CN109350629A - A kind of probiotics composite preparation and preparation method thereof for treating alcohol withdrawal syndrome - Google Patents
A kind of probiotics composite preparation and preparation method thereof for treating alcohol withdrawal syndrome Download PDFInfo
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- CN109350629A CN109350629A CN201811356719.3A CN201811356719A CN109350629A CN 109350629 A CN109350629 A CN 109350629A CN 201811356719 A CN201811356719 A CN 201811356719A CN 109350629 A CN109350629 A CN 109350629A
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/733—Fructosans, e.g. inulin
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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
- A61K35/742—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
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
Abstract
The invention belongs to field of biotechnology, and in particular to a kind of probiotics composite preparation and preparation method thereof for treating alcohol withdrawal syndrome.Currently preferred probiotics is the common nonpathogenic dominant bacteria of human body, this kind of bacterium can be colonized in the enteron aisle of human body, and it is largely proliferated, by dominant microflora, biological antagonist, generate the effects of beneficial metabolite, directly stimulation epithelium of intestinal mucosa, improve intestine microenvironment, and brain is acted on by " intestines-brain-axis ", to reach alleviation and treatment alcohol dependence syndrome.The unique coating technique of the present invention can extend the pot-life of probiotic active, overcome the disadvantage that the existing probiotic products pot-life is short, in addition can effectively resist due to the influence for making internal alcohol to probiotics of drinking.
Description
Technical field
The invention belongs to field of biotechnology, and in particular to multiple to a kind of probiotics for treating alcohol withdrawal syndrome
Close preparation and preparation method thereof.
Background technique
Drinking is a kind of rather long and universal living habit and social custom, but excessive drinking will cause body or essence
The damage of mind, and bring undesirable societal consequence.If the time and amount drunk reache a certain level, will lead to alcohol user can not
The drinking behavior to draw oneself up, and somzatization and withrawal symptom occur, referred to as alcohol dependence syndrome.Clinical manifestation is
Patient the symptoms such as craves for, indulges in excessive drinking strongly to alcohol.It shows as trembling after forcing abstinence from alcohol, it is out of strength, it perspires, exagger, gastrointestinal tract
Symptom and epilepsy, it is serious to show as serious clouding of consciousness, unorientation, illusion, anxious, insomnia etc..Wine
Essence, which is relied on, brings very big harm to society and family, and alcohol dependence and its relevant issues are to be only second to cardiovascular disease at present
And tumour, occupy the global public health problem of third.Every year since abstinence from alcohol and treatment abstinence syndrome are costly, to disease
People brings very huge economic loss.Therefore, this kind of disease should cause people to pay much attention to.
The drug for the treatment of alcohol withdrawal syndrome mainly has disulfiram, Acamprosate, naltrexone etc. at present, although these drugs
It is approved by the FDA in the United States in clinical use, these drugs mainly act on the reward system of excitation alcohol dependence, prevent alcohol addiction
Formation.However, using these drug therapy alcohol addictions and abstinence syndrome offer limited effectiveness, and have very big side effect, such as
Disulfiram has liver damage and Central neurotoxicity.Therefore need to develop a kind of new and effective, Small side effects, easy to use
Drug treats alcohol withdrawal syndrome.Applicants have found that enteric microorganism played in alcohol dependence is formed it is important
Effect, drinking can induce intestinal bacilli illness, intestinal wall permeability is caused to increase, to make for example short chain of some metabolites of bacterium
Fatty acid, amine and some neurotransmitters act on central nervous system directly or indirectly through " intestines-brain-axis ", and cause and rely on
Property disease, including alcohol dependence.Therefore, the present invention from intestinal microbial balance, set about by this mechanism of action, develops a kind of novel
Prebiotics probiotics compound, lead to intestinal bacilli illness for adjusting alcohol and ethanol withdrawal, and reach alleviation and treatment
Alcohol withdrawal syndrome.
