CN106943436B - One kind treats ulcerative colitis compound lactobacillus acidophilus piece and its pharmaceutical applications - Google Patents
One kind treats ulcerative colitis compound lactobacillus acidophilus piece and its pharmaceutical applications Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
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- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
- A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
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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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Abstract
The invention belongs to field of medicaments, is related to a kind of compound lactobacillus acidophilus piece and pharmaceutical applications for treating ulcerative colitis.The composite tablet that the compound lactobacillus acidophilus piece is made up of strain in China lactobacillus acidophilus, Japanese strain lactobacillus acidophilus, streptococcus fecalis and hay bacillus, every contains lactobacillus acidophilus 5 × 106It is individual.The compound lactobacillus acidophilus piece can be used for the medicine for preparing treatment ulcerative colitis, can be used for preparing the dull-witted medicine of prevention.
Description
Technical field
The invention belongs to field of medicaments, is related to a kind of compound lactobacillus acidophilus piece and pharmaceutical purpose for treating ulcerative colitis
On the way.
Background technology
Compound lactobacillus acidophilus piece, by strain in China lactobacillus acidophilus, Japanese strain lactobacillus acidophilus, streptococcus fecalis and withered grass bar
The composite tablet of four kinds of bacterium powder compositions of bacterium.Medicine is adjusted for gut flora.Decomposable asymmetric choice net carbohydrate produces lactic acid, improves enteron aisle acidity, from
And suppress pathogenic entero becteria breeding.
Compound lactobacillus acidophilus piece can be made by oneself, commercially available can also purchase, and compound lactobacillus acidophilus piece is Chinese main raw
Producing enterprise is produced by Tonghua Golden-Horse Pharmaceutical Industry Co., Ltd., and its authentication code is：Chinese medicines quasi-word H10940114, rule
Lattice are：Every 0.5g, every contains lactobacillus acidophilus 5 × 106It is individual.
The indication of compound lactobacillus acidophilus piece is for bowel dysfunction caused by intestinal bacilli illness, is such as made the transition acute
Diarrhoea etc..Usage is oral.Adult one time 1~2,3 times a day.
The invention of this patent undertake 13 state keys research and development planning item " intestinal microecology control technique study and
Nutritious and healthy food is formulated and industrialization " (bullets：In scientific research project 2016YFD0400605), to compound acidophilus breast bar
Bacterium piece has carried out systematic Study, has been surprisingly found that compound lactobacillus acidophilus piece all has to ulcerative colitis, dementia under study for action
There is certain effect, especially make us the effect of unexpected excellent having in terms of preventing vascular dementia, then to the class
The experimental study of carry out system is inscribed, and then has obtained technical scheme.
The content of the invention
It is an object of the invention to provide a kind of compound lactobacillus acidophilus piece for treating ulcerative colitis.
It is a further object of the present invention to provide the preparation method of compound lactobacillus acidophilus piece.
It is a still further object of the present invention to provide the new pharmaceutical use of the compound lactobacillus acidophilus piece.
The purpose of the present invention is achieved in the following ways：
A kind of compound lactobacillus acidophilus piece for treating ulcerative colitis, the compound lactobacillus acidophilus piece is thermophilic by strain in China
The composite tablet that Lactobacillus lactis, Japanese strain lactobacillus acidophilus, streptococcus fecalis and hay bacillus form, every contains lactobacillus acidophilus 5
×106It is individual.
A kind of compound lactobacillus acidophilus piece prepare prevent anti-dementia agent in application, the compound lactobacillus acidophilus piece be by
The composite tablet that strain in China lactobacillus acidophilus, Japanese strain lactobacillus acidophilus, streptococcus fecalis and hay bacillus form, every contains acidophilus
Lactobacillus 5 × 106It is individual.
A kind of described compound lactobacillus acidophilus piece is preparing the application in preventing anti-dementia agent, preferably compound acidophilus breast
Bacillus piece is preparing the application in preventing vascular dementia medicine.
