CN116617272A - Application of lactobacillus reuteri in preparing functional product for preventing and treating acute radiation intestinal injury - Google Patents
Application of lactobacillus reuteri in preparing functional product for preventing and treating acute radiation intestinal injury Download PDFInfo
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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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
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- 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
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- 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
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Abstract
The invention belongs to the technical field of microorganisms and the technical field of medicines, and relates to application of breast milk-derived lactobacillus reuteri in preparation of functional products for preventing and treating acute radiation intestinal injury. The invention provides a new application of lactobacillus reuteri FN041 in preventing and/or treating acute radiation intestinal injury, which can prevent the occurrence of the acute radiation intestinal injury of mice, inhibit weight loss, inflammation and the like of the mice; the number of the colon goblet cells of the mice is obviously improved, the expression of Muc2 is obviously improved, and the recovery of intestinal barriers is promoted; meanwhile, the dysbacteriosis can be regulated, the KPS index of a patient with pelvic radiotherapy can be improved, and the diarrhea frequency of the patient can be reduced. Therefore, lactobacillus reuteri FN041 has great application prospect in preparing drugs for preventing and/or treating acute radiation intestinal injury.
Description
Technical field:
the invention belongs to the technical field of microorganisms and the technical field of medicines, and relates to application of breast milk-derived lactobacillus reuteri in preparation of functional products for preventing and treating acute radiation intestinal injury.
The background technology is as follows:
pelvic cancer refers to cancers that occur within the pelvic cavity (i.e., from lumbar vertebra L4 to the anal verge), including gynecological tumors, urinary system tumors, or lower gastrointestinal tumors. Radiotherapy is commonly used in the treatment of abdominal and pelvic cancers. In radiotherapy of tumors of the abdominal cavity or of the pelvic bones, parts of the small intestine, colon or rectum are inevitably included in the therapeutic range, where gastrointestinal side effects are common, and more than 70% of patients develop acute gastrointestinal symptoms. Patients with acute radiation intestinal injury mainly suffer from diarrhea, abdominal pain, constipation, hematochezia, weight loss, and the like. The progression of acute radiation intestinal injury is associated with different pathological mechanisms, the overall acute outcome of radiation to the intestine being a decrease in tight junction integrity, death of crypt epithelial cells and villus upper cells, depending on the intensity of the radiation. These effects can lead to the development of inflammation and disruption of the mucosal barrier, causing the luminal contents, particularly microorganisms, to flow into the lamina propria, causing further inflammation.
As more and more cancers of the abdomen and pelvis receive radiation therapy, the incidence of gastrointestinal disorders (including diarrhea) caused by radiation therapy or radiation therapy has increased. The incidence of malignant tumors in the abdomen, pelvis and peritoneum is high, and the effect of radiation therapy is indispensable in the selection of treatment schemes. In the uk 17000 patients receive pelvic radiotherapy each year; in fact, in developed countries, it is estimated that 15 to 30 tens of thousands of patients receive this treatment each year. However, the application of "physical precision" cannot completely solve the serious adverse reaction caused by the toxicity of the radiation to the peripheral normal organs, structures, etc. Strategies to reduce side effects are also considered to be increasingly important as the number of long-term survivors of pelvic cancers continues to increase.
The current treatment of intestinal damage caused by pelvic radiotherapy mainly comprises nutrition support, drug treatment, probiotic preparation, hyperbaric oxygen treatment, endoscopic treatment, operation treatment and stem cell treatment. The guidelines for the treatment of cancer support multi-national institute (Mulinational Association of Supportive Care in Cancer, MASCC) in 2019 were updated and the use of probiotics containing lactobacillus for the prevention of radiation-induced diarrhea was suggested. The lactobacillus can maintain intestinal machinery and immune barrier, the expression of the tight junction protein and the thickness of a mucus layer are reduced after the intestinal tract is irradiated, the intestinal permeability is increased, and the lactobacillus can up-regulate the intestinal tight junction protein ZO-1 and the occluding protein, promote the goblet cells to produce mucus, thereby maintaining the intestinal health.