Summary of the invention
The probiotics composite preparation and its preparation that the object of the present invention is to provide a kind of for treating alcohol withdrawal syndrome
Method, the probiotics composite preparation are compound probiotics, do not generate drug resistance, without any toxicity and side effects.
To achieve the above object, the technical solution adopted by the present invention is that: it is a kind of for treating the benefit of alcohol withdrawal syndrome
The preparation method of raw bacterium compound formulation, comprising the following steps:
1. clostridium butyricum, lactobacillus acidophilus, lactobacillus plantarum, Bifidobacterium are inoculated into respectively in respective optimum medium, 37
DEG C culture 24 hours, respectively take culture solution 150mL to be transferred in fermentor and expand culture, when viable bacteria concentration reaches in fermentation liquid
5×109When CFU/ml or more, stop culture, fermentation liquid is taken to be centrifuged, 4000 revs/min carry out centrifugation 20 minutes, collect bacterium
Body;
2. 1. clostridium butyricum that step is collected, lactobacillus acidophilus, lactobacillus plantarum, Bifidobacterium by weight 2 ~ 3: 1: 1.5 ~
2: 1 ~ 2 be uniformly mixed obtain probiotic composition;
3. probiotic composition is mixed with absorption carrier by weight 1 ︰ 2 ~ 3, is stirred at not higher than 10 DEG C, keep thallus thorough
It is adsorbed on absorption carrier;
4. 3. mixture that step is prepared is mixed with prebiotics by weight 1 ︰ 1.5 ~ 5, it is stirred at room temperature uniformly;
5. by 4. mixture that step is prepared, 1 ︰ 10 ~ 20 is added in coating carrier solution by volume, continues stirring 30
Minute, room temperature aeration-drying is packed to obtain the final product.
Preferably, the prebiotics are by any one or more of galactooligosaccharide (GOS), inulin, stachyose, chitosan
Composition.
Preferably, the absorption carrier is wheat bran, in cornstarch, skimmed milk power, zeolite powder, sucrose, sodium alginate
It is any one or several.
Preferably, the coating carrier be sucrose, it is any one or two kinds of in dextrin.
Preferably, the concentration of the coating carrier solution is 5 ~ 10%(mass concentration).
The beneficial effect of generation of the invention is: 1. the object of the present invention is to provide one kind for treat ethanol withdrawal comprehensive
Complex prebiotics, the probiotics preparation of simulator sickness, the drug are compound probiotics.2. currently preferred probiotics is people
The common nonpathogenic dominant bacteria of body, this kind of bacterium can be colonized in the enteron aisle of human body, and largely be proliferated, by dominant microflora,
Biological antagonist generates the effects of beneficial metabolite, directly stimulation epithelium of intestinal mucosa, improves intestine microenvironment, and lead to
It crosses " intestines-brain-axis " and acts on brain, to reach alleviation and treatment alcohol dependence syndrome.3. the present invention is using three layers unique
Coating technique, outermost layer are that carrier protective layer can be such that probiotics is not killed in vivo and in vitro by harmful substance, can especially protect benefit
Raw bacterium enters in stomach is not destroyed by gastric acid and protease, and then reaches and play a role in enteron aisle;In the intestine, second layer prebiotics layer
Suitable living environment is provided in enteron aisle for probiotics, probiotics can largely rise in value and play a role.4. of the invention unique
Coating technique can extend pot-life of probiotic active, overcome the disadvantage that the existing probiotic products pot-life is short, in addition
It can effectively resist due to the influence for making internal alcohol to probiotics of drinking.
Detailed description of the invention
Fig. 1 is different group alcohol dependence rat withdrawal syndrome appraisal results in test one;
Fig. 2 is different group alcohol dependence mouse withdrawal syndrome appraisal results in test two.
Specific embodiment
The present invention will be further described combined with specific embodiments below, and but the scope of the present invention is not limited thereto.This
Clostridium butyricum used, lactobacillus acidophilus, lactobacillus plantarum, Bifidobacterium are conventional commercially available strain in invention.