A kind of compound lactobacillus acidophilus piece is preparing the application in preventing anti-dementia agent, preferably the compound lactobacillus acidophilus piece
Preparing the application in preventing senile dementia medicine.
A kind of compound lactobacillus acidophilus piece is preparing the application in treating anti-dementia agent.
A kind of described compound lactobacillus acidophilus piece is preparing the application in treating anti-dementia agent, preferably compound acidophilus breast
Bacillus piece is preparing the application in treating vascular dementia medicine.
A kind of described compound lactobacillus acidophilus piece is preparing the application in treating anti-dementia agent, preferably compound acidophilus breast
Bacillus piece is preparing the application in treating senile dementia medicine.
A kind of compound lactobacillus acidophilus piece is preparing the application in treating anti-diarrhea drug.
A kind of described compound lactobacillus acidophilus piece is preparing the application in treating anti-diarrhea drug, preferably compound acidophilus breast
Bacillus piece is preparing the application in treating transition acute diarrhea medicine.
A kind of compound lactobacillus acidophilus piece is preparing the application in treating ulcerative colitis medicine, the compound acidophilus breast bar
The composite tablet that bacterium piece is made up of strain in China lactobacillus acidophilus, Japanese strain lactobacillus acidophilus, streptococcus fecalis and hay bacillus, often
Piece contains lactobacillus acidophilus 5 × 106It is individual.
Compound lactobacillus acidophilus piece of the present invention is by strain in China lactobacillus acidophilus, Japanese strain lactobacillus acidophilus, excrement hammer
Bacterium and the composite tablet of hay bacillus composition.
Figure of description
Fig. 1 be rats in normal control group Ulcerative Colitis Model colon pathological examination result figure (HE dye, ×
200)。
Fig. 2 be model group rats Ulcerative Colitis Model colon pathological examination result figure (HE dye, ×
200)。
Fig. 3 for positive group rats with ulcerative colitis colon pathological examination result figure (HE is dyed, ×
200)。
Fig. 4 is compound lactobacillus acidophilus Pian Zu rats with ulcerative colitis colon pathological examination result figure
(HE is dyed, × 200).
Embodiment
The present invention is further elaborated below by way of specific embodiment：
Embodiment 1：The medicament screening experiment for preventing vascular dementia rats damage in learning and memory is studied
This experiment is detected by behaviouristics, observes each medicine to the pre- of vascular dementia rats damage in learning and memory
Anti- effect.
1 material and method
1.1 experimental animal
Adult healthy Wistar male rats, body weight (200 ± 20) g, quality certification number P00102013, by Heilungkiang
Medical pharmaceutical university Drug safety assessment center provides.
1.2 medicines and reagent
Medicine first：Compound lactobacillus acidophilus piece, is produced, authentication code by Tonghua Golden-Horse Pharmaceutical Industry Co., Ltd.：
Chinese medicines quasi-word H10940114, lot number：160415-6, specification：Every 0.5g, every contains lactobacillus acidophilus 5 × 106It is individual.It is purchased from Kazakhstan
The medicine group people are the same as safe chain pharmacy.
Medicine second：Lactobacillus acidophilus piece, self-control, is made up, specification of strain in China lactobacillus acidophilus：Every 0.5g, every contains
Lactobacillus acidophilus 5 × 106It is individual.
Medicine third：Streptococcus fecalis piece, self-control, is made up, specification of streptococcus fecalis：Every 0.5g, every containing streptococcus fecalis 5 ×
106It is individual.
Medicine fourth：Hay bacillus viable capsule, is produced by Huarun Zizhu Pharmaceutical Co., Ltd., authentication code：Chinese medicines quasi-word
S20030018, lot number, 151227-3, specification：0.25g (is not less than 2.5 × 10 containing viable count7CFU).It is purchased from people from Harbin Pharmaceutical Group
The people are the same as safe chain pharmacy.
Compound desert cistanche yizhi capsule：Produced by Liaoyuan Yulongya Pharmaceutical Co.ltd, authentication code：Chinese medicines quasi-word
Z20080047, specification：Every dress 0.3g.The Harbin Pharmaceutical Group people are purchased from safe chain pharmacy.
