CN113583923B - Probiotic composition and application thereof in preparation of medicine for treating constipation and depression - Google Patents

Probiotic composition and application thereof in preparation of medicine for treating constipation and depression Download PDF

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CN113583923B
CN113583923B CN202111145201.7A CN202111145201A CN113583923B CN 113583923 B CN113583923 B CN 113583923B CN 202111145201 A CN202111145201 A CN 202111145201A CN 113583923 B CN113583923 B CN 113583923B
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depression
lactobacillus
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CN113583923A (en
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任发政
陈善斌
王然
李依璇
任怡镁
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China Agricultural University
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Abstract

The invention provides a probiotic composition and application thereof in preparation of drugs for treating constipation and depression, wherein the composition comprises animal bifidobacterium lactis subspecies U9, lactobacillus paracasei L55, lactobacillus rhamnosus LL23, bifidobacterium adolescentis BQ23 and lactobacillus acidophilus RA 15. The invention carries out the probiotic intervention on the depressed patients by carrying out a random double-blind test. A total of 63 depressed patients were recruited, of which 31 patients suffered from constipation. As a result, it was found that after 8 weeks of intervention, the hamilton depression (HAMD) score of the depressed population suffering from constipation decreased to 14.2 ± 8.0, which was significantly lower than that of the placebo group (22.9 ± 9.9, P < 0.05), while the HAMD score of the depressed population without constipation was not significantly different from that of the placebo group. The probiotic composition can effectively relieve depression symptoms of co-morbid constipation depressed people.

Description

Probiotic composition and application thereof in preparation of medicine for treating constipation and depression
Technical Field
The invention belongs to the technical field of probiotics, and particularly relates to a probiotic composition and application thereof in preparation of a co-morbid constipation and depression medicament.
Background
Depression is a common and extremely harmful group of mental disorders. According to the report of the world health organization, the number of patients with depression in 2015 accounts for about 4.4% of the total population, and the total number of patients is as high as 3.22 hundred million. Although both depression and constipation can occur independently, studies have shown a high rate of co-morbidity between the two. 57.7% of depressed patients are reported to be accompanied by constipation symptoms, which are 1.8 times more likely to suffer from constipation than ordinary people. Patients with gastrointestinal disorders are also more prone to depression, with prevalence of depression in patients with chronic constipation reaching as high as 33%. It is seen that depression patients are large in number and have a relationship with constipation.
Drugs acting on the monoamine neurotransmitter system are currently the most widely used antidepressants in clinical use. Such antidepressants are generally capable of alleviating the symptoms of depression, but the clinical manifestations of antidepressant use vary significantly among patients. About 30% of patients use the drug with little effect, and even the same patient cannot maintain stable drug effect in different periods. There is thus a need to develop new drugs or treatments, or as an adjunct to existing antidepressant treatments.
Disclosure of Invention
The invention aims to solve the problem that the effect difference of probiotics on improving the depression symptoms of patients is large in the prior art, and provides a probiotic composition and application thereof in preparing a co-morbid constipation and depression medicament.
The purpose of the invention is realized by the following technical scheme:
the invention provides a bifidobacterium animalis subsp lactis U9, which is preserved in China general microbiological culture Collection center (CGMCC) at 11-04.2015, wherein the CGMCC is recorded in the West Lu No.1 Hospital No. 3 of the Korean area of Beijing, the institute of microbiology of the Chinese academy of sciences, the postal code 100101 and the classified name of the bifidobacterium animalis subsp lactisBifidobacterium animalis subsp. lactis,The preservation number is CGMCC number 11560.
The invention provides lactobacillus paracasei L55, which is preserved in China general microbiological culture Collection center (CGMCC) in 04.07.2017 by the China Committee for culture Collection of microorganisms, and the address is No. 3 of West Lu No.1 of Beijing City Kogyo-Yang district, the institute of microbiology of China academy of sciences, the postal code 100101, which is named as lactobacillus paracasei in classificationLactobacillus paracasei,The preservation number is CGMCC number 13996.
The invention provides lactobacillus rhamnosus LL23, which is preserved in China general microbiological culture Collection center (CGMCC) in 04.07.2017, and the address is No. 3 of Xilu-1 of Beijing city facing Yang district, the institute of microbiology of Chinese academy of sciences, zip code 100101, and the classification is named as lactobacillus rhamnosusLactobacillus rhamnosus,The preservation number is CGMCC number 13994.
The invention provides a bifidobacterium adolescentis BQ23, which is preserved in China general microbiological culture Collection center (CGMCC) in 04.07.2017, wherein the strain is prepared by the method that the strain is No. 3 of Xilu No.1 of Beijing city northwest Chen of the Korean district, the institute of microbiology of Chinese academy of sciences, a postal code of 100101, and the strain is classified and named as bifidobacterium adolescentisBifidobacterium adolescentis,The preservation number is CGMCC number 13999.