Embodiment 1
It is a kind of for treating the preparation method of the probiotics composite preparation of alcohol withdrawal syndrome, comprising the following steps:
1. clostridium butyricum, lactobacillus acidophilus, lactobacillus plantarum, Bifidobacterium are inoculated into respectively in respective optimum medium, 37
DEG C culture 24 hours, respectively take culture solution 150mL to be transferred in fermentor and expand culture, when viable bacteria concentration reaches in fermentation liquid
5×109When CFU/ml or more, stop culture, fermentation liquid is taken to be centrifuged, 4000 revs/min carry out centrifugation 20 minutes, collect bacterium
Body;
2. 1. clostridium butyricum that step is collected, lactobacillus acidophilus, lactobacillus plantarum, Bifidobacterium are by weight 2: 1: 1.5: 2
It is uniformly mixed and obtains probiotic composition;
3. probiotic composition is mixed with absorption carrier by weight 1 ︰ 3, in 10 DEG C of environment, stirred by 75 revs/min of speed
It mixes 25 minutes, is adsorbed onto thallus thoroughly on carrier;Absorption carrier is made of the raw material of following parts by weight: 50 parts of wheat bran takes off
200 parts of rouge milk powder, 30 parts of sucrose, 20 parts of sodium alginate;
4. 3. mixture that step is prepared is mixed with prebiotics by weight 1 ︰ 3.33, at room temperature, by 50 revs/min
Speed stir 30 minutes;Prebiotics are made of the raw material of following portions by weight: 30 parts of galactooligosaccharide (GOS), inulin 15
Part, 20 parts of stachyose;
5. by 4. mixture that step is prepared, 1 ︰ 20 is added to coating carrier solution (in coating carrier solution by volume
Dextrin containing 5wt% and 2wt% sucrose) in, continue stirring 30 minutes, room temperature aeration-drying, packaging by 100 revs/min of speed
To obtain the final product.
Embodiment 2
It is a kind of for treating the preparation method of the probiotics composite preparation of alcohol withdrawal syndrome, comprising the following steps:
1. clostridium butyricum, lactobacillus acidophilus, lactobacillus plantarum, Bifidobacterium are inoculated into respectively in respective optimum medium, 37
DEG C culture 24 hours, respectively take culture solution 150mL to be transferred in fermentor and expand culture, when viable bacteria concentration reaches in fermentation liquid
5×109When CFU/ml or more, stop culture, fermentation liquid is taken to be centrifuged, 4000 revs/min carry out centrifugation 20 minutes, collect bacterium
Body;
2. 1. clostridium butyricum that step is collected, lactobacillus acidophilus, lactobacillus plantarum, Bifidobacterium are mixed by weight 3: 1: 2: 1
It closes and uniformly obtains probiotic composition;
3. probiotic composition is mixed with absorption carrier by weight 1 ︰ 2.1, in 10 DEG C of environment, by 175 revs/min of speed
Stirring 25 minutes, is adsorbed onto thallus thoroughly on carrier;Absorption carrier is made of the raw material of following parts by weight: wheat bran 150
Part, 100 parts of skimmed milk power, 20 parts of sucrose, 40 parts of sodium alginate;
4. 3. mixture that step is prepared is mixed with prebiotics by weight 1 ︰ 1.6, at room temperature, by 100 revs/min
Speed stir 20 minutes;Prebiotics are made of the raw material of following portions by weight: 20 parts of galactooligosaccharide (GOS), inulin 45
Part, 10 parts of stachyose, 20 parts of chitosan;
5. by 4. mixture that step is prepared, 1 ︰ 10 is added to coating carrier solution (in coating carrier solution by volume
Dextrin containing 6wt% and 3wt% sucrose) in, continue stirring 30 minutes, room temperature aeration-drying, packaging by 100 revs/min of speed
To obtain the final product.
Embodiment 3
Be except embodiment 3 and the difference of embodiment 1, step 2. in clostridium butyricum, lactobacillus acidophilus, lactobacillus plantarum, double
The weight ratio of discrimination bacillus thallus is 1: 1: 1: 1.
