in 1mL of sterile PBS, fully and uniformly mixing, and then carrying out gradient dilution;
(2) 100 mu L of the diluted solution is taken on a PYG culture medium plate, then the diluted solution is coated, and the coated solution is placed in an anaerobic environment at 37 ℃ for culture, wherein the anaerobic gas composition is as follows: nitrogen: hydrogen: carbon dioxide = 90:5:5; the PYG medium was the same as "isolated culture of 1.1.2 strain";
(3) Culturing for 4 days, and after colonies grow on the flat plate, selecting single colonies for streaking and purity division, and performing anaerobic culture at 37 ℃;
(4) And (5) performing glycerol preservation and vacuum freeze drying preservation on the separated single bacteria.
1.2.2 16S rDNA identification of AM13-1
Extracting genome DNA, carrying out 16S rDNA amplification by taking the DNA as a template, adopting a general primer of the 16S rDNA, and carrying out amplification under the condition of pre-denaturation at 95 ℃ for 4min, and then entering 30 cycles: denaturation at 95℃for 30s, annealing at 57℃for 40s, extension at 72℃for 1min 30s. The amplified PCR product was purified and sequenced 3730 to obtain the full-length 16S rDNA sequence of AM13-1, and the 16S rDNA sequence of AF13-1 was aligned in NCBI database.
The 16S rDNA universal primer and PCR amplification system of this test was identical to "16S rDNA identification of 1.1.3 strain". The 16S rDNA sequence of the strain AM13-1 obtained by isolation has the sequence shown in SEQ ID NO. 4. The NCBI blast comparison result shows that the AM13-1 strain isolated in the example has the highest homology with Lactobacillus acidophilus and the similarity is 100 percent, so that the AM13-1 is judged to be lactobacillus acidophilus, named lactobacillus acidophilus AM13-1 and is preserved.
1.3 Pseudo-bifidobacterium catenulatum TM12-14
The pseudocatenulate bifidobacterium TM12-14 was isolated using PYG medium at 37℃anaerobically. The colony of TM12-14 cultured in PYG culture medium for 2 days is white, convex, round and neat in edge, the diameter of the colony is about 1-2mm, the thallus microscopic morphology shows a branched rod shape, gram staining is positive, and no spores and flagella are generated. The strain is deposited in the microorganism strain collection of Guangdong province with the deposit number of GDMCC 60089.
The specific isolation and identification steps of the bifidobacterium pseudocatenulatum TM12-14 are as follows:
1.3.1 sample collection
The isolated samples were obtained from a 14 year old healthy male faeces, which were collected into sterile sample tubes and returned to the laboratory for sorting within 1 hour.
1.3.2 Isolation and purification of pseudocatenulate bifidobacterium
The collected fresh samples are immediately transferred to an anaerobic operation box, 0.2g of the samples are taken and fully and evenly mixed by shaking in 1mL of sterile PBS, then gradient dilution coating is carried out, the culture medium is a PYG culture medium plate, anaerobic culture is carried out at 37 ℃, and the anaerobic gas component is N 2∶CO2∶H2 =90:5:5. After 3 days of culture, single colonies are picked for streaking and purity division, and the pure culture of each single strain is obtained. Wherein the PYG medium is the same as "isolated culture of 1.1.2 strain".
1.3.3 Preservation of seed
The obtained pure culture strain is cultured until the concentration is about 10 9 cfu/mL, 400 mu L of bacterial liquid is taken, 40% glycerol is added into 400 mu L of bacterial liquid, the glycerol concentration reaches 20%, and then ultralow temperature preservation is carried out at the temperature of minus 80 ℃.
1.3.4 16S rDNA identification
Culturing the obtained isolated strain in liquid PYG culture medium for 24 hr, centrifuging 1mL of bacterial liquid for 5min at 10000r/min, collecting thallus, and extracting genome DNA. The genomic DNA was used as a template for PCR amplification using the 16S rDNA universal primer, and the PCR amplification primer, system and conditions were the same as those of "16S rDNA identification of 1.1.3 strain".
And (3) performing electrophoresis detection, purification and 3730 sequencing on the obtained 16S rDNA amplification product to obtain the 16S rDNA sequence of the strain, and then performing NCBI database comparison.