Co-dergocrine Mesylate piece：By the production of Shanghai medicine-feeding Xinyi Pharmaceutical Factory Co., Ltd, authentication code：Chinese medicines quasi-word
H31021182, specification：1mg.The Harbin Pharmaceutical Group people are purchased from safe chain pharmacy.
The foundation of 1.3 creations
In modeling operation consent 4 weeks, rat will be survived and be randomly divided into 8 groups, every group 25, i.e. model group (gastric infusion physiology
Salt solution, dosage：Physiological saline l0mL/Kg), medicine first group (gastric infusion medicine first, dosage：3.0g/Kg), medicine second group (fills
Stomach administration medicine second, dosage：3.0g/Kg), third group of (gastric infusion medicine third, dosage of medicine：3.0g/Kg), medicine fourth group (fills
Stomach administration medicine fourth, dosage：3.0g/Kg), chemical drugs positive control Co-dergocrine Mesylate piece group (gastric infusion first sulphur
Sour dihydroergotoxine alkali, dosage：0.5mg/Kg), Chinese medicine positive control compound desert cistanche yizhi capsule group (gastric infusion compound Cistanche deserticola
Cognex, dosage：30mg/Kg).Separately add sham-operation group 10 (gastric infusion physiological saline, dosage：Physiological saline 10mL/
Kg).The daily gastric infusion of each group 1 time, continuous 4 weeks.
The preoperative 12h fasting of rat, 5h prohibit water.With 12% chloraldurate intraperitoneal injection of anesthesia, fixation of lying on the back, throat portion unhairing
Along neck midsection after sterilization, exposure left and right side arteria carotis communis is separated, is covered with the dual ligation of " 0 " number silk thread, layer-by-layer suture.It is false
Operation group rat removes and does not ligature arteria carotis communis, remaining same model group.Rat anus temperature is maintained at 36.5 DEG C~37.5 DEG C in art, and art finishes
Give the benzylpenicillin sodium for injection aqueous solution appropriate local coating, be put into cage and raise, the U/ of Benzylpenicillin sodium salt 300,000 is injected intraperitoneally daily
Only, 4d, preventing and treating infection is used in conjunction.
1.4 experimental animals are grouped and administration
Modeling Post operation 1 week, rat (survival rate is about 60%) will be survived and be randomly divided into 8 groups, every group 10, i.e. model group
(gastric infusion physiological saline, dosage：Physiological saline l0mL/Kg), medicine first group (gastric infusion medicine first, dosage：3.0g/
Kg), medicine second group (gastric infusion medicine second, dosage：3.0g/Kg), third group of (gastric infusion medicine third, dosage of medicine：3.0g/
Kg), medicine fourth group (gastric infusion medicine fourth, dosage：3.0g/Kg), chemical drugs positive control Co-dergocrine Mesylate piece
Group (gastric infusion Co-dergocrine Mesylate, dosage：0.5mg/Kg), Chinese medicine positive control compound desert cistanche yizhi capsule group
(gastric infusion compound desert cistanche yizhi capsule, dosage：30mg/Kg).Separately add sham-operation group 10 (gastric infusion physiological saline, agent
Amount：Physiological saline 10mL/Kg).The daily gastric infusion of each group 1 time, continuous 10 weeks.
1.5 learning and memory functions detect
Using the ability of learning and memory of rat shuttle box detection each group rat, start to detect after 10 weeks in successive administration,
1 time a day, continuous 7d, systematic parameter are set to cycle-index 20 times, interval time 5s, buzzing time 5s, shock by electricity time l0s.Note
Record the number that gets shocked of every rat, the total time to get shocked and total actively escape the time.
1.6 statistical data Piao Li
Using SPSS15.0For Windows statistical softwares, multigroup is compared using variance analysis, as a result withTable
Show.
2 results
Influence to vascular dementia rats learning and memory function, experimental result are shown in Table 1, table 2, table 3.