Influence (test one) of the drug of the present invention to alcohol addiction rat alcohol withdrawal syndrome
1. experimental animal: 6 week old Sprague Dawley (SD) rat 60, original body mass (190-201g) are purchased from Beijing connection
Close benefit China, number of animals SCXK (Jing) 2016-0011 (No. 11400700259454).
The foundation of alcohol dependence model: it is divided into 2 groups according to completely random method, control group (20) and experimental group (40).
Animal feeding is tested after 1 week again in clean animal house, 21 ± 2 DEG C of temperature and humidity 50 ± 5%, adaptive feeding.Experiment periods
Between each group rat be freely eaten, feed is SPF grades, is pulled together Science and Technology Ltd. purchased from Beijing Australia of section.It presses within experimental group first week
1%, 2%, 3%, 4%, 5%, 6% incremental mode (is incremented by 1% daily, also opens 6%) freely to drink to rat from second week within 7th
Beginning experimental group gives 6%(v/v) alcohol water blend freely drink for 24 hours 6 weeks, it is daily 9 points prepare simultaneously replace alcohol water blend;It is right
According to giving drinking purpose of tap water always.From the 7th week, experimental group removes alcohol, is then divided into two groups, and one group is to give up group (20
Only), tap water is individually given, another group, to give up intervention group (20), is given tap water and add 1 probiotics of the embodiment of the present invention multiple
Preparation is closed, dosage is 5g/ days/, successive administration 10 days.
Alcohol withdrawal syndrome scoring: alcohol withdrawal syndrome (ethanol withdrawal syndrome, EWS) is commented
Divide referring to improved Erden etc. (1999) method, is given up respectively at assessment in ethanol withdrawal the 1st day, the 3rd day, the 5th day and the 9th day
The abstinence syndrome of group rat, predominantly detects that stereotypic behavior, challenges, tail is tetanic, abnormal posture and listens source property epilepsy etc. and guards against
A situation arises for disconnected symptom, and for the accuracy for guaranteeing test result, all tests select to carry out in morning 9:00, and use
Double blind experiment, detailed standards of grading bibliography (B. F. ERDEN, S. OZDEMIRCI, G. YILDIRAN, T.
UTKAN, N. GACAR AND G. ULAK, 1999, Dextromethorphan Attenuates Ethanol
Withdrawal Syndrome in Rats, Pharmacology Biochemistry and Behavior, 62(3):
537-541).
Statistical analysis: all data are indicated with x ± S, for statistical analysis using 19.0 software of SPSS, two groups of ratios
It is examined compared with using t;More comparison among groups are analyzed using One-Way ANOVA.
Experimental result
5.1 give up appraisal result: this research use freely drinks 6% alcohol and establishes Rat Alcohol Dependent Model, is examined by double blind
Survey method determines ethanol withdrawal syndrome index, drinks group as the result is shown compared with the control group, and ethanol withdrawal scoring has significance difference
Different (Fig. 1).Experimental group alcohol dependence after giving up activity increase, it is highest give up scoring giving up 3 days occur.With control group
It compares, after giving up 9 days, gives up overall score without significant difference.And at first three after use 1 probiotics composite preparation of the embodiment of the present invention
There was no significant difference with intervention group is given up for its ethanol withdrawal group, but aobvious after the 5th day, giving up group and giving up intervention group difference
It writes, and has reached within 5 days control group level (Fig. 1) after giving up intervention, show 1 probiotics composite preparation of embodiment to alcohol dependence
Syndrome has good curative effect.