Sequencing results show that the length of 16S rDNA of the strain TM12-14 is 1400bp, and the sequence is shown as SEQ ID NO. 5. NCBI blast comparison shows that the homology of the strain TM12-14 and Bifidobacterium pseudocatenulatum is highest, the strain is identified as the pseudobifidobacterium catenulatum Bifidobacterium pseudocatenulatum, named the pseudobifidobacterium catenulatum TM12-14, and is preserved.
2. Mouse model
The mouse model selected in this example was: DSS (Dextran sodium Sulfate, na, molecular weight 36000-50000) induced ulcerative enteritis mouse model.
Specifically, 48 mice of C57bl/6 mice were used as mice strain purchased from Hubei medical laboratory animal center, all mice were 8 weeks old, and were kept in SPF-grade mouse house environment with a weight of 20 g.+ -. 2 g. The 48 mice were randomly divided into 4 groups, each group being 12 for the subsequent trial.
DSS molding: and (5) continuing to drink 0.15% DSS for seven days to the mice to obtain the ulcerative enteritis mouse model.
3. Test method
The 48 mice were randomly divided into 4 groups of 12, each, and the 4 groups were a normal group (i.e., control group), a model group, a probiotic composition-treated group, and a VSL # -treated group, each group being treated as follows:
Normal group: the mice were fed with normal feed and each had a daily lavage of 0.2mL of PBS buffer.
Model group: feeding with the same feed, and performing DSS molding: DSS was added to the mice drinking water at a final concentration of 0.15% and fed for seven days, each mouse was perfused daily with 0.2mL of PBS buffer.
Probiotic composition treatment group: feeding with the same feed, feeding each mouse with 0.2mL of probiotic composition bacterial liquid per day 3 days before DSS molding, and then DSS molding: DSS was added to the drinking water of mice in an amount of 0.15% final concentration, and fed for seven days, each mouse was perfused with 0.2mL of probiotic composition bacteria solution daily.
VSL # treatment group: feeding with the same feed, feeding each mouse with 0.2mL of VSL # bacterial liquid per day 3 days before DSS molding, and then DSS molding: DSS was added to the drinking water of mice in an amount of 0.15% final concentration, and fed for seven days, each mouse was perfused with 0.2mL of VSL # bacterial liquid per day.
The probiotic composition bacterial liquid is prepared by the following method:
Lactobacillus gasseri TF08-1, lactobacillus acidophilus AM13-1 and Bifidobacterium pseudocatenulatum TM12-14 are respectively cultured for 24 hours, the cells are collected by centrifugation, PBS is used for suspending, the concentration of the cells is regulated to 10 9 cfu/mL, and three strains are mixed according to the ratio of 1:1:1, so that Cheng Yi bacteria composition bacterial liquid is prepared.
The VSL # bacterial liquid is prepared by the following method:
VSL #, available from ALFASIGMA, is a complex probiotic comprising 8 beneficial bacteria including Lactobacillus casei, lactobacillus plantarum, lactobacillus acidophilus, lactobacillus delbrueckii subsp. Bulgaricus, streptococcus thermophilus, bifidobacterium longum, bifidobacterium breve, bifidobacterium infantis, etc.; and (3) suspending the VSL # by using PBS, and regulating the concentration to 10 9 cfu/mL to obtain VSL # bacterial liquid.
The body weight, diet and drinking water conditions of the mice are recorded every day after DSS molding, the fecal character and fecal occult blood condition of the mice are observed, and disease activity indexes (abbreviated DAI) of the mice are calculated on days 1,3, 5 and 7, respectively, and the DAI scoring criteria are shown in table 1. Mice were sacrificed after the end of the experiment, all mice were bled, necked off, colon was taken, photographed, weighed, and colon length was measured. Colon tissue was stored in-80 ℃ freezer and paraformaldehyde. Wherein the recording time of the normal group is the same as that of DSS modeling.