Table 1 is shown, on a declining curve with the increase of training number of days, number of shocks.4d before training, model group and sham-operation group
Comparison, administration group are compared with model group, number of shocks there are no significant difference.
Compare since 5d, between group and significant difference occur.To 7d is trained, model group is compared with sham-operation group, electricity
Hit number and dramatically increase (P<0.01)；Compared with model group, medicine first group has pole significant difference (P<0.01), number of shocks has bright
Aobvious reduction；Compared with model group, medicine second group, third group of medicine, medicine fourth group there are no significant difference, number of shocks is bright
Aobvious reduction；Compared with model group, the positive group of Western medicine and the positive group of Chinese medicine there were significant differences (P<0.05), number of shocks has difference
The reduction of degree.
The rat Shuttle box number of shocks test result of table 1
Note：Compared with sham-operation group,*P<0.01；Compared with model group,#P<0.05,##P<0.01。
Table 2 is shown, on a declining curve with the increase of training number of days, electric shock time.3d before training, model group and sham-operation group
Comparison, administration group are compared with model group, difference that the electric shock time, there are no significant.
Compare since 4d, between group and significant difference occur.Since 5d, model group is compared with sham-operation group, electricity
Hitting the time dramatically increases (P<0.01)；Compared with model group, the electric shock time of the positive group of medicine first group, Western medicine positive group, Chinese medicine
Substantially reduce (P<0.05)；Compared with model group, medicine second group, third group of medicine, medicine fourth group there are no significant difference, electric shock
Time is not reduced significantly.
The rat Shuttle box of table 2 electric shock time test result
Note：Compared with sham-operation group,*P<0.05,**P<0.01；Compared with model group#P<0.005。
Table 3 is shown, with the increase of training number of days, it is in rising trend actively to escape the time.4d before training, model group is with doing evil through another person
Art group compares, administration group compared with model group, actively escape the time there are no significant difference.
Compare since 5d, between group and significant difference occur.Compared with sham-operation group, actively escape the time shows model group
Write and reduce (P<0.01)；Compared with model group, the time of actively escaping of the positive group of medicine first group, Western medicine positive group, Chinese medicine shows
Write increase (P<0.05, P<0.01)；Compared with model group, medicine second group, third group of medicine, medicine fourth group there are no significant difference,
Actively escaping the time does not increase significantly.
The rat Shuttle box of table 3 actively escapes time test result
Note：Compared with sham-operation group,*P<0.05,**P<0.01；Compared with model group,#P<0.05,##P<0.01
3 conclusions
Damage in learning and memory is the core symptom of vascular dementia clinical manifestation, be judge vascular dementia model into
Work(whether key.It can clinically be caused according to vascular dementia by long-term Cerebral hypoperfusion, this research is using permanent
Property ligation bilateral common carotid arteries method replicate rat vascular dementia model.This experimental study shows, modeling Post operation the
10 weeks, there is obvious damage in learning and memory compared with sham-operation group in model group, illustrated that the animal model is successful.
This experiment is prevention administration, and the time point of administration is scheduled on operation consent 4 weeks and after modeling performs the operation 1 week, it is therefore an objective in blood
The initial stage for being slowly formed early stage and vascular dementia process that pipe dementia is not formed carries out pharmaceutical intervention to it, so as to prevent blood
Damage in learning and memory after the dull-witted formation of pipe.Shuttle box is a kind of important method in behaviouristics detection method, it
By the active fugue reaction for detecting rat and passive fugue reaction, carry out the objective ability of learning and memory for reacting rat.
By being trained to the continuous 7d of rat shuttle box, each group shows the difference of ability of learning and memory, mould for this experiment
There is significant damage in learning and memory compared with sham-operation group in type group, and medicine first group has substantially compared with model group learning and memory function
Improvement, i.e. compound lactobacillus acidophilus piece has significant prevention effect to the damage in learning and memory of vascular dementia rats.
