CN110339218A - A kind of probiotic composition and its application in improvement is sleep disordered - Google Patents
A kind of probiotic composition and its application in improvement is sleep disordered Download PDFInfo
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Classifications
-
- 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
-
- 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
-
- 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
-
- 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
- A61P25/20—Hypnotics; Sedatives
Abstract
This application discloses a kind of probiotic composition, including Bacillus acidi lactici, it is difficult to understand in bacillus and Rothia.The application can be by giving probiotic composition, it is sleep disordered to adjust Patients With Head Trauma to adjust intestinal flora, specify meaning of the intestinal flora in terms of the function and behavior for adjusting brain control, prevention and treatment is sleep disordered to provide some theoretical foundations to be adjusted by intestinal microecology, for instructing sleep disordered prevention and treatment after clinical craniocerebral trauma.
Description
Technical field
This application involves probiotics technical field, in particular to a kind of probiotic composition is improving answering in sleep disordered
With.
Background technique
Sleep depends on the complicated interaction of Sleep-Wake balance and circadian rhythms in human body.These rhythm and pace of moving things tables
Up to largely by be located at hypothalamus hypothalamus suprachiasmatic nucleus regulate and control, pass through related environmental cues such as illumination, activity, drink
The regulation such as food is at daily nearly 24 circadian rhythm 24.The clock gene for regulating and controlling this biological rhythm molecular mechanism passes through adjust automatically
Feedback control loop adjusting is adjusted.Key gene of the Bmal1 and CLOCK gene as loop forms a heterodimer and adjusts
The expression of clock-controlled genes, therefore drive the output of hypothalamus suprachiasmatic nucleus biological rhythm.BMAL1/CLOCK compound can also
The expression of Period (Per) and Cryptochrome (Cry) gene is activated, and product Pers and Crys are the passes of feedback loop
Key gene can inhibit the expression of BMAL1/CLOCK compound.In other one stable loop, Rev-Erb α and orphan
Acceptor gene adjusts rhythmic expression by major loop.Different with other Pers albumen, Per2 can direct and Rev-Erb α
Interaction, adjusts the expression of Bmal1.
Hypothalamus suprachiasmatic nucleus transmits biological rhythm to peripheral tissues by the mechanism of nerve and hormone, keeps whole body
Consistent biological rhythm.Since the output of the internal rhythm and pace of moving things is generated by hypothalamus suprachiasmatic nucleus, so as melatonin and skin
The endocrine parameters such as matter alcohol can be used to primary biochemical clock in marked body.Studies have found that in schizophreniac, interior life
Biological rhythm change can be marked with melatonin, corticosteroid hormone etc..Although researcher is about relative to sleep disordered next
Say that the rhythm and pace of moving things expression of melatonin is different, but its research shows the sleep-wake cycle rhythm and pace of moving things in schizophreniac
There are apparent inconsistencies with the expression of the melatonin rhythm and pace of moving things.But it is sleep disordered for patients with sevious craniocerebral injury whether with maincenter
There is connection in biological rhythm and detailed molecular mechanism there is no research at present.
It is very few for the understanding of sleep disordered caused by wound and emotional change mechanism at present, for how effectively to handle phase
Pass problem lacks effective method.But the appearance that more and more patients with sevious craniocerebral injury are sleep disordered, moreover, craniocerebral trauma
Caused sleep disordered form and other kinds of sleep disordered there are notable differences.
Summary of the invention
A kind of probiotic composition of being designed to provide of the application is improving the application in sleep disordered, current to solve
Shortage is effectively improved the sleep disordered problem of patients with sevious craniocerebral injury.
In a first aspect, according to an embodiment of the present application, providing a kind of probiotic composition, comprising: Bacillus acidi lactici, in difficult to understand
Bacillus and Rothia.
Further, the Bacillus acidi lactici, it is described it is difficult to understand in the mass ratio of bacillus and the Rothia be 1:(1-1.3):
(1.2-1.5)。
Second aspect, according to an embodiment of the present application, providing probiotic composition is improving the application in sleep disordered.
It is disorderly in improvement patients with sevious craniocerebral injury sleep to provide probiotic composition according to an embodiment of the present application for the third aspect
Application in unrest.
