CN117899129A - Pharmaceutical composition for improving tic disorder and application thereof - Google Patents
Pharmaceutical composition for improving tic disorder and application thereof Download PDFInfo
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- CN117899129A CN117899129A CN202311721111.7A CN202311721111A CN117899129A CN 117899129 A CN117899129 A CN 117899129A CN 202311721111 A CN202311721111 A CN 202311721111A CN 117899129 A CN117899129 A CN 117899129A
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 18
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- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 1
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- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention provides a pharmaceutical composition for improving tic disorder, which comprises rhodosporidium ttys-997 and lactobacillus rhamnosus TT628. The invention also provides a food and a health-care product, and the pharmaceutical composition, the food and the health-care product can improve tic disorder.
Description
Technical Field
The invention relates to a pharmaceutical composition for improving tic diseases and application thereof.
Background
Tic Disorders (TD) are neuropsychiatric disorders that are primarily manifested by tic movements during childhood, often combined with hyperactivity, obsessive-compulsive disorders, learning difficulties, anxiety, depression, conduct disorders, and other mental disorders that affect 1% of children's normal development. Because of the unknown etiology, antipsychotics, although commonly used in therapy, are only symptomatic treatments and not etiology, with insignificant efficacy and large side effects. Epidemiological and laboratory studies have shown that respiratory tract infections and autoimmune dysfunctions, as well as problems around the perinatal period, may be involved in the etiologic mechanism of tic patients. Evidence of inflammation and the role of the microbial-intestinal-brain axis in neural development and behavior is increasing. The study finds that the quantity of CD3+ and CD4+ subgroups in peripheral blood T cells of patients and the CD4+/CD8+ ratio are also obviously lower than those of healthy control groups, and Chinese scholars in (Parker-Athill EC,Ehrhart J,Tan J,Murphy TK.Cytokine correlations in youth with tic disorders.J Child Adolesc Psychopharmacol.2015Feb;25(1):86-92.doi:10.1089/cap.2014.0103.Epub 2015 Feb 6.PMID:25658821;PMCID:PMC4340338.).2020 years, who are accompanied with the rise of proinflammatory cytokines such as blood plasma tumor necrosis factor alpha, interleukin-12, interleukin-6, interleukin-1 beta and the like, report that the use of fecal fungus transplantation can effectively treat tic disease (Zhao HJ.The Efficacy of Fecal Microbiota Transplantation for Children With Tourette Syndrome:A Preliminary Study.Front Psychiatry.2020Dec 23;11:554441.doi:10.3389/fpsyt.2020.554441.PMID:33424650;PMCID:PMC7793740.). to regulate intestinal microecology and reduce body inflammation is expected to become an effective method for improving tic disorder for the first time.
Armillariella cinnabarina ttys-997 is a fungal microorganism homologous to drugs and foods, and is called "yellow glossy ganoderma (yellow glossy ganoderma)" in the book of the compendium of materia medica. The wine is mainly used for tonifying spleen qi and soothing nerves of heart and abdomen five pathogens, so that people waiting for the heart are honest, familiarity and easy to approach, people can eat the wine frequently, people can be light and not aged, and people can become immortal after a long time. Tujia has long been used to treat colitis, rheumatism and rheumatoid arthritis. The main active ingredient, namely the acid, is extracted from mycelium cultivated by a special process, has anti-inflammatory capability, can reduce neuroinflammatory reaction, obviously inhibit lipopolysaccharide from inducing microglial cells to release pro-inflammatory factors, and reduce inflammatory factor expression. The Ardisia crenata ttys-997 is preserved in China general microbiological culture Collection center (CGMCC) with the preservation number of CGMCC No.21084 in the year of 12 and 3 of 2020. And lactobacillus rhamnosus TT628 play a dual role in neurotransmitter synthesis and balance. Lactobacillus rhamnosus TT628, which is a human intestinal tract-derived bacterium, was initially isolated in a body of a baby, and later a strain with a percent similarity was isolated in the intestinal tract of a healthy infant, identified as lactobacillus rhamnosus (Lactobacillus rhamnosus) TT628. The strain is a probiotic and is preserved in China general microbiological culture Collection center (CGMCC) with the preservation number of CGMCC21611 and the address: the preservation time of the Qingyang area beichen West way No. 1, 3 of Beijing city: the lactobacillus rhamnosus is identified by 16SrDNA gene sequencing on day 13 and 1 in 2021, and has been marketed for 1 year, and no obvious adverse reaction report is found at present. The two are combined, and the effect of improving tic disorder can be achieved aiming at a multi-target action mechanism.