Embodiment 2：Experiment to the improvement result of senile dementia rat symptom caused by intracerebroventricular injection A β 1-42 albumen
Research
1 medicine, materials and methods
1.1 medicine
Medicine first：Compound lactobacillus acidophilus piece, is produced, authentication code by Tonghua Golden-Horse Pharmaceutical Industry Co., Ltd.：
Chinese medicines quasi-word H10940114, lot number：160415-6, specification：Every 0.5g, every contains lactobacillus acidophilus 5 × 106It is individual.It is purchased from Kazakhstan
The medicine group people are the same as safe chain pharmacy.
Medicine second：Lactobacillus acidophilus piece, self-control, is made up, specification of strain in China lactobacillus acidophilus：Every 0.5g, every contains
Lactobacillus acidophilus 5 × 106It is individual.
Medicine third：Streptococcus fecalis piece, self-control, is made up, specification of streptococcus fecalis：Every 0.5g, every containing streptococcus fecalis 5 ×
106It is individual.
Medicine fourth：Hay bacillus viable capsule, is produced by Huarun Zizhu Pharmaceutical Co., Ltd., authentication code：Chinese medicines quasi-word
S20030018, lot number, 151227-3, specification：0.25g (is not less than 2.5 × 10 containing viable count7CFU).It is purchased from people from Harbin Pharmaceutical Group
The people are the same as safe chain pharmacy.
Positive drug：Donepezil hydrochloride tablet, produced by Fangzhou Pharmaceutical Co., Ltd., Shaanxi, Chinese medicines quasi-word H20030583,
5mg × 28 piece/box；
1.2 reagent
A β 1-42 (beta amyloid peptide) are purchased from Shanghai Mo Xi bio tech ltd；Acetylcholine ester enzyme reagent kit, by
The enzyme-linked bio tech ltd's production in Shanghai.
1.3A β 1-42 preparation
0.1mgA β 1-42 are dissolved in 50 μ L physiological saline, concentration 2mg/L, and 37 DEG C of temperature incubate 5d, and -20 DEG C of refrigerators preserve, never
Multigelation.
1.4 dementia animal models replicate
Chloral hydrate anesthesia rat is injected intraperitoneally with 400mg/Kg dosage, anesthetized rat is fixed on rat Naoliqing capsule
On instrument, positioning is with reference to the written 5th edition rat brain stereotaxic atlas of George Paxinos.Every rat microsyringe
2mg/mL A β 1-42 reagent l5 μ L are injected, slowly injection, note that let the acupuncture needle remain at a certain point to ensure its abundant disperse, and then suture sterilizes.
1.5 animals and packet
SD rats, male, body weight 180~220g, SPF level, quality certification number P00102013 are big by Heilungkiang traditional Chinese medicine
Drug safety assessment center is learned to provide.
Animal is randomly divided into normal group, model group, positive drug (donepezil) group, medicine first group, medicine second group, medicine third
Group, medicine fourth group, every group 10.Normal group SD rats are in the μ L of intracerebroventricular injection physiological saline 5；Positive drug control group, model group,
Medicine first group, medicine second group, third group of medicine, each administration group of medicine fourth group are respectively at μ L (10 μ of intracerebroventricular injection A β 1-42 albumen 5
g).The postoperative gastric infusion of rat, donepezil, medicine first group, medicine second group, third group of medicine, each administration group of medicine fourth are with life
Manage salt solution dissolving.Dosage is：3mg/Kg, administered volume 0.1mL/10g, one time a day, 8d is administered altogether.
1.6 water maze laboratory
Using orientation navigation, space exploration as index.Follow-on test 4d, observation experiment animal find and climb up platform and taken
Between, i.e. incubation period.Last 1d carries out space exploration experiment, the 1st time for reaching original platform position of record animal, passes through Yuanping City
The number of platform and the percentage of time in target quadrant activity.