The effect of lactobacillus on protecting intestinal mucosa is strain dependent, and it is highly desirable to find lactobacillus which can protect intestinal mucosa to play a role in treating and preventing acute radiation intestinal injury.
The invention comprises the following steps:
the invention aims to overcome the defects of the prior art and provides a novel application of Lactobacillus reuteri (Lactobacillus reuteri) FN041 for relieving acute radiation intestinal injury.
In order to achieve the above purpose, the invention provides an application of lactobacillus reuteri (Lactobacillus reuteri) FN041 in preparing a product for preventing and/or treating acute radiation intestinal injury after radiotherapy of a target population; the target crowd is a pelvic cavity radiotherapy patient.
The lactobacillus reuteri (Lactobacillus reuteri) FN041 is deposited in the microorganism strain collection center of Guangdong province, the deposited number is GDMCC No.60546, and the deposited address is building 5 No. 59 of the 100 th Mitsui of Guangzhou City. The lactobacillus reuteri FN041 has been disclosed in the patent document with publication number CN110205261 a.
The invention relates to the prevention and/or treatment of acute radiation intestinal injury, which comprises any one of the following (a) - (e):
(a) Relieving diarrhea and abdominal distention after radiotherapy;
(b) Weight loss after radiotherapy is reduced;
(c) Reducing inflammatory cell infiltration, and remodelling intestinal crypt structure;
(d) Reducing changes in intestinal permeability;
(e) Enhancing the expression of the tight junction protein and improving the intestinal barrier function.
The use period of the product is before and during the whole course of radiotherapy.
The products of the present invention include, but are not limited to, food products, pharmaceutical or pharmaceutical compositions and/or nutraceuticals.
The medicine or the medicine composition also comprises a pharmaceutically acceptable freeze-drying protective agent and an excipient; the pharmaceutically acceptable excipients refer to any diluent, adjuvant and/or carrier that may be used in the pharmaceutical arts.
The food comprises solid beverage, tablet, soft candy and drop containing the lactobacillus reuteri, and dairy product, bean product, fruit and vegetable product or beverage produced by using the starter containing the lactobacillus reuteri.
In one embodiment, the food and health care products further comprise conventional auxiliary materials, wherein the auxiliary materials comprise one or more of a lyoprotectant, a filling agent, a flavoring agent, an adhesive, a disintegrating agent, a lubricant, an antacid and a nutrition enhancer.
The product of the invention has viable count not lower than 1 multiplied by 10 9 The CFU/day dose is provided to pelvic radiotherapy patients.
The form of lactobacillus reuteri according to the present invention includes a form of living cells, inactivated cells or a fermentation product or metabolite of lactobacillus reuteri, or a mixture of any of the above forms.
The content of the lactobacillus reuteri in the product is not less than 1 multiplied by 10 9 CFU/mL or 1X 10 9 CFU/g。
Dosage forms of the products of the present invention include, but are not limited to: tablets, granules, capsules, powders, liquids or jellies.
Compared with the prior art, the novel application of the lactobacillus reuteri FN041 in relieving the acute radiation intestinal injury is provided, the effect is good, animal experiments show that the lactobacillus reuteri FN041 has the effect of preventing the acute radiation intestinal injury, and the application prospect in preparing products for preventing and/or treating the acute radiation intestinal injury after radiotherapy of target people is great.
Animal experiments show that:
(1) The administration of lactobacillus reuteri FN041 to mice from one week prior to irradiation can prevent acute radiation intestinal injury, which is manifested by significant inhibition of weight loss in mice and alleviation of diarrhea symptoms after irradiation in mice;
(2) The lactobacillus reuteri FN041 is taken by the mice from one week before irradiation, so that the intestinal mucosa swelling degree and inflammatory cell infiltration level of the mice can be improved, and the intestinal crypt morphology is remodeled;
(3) Administration of lactobacillus reuteri FN041 to mice one week prior to irradiation may decrease intestinal epithelial permeability of the mice;
(4) Administration of lactobacillus reuteri FN041 to mice one week prior to irradiation may enhance the expression of the claudin, improving intestinal barrier function.
