CN113181342B

CN113181342B - Depression treating bacillus coagulans preparation

Info

Publication number: CN113181342B
Application number: CN202110545424.6A
Authority: CN
Inventors: 李宝恒; 李倩; 舒威
Original assignee: Tianjin Baoheng Biotechnology Co ltd
Current assignee: Tianjin Baoheng Biotechnology Co ltd
Priority date: 2021-05-19
Filing date: 2021-05-19
Publication date: 2022-11-08
Anticipated expiration: 2041-05-19
Also published as: CN113181342A

Abstract

The invention provides a pharmaceutical composition for treating depression, which comprises bacillus coagulans and a nutritional polypeptide; the pharmaceutical composition can up-regulate the level of the brain-derived neurotrophic factor and improve the depressive symptoms of animals in depression models. The pharmaceutical composition can be used as an effective candidate therapeutic drug for clinical depression treatment, and has potential drug development value.

Description

Depression treating bacillus coagulans preparation

The technical field is as follows:

the invention relates to application of bacillus coagulans and polypeptide in preparation of preparations for preventing or treating depression, in particular to application of bacillus coagulans and anti-depression polypeptide in reduction of depression symptoms.

Background art:

depression is the most common depressive disorder, with significant and persistent mood swings as the primary clinical feature, the major type of mood disorder. The low mood is not matched with the situation in clinic, the depression of the mood can be from sultriness to sadness, and the self-declining depression and even the pessimism are taken away, and suicide attempts or behaviors can be caused; even the occurrence of stupor; in some cases, anxiety and motility were evident; in severe cases, psychotic symptoms such as hallucinations and delusions may occur. Each episode lasts at least 2 weeks or more, long or even years, and in most cases, the episodes tend to be recurrent, with most episodes being remitting, and some remaining symptoms or becoming chronic.

At present, in a modern society developing at a high speed, under the condition of noisy and busy complexion, as the life rhythm is accelerated, the living pressure of people is increased, people suffering from sleep disorder, anxiety and depression tend to be gradually younger, depression in young people also has a gradually increased incidence rate, and the suicide is caused to be high due to severe depression. Data from the world health organization shows that approximately 80 million people die of suicide worldwide each year. This is a serious and painful topic. Suicide behavior has a tremendous and profound impact on personal health, family well-being, or social development.

In recent years, the number of people suffering from mental diseases in China is increasing year by year, and the prevalence rate of depression also shows a rising trend. The major causes of the huge working pressure of life are major moderate and major depression, and the ideal clinical curative effect can not be achieved by the simple psychotherapy. Therefore, clinical treatment is necessary to patients for comfort, dispersion and guidance, and drug control is also a major direction of current depression treatment, the current main antidepressants mainly comprise 5-hydroxytryptamine reuptake inhibitors, 5-hydroxytryptamine and norepinephrine reuptake inhibitors, monoamine oxidase inhibitors are eliminated due to serious adverse reactions, and the traditional tricyclic and tetracyclic drugs are rarely applied due to the serious adverse reactions. Even these drugs have many drawbacks such as high toxic and side effects and addiction, and cause serious health problems in the human body while treating mental diseases.

In recent years, researches show that the bacillus coagulans can generate short-chain fatty acid components such as acetic acid, propionic acid, butyric acid and the like, can inhibit the expression of peripheral TNF-alpha, hippocampal IFN-Y and TNF-alpha, improve negative emotions such as anxiety, depression and the like of a human body, improve the secretion of BNDF (brain-derived neural factor), and effectively relieve the negative emotions of patients. But it is difficult to achieve the same effect as conventional antidepressants using probiotic preparations alone.

Therefore, the development of drugs that can effectively treat depression, are safe and free of any toxic and side effects, is still in urgent clinical need.

Disclosure of Invention

The inventor finds that the short peptide can effectively treat depression and reduce depression symptoms by combining the short peptide with bacillus coagulans; in addition, the animal model research shows that the combination of the invention can effectively up-regulate the expression level of Brain Derived Neurotrophic Factor (BDNF). Most importantly, the bacillus coagulans preparation is safe, free of toxic and side effects and great in clinical application potential.

The polypeptide sequence of the invention is shown as SEQ ID NO:1, the BDNF expression agonist is used in combination with bacillus coagulans, can obviously improve the BDNF expression level and obviously improve depression symptoms.

Accordingly, the present invention provides a bacillus coagulans preparation for treating depression, the preparation comprising bacillus coagulans and SEQ ID NO: 1. The nutrient polypeptide can be chemically synthesized by a solid phase synthesis method, and can also be prepared by constructing recombinant cell engineering bacteria to express and ferment.

Preferably, the bacillus coagulans of the present invention is bacillus coagulans BC30.

Furthermore, the invention takes the effective dose of the bacillus coagulans and the nutritional polypeptide as main active ingredients, and prepares any viable bacteria dosage form suitable for use according to a certain preparation process, such as tablets, capsules, granules, powder, liquid preparations and powder.

Furthermore, the content of the bacillus coagulans in the live bacterial preparation is 1 multiplied by 10 when the preparation is a solid preparation ⁶ CFU/g or more, preferably 1X 10 ⁷ CFU/g; when the preparation is liquid, its content is 1 × 10 ⁵ CFU/ml or more, preferably 1X 10 ⁶ CFU/ml。

Further, in the live bacterial preparation of the present invention, SEQ ID NO:1, when the preparation is a solid preparation, the content of the nutritional polypeptide is 10-50mg/g, preferably 20mg/g or 40mg/g; when the preparation is a liquid preparation, the content is 1-5mg/ml, preferably 2mg/ml or 4mg/ml.

