CN106389480A - Complex probiotic preparation for reducing 5-hydroxytryptamine side effects after chemotherapy - Google Patents
Complex probiotic preparation for reducing 5-hydroxytryptamine side effects after chemotherapy Download PDFInfo
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- CN106389480A CN106389480A CN201610713637.4A CN201610713637A CN106389480A CN 106389480 A CN106389480 A CN 106389480A CN 201610713637 A CN201610713637 A CN 201610713637A CN 106389480 A CN106389480 A CN 106389480A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
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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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
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Abstract
The invention discloses a complex probiotic preparation for reducing 5-hydroxytryptamine side effects after chemotherapy, the complex probiotic preparation is characterized in that the complex probiotic preparation is prepared by mixing the following probiotics: bifidobacterium breve, lactobacillus acidophilus, lactobacillus casei and Streptococcus thermophilus according to viable number proportion ratio of 1:1-3:1-3:1-3, and the total viable number of the composite probiotic preparation is 20 billion-80 billion; application of the complex probiotic preparation in preparation of drugs for preventing nausea and vomiting after the chemotherapy and application of the complex probiotic preparation in preparation of drugs for improving intestinal mucositis are disclosed.
Description
Technical field
A kind of the present invention relates to composite probiotics preparations, and the concrete application of this composite probiotics preparations.
Background technology
Chemotherapy is one of important means for the treatment of cancer, but after chemotherapy, bad reaction is more, especially gastrointestinal reaction, bag
Include esoenteritis and n and V etc..Accept the patient of routine dose chemotherapeutics, clinical onset rate is 40%, and nearly all
Accept the patient of high dose chemotherapy medicine, esoenteritis all can occur.N and V is another important gastrointestinal reaction of chemotherapy,
Mainly with chemotherapy after serotonin（5-HT）Release is relevant, and the incidence of disease is equally higher, especially almost reaches after injection cis-platinum
100%, this quality of life having a strong impact on patient and chemotherapy effect.Gastrointestinal reaction is even more the major reason that patient postpones chemotherapy,
The death rate leading to cancer patient greatly increases.
Content of the invention
The present invention is to solve the above-mentioned deficiency existing for prior art, proposing one kind and can effectively reduce pair after chemotherapy
The composite probiotics preparations of effect, and the concrete application of this kind of composite probiotics preparations.
The technical solution of the present invention is：A kind of compound probiotic system for reducing serotonin side effect after chemotherapy
Agent it is characterised in that：Described composite probiotics preparations are mixed according to following number of viable ratio by following probio：
Bifidobacterium breve：Lactobacillus acidophilus：Lactobacillus casei：Streptococcus thermophilus=1：1-3:1-3:1-3, and described compound benefit
Total number of viable of probiotics preparation is 200-800 hundred million.
Application in described composite probiotics preparations medicine of n and V after preparation prevents chemotherapy.
Described composite probiotics preparations improve the application in esoenteritis medicine in preparation.
The present invention compared with the existing technology, has the advantage that：
This kind of composite probiotics preparations, its all of bacterial strain derives from human body, through through screening, domestication and prescription checking, safety
Property high, there is good ecological mutual aid, safe, clinical practice is secure.It can effectively reduce the water of serotonin
Flat, esoenteritis can also be improved simultaneously.Therefore this composite probiotics preparations as enteral Tiny ecosystem nutritional preparation, for changing
Treat the product development of the enteral nutrition preparation of patient, it uses quite varied.Its viable count consumption is big, belongs to medical food,
No dosage limits, and has no toxic side effect, easy to use, can be used for the battalion of clinical patient together with other nutrients as nutrition assembly
Cure is treated, and allows patient just can complete auxiliary treatment during diet at ordinary times, can significantly mitigate patient suffering.
Brief description
Fig. 1 is each group rat average kaolin food ration variation diagram.