From the above technical scheme, the embodiment of the present application provides a kind of probiotic composition, including Bacillus acidi lactici, in difficult to understand
Bacillus and Rothia.The application can adjust intestinal flora by giving probiotic composition to adjust Patients With Head Trauma
It is sleep disordered, meaning of the intestinal flora in terms of the function and behavior for adjusting brain control is specified, to adjust by intestinal microecology
Prevent and treat it is sleep disordered some theoretical foundations are provided, for instructing sleep disordered prevention and treatment after clinical craniocerebral trauma.
Detailed description of the invention
In order to illustrate the technical solutions in the embodiments of the present application or in the prior art more clearly, below will be to institute in embodiment
Attached drawing to be used is needed to be briefly described, it should be apparent that, the accompanying drawings in the following description is only some implementations of the application
Example, for those of ordinary skill in the art, without creative efforts, can also obtain according to these attached drawings
Obtain other attached drawings.
Fig. 1 is the Technology Roadmap shown in the application.
Specific embodiment
For Patients with Cerebral Trauma, over the course for the treatment of, gastrointestinal dysfunction incidence is very high.Gastrointestinal function not only by
Brain regulation, can also react on brain, and brain-gut axis is the bridge of the two interaction.Brain-gut axis is brain and gastrointestinal tract phase
The bidirectional modulation axis of interaction comprising central nervous system (CNS), autonomic nerves system (ANS), nervous system in enteron aisle
(ENS), the structures such as hpa axis, functions are mutually coordinated.Gastrointestinal tract is uniquely dominated jointly by CNS, ANS, ENS in body
Organ, that is, function of feeling also has motor function, referred to as " reactor of mood ".
There is a variety of normal microbiologic populations in healthy human body enteron aisle, and there is symbiosis by they and host, altogether
It is same to maintain the physiological equilibrium of host.Under normal circumstances, about 10 are colonized in adult enteron aisle14A microorganism, be averaged everyone intestines
The total number of bacteria colonized in road helps meter, and there are about 1000 kinds.Therefore, these are colonized in interacting between the microorganism of enteron aisle and enteron aisle
It is set to take part in the functional response of brain intestines axis.In recent years, intestinal flora institute's role in brain intestines axis was gradually realized
And become research hotspot；Also, one relates to central nervous system, neuroendocrine and nerve immunity system, autonomic nerve
Sympathetic nerve and parasympathetic nerve in system, the novel concept of enteric nervous system and enteric microorganism, brain-intestines-microorganism axis
It is suggested.It is existing research shows that the effect of brain and intestinal flora is also two-way.
Intestinal microecology is also studied now as the important adjuster of function of intestinal canal is adjusted and shows to participate in body rhythm
Expression.Some researches show that enteric microorganism signals to have key in terms of maintaining body enteron aisle built-in function and the host organism rhythm and pace of moving things
Property effect.
Intestinal flora be functionally it is diversified, participate in body carbohydrate metabolism, fibr tissue degenerate,
The maintenance etc. of immune system.The change and behavior of enteric microorganism ingredient and changing for cognition aspect have certain connection, and one
The intestinal microflora of a health is essential for maintaining brain-intestines-microorganism axis of health.Adjusting brain-gut axis
In stable potential factor, the metabolite of microorganism may be important medium.
In conclusion the application intends, clear Patients With Head Trauma is sleep disordered and biological rhythm expression whether there is relationship,
And the relationship of biological rhythm expression disorder and intestinal disorder；Whether further clarify can be by adjusting intestinal flora to adjust
Patients With Head Trauma is sleep disordered, with meaning of the clear intestinal flora in terms of the function and behavior for adjusting brain control, while can
Further to increase clinical application.It is final to use to provide some theoretical foundations by the way that intestinal microecology adjusting prevention and treatment is sleep disordered
The sleep disordered prevention and treatment after instructing clinical craniocerebral trauma.
The application has done following experiment:
1. patient selection
30 patients of quasi- selection, 10 sleep disordered persons of after craniocerebral injury, 10 normal persons of after craniocerebral injuries sleep, 10
Normal person is as a control group.Gender is unlimited, and the age is unlimited.Patient is -3 months January after wound.
1.1 patient's inclusion criterias
1.1.1 the Minimal Head Injury patient loss of consciousness < 30 minute and (or) of short duration retrograde amnesia < 24 hour, GCS
Scoring is at 13-15 points.