It listens source property epilepsy result: being stimulated 1 minute with 100 decibel sounds, the results are shown in Table 1.Alcohol dependence gives up group within first day
The disease incidence of source property epilepsy is listened to reach 80%, and control group is only 10%, these results show that 6% alcohol long-term drinking can make greatly
Mouse generates body and relies on.But it gives up group giving up within first day and gives up intervention group there was no significant difference, since third day, use
The incidence for listening source property epilepsy can be substantially reduced after pharmaceutical intervention of the present invention, drop to 15% to the 5th Tianting source property epilepsy incidence,
And it is 65% that the rat that drug is not used, which listens source property epilepsy incidence,.As it can be seen that 1 probiotics composite preparation of the embodiment of the present invention can be big
Big reduction alcohol dependence rat listens source property epilepsy incidence.
1. tins of source property epilepsy incidences of table
。
Influence (test two) of the drug of the present invention to Chronic Alcohol habituation mouse alcohol withdrawal syndrome
1. experimental animal: 6 week old BALB/c mouses 60, original body mass (19-25g) are purchased from Beijing Uniliver, number of animals
SCXK (Jing) 2017-0014 (No. 11000830258653)。
The foundation of alcohol dependence model: it is divided into 2 groups according to completely random method, control group (15) and experimental group (45).
Animal feeding is tested after 1 week again in clean animal house, 21 ± 2 DEG C of temperature and humidity 50 ± 5%, adaptive feeding.Experiment periods
Between each group mouse be freely eaten, feed is SPF grades, is pulled together Science and Technology Ltd. purchased from Beijing Australia of section.It presses within experimental group first week
1%, 2%, 3%, 4%, 5%, 6% mode being incremented by (is incremented by 1%, the 7th is also 6%) freely to drink to mouse, later continuously certainly daily
By drinking aqueous solution 6 weeks (daily 9 points of preparations simultaneously replace alcohol water blend) containing low-concentration ethanol (6%), alcohol dependence animal is established
Model.Drinking purpose of tap water is given in control.From the 7th week, experimental group removes alcohol, is then divided into three groups, and one group is to give up group (15
Only), tap water is individually given, second group is to give up intervention group I(15 only), it gives tap water and adds 2 probiotics of the embodiment of the present invention
Compound formulation, dosage are 5g/ days/, successive administration 10 days;Third group is to give up intervention group II(15 only), it gives originally
3 probiotics composite preparation of water and the embodiment of the present invention.
Alcohol withdrawal syndrome scoring: alcohol withdrawal syndrome (ethanol withdrawal syndrome, EWS) is commented
Divide referring to improved Erden etc. (1999) method, is given up respectively at assessment in ethanol withdrawal the 1st day, the 3rd day, the 5th day and the 9th day
The abstinence syndrome of group mouse, predominantly detects that stereotypic behavior, challenges, tail is tetanic, abnormal posture and listens source property epilepsy etc. and guards against
A situation arises for disconnected symptom, and for the accuracy for guaranteeing test result, all tests select to carry out in morning 9:00, and use
Double blind experiment, detailed standards of grading bibliography (B. F. ERDEN, S. OZDEMIRCI, G. YILDIRAN, T.
UTKAN, N. GACAR AND G. ULAK, 1999, Dextromethorphan Attenuates Ethanol
Withdrawal Syndrome in Rats, Pharmacology Biochemistry and Behavior, 62(3):
537-541).
Statistical analysis: all data are indicated with x ± S, for statistical analysis using 19.0 software of SPSS, two groups of ratios
It is examined compared with using t;More comparison among groups are analyzed using One-Way ANOVA.
Experimental result
5.1 give up appraisal result: this research use freely drinks 6% alcohol and establishes alcohol dependence mouse model, is examined by double blind
Survey method determines ethanol withdrawal syndrome index, drinks group as the result is shown compared with the control group, and ethanol withdrawal scoring has significance difference
Different (Fig. 2).Experimental group alcohol dependence after giving up activity increase, it is highest give up scoring giving up 3 days occur.With control group
It compares, after giving up 9 days, gives up overall score without significant difference.And in first three days ethanol withdrawal group and ring after use drug of the present invention
There was no significant difference for disconnected intervention group, but after the 5th day, gives up group and give up intervention group significant difference, and gives up 5 after intervention
It has reached control group level (Fig. 2), shows that probiotics prebiotic preparation of the present invention has good treatment to alcohol dependence syndrome
Effect;While being compared with intervention group II is given up, in giving up intervention group II, although having used 1 probiotics complexing agent of embodiment,
Effect is poor, its withrawal symptom of entire experiment periods is similar with group is given up, but there were significant differences with intervention group I is given up, and illustrates difference
Clostridium butyricum, lactobacillus acidophilus, lactobacillus plantarum, Bifidobacterium ratio have the effect of probiotics composite preparation of the invention
There is significant impact.