Fig. 2 is model group Bacteria from Gl Tract of Rats change in time after cisplatin treated, PCR-DGGE fingerprint analysis collection of illustrative plates
(A), principal component（PCA）Analysis (B) and UPGMA similitude cluster analysis (C).
Note：This in figure, #1-#5 is 0 day model group rats gut flora after cisplatin treated, and #6-#10 is 3 after cisplatin treated
Its model group rats gut flora, #11-#15 is 6 days model group rats gut floras after cisplatin treated.
Fig. 3 is probiotic group Bacteria from Gl Tract of Rats change in time after cisplatin treated, PCR-DGGE fingerprint analysis collection of illustrative plates
(A), principal component（PCA）Analysis (B) and UPGMA similitude cluster analysis (C).
Note：This in figure, #1-#5 is 0 day probiotic group Bacteria from Gl Tract of Rats after cisplatin treated, after #6-#10 is cisplatin treated
3 days probiotic group Bacteria from Gl Tract of Rats, #11-#15 is 6 days probiotic group Bacteria from Gl Tract of Rats after cisplatin treated.
Fig. 4 compares the 3rd day model group and probiotic group Bacteria from Gl Tract of Rats after cisplatin treated, PCR-DGGE fingerprint analysis
Collection of illustrative plates (A), principal component（PCA）Analysis (B) and UPGMA similitude cluster analysis (C).
Note：This in figure, #1-#5 is the 3rd day model group rats gut flora after cisplatin treated, after #6-#10 is cisplatin treated
3rd day probiotic group Bacteria from Gl Tract of Rats.
Fig. 5 is to compare the 6th day model group and probiotic group Bacteria from Gl Tract of Rats after cisplatin treated, PCR-DGGE fingerprint analysis
Collection of illustrative plates (A), principal component（PCA）Analysis (B) and UPGMA similitude cluster analysis (C).
Note：This in figure, #1-#5 is the 6th day model group rats gut flora after cisplatin treated, after #6-#10 is cisplatin treated
6th day probiotic group Bacteria from Gl Tract of Rats.
Fig. 6 is different times each group rat intestine histogenic immunity fluoroscopic examination result after cisplatin treated.
Note：Intestinal tissue Chromogranin A immunofluorescence dyeing（Left side）, 5-HT（Middle）, merge（Right side）；Con-3 is
3rd day blank group after cisplatin treated, cis-3 is the 3rd day model group after cisplatin treated, and pro-3 is prebiotic for the 3rd day after cisplatin treated
Bacterium group, con-6 is the 6th day blank group after cisplatin treated, and cis-6 is the 6th day model group after cisplatin treated, and pro-6 is at cis-platinum
6th day probiotic group after reason.
Fig. 7 is the change of 5-HT in each group rat blood serum.
Note：A is represented and is compared with con-3p<0.05, b is represented and is compared with con-6p<0.05, c is represented and is compared with cis-3p<
0.05, d is represented and is compared with cis-6p<0.05；Con-3 is the 3rd day blank group after cisplatin treated, and cis-3 is the 3rd after cisplatin treated
Its model group, pro-3 is the 3rd day probiotic group after cisplatin treated, and con-6 is the 6th day blank group after cisplatin treated, and cis-6 is
6th day model group after cisplatin treated, pro-6 is the 6th day blank group after cisplatin treated.
5-HT change in Fig. 8 each group rat colon tissue.
Note：A represents and compares p with con-3<0.05, b represents and compares p with con-6<0.05, c represents and compares p with cis-3<
0.05, d represents and compares p with cis-6<0.05；Con-3 is the 3rd day blank group after cisplatin treated, and cis-3 is the 3rd after cisplatin treated
Its model group, pro-3 is the 3rd day probiotic group after cisplatin treated, and con-6 is the 6th day blank group after cisplatin treated, and cis-6 is
6th day model group after cisplatin treated, pro-6 is the 6th day blank group after cisplatin treated.