TABLE 1 DAI index scoring Table
In table 1, "feces properties", "normal" feces refer to formed feces, "loose" feces refer to pasty, semi-formed feces which do not adhere to the anus, and "loose" feces refer to loose water feces which can adhere to the anus. In the fecal occult blood/weak ocular blood stool, the term "normal" means that the mouse blood is negative; "macroscopic hematochezia" means that red or brown hematochezia can be directly observed by naked eyes; "occult blood positive" refers to unobvious macroscopic hematochezia, which is detected as hematochezia positive using tetramethylbenzidine. The DAI index is equal to the sum of three points of body weight, "stool character" and "stool occult blood/weak ocular blood stool".
2. Results and analysis
1. Weight change
The weights of the mice on day 1, day 3, day 5 and day 7, respectively, were counted, and the average weights of the mice of each group are shown in table 2 and fig. 1.
Table 2 average body weight of each mouse
| Grouping | Day 1 (g) | Day 3 (g) | Day 5 (g) | Day 7 (g) |
| Control | 22.32±0.45 | 23.73±0.64 | 24.98±0.96 | 25.52±1.26 |
| Model group | 22.41±0.52 | 21.65±0.71* | 20.02±1.26* | 18.21±1.57** |
| Probiotics | 22.38±0.61 | 21.97±0.85 | 21.47±1.35 | 21.32±1.49▲ |
| VSL#3 | 22.54±0.71 | 21.87±0.92 | 21.32±1.48 | 20.01±1.66▲ |
In table 2, "Control" refers to the normal group, "probiotic" i.e., probiotic composition-treated group, and "VSL # 3" i.e., VSL # -treated group. "+" means that the significant level of difference P < 0.05 in the model group relative to the weight of the normal group mice, "+" means that the significant level of difference P < 0.01 in the model group relative to the weight of the normal group mice, "+" means that the significant level of difference P < 0.05 in both the "probiotic" and "VSL #" groups relative to the model group mice.
The results in table 2 and fig. 1 show that the body weight of normal mice tended to increase slowly, DSS-induced mice, i.e. model group, "probiotic" group and "VSL #" group, all of which had a sustained decrease in body weight, and model group had a significant onset of body weight decrease on day 3 (i.e. P < 0.05) and a more significant degree of difference between the two (i.e. P < 0.01) compared to the control group. While intervention with the probiotic composition and VSL # 3 slowed the weight loss in UC mice, the control of weight loss was more pronounced in both groups of "probiotic" and "VSL # 3" relative to the model group on day 7 (i.e. < P < 0.05). It is demonstrated that probiotic composition and VSL # 3 can control the weight loss caused by UC. Also, the body weight of mice in the probiotic composition group (i.e., "probiotic") was slightly higher than VSL # 3 on day 7, indicating that the probiotic composition was slightly better than VSL # in controlling the weight loss in UC mice.
Variation of DAI
DSS-induced ulcerative enteritis mice were shown to have a change in DAI index due to weight loss, stool traits and changes in hematocrit, and the statistics of the DAI index at day 1, day 3, day 5 and day 7 are shown in table 3 and fig. 2. In Table 3, the DAI of each group of mice was averaged for each group of mice.
TABLE 3 mouse DAI values
| Grouping | Day 1 | Day 3 | Day 5 | Day 7 |
| Control | 1.1±0.5 | 1.1±0.7 | 1.2±0.8 | 1.3±0.8 |
| Model group | 1.1±0.5 | 3.6±1.1* | 7.2±1.6** | 9.4±2.0** |
| Probiotics | 1.2±0.4 | 3.3±1.2 | 6.0±1.5▲ | 6.5±1.8▲ |
| VSL#3 | 1.1±0.4 | 3.4±1.3 | 6.6±1.6 | 7.8±1.9▲ |
In table 3, "Control" refers to the normal group, "probiotic" i.e., probiotic composition treated group, and "VSL # 3" i.e., VSL # treated group. "indicates that the significant level of difference P < 0.05 in model versus normal group mouse DAI index," indicates that the significant level of difference P < 0.01 in model versus normal group mouse DAI index, "" indicates that the significant level of difference P < 0.05 in both "probiotic" and "VSL #" mice versus model group.