It listens source property epilepsy result: being stimulated 1 minute with 100 decibel sounds, the results are shown in Table 2.Alcohol dependence gives up group within first day
The disease incidence of source property epilepsy is listened to reach 86.67%, and control group is only 13.34%, these results show that 6% alcohol long-term drinking
Rat can be made to generate body to rely on.But it gives up group giving up within first day and gives up intervention group there was no significant difference, opened from third day
Begin, using the incidence for listening source property epilepsy can be substantially reduced after pharmaceutical intervention of the present invention, to the 5th Tianting source property epilepsy incidence
20% is dropped to, and it is 73.33% that the rat that drug is not used, which listens source property epilepsy incidence,.Simultaneously from the result for giving up intervention group II
From the point of view of, alcohol dependence symptom object is significantly improved using probiotics complexing agent, it is seen then that the compound system of 2 probiotics of the embodiment of the present invention
Agent can substantially reduce alcohol dependence rat and listen source property epilepsy incidence.
2. tins of source property epilepsy incidences of table
。
Claims (6)
1. a kind of for treating the preparation method of the probiotics composite preparation of alcohol withdrawal syndrome, it is characterised in that including following
Step:
1. clostridium butyricum, lactobacillus acidophilus, lactobacillus plantarum, Bifidobacterium are inoculated into respectively in respective optimum medium, 37
DEG C culture 24 ~ 48 hours, take culture solution to be transferred in fermentor and expand culture, when in fermentation liquid viable bacteria concentration reach 5 ×
109When CFU/ml or more, stop culture, fermentation liquid is taken to be centrifuged, collects thallus;
2. 1. clostridium butyricum that step is collected, lactobacillus acidophilus, lactobacillus plantarum, Bifidobacterium by weight 2 ~ 3: 1: 1.5 ~
2: 1 ~ 2 be uniformly mixed obtain probiotic composition;
3. probiotic composition is mixed with absorption carrier by weight 1 ︰ 2 ~ 3, stirs, thallus is made thoroughly to be adsorbed onto absorption carrier
On;
4. 3. mixture that step is prepared is mixed with prebiotics by weight 1 ︰ 1.5 ~ 5, it is stirred at room temperature uniformly;
5. by 4. mixture that step is prepared, 1 ︰ 10 ~ 20 is added in coating carrier solution by volume, is stirred evenly,
Room temperature aeration-drying, is packed to obtain the final product.
2. as described in claim 1 for treating the preparation method of the probiotics composite preparation of alcohol withdrawal syndrome, feature
It is that the prebiotics are made of any one or more of galactooligosaccharide (GOS), inulin, stachyose, chitosan.
3. as described in claim 1 for treating the preparation method of the probiotics composite preparation of alcohol withdrawal syndrome, feature
It is that the absorption carrier is any one of wheat bran, cornstarch, skimmed milk power, zeolite powder, sucrose, sodium alginate or several
Kind.
4. as described in claim 1 for treating the preparation method of the probiotics composite preparation of alcohol withdrawal syndrome, feature
Be: the coating carrier is sucrose, any one or two kinds of in dextrin.
5. as described in claim 1 for treating the preparation method of the probiotics composite preparation of alcohol withdrawal syndrome, feature
Be: the concentration of the coating carrier solution is 5 ~ 10wt%.
6. the probiotics composite preparation for being used to treat alcohol withdrawal syndrome being prepared such as claim 1-5 either method.
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