1.7 Jumping test
Jumping test device is lucite case.There are copper grid at plate bottom, can indirect current, voltage be 40 volts.On base copper grid
One jiao to place rubber garden platform be place of safety, animal can jump on round platform wall of hiding and shock by electricity.When experiment starts, animal is first put into case
Interior freely activity 2 minutes, are familiar with environment, then connect copper grid power supply, and animal, which will jump to, under normal circumstances avoids electricity on rubber platform
Hit.
(1) learning test：It is " correct response " that rat jumps directly to place of safety after being shocked by electricity from starting area, to reach continuous
10 electric shocks are that required number of shocks (i.e. number of attempt) before correct response (i.e. 10/10) represents its study capacitation.
The not re-test if number of attempt is more than 30 times, it is that maximum counts with 30 times.
(2) memory reproduces test：Choosing the rat stated and reach 10/10 standard, same method is tested again after rest 24h,
To represent to remember reproduction up to the number of attempt before 10/10 standard.
2 results
2.1 orientation navigation experiment
Table 4 to senile dementia rat escape latency caused by A β 1-42 albumen influence (N=10)
Note：Compared with model group*P<0.05,**P<0.01；
As a result show, each group experimental animal finds the incubation period of platform as training is gradually shortened.Model group is from training the
Start within two days, the prolongation of latency of animal, the incubation period of 2~4 days and the statistically significant (P of normal group comparing difference<
0.05, P<0.01).After giving positive drug, the incubation period of Senile Dementia Model Rats significantly reduces, compared with model group, difference
Statistically significant (P<0.01).Medicine first group, medicine second group, third group of medicine, the incubation period of medicine fourth group are slightly reduced, but with
Model group compares, and difference is not statistically significant.
2.2 space search are tested
Table 5 to senile dementia rat spatial search capability caused by A β 1-42 albumen influence (N=10)
Note：Compared with model group**P<0.01；
The number and the percentage of target quadrant activity time of model group animal travels position of platform are significantly lower than normal group
(P<0.01)；The number of positive controls rat spanning platform position substantially increases, the percentage of target quadrant activity time
Significantly rise, relatively there is significant difference (P with model group<0.01).Medicine first group, medicine second group, third group of medicine, medicine fourth group
The number of rat spanning platform position is increased slightly, and the percentage of target quadrant activity time slightly raises, but with model group ratio
Compared with without significant difference.
2.3 step down test
The each group rat Jumping test errors number of table 6 compares
Note：Compared with model group**P<0.01；
As a result show, after modeling compared with normal group, model group remembered and remembered reproduce number of animals decline, number
Rise, remembered and remembered reproduction number of animals after positive controls administration and be significantly increased, obtain memory number and memory
Reproductions are decreased obviously, with model group comparing difference significantly (P<0.01)；Medicine first group, medicine second group, third group of medicine, medicine
Remembered and remembered reproduction number of animals after the administration of fourth group not to be significantly increased, obtaining memory number and memory reproductions does not have
It is decreased obviously, there was no significant difference compared with model group.Medicine first group, medicine second group, third group of medicine, medicine fourth group are prompted to note
Recall obstacle not to be significantly improved.
Result above synthesis shows that medicine first group, medicine second group, third group of medicine, medicine fourth group can not be obviously improved dementia
Spatial memory ability, Behavioral feature and the brain lesionses of animal, do not have obvious therapeutic action to senile dementia.
Embodiment 3：The medicament screening experiment of rats with ulcerative colitis is studied
In order to inquire into the therapeutic action to ulcerative colitis, ulcerative colitis in rats is established using TNB
Model, observe influence of each probiotics to ulcerative colitis in rats serum inflammatory factors of senile and colon pathology damage.