The invention provides lactobacillus acidophilus RA15, which is preserved in China general microbiological culture Collection center (CGMCC) in 04.07.2017, and the address is No. 3 of West Lu No.1 of Beijing city Kogyo-Chen-Yang district, the institute of microbiology of China academy of sciences, postal code 100101, and the classification is named as lactobacillus acidophilusLactobacillus acidophilus,The preservation number is CGMCC number 13993.
The invention provides a probiotic composition, which comprises bifidobacterium animalis subsp lactis U9, lactobacillus paracasei L55, lactobacillus rhamnosus LL23, bifidobacterium adolescentis BQ23 and lactobacillus acidophilus RA15, and the probiotic composition comprises the following components in parts by weight:
bifidobacterium animalis subsp lactis U91-10
Lactobacillus paracasei L551-10
Lactobacillus rhamnosus LL 231-10
Bifidobacterium adolescentis BQ 231-10
Lactobacillus acidophilus RA 151-10;
bifidobacterium animalis subsp lactis U9 (Bifidobacterium animalis subsp. lactis,U9) and preserved in the China general microbiological culture Collection center on 04 th month 11 in 2015 with the preservation number of CGMCC 11560;
the lactobacillus paracasei L55 (Lactobacillus paracaseiL55) is preserved in China general microbiological culture Collection center on the 07 th 04 th month in 2017, and the preservation number is CGMCC NO. 13996;
the lactobacillus rhamnosus LL 23: (Lactobacillus rhamnosusLL 23) stored in China general microbiological culture Collection center on the number of CGMCC No.13994 in 2017 at 04.07.8;
said Bifidobacterium adolescentis BQ23 (Bifidobacterium adolescentisBQ 23) stored in China general microbiological culture Collection center on the number of CGMCC 13999 in 2017 at 04.07.8;
said Lactobacillus acidophilus RA15 (Lactobacillus acidophilusRA 15) which is deposited in China general microbiological culture Collection center on the number of CGMCC 13993 on the number of 04/07 in 2017.
A probiotic product comprises the probiotic composition and a food, health product or medically acceptable carrier, adjuvant or additive.
Further, prebiotics are included in the probiotic product.
Furthermore, the probiotic product is in a dosage form of capsules, tablets, granules, powder or sustained release preparations.
Another aspect of the invention:
the probiotic composition is applied to preparation of medicines for treating constipation and depression.
Compared with the prior art, the invention has the beneficial effects that:
although the results of the prior art studies show that probiotics can improve the depression symptoms of patients, the effect of each study is very different, and the different strains are also very different. The difference in the effect of these probiotics on depression symptoms may be due, on the one hand, to the characteristics of the probiotics themselves, and although certain health-related mechanisms of action are common among various probiotic genera and species, some functions may be species-specific, even strain-specific, or may require interaction between different strains to be effective. On the other hand, depression itself is a very heterogeneous disease, the causes or pathophysiology of the attacks are different in different patients, even the causes of the attacks of the same patient at different times may be different, and both psychosocial stress and physiological stress (such as postpartum depression) may cause different pathogenesis. On the basis of the existing research, the probiotic composition obtained by compounding various probiotics can effectively relieve the depression symptoms of the depressed people who commonly suffer from constipation.
Detailed Description
The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.
The inventor of the invention skillfully discovers in the research process that the probiotic composition obtained by mixing five probiotics, namely bifidobacterium animalis subsp lactis U9, lactobacillus paracasei L55, lactobacillus rhamnosus LL23, bifidobacterium adolescentis BQ23 and lactobacillus acidophilus RA15, replaces the existing single probiotic to intervene in depression patients, and can effectively relieve depression symptoms of depression people suffering from constipation.
The present invention will be described in detail below by way of examples. It should be understood that the following examples are only for illustrative purposes to further explain and illustrate the contents of the present invention in detail, and are not intended to limit the present invention.
In the following examples, Bifidobacterium animalis subsp. lactococcus U9, Lactobacillus paracasei L55, Lactobacillus rhamnosus LL23, Bifidobacterium adolescentis BQ23 and Lactobacillus acidophilus RA15 were all provided by Beijing and Yiyuan Biotechnology Ltd. The five strains are all preserved in China general microbiological culture collection center. The five strains are all sourced from human intestinal tracts. Other chemicals were purchased from the normal chemical supplier and were of analytical purity.