The data in table 3 and fig. 2 show that the DAI of the normal mice is substantially leveled, whereas the DAI of the model, probiotic and VSL # mice gradually increased as DSS was induced, the DAI became significant in the model group on day 3 compared to the control group (i.e., P < 0.05), and reached the highest level in the model group on day 7 (i.e., P < 0.01 relative to the control group). The probiotic intervention can control the elevation of DAI, the DAI values of the probiotic mice on days 5 and 7 were significantly controlled relative to the model group (i.e.,. Mu.P < 0.05), and the DAI of the probiotic-interfered mice on day 7 was slightly lower than VSL#3, indicating that the probiotic composition of this example was superior to VSL#3 in controlling the elevation of DAI in UC mice.
3. Variation of colon length
The colon tissue of the UC model mice was changed mainly because the occurrence of ulcers and inflammation resulted in shortening of the colon tissue, and the colon length of the mice after the end of treatment, as measured by anatomy, is shown in table 4.
TABLE 4 colon length of mice
| Grouping | Colon length (cm) |
| Control | 8.38±0.49 |
| Model group | 5.02±0.87** |
| VSL#3 | 6.30±0.67▲ |
| Probiotics | 6.63±0.71▲ |
In table 4, "Control" refers to the normal group, "probiotic" i.e., probiotic composition-treated group, and "VSL # 3" i.e., VSL # -treated group. "indicates that the colon length difference significant level P < 0.01 in the model group relative to the normal group mice, and" on "indicates that the colon length difference significant level P < 0.05 in both the" probiotic "and" VSL # 3 "groups relative to the model group mice.
The results in table 4 show that the mice after 7 days of DSS induction had a more severe shortening of the colon tissue in the model group, which was very pronounced compared to the control group (P < 0.01). While the intervention of the probiotic composition and VSL # 3 significantly controlled the shortening of the colon of the mice, significant control was obtained relative to the model group (< 0.05). The data in the table shows that the colon length of mice in the group of the probiotic composition is longer than that of the mice in the group of VSL #, and the probiotic composition can be demonstrated to have stronger capability of controlling the colon shortening of UC mice than that of VSL #.
The results in tables 2 to 4 and figures 1 and 2 show that the probiotic composition of this example has therapeutic and prophylactic effects on ulcerative enteritis and its therapeutic effect is slightly better than that of the existing VSL # product.
Example two
The composition with the curative and preventive effects on ulcerative enteritis is prepared into common foods in the embodiment, and the common foods are specifically as follows:
Mixing milk, vitamin C and white sugar with cultured Lactobacillus gasseri TF08-1, lactobacillus acidophilus AM13-1 and Bifidobacterium pseudocatenulatum TM12-14 according to the formula shown in Table 5, and making into food with ulcerative enteritis treatment and prevention function.
Table 5 food formulation containing probiotic compositions
| Raw materials | Mass percent (%) |
| Lactobacillus gasseri TF08-1 | 0.15 |
| Lactobacillus acidophilus AM13-1 | 0.15 |
| Bifidobacterium pseudocatenulatum TM12-14 | 0.15 |
| Milk | 90.0 |
| White sugar | 9.0 |
| Vitamin C | 0.55 |
Mixing milk and white sugar according to the formula ratio of Table 5, stirring to completely mix, preheating, homogenizing under 20Mpa, sterilizing at about 90deg.C for 5-10 min, cooling to 40-43deg.C, mixing with protective agent (vitamin C), and inoculating three kinds of mixed probiotic food composition comprising Lactobacillus gasseri GASSERI TF-08-1, lactobacillus acidophilus Lactobacillus acidophilus AM-1 and Bifidobacterium pseudocatenulatum Bifidobacterium pseudocatenulatum TM-14 of 1-100×10 6 cfu/g.
The milk product of this example was added to DSS-molded mouse feed and fed and tested according to the probiotic composition treatment group of example one, except that the milk product of this example was added only to the feed without additional gastric lavage of the probiotic composition bacteria liquid. The detection result shows that the cow milk product of the embodiment can also control the weight reduction of UC mice, reduce the disease activity index DAI of the mice, improve intestinal lesions and have the treatment and prevention effects of ulcerative enteritis.