1 material
1.1 reagent
Compound lactobacillus acidophilus piece, is produced, authentication code by Tonghua Golden-Horse Pharmaceutical Industry Co., Ltd.：Chinese medicines quasi-word
H10940114, lot number：160415-6, specification：Every 0.5g, every contains lactobacillus acidophilus 5 × 106It is individual.It is purchased from people from Harbin Pharmaceutical Group
The people are the same as safe chain pharmacy.Sulfasalazine tablet, produced by Shanghai Zhongxi Sunve Pharmaceutical Co., Ltd., authentication code：Chinese medicines quasi-word
H31020450, lot number：160221, specification：0.25g/ pieces；2,4,6- TNBs, it is limited by the graceful biotechnology of upper Hypon
Company produces, purity：99%, lot number：15122；IL-1 kits, produced by upper thing Science and Technology Ltd. of Haikang nangzan, lot number：
20160314-5；IL-6ELSIA kits, produced by Beijing equation bio tech ltd, lot number：20160303；IL-
8ELSIA kits, produced by Shanghai crystalline substance antibiont Engineering Co., Ltd, lot number：20160112；Pentobarbital sodium injection, by
Beijing Pu Bosi bio tech ltd produces, lot number：20151212-6；Absolute ethyl alcohol, had by abundant liter of Shandong biotechnology
Limit company produces, lot number：20151116-2.
1.2 experimental animal
SD rats, 120, SPF levels, male, 240~260g of body weight, it is purchased from Heilongjiang University of Chinese Medicine's drug safety
Assessment centers, quality certification number P00102013.
1.3 instrument
AUY assay balances, by the experimental instruments and equipment limited manufacture of one section of Chengdu, precision：0.01g；96A ELIASAs, by north
Jing Beideng Medical Devices Co., Ltd manufactures；Biomicroscope, manufactured by Shanghai Yi Yuan optical instrument factories；RM2235 paraffin sections
Machine, industrial development in science and technology Co., Ltd is praised by Beijing section and manufactured；Automation-tissue-dehydrating machine TP1020, safe row science and technology is pleased by Beijing
Development Co., Ltd manufactures；HI1220 bakes piece machine, is manufactured by German Leica companies；HI1210 spreads out piece machine, and a gram medical treatment is come by Hubei
Instrument Ltd. manufactures；EG1150H+C tissue embedding machines, experimental instruments and equipment limited of newly being shaken by Shanghai manufacture；DFC420C diseases
Imaging system is managed, is manufactured by German Leica companies.
2 methods
2.1 animal models prepare and packet
Male SD rat, 240~260g of body weight, each group Rat Fast can't help water 48h before experiment, with 2% yellow Jackets
Intraperitoneal anesthesia.Rat is taken, with diameter 2.0mm, 12cm silicone tube is about by the light and slow insertion 8cm of anus, injects 2,4,6 nitrobenzene
Sulfonic acid is with absolute ethyl alcohol with 1：1 ratio mixes, by 60mgkg-1Admixing medical solutions volume is injected, down, anus is upward for rat head
Hand rest 20s, 2d after modeling, there is lazy move in animal, spirit is poor, hair color is coarse, matt, in disorder, appetite is poor, and stool is dilute or not
Shaping, crissum fur faecal contamination, the successful rat 30 of modeling is chosen according to above-mentioned symptom, 3 groups are randomly divided into by body weight,
Respectively model control group, sulfasalazine tablet group, compound lactobacillus acidophilus piece group, separately take 10 rat conducts by every group 10
Normal group.
2.2 administration
Normal group and model control group give distilled water 10mLkg-1, gavage gives willow nitrogen sulphur to remaining each group respectively
Pyridine piece (dosage：500mg·kg-1), compound lactobacillus acidophilus piece (dosage：5g·kg-1) decoction, 1 d-1, continuously
14d, 30min after last dose, the anesthesia of the yellow Jackets of each group rats by intraperitoneal injection 2%, abdominal aortic blood, 5000r
min-110min is centrifuged, takes supernatant to be measured.
Colon is taken, 10% formalin is fixed, and HE dyeing, Microscopic observation colonic mucosal tissue pathological characteristicses, is commented
Minute mark standard is：Not damaged is 0 point；Intestinal wall is normal or normal, and body of gland and epithelium shape are 1 point；Epithelium covering it is incomplete or not into
Ripe, mucous layer and a large amount of chronic inflammatory cell infiltrations of submucosa are 2 points；Obvious congestion and edema, mucous layer and submucosa are big
Neutrophil infiltration is measured, the swollen necrosis of crypts and ulcer are formed as 3 points.