Crowd experiments show that: after the probiotic bacteria powder containing lactobacillus reuteri FN041 is taken by patients suffering from pelvic radiotherapy, the dysbacteriosis of the patients can be regulated, and the diarrhea function state score (KPS) and diarrhea frequency of the patients can be obviously reduced.
Description of the drawings:
FIG. 1 is a schematic diagram of the experimental procedure of the effect of Lactobacillus reuteri FN041 of the present invention on prevention of radiation intestinal injury.
FIG. 2 is a schematic diagram showing experimental results of the effect of Lactobacillus reuteri FN041 of the present invention on prevention of radiation intestinal injury, wherein A is a weight monitoring chart of mice; b is a colon slice of each group of mice; c is a colon pathological section graph of each group of mice; d is a graph of colon injury scores for each group of mice.
FIG. 3 is a schematic diagram showing the experimental results of the effect of Lactobacillus reuteri FN041 of the present invention on intestinal barrier of irradiated mice, wherein A is colon tissue AB-PAS staining; b is colon tissue mucin 2 (Muc 2) immunofluorescence staining; c is the depth measurement of the colon crypt; d is the staining intensity statistics of goblet cells in the colon crypt; e is the statistic of Muc2 staining intensity in colon tissue; f is ZO-1 and the blocked protein immunofluorescence staining.
Fig. 4 is a schematic diagram of experimental results of influence of lactobacillus reuteri FN041 on inflammatory factors of intestinal mucosa according to example 3 of the present invention, wherein a is the content of serum lipopolysaccharide; b is the content of serum diamine oxidase; c is the content of interleukin 6 in intestinal tissue; d is the content of tumor necrosis factor alpha in intestinal tissue.
Fig. 5 is a flow chart of a clinical trial of the effect of FN041 on alleviating diarrhea in pelvic radiotherapy patients in example 4 according to the present invention.
The specific embodiment is as follows:
the invention is further illustrated by the following examples in conjunction with the accompanying drawings.
The enzymatic hydrolysis skim milk, glucose, tryptone and yeast extract referred to in the examples below were purchased from Shanghai pharmaceutical Co., ltd.
The detection method involved in the following examples is as follows:
the method for detecting the number of living bacteria comprises the following steps: the national standard GB 4789.35-2016 food safety national standard food microbiology detection of lactobacillus detection is adopted.
Lactobacillus reuteri FN041 used in the following examples is disclosed in patent publication No. CN110205261 a.
Example l:
the present example relates to experiments of lactobacillus reuteri FN041 on the prevention of radiation intestinal injury, the specific experimental procedure is as follows:
60 male C57BL6J mice of 8 weeks old were kept in polypropylene cages and randomly divided into 4 groups after one week of adaptive feeding: blank (CN), radiation model (TAI), radiation and gavage lactobacillus reuteri FN041 (FN 041), radiation and gavage lactobacillus rhamnosus GG (LGG), wherein both FN041, LGG are treatment groups.
Gastric lavage treatment was started one week prior to irradiation: blank and radiation model groups were gavaged with PBS (1 X.200. Mu.L each time) and FN041 groups were gavaged with Lactobacillus reuteri FN041 (1X 10) each day 9 CFU/day, 1 times daily, 200 μl each time), LGG group was irrigated daily with Lactobacillus rhamnosus GG (1×10) 9 CFU/day, 1 time per day, 200 μl each); performing radiation treatment on the rear radiation model group, the FN041 group and the LGG group, after the mice are anesthetized, placing the mice in a 6-MV linear accelerator for performing X-ray abdominal radiation, exposing all the abdomen, irradiating the whole abdomen with the irradiation field from the xiphoid process of the sternum to the pubic symphysis, and irradiating at a dosage rate of 500cGy/min, wherein the total irradiation dosage is 12Gy for 2.4 minutes; the blank group was not irradiated. Continuing to irrigate stomach for feeding, and radiatingMice (5 mice per group) were sacrificed 3.5 days, and the remaining mice were subjected to 30-day survival experiments, continuing gastric lavage intervention until the end of the entire survival experiment period. The body weight of the mice was monitored throughout the experiment, and the colon of the sacrificed mice was subjected to histological analysis, and the experimental results are shown in fig. 2.