Example III
In this example, the probiotic composition with the curative and preventive effects on ulcerative enteritis is prepared into a medicament for treating ulcerative enteritis, and the formulation is shown in table 6:
Table 6 pharmaceutical formulations containing probiotic compositions
| Raw materials | Mass percent (%) |
| Lactobacillus gasseri TF08-1 | 0.5％ |
| Lactobacillus acidophilus AM13-1 | 0.5％ |
| Bifidobacterium pseudocatenulatum TM12-14 | 0.5％ |
| Lactose and lactose | 2.0％ |
| Yeast powder | 2.0％ |
| Peptone | 1.0％ |
| Purified water | 93％ |
| Vitamin C | 0.5％ |
Mixing lactose, yeast powder and peptone with purified water according to the proportion shown in Table 6, preheating to 60-65deg.C, homogenizing under 20Mpa, sterilizing at about 90deg.C for 20-30 min, cooling to 36-38deg.C, mixing with protective agent (vitamin C), inoculating 1-50×10 6 cfu/mL Lactobacillus gasseri GASSERI TF-1, lactobacillus acidophilus Lactobacillus acidophilus AM-1 and Lactobacillus pseudocatenulatus Bifidobacterium pseudocatenulatum TM-14, fermenting at 36-38deg.C to pH 6.0, centrifuging, lyophilizing to water content less than 3%, and making into lyophilized product. Weighing 0.5 g of freeze-dried product, mixing with equal amount of maltodextrin, and encapsulating to obtain the capsule pharmaceutical composition containing three strains of Lactobacillus gasseri GASSERI TF-1, lactobacillus acidophilus Lactobacillus acidophilus AM-13-1 and Bifidobacterium pseudocatenulatum Bifidobacterium pseudocatenulatum TM-14.
The capsule pharmaceutical composition of this example was used to replace the probiotic composition bacterial liquid in the probiotic composition treatment group of example one, and the capsule pharmaceutical composition of this example was filled in the same manner as in example one, and one capsule was filled in each day and tested in the same manner as in example one. The result shows that the capsule pharmaceutical composition of the embodiment can also control the weight reduction of UC mice, reduce the disease activity index DAI of the mice, improve intestinal lesions and have the treatment and prevention effects of ulcerative enteritis.
Example IV
Preparation method of medicine for treating ulcerative enteritis (UC)
1. Preparing bacterial liquid: 1X 10 9 cfu/mL Lactobacillus gasseri GASSERI TF-1, lactobacillus acidophilus Lactobacillus acidophilus AM-1 and Bifidobacterium pseudocatenulatum Bifidobacterium pseudocatenulatum TM-14 are subjected to anaerobic culture respectively, the anaerobic culture medium adopts PYG culture medium, anaerobic fermentation is carried out at 37 ℃ for 2-3 days, and then equal-proportion mixing is carried out, wherein the final concentration is about 1X 10 9 cfu/mL.
2. Preparing a growth factor: mixing skimmed milk and casein, centrifuging, and ultrafiltering to obtain milk growth factor crude extract containing vitamins, purines, and pyrimidines.
3. Preparation of a pharmaceutical dosage form: adding 5 volumes of growth factors and 1 volume of protective agent (namely vitamin C) into 100 volumes of fermented bacterial liquid mixture, fully stirring and mixing uniformly, and then adding starch auxiliary materials such as maltodextrin to prepare the pharmaceutical dosage form.
The pharmaceutical dosage form can be further prepared into slurry, powder or granule.
The pharmaceutical formulation of this example was directly added to DSS-molded mouse feed and fed and tested as per the probiotic composition treatment group of example one, except that the pharmaceutical formulation of this example was added only to the feed without additional gastric lavage of the probiotic composition bacterial liquid. The detection result shows that the medicine product of the embodiment can also control the weight reduction of UC mice, reduce the disease activity index DAI of the mice, improve intestinal lesions and have the treatment and prevention effects of ulcerative enteritis.
The above examples demonstrate that the combination of Lactobacillus gasseri, lactobacillus acidophilus and Bifidobacterium pseudocatenulatum can treat and prevent ulcerative enteritis; and the composition of the three bacteria can be prepared into various foods or medicines for use; of course, it will be appreciated that since the three bacteria composition can be formulated into various foods and medicines, it can also be formulated into various health products or food additives.
In addition, research shows that the treatment effect of the three bacteria is largely based on the improvement of microecology, and the improvement of microecology has the treatment and prevention effects on ulcerative enteritis and other microecological related diseases, such as common enteritis, gastritis and the like; therefore, the composition of the present application can be used for preventing or treating inflammation or inflammation-related diseases, particularly various enteritis and gastritis.