Specific embodiment
The specific embodiment of the present invention is described below：
A kind of composite probiotics preparations, are mixed according to following number of viable ratio by following probio：
Bifidobacterium breve：Lactobacillus acidophilus：Lactobacillus casei：Streptococcus thermophilus=1：1-3:1-3:1-3, and described compound benefit
Total number of viable of probiotics preparation is 200-800 hundred million.
Composite probiotics preparations as above reduce the application in serotonin medicine in preparation.
Composite probiotics preparations as above improve the application in esoenteritis medicine in preparation.
Embodiment
SPF level SD male rat.It is randomly divided into 3 groups, every group 14, respectively blank group, cis-platinum+physiological saline group (mould
Type group：Cis-0 represents cisplatin treated the 0th day, and cis-3 represents cisplatin treated the 3rd day, and cis-6 represents cisplatin treated the 6th day), suitable
Platinum+probiotic group (probiotic group：Pro-0 represents cisplatin treated the 0th day, and pro-3 represents cisplatin treated the 3rd day, and pro-6 represents
Cisplatin treated the 6th day).Probiotic group rat press composite probiotics preparations disclosed in this invention total bacteria count be 1 ×
1010CFU/ probio carries out gavage, and blank group and model group carry out gavage with equal-volume physiological saline, and the gavage time is total up to
13 days, the 6th day after gavage, set up animal model, to rat, end of line is entered by 6mg/kg cisplatin dose to model group and probiotic group
Intravenous injection, blank group injects equal-volume physiological saline, and after injection, the rat of the 3rd day every group of execution half quantity, remains
Under in the 6th day put to death.Observe during experiment：The feed inflow of rat, kaolin intake and the death rate, denatured gradient coagulate
Gel electrophoresis（DGGE）Method detection gut flora diversity, immunofluorescence method detection enterochromaffin cell release 5-HT situation,
ELISA kit detects the concentration of 5-HT in serum 5-HT and colon intestinal tissue.
Experimental result is as follows：
From rat average kaolin food ration block diagram（Fig. 1）As can be seen that compared with blank group, the 1st, 2,3 after cis-platinum modeling
My god, model group and probiotic group rat have kaolin behavior of significantly ingesting, and wherein the 1st day is the most serious, the 2nd, 3 days height of ingesting
Ridge soil behavior has obvious mitigation.Compared with model group, probiotic group rat reduces substantially to kaolin food ration.
The multifarious change of each group Bacteria from Gl Tract of Rats after cisplatin treated, from DGGE electrophoretogram（Fig. 2) can be seen that
Compared with before cisplatin treated, 3 days and 6 days after cis-platinum injections, DGGE band number significantly reduces model group（It is shown in Table 1）, model group 0
My god, each swimming lane of DGGE averagely has 18.25 ± 1.26 bands, and the 3rd day after cisplatin treated, DGGE collection of illustrative plates shows averagely have
12.60 ± 1.67 bands.Process latter 6 days, DGGE collection of illustrative plates shows averagely 10.20 ± 3.77 bands, and cisplatin treated is described,
Bacteria from Gl Tract of Rats diversity can be made to reduce.As seen from Figure 2, model group 6 days, Bacteria from Gl Tract of Rats has obvious disorder.
Table 1 each group Bacteria from Gl Tract of Rats diversity strip analysis（X ± S）
In probiotic group, compared with before cisplatin treated, 3 days to 6 days after cis-platinum injections, DGGE band number reduces inconspicuous（Fig. 3）,
Probiotic group 0 day, each swimming lane of DGGE averagely has 17.33 ± 1.15 bands, and 3 days after cisplatin treated, DGGE collection of illustrative plates shows
Averagely there are 15.00 ± 1.41 bands.Process latter 6 days, DGGE collection of illustrative plates shows averagely 15.20 ± 1.64 bands, and warp is described
Probio is intervened, and Bacteria from Gl Tract of Rats change is inconspicuous, and in conjunction with Fig. 4, Fig. 5 with Biao 1 can be seen that compared with model group, suitable
Platinum is processed latter 3 days, and probiotic group Bacteria from Gl Tract of Rats diversity increases, and after cisplatin treated, 6 days gut flora diversity are also no bright
Aobvious disorder.