1.1.2 moving related craniocerebral injury causes cerebral concussion with altered mental status.
1.1.3 medium-sized patients with sevious craniocerebral injury GCS scoring is not more than 12 points, and retrograde amnesia is more than 24 hours.
1.1.4 cerebral CT prompt Marshal CT is classified as I/II grade.
1.1.5 it is selected in research object and does not take (or use) antibiotic or Tiny ecosystem adjusting in two months before sampling
Agent.
1.1.6 agreeing to signature informed consent form
1.2 exclusion criterias:
1.2.1 meet patients with sevious craniocerebral injury, without sleep disordered presence.
1.2.2 levels of thyroid hormone in craniocerebral trauma patients.
1.2.3 signature informed consent form person is disagreed
2. diagnostic criteria:
Pittsburg Sleep Quality Index scale (Pittsburgh Sleep Quality is applied to patient in group is met
Index, PSQI) tentatively evaluated and tested.
It carries out leading sleep detection (polysomnography, PSG) to patient in group is met more
3. specific experiment content (referring to Fig. 1):
First part
Pass through the sleep disordered persons of different time points after craniocerebral injury, after craniocerebral injury such as at 8 points, 12 points, 16 points, 20 points of detection
Sleep normal person, normal population clock gene expression variation, to understand the sleep disordered patient's molecular biosciences of after craniocerebral injury
Whether clock changes and the changing rule of biological rhythm.
The sleep disordered person of after craniocerebral injury, the normal person of after craniocerebral injury sleep and normal control population are detected by RT-PCR
Biological species gene C lock, Per2, the Bmal1mRNA different time points in the Oral Mucosal Cells that fall off express difference.
Detect the sleep disordered person of after craniocerebral injury by Western-blot, after craniocerebral injury sleep normal person with it is normally right
Difference is expressed according to different time points in crowd's biological species gene C lock, Per2, Bmal1 albumen Oral Mucosal Cells.
Pass through the difference of detection monocyte clock gene expression.
Pass through the sleep disordered person of detection after craniocerebral injury, the normal person of after craniocerebral injury sleep and normal control population's venous blood
Middle biological species gene C lock, Per2, Bmal1mRNA expression whether there is difference.
Second part
We are using the sleep disordered person of full group gene sequencing preliminary analysis after craniocerebral injury, the normal person of after craniocerebral injury sleep
With the diversity of normal population intestinal microflora.
By the way that abundance is constituted and is distributed to the sleep disordered Intestinal Mucosal Injury in Patients Undergoing Tiny ecosystem of faecal microbiota characteristic analysis
By expressing dominant microflora the analysis of albumen, dominant microflora albumen and life are further appreciated that using biological software
Object clock gene Clock, Per2, Bmal1 expression correlation.
Part III
According to the analysis of patient's excrement high-flux sequence as a result, giving after craniocerebral injury sleep disordered patient's probiotic oral,
Patient sleeps' variation is observed, again Bacterial community variation in high-throughput repetition measurement excrement.
4. experimental result:
Clock gene Clock, Bmal1 and Per2mRNA are expressed in Oral Mucosal Cells and monocyte 12:
00, peak period is presented, and disappear in sleep disordered group of three kinds of gene expression rhythmicity, normal three kinds of genes of group of sleeping have section
The expression of rule property.In sleep disordered group of Oral Mucosal Cells of patients with sevious craniocerebral injury and monocyte the expression of Clock mRNA compared with
The normal group expression of sleep is substantially reduced, and difference has statistical significance (p=0.0003, Oral Mucosal Cells；P < 0.0001, it is single
Nucleus).At sleep disordered group and in normal group of sleep, in Bmal1mRNA either Oral Mucosal Cells or monocyte
Expression counts no difference of science of statistics (p=0.1187, Oral Mucosal Cells without significant difference, statistics；P=0.2094, monokaryon are thin
Born of the same parents).At sleep disordered group and in normal group of sleep Per2mRNA expression either in Oral Mucosal Cells or monocyte
12:00,18:00, which exist, to be substantially reduced, difference statistically significant (p=0.0102, Oral Mucosal Cells when 12:00；P=
0.0006, monocyte；The p=0.0004 in 18:00, Oral Mucosal Cells；P=0.0015, monocyte).But 24:
Without significant difference, difference is not statistically significant for Per2mRNA expression in Oral Mucosal Cells and monocyte by two groups of patients when 00
(p=0.7838, Oral Mucosal Cells；P=0.2808, monocyte).