As can be seen from fig. 2, both treatment groups FN041 and LGG significantly inhibited weight loss (P < 0.05) in mice after irradiation (fig. 2A), and mice in lactobacillus reuteri FN041 had higher survival and recovered more quickly after irradiation than in LGG group. On day 3.5 post-irradiation, the irradiation reduced the solid content of the mouse intestine, with water-like content in it, and colon sections of the mice (fig. 2B) showed that FN041 intervention reduced the extent of irradiation intestinal injury. As can be seen by HE staining of the colon sections of mice (fig. 2C), the radiation model group mice had inflammatory cell infiltration and epithelial cell damage in the colon. Compared to the radiation model group, FN041 group colonic epithelial inflammatory cell infiltration and injury were significantly improved.
Example 2:
this example relates to experiments on the effect of lactobacillus reuteri FN041 on the intestinal barrier of irradiated mice, and the results of immunofluorescence and immunohistochemical barrier-associated protein detection of colon tissue from mice sacrificed 3.5 days after irradiation are shown in fig. 3.
As can be seen from fig. 3, the effect of FN041 on the barrier function of TAI-induced acute radiation intestinal injury mice was evaluated by detecting barrier-related proteins in colon tissue using immunofluorescence and immunohistochemical techniques, which showed that after drying the mice in group FN041 by pretreatment with lactobacillus reuteri FN041, the depth of crypt was improved to normal level (P < 0.05) and the number of goblet cells was increased, corresponding to increased expression of Muc2 in colon (P < 0.05). The expression of zona-1 and occluding proteins was reduced in mice treated with the radiation model group after irradiation, while the expression of ZO-1 and occluding proteins was restored in FN041 group in mice pre-treated with FN041, similar to the blank group treated mice, these data indicate that irradiation resulted in disruption of the intestinal barrier, while FN041 intervention was able to maintain intestinal barrier integrity.
Example 3:
this example relates to experiments on the effect of Lactobacillus reuteri FN041 on colonic inflammatory factors, and the results of the experimental procedures were the same as in example 1, except that the colonic inflammatory factors were detected in groups of mice sacrificed 3.5 days after irradiation, as shown in FIG. 4.
As can be seen from fig. 4, both interleukin 6 levels and tumor necrosis factor alpha levels were lower in the FN041 group than in the radiation model group, indicating that intervention by lactobacillus reuteri FN041 significantly reduced interleukin 6 levels (P < 0.05) in the colon of the mice after radiation. The lipopolysaccharide level of FN041 group was lower (P < 0.05) than that of the pure radiation group, indicating that the intervention of Lactobacillus reuteri FN041 was able to inhibit the increase of intestinal permeability in mice. In addition, lactobacillus reuteri FN041 has a tendency to decrease serum diamine oxidase levels.
Example 4:
the example relates to an influence test of lactobacillus reuteri FN041 on diarrhea of patients with pelvic radiotherapy, and the specific test process is as follows:
in the clinical trial, 41 patients with pelvic radiotherapy are recruited together, all patients are randomly divided into 2 groups, and 18 patients in a control group adopt pure radiotherapy (20 persons); test group 18 patients were treated with radiation therapy + prophylactic oral lactobacillus reuteri FN041 solid drink (21 humans). Each patient was treated with more than 2 cycles (6 weeks) of radiation, and the patients in the test group were orally administered lactobacillus reuteri FN041 solid drink 1 bar 1 time a day, beginning 1 day before radiation, and continuously administered for 6 weeks. Conventional blood-checking biochemistry, conventional stool and the like before radiotherapy. Wherein, the control group is only treated with radiotherapy; the test group was administered with a feed containing Lactobacillus reuteri FN041 (viable count 1X 10) 9 CFU/bar) probiotic solid beverage.