Example 1
This example provides a probiotic composition consisting of Bifidobacterium animalis subspBifidobacterium animalis subsp. lactis) U9 Lactobacillus paracasei, Lactobacillus paracasei (II)Lactobacillus paracasei) L55, Lactobacillus rhamnosus (L)Lactobacillus rhamnosus) LL23 Bifidobacterium adolescentis (Bifidobacterium adolescentis) BQ23, and Lactobacillus acidophilus (L.) (Lactococcus acidophilus) RA15, each part of the bacterial powder weighs 2g, and the content of each bacterium is 3 multiplied by 1010CFU;
The bifidobacterium animalis subsp lactis U9 is preserved in the China general microbiological culture Collection center on 04 th month 11 in 2015 with the preservation number of CGMCC No. 11560;
the lactobacillus paracasei L55 is preserved in China general microbiological culture Collection center on the 07 th 04 th month in 2017 with the preservation number of CGMCC NO. 13996;
the lactobacillus rhamnosus LL23 is preserved in China general microbiological culture Collection center on the 07 th 04 th month in 2017, and the preservation number is CGMCC NO. 13994;
the bifidobacterium adolescentis BQ23 is preserved in China general microbiological culture Collection center on 07/04 in 2017, and the preservation number is CGMCC No. 13999;
the lactobacillus acidophilus RA15 is preserved in China general microbiological culture Collection center on the 07 th 04 th month in 2017, and the preservation number is CGMCC No 13993.
Test example
To explore the effect of the probiotic composition of example 1 on depressed persons with comorbid constipation, the test example conducted a randomized double blind trial with probiotic intervention on depressed patients.
The preparation method is completed under the supervision of the ethical committee of human research of the university of Chinese agriculture by referring to good clinical operation specifications established by the international medical regulatory agreement. The study should be performed according to the operating instructions. The protocol of the study and materials such as subject informed consent were approved by the ethical committee prior to the start of the study (ethical approval: CAUHR-2018029).
Patients participating in the study met the following conditions:
a)18 to 60 years old, with no restriction;
b) the Chinese mental disease classification scheme and the diagnosis standard (CCMD) depression attack diagnosis standard are met;
c) hamilton Depression Scale (HAMD, item 17) is not less than 8 points;
d) understand and voluntarily participate in the trial, sign informed consent.
And patients participating in this study had no:
a) there are serious or unstable body diseases such as heart, liver, kidney, endocrine, digestion, blood, etc.;
b) drug or alcohol abuse over the past year;
c) pregnant, lactating women or persons who have recently planned pregnancy
In the study, 60 depression patients were enrolled, 63 depression patients were actually enrolled, and 53 patients completed the experiment, all from Pinggu Chinese medical hospital in Beijing.
According to the screening standard, the depression patients meeting the diagnosis standard of Chinese mental disease classification scheme and diagnosis standard (CCMD) are recruited. Eligible subjects entered the group after signing an informed consent and were randomized into the probiotic group (probiotic group) and the placebo group (placebo group). Patients to be enrolled had to undergo an emptying phase of 1 week, during which time no probiotic product (including yoghurt, probiotic tablets, powders, capsules) could be consumed. After the end of the emptying period, subjects were evaluated for their degree of Depression using the Hamilton's Depression Scale (HAMD), the constipation patient self-rating Scale (PAC-SYM) was evaluated, subjects were evaluated for constipation symptoms, co-morbid constipation people were screened, and subjects' demographics, medical history, and drug treatment were recorded.
The dry expectation was 2 months total, during which the probiotic composition formed from 5 probiotic bacteria powders described in example 1, or placebo, was taken daily. During the intervention the subject will continue on a normal diet but not eat other fermented dairy products. The subject fills out the log every day, and the content comprises the taking condition and the defecation condition. At the end of the expectation, subjects were again subjected to HAMD and PAC-SYM to assess the extent of their depressive and constipation symptoms.
In order to research the influence of probiotics on constipation-related depressed people, a randomly designed blind person group experiment for the depressed people who intervene in constipation co-morbidity by using probiotics is carried out. 63 persons are eligible to participate in the study, the population is randomly divided into a probiotic group or a placebo group, and 53 persons complete the experiment. There were no significant differences in age, gender composition between the two groups (table 1). Of these 27 people met the ROME III constipation diagnostic criteria (constipation was diagnosed as two or more of: at least 25% of defecation experienced strenuous, at least 25% of defecation was dry, globular or hard, at least 25% of defecation was incomplete, at least 25% of defecation was anorectal obstructive, at least 25% of defecation needed help, less than 3 times per week).