As shown in table 1, it according to the sleep disordered patient of after craniocerebral injury and sleep normal patient analysis of intestinal microflora, filters out
13 kinds of intestinal flora, wherein craniocerebral injury is sleep disordered compared with normal group of sleep, Bacillus acidi lactici (Lactobacillus), Austria
In bacillus (Oribacterium), Rothia (Rothia), actinomyces (Actinomyces), chain plant category
(Streptophyta), the quantity such as TM7-3 bacterium, Serratieae (Serratia) occur in various degree reduce, Odoribacter and
Thermophilic gallbladder Pseudomonas (Bilophila) increases.
Table 1
5. conclusion
There is unconventionality expression, and the rhythm and pace of moving things in patients with sevious craniocerebral injury sleep disordered group of clock gene Per2, Bmal1, Clock
Property disappear, these discoveries show that craniocerebral injury merges sleep disordered patient's molecular biosciences clock and destroyed, further for us
The correlative study for understanding sleep disordered rear biological rhythm disorder is significant.
Patients with sevious craniocerebral injury is sleep disordered related with intestinal flora disorder, may be done due to the reduction of beneficial bacterium
Disturb the harmful bacteria of biological rhythm.
Based on the above experimental result and analysis, this application provides a kind of probiotic compositions, comprising: Bacillus acidi lactici, it is difficult to understand
In bacillus and Rothia.
Further, the Bacillus acidi lactici, it is described it is difficult to understand in the mass ratio of bacillus and the Rothia be 1:(1-1.3):
(1.2-1.5)。
Specifically, Bacillus acidi lactici, bacillus and Roche bacterium in Austria are determined according to sleep disordered Intestinal Mucosal Injury in Patients Undergoing Flora Disturbance degree
The specific ratio and dosage belonged to.According to intestinal flora 16sDNA analysis of intestinal microflora, it is found that composite flora analysis result is obviously excellent
In single analysis of intestinal microflora result.
The embodiment of the present application, which provides probiotic composition, is improving the application in sleep disordered.
The embodiment of the present application provides application of the probiotic composition in improvement patients with sevious craniocerebral injury is sleep disordered.
From the above technical scheme, the embodiment of the present application provides a kind of probiotic composition, including Bacillus acidi lactici, in difficult to understand
Bacillus and Rothia.The application can adjust intestinal flora by giving probiotic composition to adjust Patients With Head Trauma
It is sleep disordered, meaning of the intestinal flora in terms of the function and behavior for adjusting brain control is specified, to adjust by intestinal microecology
Prevent and treat it is sleep disordered some theoretical foundations are provided, for instructing sleep disordered prevention and treatment after clinical craniocerebral trauma.
Those skilled in the art will readily occur to its of the application after considering specification and practicing application disclosed herein
Its embodiment.This application is intended to cover any variations, uses, or adaptations of the application, these modifications, purposes or
Person's adaptive change follows the general principle of the application and including the undocumented common knowledge in the art of the application
Or conventional techniques.The description and examples are only to be considered as illustrative, and the true scope and spirit of the application are by following
Claim is pointed out.
It should be understood that the application is not limited to the precise structure that has been described above and shown in the drawings, and
And various modifications and changes may be made without departing from the scope thereof.Scope of the present application is only limited by the accompanying claims.
Claims (4)
1. a kind of probiotic composition characterized by comprising Bacillus acidi lactici, it is difficult to understand in bacillus and Rothia.
2. probiotic composition according to claim 1, which is characterized in that the Bacillus acidi lactici, it is described it is difficult to understand in bacillus and
The mass ratio of the Rothia is 1:(1-1.3): (1.2-1.5).
3. probiotic composition described in claim 1 is improving the application in sleep disordered.
4. application of the probiotic composition described in claim 1 in improvement patients with sevious craniocerebral injury is sleep disordered.
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| CN201910749684.8A CN110339218A (en) | 2019-08-14 | 2019-08-14 | A kind of probiotic composition and its application in improvement is sleep disordered |
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| CN111329850A (en) * | 2020-03-05 | 2020-06-26 | 夏鹤春 | Amino acid composition and application thereof in improving sleep disorder |
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