Patient inclusion criteria were: 1) The diagnosis of malignant tumor patients of abdomen or pelvis is clear through the verification of cytology or pathology results; 2) Receiving strong radiation treatment, and partially or completely irradiating the pelvic cavity and abdomen; 3) KPS score >70 score; 4) No radiotherapy contraindication, and can tolerate radiotherapy; 5) The survival time is more than 3 months, and the acute radioactive intestinal injury can be accurately estimated.
Exclusion criteria: 1) Interruption of radiotherapy, incomplete radiotherapeutics due to reasons or the fact that the jeopardy organ in the range of the radiation field does not involve the small intestine; 2) Past history of inflammatory bowel disease and onset during acute observation period; 3) Tumor affects the compression of the intestinal tract; 4) Accurate assessment of acute radiation intestinal injury graders is difficult during follow-up; 5) There are cases of diarrhea (which is not due to radiation-related diarrhea, but is caused by the tumor itself) already before radiation therapy.
During the whole test, lactobacillus reuteri FN041 is administered in the form of probiotic solid drink, and the dosage is 1 strip/day.
The trial preparation period was 1 week, the clinical trial period was 6 weeks, and a total of 7 weeks.
Preparation period: the patients with pelvic radiotherapy are contacted 1 week before the test, the number of people who are intentionally involved in the test is counted, the nature and the content of the test are explained for the patients and family members thereof, the informed consent is signed, the time of the hospital and the doctor is coordinated, and the materials required by the test are prepared.
Clinical trial period: the patients who were confirmed by doctors, voluntary, and the family members agreed to participate in the test took the probiotic solid drink for 6 weeks. Before the experiment, the patients and the families are intensively educated for one time, which explains the cause of the acute radiation intestinal injury and the measures for avoiding diarrhea in diet and life, and hopes that the patients and the families adhere to the corresponding principles during the experiment.
Diagnosis is performed after the end of the preparation period, at the beginning and after the end of the clinical trial. The number of diarrhea was recorded, KPS scoring was performed on the patient, and adverse reactions were recorded. The extent of mild acute radiation bowel injury was assessed using dysbacteriosis, KPS score, diarrhea frequency, and the like, including:
1. placing a stool specimen of a patient in a sterile container, carrying out gram staining, and carrying out percentage measurement on the distribution condition of bacterial groups, wherein more than or equal to 50% of gram staining positive cocci are defined as dysbacteriosis;
2. diagnostic criteria and grading of diarrhea
Diarrhea means that the number of times of defecation is increased by more than 3 times per day or the total daily amount is more than 200g, the feces are thin, and the water content is more than 80%. Clinical manifestations are painless diarrhea or slight abdominal pain during radiotherapy, watery stool, several times or tens of times a day;
3. grading criteria for diarrhea are uniformly judged according to NCI CTC3.0 criteria:
(1) grade I, increased number of bowel movements (< 4 times/day), slightly increased discharge;
(2) the number of times of defecation is increased (4-6 times per day), the discharge amount is moderately increased, and the daily life is not influenced;
(3) grade III, increasing the number of times of defecation (more than or equal to 7 times/day), incontinence, intravenous fluid infusion for 24 hours, hospitalization, and increasing the weight of discharged substances, which affects daily life;
(4) class IV: life threatening (e.g., hemodynamic failure);
and observing indexes including dysbacteriosis, changes of diarrhea functional state scores (KPS) of patients before and after radiotherapy and diarrhea frequency.