Bacteria from Gl Tract of Rats DGGE collection of illustrative plates is digitized process using Quantity One software, then adopts non-
It is weighted to arithmetic average algorithm（UPGMA）Carry out each swimming lane type of strip cluster analysis.Result shows：In model group, remove
Model group is polymerized to outside single cluster for 0 day, and model group 3 days and model group have intersection in 6 days, and differ greatly in group.Cis-platinum is described
After process, 3 days and 6 days enteric flora disturbances.
Probiotic group 6 days and 0 day in probiotic group, fail substantially to divide into two big clusters, illustrate through probio intervention
Rat, gut flora has obvious recovery.
The change of the quantity of 4 kinds of dominant microfloras of different times each group rat after cisplatin treated：
Lactobacillus from every gram of excrement of rat, Bifidobacterium,Clostridium cluster IV,Clostridium cluster XIVChanges of contents, table 2 can be seen that：Compared with model group before processing, model group process after the 3rd day and process after
Lactobacillus in 6th day Bacteria from Gl Tract of Rats, Bifidobacterium is greatly reduced (p<0.05), Clostridium cluster IV,Clostridium cluster XIVCopy number increases notable (p<0.05)；Compared with the 3rd day after processing with model group, model
The 6th day after group process, lactobacillus, Bifidobacterium reduces,Clostridium cluster IVIncrease, butClostridium cluster XIVReduce.
The expression of table 24 kinds of dominant microfloras of enteron aisle（Copy number/every gram of excrement.Copy number/gram excrement, x ± s）
Note：E is represented and is compared with cis-0p<0.05, c is represented and is compared with cis-3p<0.05, d is represented and is compared with cis-6p<0.05
, f represented and compared with pro-0p<0.05, g is represented and is compared with pro-3p<0.05；Cis-0 is the 0th day model group after cisplatin treated,
Cis-3 is the 3rd day model group after cisplatin treated, and cis-6 is the 6th day model group after cisplatin treated, and pro-0 is the after cisplatin treated
0 day probiotic group, pro-3 is the 3rd day blank group after cisplatin treated, and pro-6 is the 6th day model group after cisplatin treated.
Compared with probiotic group before processing, probiotic group process after the 3rd day and breast in the 6th day Bacteria from Gl Tract of Rats after processing
Bacillus and Bifidobacterium all do not have significant changes,Clostridium cluster IVQuantity increases, but and probiotic group
Before processing is compared,Clostridium cluster XIVQuantity no significant change;Compared with the 3rd day after processing with probiotic group, benefit
Lactobacillus no significant change in 6th day Bacteria from Gl Tract of Rats after raw bacterium group process, Bifidobacterium copy number is reduced trend,Clostridium cluster IVWithClostridium cluster XIVQuantity declines substantially (p<0.05)
The 3rd day and after processing compared with the 6th day after processing with model group, probiotic group process after the 3rd day and the 6th day after processing, newborn
Bacillus, Bifidobacterium increases considerably (p<0.05), andClostridium cluster IV,Clostridium cluster XIV(p is all greatly reduced<0.05).
Different times each group rat intestine histogenic immunity fluoroscopic examination after cisplatin treated：
From immunofluorescence results（Fig. 6）As can be seen that in intestinal tissue model group the 3rd day, enterochromaffin cell discharge 5-HT amount
Increase, and compared with model group the 3rd day, probiotic group the 3rd day, the enterochromaffin cell of release 5-HT reduces.The 6th after cisplatin treated
My god, in model group, the amount of enterochromaffin cell's release 5-HT has reduced, and now probiotic group is not notable compared with blank group
Difference.