The polypeptide has a brand-new sequence, can remarkably increase the BDNF content in the brain tissue of a chronic unpredictable stress model rat by combining the polypeptide with bacillus coagulans, improves the depression symptoms of acute and chronic depression model animals, and can be used as an effective candidate treatment method for clinical depression.

Detailed Description

The following examples further illustrate the present invention but should not be construed as limiting the invention and modifications or alterations to the methods, procedures and conditions of the present invention may be made without departing from the spirit and substance of the invention.

Example 1: experiment for influence of BDNF content in brain tissue of chronic unpredictable stress model rat

The nutritional polypeptide is chemically synthesized by a solid phase synthesis method in a laboratory, and the sequence of the nutritional polypeptide is verified.

SD rats are used as test animals, 84 rats are selected, the weight of each rat is 200-220g, and the rats are randomly divided into 6 groups, namely a model group and an experimental group 1-5. Each group was given the same diet and experiments were performed under the same feeding conditions; bacillus coagulans, fluoxetine, and polypeptide were all formulated in solution using 0.9% saline.

Referring to the patent methods, a chronic unpredictable stress model of rats is established: fasting for 24h, water deprivation for 24h, tail clamping for 5min, day and night reversing for 24h, cold water swimming for 5min at 4 ℃, environment at 45 ℃ for 5min, padding for 24h with damp, inclining for 24h at 45 degrees, behavior binding for 4h, and horizontal shaking for 60 times/min for 45min. The above method is performed randomly within 4 weeks, one method per day, the same stimulus cannot occur continuously and at least 7 days apart, and a rat depression model is established. Administration was after the last stimulation.

The administration scheme is as follows: preparing drugs with corresponding concentrations according to the following table, wherein each rat is drenched with 1ml of drugs every day, and the blank group is given with normal saline; are administered continuously for 7 days. 1h after the administration on the 7 th day, the rat is killed by decapitation, brain tissues are removed, homogenate and centrifugation are carried out, supernatant is taken, the BDNF content is detected by adopting an ELISA method, and the experimental scheme and the result are shown in the following table:

the experimental results show that the bacillus coagulans hardly influences the BDNF content in the rat brain, the polypeptide disclosed by the invention can achieve the similar effect of increasing the BDNF content as fluoxetine, but the bacillus coagulans and polypeptide composition can obviously increase the BDNF content in the brain tissue of the model rat.

Example 2: depression model rat behavioral change observation

An animal model was established and a treatment experiment was carried out in the same manner as in example 1.

The administration scheme is as follows: preparing drugs with corresponding concentrations according to the following table, wherein each rat is drenched with 1ml of drugs every day, and the blank group is given with normal saline; all administered continuously for 7 days. After 1h after the 7 th day dosing, behavioral assessments including forced swim test and sugar water preference test were performed. Data were statistically analyzed using SPSS 21.0.

The experimental protocol and results are shown in the following table:

the experimental results show that the bacillus coagulans hardly influences the forced swimming time of rats, but the polypeptide of the invention can play a similar effect to fluoxetine; however, the combination of bacillus coagulans and the polypeptide of the invention can achieve the effect of reducing the forced swimming time of rats which is obviously better than that of fluoxetine.

The results of sugar water preference experiments are similar, bacillus coagulans has almost no influence on rats, but the combination of bacillus coagulans and the polypeptide of the invention can obviously improve the sugar water intake in the rat sugar water experiments.

Sequence listing

<110> Tianjin City Henbang Biotech Co., ltd

<120> A Bacillus coagulans preparation for treating depression

<160> 1

<170> SIPOSequenceListing 1.0

<210> 1

<211> 21

<212> PRT

<213> Synthetic sequences

<400> 1

Leu Ser Asp Met Glu Leu Gln Asn Ala Ala Gly Cys Ile Ile Gly Phe

1 5 10 15

Trp Val Phe Val Trp

20

Claims

1. A bacillus coagulans pharmaceutical composition for treating depression, the composition comprising bacillus coagulans BC30 and SEQ ID NO: 1;

the dosage form of the pharmaceutical composition is selected from tablets, capsules, granules, powder and liquid preparations;

when the pharmaceutical composition is selected from tablets, capsules, granules and powders, the content of the bacillus coagulans BC30 is 1 x 10 ⁶ More than CFU/g, the content of the nutritional polypeptide is 10-50mg/g;

when the pharmaceutical composition is a liquid preparation, the content of the bacillus coagulans BC30 is 1X 10 ⁵ CFU/ml or above, and content of nutritional polypeptide is 1-5mg/ml.

2. The pharmaceutical composition of claim 1, wherein when the pharmaceutical composition is selected from the group consisting of a tablet, a capsule, a granule, and a powder, the bacillus coagulans BC30 content is 1 x 10 ⁷ CFU/g；

When the pharmaceutical composition is a liquid preparation, the content of the bacillus coagulans BC30 is 1X 10 ⁶ CFU/ml。

3. The pharmaceutical composition of claim 1, wherein when the pharmaceutical composition is selected from the group consisting of a tablet, a capsule, a granule, a powder, the nutritional polypeptide is present in an amount of 20mg/g or 40mg/g;

when the pharmaceutical composition is a liquid formulation, the nutritional polypeptide is present in an amount of 2mg/ml or 4mg/ml.