TABLE 1 basic conditions of the population
Figure 572413DEST_PATH_IMAGE001
1. Effect of probiotics on depressive symptoms of co-morbid constipation in depressed people
In the dry prognosis, the hamilton depression scale (HAMD) scores were significantly lower in the placebo and probiotic groups than in the baseline phase. During baseline, the HAMD score of the probiotic group was not different from that of the placebo group; whereas post-intervention probiotic group had a HAMD score significantly lower than placebo group (15.6 ± 8.5 vs 20.5 ± 8.6, P < 0.05) (table 2). The response of both the constipated and non-constipated depressed population to probiotic intervention was further analyzed. It can be seen that during baseline, the HAMD score was significantly higher in the constipated depressed population than in the non-constipated population, but there was no significant difference between the probiotic and placebo groups, and therefore this difference did not affect the quality of the experiment. HAMD scores were significantly lower (14.2 + -8.0 vs 22.9 + -9.9, P < 0.05) after probiotic intervention in depressed patients with comorbid constipation than in placebo, while HAMD scores were not significantly different after probiotic intervention in depressed patients without comorbid constipation than in placebo.
TABLE 2 Effect of probiotics on HAMD Depression score in Copathy Constipation Depression patients
Figure 364789DEST_PATH_IMAGE002
Note: significant differences compared to placebo,P<0.05。
2. effect of probiotics on constipation symptoms of co-morbid constipation depression patients
For those who co-morbid constipation, the study also evaluated constipation symptoms using a constipation patient self-rating scale (PAC-SYM). PAC-SYM has 12 items in total and can be divided into 3 types of symptoms: abdominal symptoms (item 4, including abdominal discomfort, abdominal pain, abdominal swelling, gastrospasm), rectal symptoms (item 3, including painful defecation, burning of the rectum during or after defecation, rectal laceration or bleeding after defecation) and fecal symptoms (item 5, including feeling of incomplete defecation, difficult defecation, too little stool, exertion of force or pressure to defecate, deliberate but not defecation), are clinically common scales that can effectively assess the degree of constipation. Probiotic intervention PAC-SYM scores for patients with depressed constipation are shown in table 3. After probiotic intervention, the fecal symptom score was lower than that of the placebo group (7.17 + -4.38 vs 11.33 + -3.21, P < 0.05), which was also significantly lower than that before intervention; the abdominal symptoms and rectal symptoms of the probiotic group are not significantly different from those of the placebo group; the PAC-SYM total score of the probiotic group is significantly different from that of the placebo group (8.8 +/-5.47 vs 15.33 +/-5.03, P < 0.05). The probiotics have obvious improvement effect on constipation symptoms of depression patients with combined constipation, and particularly has obvious effect on fecal symptoms.
TABLE 3 Effect of probiotics on PAC-SYM constipation score in depressed people with comorbid constipation
Figure 768088DEST_PATH_IMAGE003
Note: significant differences compared to placebo,P<0.05。
the foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims (6)

1. The probiotic composition is characterized by comprising bifidobacterium animalis subsp lactis U9, lactobacillus paracasei L55, lactobacillus rhamnosus LL23, bifidobacterium adolescentis BQ23 and lactobacillus acidophilus RA15, and comprises the following components in parts by weight:
bifidobacterium animalis subsp lactis U91-10
Lactobacillus paracasei L551-10
Lactobacillus rhamnosus LL 231-10
Bifidobacterium adolescentis BQ 231-10
Lactobacillus acidophilus RA 151-10;
the bifidobacterium animalis subsp lactis U9 is preserved in the China general microbiological culture Collection center on 04 th month 11 in 2015 with the preservation number of CGMCC No. 11560;
the lactobacillus paracasei L55 is preserved in China general microbiological culture Collection center on the 07 th 04 th month in 2017 with the preservation number of CGMCC NO. 13996;
the lactobacillus rhamnosus LL23 is preserved in China general microbiological culture Collection center on the 07 th 04 th month in 2017, and the preservation number is CGMCC NO. 13994;
the bifidobacterium adolescentis BQ23 is preserved in China general microbiological culture Collection center on 07/04 in 2017, and the preservation number is CGMCC No. 13999;
the lactobacillus acidophilus RA15 is preserved in China general microbiological culture Collection center on the 07 th 04 th month in 2017, and the preservation number is CGMCC No 13993.
2. The probiotic composition according to claim 1, characterized in that the weight parts of each bacterium in the composition are the same.
3. A probiotic product, characterized in that it comprises a probiotic composition according to claim 1 or 2 and a food, nutraceutical or medically acceptable carrier, adjuvant or additive.
4. The probiotic product according to claim 3, characterized in that prebiotics are included in the probiotic product.
5. The probiotic product according to claim 3 or 4, characterized in that its dosage form comprises capsules, tablets, granules, powders or sustained release formulations.
6. Use of a probiotic composition according to claim 1 or 2 for the preparation of a medicament for co-morbid constipation and depression.
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