The change in concentration of 5-HT in different times each group rat blood serum and colon after cisplatin treated：
Compare with blank group, in the model group serum of the 3rd day and the 6th day, 5-HT level is significantly raised（p<0.05), and the 6th day with
IL-10 level change in 3rd day is inconspicuous（p<0.05）.Compare with model group, the probiotic group colon of the 3rd day and the 6th day
Middle 5-HT level significantly reduces（p<0.05）Closer to blank group level.（Fig. 7）
In rat colon tissue, the content of each group 5-HT is shown in Fig. 8.Compared with blank group, in the model group serum of the 3rd day and the 6th day
5-HT level is significantly raised（p<0.05), but returned fall than the 3rd day 5-HT level within the 6th day（p<0.05）.Compare with model group,
In the probiotic group colon of the 3rd day and the 6th day, 5-HT level significantly reduces（p<0.05）Closer to blank group level.
Claims (3)
1. a kind of composite probiotics preparations for reducing serotonin side effect after chemotherapy it is characterised in that：Described is compound
Probiotics preparation is mixed according to following number of viable ratio by following probio：
Bifidobacterium breve：Lactobacillus acidophilus：Lactobacillus casei：Streptococcus thermophilus=1：1-3:1-3:1-3, and described compound benefit
Total number of viable of probiotics preparation is 200-800 hundred million.
2. a kind of composite probiotics preparations for reducing serotonin side effect after chemotherapy as claimed in claim 1, it is special
Levy and be：Application in described composite probiotics preparations medicine of n and V after preparation prevents chemotherapy.
3. a kind of composite probiotics preparations for reducing serotonin side effect after chemotherapy as claimed in claim 1, it is special
Levy and be：Described composite probiotics preparations improve the application in esoenteritis medicine in preparation.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107684567A (en) * | 2017-11-07 | 2018-02-13 | 大连医科大学 | It is a kind of to be used to improve composite probiotics preparations that are fat and reducing blood fat |
| CN114947134A (en) * | 2022-05-06 | 2022-08-30 | 河北一然生物科技股份有限公司 | Application of streptococcus thermophilus S131 in improving intestinal health and regulating intestinal flora |
| CN115927050A (en) * | 2022-07-14 | 2023-04-07 | 江南大学 | Preparation method of streptococcus thermophilus fermentation product with anxiety relieving function |
| CN116064272A (en) * | 2022-07-14 | 2023-05-05 | 江南大学 | Streptococcus thermophilus with serotonin level improving function and application thereof |
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| CN104398538A (en) * | 2014-10-28 | 2015-03-11 | 大连医科大学 | Composite probiotics preparation for mitigating chemotherapy side effect |
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| CN104398538A (en) * | 2014-10-28 | 2015-03-11 | 大连医科大学 | Composite probiotics preparation for mitigating chemotherapy side effect |
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| P DELIA等: "Use of probiotics for prevention of radiation-induced diarrhea", 《WORLD JOURNAL OF GASTROENTEROLOGY》 * |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107684567A (en) * | 2017-11-07 | 2018-02-13 | 大连医科大学 | It is a kind of to be used to improve composite probiotics preparations that are fat and reducing blood fat |
| CN114947134A (en) * | 2022-05-06 | 2022-08-30 | 河北一然生物科技股份有限公司 | Application of streptococcus thermophilus S131 in improving intestinal health and regulating intestinal flora |
| CN114947134B (en) * | 2022-05-06 | 2024-01-26 | 河北一然生物科技股份有限公司 | Application of streptococcus thermophilus S131 in improving intestinal health and regulating intestinal flora |
| CN115927050A (en) * | 2022-07-14 | 2023-04-07 | 江南大学 | Preparation method of streptococcus thermophilus fermentation product with anxiety relieving function |
| CN116064272A (en) * | 2022-07-14 | 2023-05-05 | 江南大学 | Streptococcus thermophilus with serotonin level improving function and application thereof |
| CN115927050B (en) * | 2022-07-14 | 2024-04-30 | 江南大学 | Preparation method of streptococcus thermophilus fermentation product with anxiety relieving function |
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