The clinical test flow of this example is shown in fig. 5, excluding 5 patients, and a total of 36 completed the clinical study, with the test group patients taking a probiotic solid drink for 6 weeks in addition to normal radiation therapy, and the control group patients were only treated with radiation therapy. The dysbacteriosis occurs in 3 cases (16.7%) of the test group, the dysbacteriosis occurs in 9 cases (50%) of the control group, the comparison difference in 2 groups has statistical significance (P < 0.05), the KPS change of the two groups of patients is shown in table 1, the KPS has no obvious change before and after the radiotherapy of the group taking the probiotic solid drink, and the difference has no statistical significance. The KPS is obviously reduced after the radiotherapy of the control group, and the difference has statistical significance (P is less than 0.05), which proves that the radiotherapy and lactobacillus reuteri FN041 solid beverage can stabilize and improve the life quality of patients.
TABLE 1 functional status score for diarrhea before and after radiation therapy (KPS)
The incidence of diarrhea after radiation therapy and the grading results for both groups of patients are shown in Table 2. As can be seen from Table 2, the incidence of diarrhea in the test groups I-II, which took the probiotic solid drink, was 33.3%, the control group was 50%, and the differences in the two groups were statistically significant (P < 0.01). The incidence rate of the diarrhea of the III grade to the IV grade of the test group taking the probiotic solid drink is 5.5 percent, the contrast group is 27.8 percent, and the difference has statistical significance (P is less than 0.01). It is demonstrated that lactobacillus reuteri FN041 can alleviate diarrhea caused by radiotherapy.
TABLE 2 incidence of diarrhea and diarrhea grading in patients after radiation therapy
Example 5:
the embodiment relates to a preparation method of a fermented fruit and vegetable beverage containing lactobacillus reuteri FN041, which comprises the following specific steps:
cleaning fresh vegetables and fruits, squeezing, sterilizing at 140deg.C for 2 seconds, immediately cooling to about 42deg.C, and mixing at 10% by weight 6 Inoculating lactobacillus reuteri FN041 to CFU/mL fruit and vegetable juice, and fermenting the inoculated fruit and vegetable juice at 42 ℃ for 16 hours to obtain the fermented fruit and vegetable beverage containing lactobacillus reuteri FN041 viable bacteria.
The detection shows that the pH value of the fermented fruit and vegetable beverage containing lactobacillus reuteri FN041 viable bacteria is 3.6, and the viable bacteria number can reach l.5 multiplied by 10 9 CFU/mL。
The fermented fruit and vegetable beverage containing lactobacillus reuteri FN041 viable bacteria is continuously taken by patients with pelvic radiotherapy for one week, so that dysbacteriosis can be effectively regulated, KPS and diarrhea rate of the patients can be reduced, and symptoms and quality of life of the patients are obviously improved.
Example 6:
the present example relates to a method for preparing fermented milk containing lactobacillus reuteri FN041, comprising the following specific steps:
adding 2% casein peptide into milk (skim milk, fresh milk, reconstituted milk and the like), performing high-strength heat treatment at 95 ℃ for 20 minutes or 140 ℃ for 2 seconds, cooling to 40 ℃, inoculating lactobacillus reuteri FN041 into sterilized milk according to the inoculum size of 3-5% by volume, inoculating commercial starter lactobacillus bulgaricus or streptococcus thermophilus which can symbiotic preparation yoghurt according to the inoculum size of 3-5% by volume in the milk inoculated with lactobacillus reuteri FN041, and finally performing mixed fermentation on the inoculated milk at 42 ℃ for 4 hours to obtain the fermented milk containing the lactobacillus reuteri FN041 viable bacteria.
Through detection, the titrated acidity of the fermented milk containing lactobacillus reuteri FN041 live bacteria reaches 75 DEG T, and the number of live bacteria reaches 1 multiplied by 10 9 CFU/mL。
The fermented milk containing lactobacillus reuteri FN041 viable bacteria is continuously taken for one week for patients with pelvic radiotherapy, so that dysbacteriosis can be effectively regulated, KPS and diarrhea rate of the patients can be reduced, and symptoms and quality of life of the patients are obviously improved.