2.3 Testing index
IL-1, IL-6 in serum, IL-8, TNF-α content are detected using ELSIA methods respectively.
2.4 statistical method
Measurement data usesRepresent, statistical information carries out statistical disposition with SPSS15.0 softwares.Measurement data
Using one-way analysis of variance, multigroup is compared with variance analysis, is compared two-by-two, is examined with q, and ranked data are using the inspection of card side
Test.
3 results
The horizontal influence of 3.1 pairs of ulcerative colitis in rats serum inflammatory factors of senile
The horizontal significantly rise (P ＜ 0.05vs Normal groups) of model control group TNF-α, IL-8, successive administration
14d, compound lactobacillus acidophilus piece can substantially reduce TNB and cause rats with ulcerative colitis serum TNF-cc level
(P ＜ 0.05) and IL-8 level (P ＜ 0.01), experimental result is shown in Table 7.
Influence of the table 7 to rats with ulcerative colitis serum inflammatory factors of senile
Note：With Normal group,*P ＜ 0.05；Compared with model control group,▲P ＜ 0.05,▲▲P ＜ 0.01.
The influence of 3.2 pairs of Colitis Model colon pathological scores of rat ulcer 15
Colon's pathological observation under microscope：Normal group animal colon surface is smooth, no rotten to the corn or ulcer, sees attached
Fig. 1；The visible obvious congestion and edema of model control group animal colon, mucous layer and a large amount of neutrophil infiltrations of submucosa,
The swollen necrosis of crypts and ulcer are formed, and see accompanying drawing 2；Sulfasalazine tablet group colonic epithelium covering it is incomplete or immature, mucous layer and
The a large amount of chronic inflammatory cell infiltrations of submucosa, are shown in accompanying drawing 3；Compound lactobacillus acidophilus piece group animal mucous layer and submucosa are few
Chronic inflammatory cell infiltration is measured, sees accompanying drawing 4.
Micro- Microscopic observation colon pathological score：There is scoring with Normal group comparing difference under model control group mirror
Statistical significance (P ＜ 0.01)；Compound lactobacillus acidophilus piece group animal colon mucous membrane tissue pathological score and model control group ratio
Relatively there is conspicuousness to reduce (P ＜ 0.05).As a result show that compound lactobacillus acidophilus piece can significantly reduce TNB and cause rat
Ulcerative colitis model colon pathological change, is shown in Table 8.
Influence of the table 8 to rats with ulcerative colitis colon pathological score
Note：Compared with Normal group,**P ＜ 0.01；Compared with model control group,▲P ＜ 0.05.
4 conclusions
The study find that compound lactobacillus acidophilus piece can substantially reduce rat UC models TNF-α, IL-8 inflammatory factors,
Colon's pathological change is obviously improved, there is obvious therapeutic action.
Described above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (2)
1. a kind of compound lactobacillus acidophilus piece is preparing the application in preventing vascular dementia medicine, it is characterised in that the compound
Lactobacillus acidophilus piece is answered by what strain in China lactobacillus acidophilus, Japanese strain lactobacillus acidophilus, streptococcus fecalis and hay bacillus formed
Square piece agent, every contains lactobacillus acidophilus 5 × 106It is individual.
2. a kind of compound lactobacillus acidophilus piece is preparing the application in treating vascular dementia medicine, it is characterised in that the compound
Lactobacillus acidophilus piece is answered by what strain in China lactobacillus acidophilus, Japanese strain lactobacillus acidophilus, streptococcus fecalis and hay bacillus formed
Square piece agent, every contains lactobacillus acidophilus 5 × 106It is individual.
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| Title |
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| "复方嗜酸乳杆菌对轻中度溃疡性结肠炎诱导和维持缓解作用";程志健，等。;《现代生物医学进展》;20111215;第4693-4695页。 * |
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