The foregoing is a further detailed description of the application in connection with specific embodiments, and it is not intended that the application be limited to such description. It will be apparent to those skilled in the art that several simple deductions or substitutions may be made without departing from the spirit of the application, and these should be considered to be within the scope of the application.
Claims (17)
1. A composition for the treatment and prevention of ulcerative enteritis characterized by: the composition comprises lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum; or the composition comprises lactobacillus gasseri and its metabolites, lactobacillus acidophilus and its metabolites, and bifidobacterium pseudocatenulatum and its metabolites;
The Lactobacillus gasseri is Lactobacillus gasseri TF08-1 with accession number GDMCC 60092, the Lactobacillus acidophilus is Lactobacillus acidophilus AM13-1 with accession number GDMCC 60091, and the Bifidobacterium pseudocatenulatum is Bifidobacterium pseudocatenulatum TM12-14 with accession number GDMCC 60089.
2. The composition of claim 1, wherein: the composition also contains other probiotics and/or prebiotics.
3. The composition of claim 2, wherein the prebiotic is selected from at least one of fructooligosaccharides, galactooligosaccharides, xylooligosaccharides, lactulose oligosaccharides, soy oligosaccharides, inulin, and oligosaccharides.
4. The composition of claim 1, wherein: the composition further comprises a substance that helps to maintain viability of at least one of lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum.
5. The composition of claim 4, wherein: the substance for helping to keep the activity of at least one of lactobacillus gasseri, lactobacillus acidophilus and bifidobacterium pseudocatenulatum is at least one selected from cysteine, glutathione, butyl hydroxy anisole, dibutyl methyl toluene, tocopherol, bamboo leaf antioxidant, D-isoascorbic acid or sodium salt thereof, sodium ascorbate, calcium ascorbate, phospholipid, vitamin C and vitamin E.
6. The composition of claim 1, wherein: the composition also comprises a pharmaceutically acceptable carrier or auxiliary material.
7. The composition of claim 6, wherein: the pharmaceutically acceptable carrier or auxiliary material is at least one selected from glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, gelatin, albumin, water and physiological saline.
8. Use of a composition according to any one of claims 1-7 in the manufacture of a medicament for the treatment or prevention of ulcerative enteritis.
9. Use of a composition according to any one of claims 1-7 in the manufacture of a medicament for controlling weight loss in a mammal due to ulcerative colitis.
10. Use of a composition according to any one of claims 1-7 in the manufacture of a medicament for reducing the disease activity index of ulcerative enteritis in a mammal.
11. Use of a composition according to any one of claims 1-7 in the manufacture of a medicament for ameliorating ulcerative enteritis in a mammal.
12. A pharmaceutical product, characterized in that: the pharmaceutical product contains the composition of any one of claims 1-7.
13. A pharmaceutical product according to claim 12, wherein: the medicine is tablet, granule, powder, enteric solvent, solution or suspension.
14. A pharmaceutical product according to claim 13, wherein: the medicine is enteric solvent, and the enteric solvent is capsule or enteric tablet.
15. The pharmaceutical product of claim 14, wherein the pharmaceutical product is an enteric coated tablet.
16. A pharmaceutical product according to claim 15, wherein: the enteric coating thickness of the enteric tablet is 5-100 μm.
17. The pharmaceutical product according to claim 16, wherein the enteric coating thickness of the enteric tablet is 20-80 μm.
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| AU2011202559B2 (en) * | 2003-12-17 | 2012-06-21 | N.V. Nutricia | Lactic Acid Producing Bacteria and Lung Function |
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| ITRM20110477A1 (en) * | 2011-09-09 | 2013-03-10 | Giovanni Mogna | COMPOSITION INCLUDING N-ACETYLCISTEIN AND / OR LYSOZYME MICROINCAPSULATE GASTROPROTECT IN ASSOCIATION WITH PROBIOTIC BACTERES ABLE TO RESTORE THE BARRIER EFFECT OF THE STOMACH THAT IS LOST DURING THE PHARMACOLOGICAL TREATMENT OF |
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