Claims (10)
1. Use of lactobacillus reuteri FN041 for the manufacture of a product for the prevention and/or treatment of radiation intestinal injury, characterized in that lactobacillus reuteri FN041 is capable of alleviating diarrhea after radiation therapy; and/or weight loss; and/or reduce inflammatory cell infiltration, remodelling intestinal crypt structures; and/or reducing changes in intestinal permeability; and/or enhancing expression of the tight junction protein, improving intestinal barrier function; the lactobacillus reuteri FN041 is deposited with the guangdong microorganism strain collection under the accession number GDMCC No:60546.
2. use of lactobacillus reuteri FN041 according to claim 1 for the manufacture of a product for the prevention and/or treatment of radiation intestinal injury, wherein the period of use of the product is pre-radiation and during radiation therapy.
3. Use of lactobacillus reuteri FN041 according to claim 1 for the manufacture of a product for the prevention and/or treatment of radiation intestinal injury, wherein said product comprises, but is not limited to, a food product, a pharmaceutical or pharmaceutical composition and/or a nutraceutical.
4. Use of lactobacillus reuteri FN041 according to claim 3 for the manufacture of a product for the prevention and/or treatment of radiation intestinal injury, wherein the medicament or pharmaceutical composition further comprises a pharmaceutically acceptable excipient; the pharmaceutically acceptable excipients refer to any diluent, adjuvant and/or carrier that may be used in the pharmaceutical arts.
5. Use of lactobacillus reuteri FN041 according to claim 3 for the manufacture of a product for the prevention and/or treatment of radiation intestinal injury, characterized in that said food product comprises solid beverages, tablets, soft candies and drops comprising said lactobacillus reuteri, and dairy, soy, fruit and vegetable products or beverages produced using a starter comprising lactobacillus reuteri.
6. Use of lactobacillus reuteri FN041 according to claim 3 for the manufacture of a product for the prevention and/or treatment of radiation intestinal injury, characterized in that said food product, health product further comprises conventional adjuvants, said adjuvants comprising one or more of fillers, flavouring agents, binders, disintegrants, lubricants, antacids and nutritional supplements.
7. Use of lactobacillus reuteri FN041 according to claim 1 for the manufacture of a product for the prevention and/or treatment of radiation intestinal injury, characterized in that said product has a viable count of not less than 1 x 10 9 The CFU/day dose is provided to pelvic radiotherapy patients.
8. Use of lactobacillus reuteri FN041 according to claim 1 for the manufacture of a product for the prevention and/or treatment of radiation intestinal injury, wherein the form of lactobacillus reuteri comprises the form of living cells, inactivated cells or fermentation products or metabolites of lactobacillus reuteri, or a mixture of any of the above forms.
9. Use of lactobacillus reuteri FN041 according to claim 1 for the manufacture of a product for the prevention and/or treatment of radiation intestinal injury, characterized in that the content of lactobacillus reuteri in said product is not less than 1 x 10 9 CFU/mL or 1X 10 9 CFU/g。
10. Use of lactobacillus reuteri FN041 according to claim 1 for the manufacture of a product for the prevention and/or treatment of radiation intestinal injury, wherein the dosage form of the product comprises, but is not limited to: tablets, granules, capsules, powders, liquids or jellies.
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| CN117286077A (en) * | 2023-11-20 | 2023-12-26 | 微康益生菌(苏州)股份有限公司 | Probiotics for preventing and treating acute radioactive intestinal injury and application thereof |
| CN117883487A (en) * | 2024-01-18 | 2024-04-16 | 广东省人民医院 | Composition for treating oral mucositis caused by radiotherapy and chemotherapy and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN117286077A (en) * | 2023-11-20 | 2023-12-26 | 微康益生菌(苏州)股份有限公司 | Probiotics for preventing and treating acute radioactive intestinal injury and application thereof |
| CN117286077B (en) * | 2023-11-20 | 2024-02-20 | 微康益生菌(苏州)股份有限公司 | Probiotics for preventing and treating acute radioactive intestinal injury and application thereof |
| CN117883487A (en) * | 2024-01-18 | 2024-04-16 | 广东省人民医院 | Composition for treating oral mucositis caused by radiotherapy and chemotherapy and preparation method thereof |
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