Disclosure of Invention
The invention provides a pharmaceutical composition for improving tic diseases and application thereof, and also provides a food and a health product.
In order to achieve the above purpose, the following technical scheme is adopted: a pharmaceutical composition for improving tic disorders, comprising rhodosporidium ttys-997 and lactobacillus rhamnosus TT628.
Preferably, the dosage ratio of the rhodosporidium ttys-997 to the lactobacillus rhamnosus TT628 is 2g:10 6 CFU; more preferably, the pharmaceutical composition contains 10 6 CFU of Lactobacillus rhamnosus TT628 viable bacteria and 2 grams of Thiobacillus cinnabarinus ttys-997 per 3 grams of the pharmaceutical composition.
Preferably, the pharmaceutical composition is an oral formulation.
The invention provides application of the pharmaceutical composition in preparation of medicines for improving tic diseases.
The invention provides a food which comprises rhodosporidium ttys-997 and lactobacillus rhamnosus TT6287.
Preferably, the dosage ratio of the rhodosporidium ttys-997 to the lactobacillus rhamnosus TT628 is 2g:10 6 CFU; more preferably, the food contains 10 6 CFU of Lactobacillus rhamnosus TT628 viable bacteria and 2g of Thiobacillus cinnabarinus ttys-997 per 3g of the food.
Preferably, the food product is an oral formulation.
The invention provides a health care product, which comprises rhodosporidium ttys-997 and lactobacillus rhamnosus TT628.
Preferably, the dosage ratio of the rhodosporidium ttys-997 to the lactobacillus rhamnosus TT628 is 2g:10 6 CFU; more preferably, each 3g of the health product contains 10 6 CFU of lactobacillus rhamnosus TT628 viable bacteria and 2g of thiobacillus cinnabarinus ttys-997.
Preferably, the health care product is an oral preparation.
The beneficial effects are that:
The invention provides a pharmaceutical composition for improving tic diseases, and also provides a food and a health-care product.
Detailed Description
For a better description of the objects, technical solutions and advantages of the present invention, the present invention will be further described with reference to the following specific examples.
Example 1
Experiments on improvement of tic model mice by composition of Thiobacillus cinnabarinus ttys-997 and Lactobacillus rhamnosus TT 628.
1 Main technical route
1. Experimental animal
SPF-class healthy ICR mice (male and female halves), 3-4 weeks old, body weight (20+ -3) g, feed feeding and free pure water drinking were given to the mice, and experiments were started after one week of adaptation to the environment.
2. Experimental method
2.1 Animal model preparation and grouping
(1) Modeling and grouping: the blank control group (10) and the model group (40) are divided into a male half and a female half at random. ① molding module: iminodipropionitrile (IDPN) intraperitoneal injection-induced mice tic model established with reference to Diamond et al, ② blank: equal amounts of physiological saline were injected 1 time a day for 7 days for molding.
(2) Experimental grouping: and after modeling is finished for seven days, the tic notch board behaviors of the mice in the tic disease model group are scored, the behavioral changes are observed, and the scoring result is more than or equal to 2 minutes, so that modeling is proved to be successful. At the same time, the body weight of the mice in the model group was significantly reduced (p < 0.05) compared to the blank group. The open field behavior result of the mice shows that the total movement amount, the average movement speed and the grid penetration times of the mice in the model group are obviously increased, which indicates that the modeling is successful. 40 mice were randomly assigned to low, medium and high dose groups of the model group, the thiothiirane cinnabarina ttys-997 and the lactobacillus rhamnosus TT628 composition group.
2.2 Intervention method
The experiment adopts a composition of cinnabar sulfur bacteria ttys-997 (with the preservation number of CGMCC No. 21084) and lactobacillus rhamnosus TT628 (with the preservation number of CGMCC No. 21611), and the composition is converted with the recommended amount of a human body according to the equal dose of mice. High dose groups were given: 5g/80ml/d (80 ml purified water containing 1.67g of Lactobacillus rhamnosus TT628 (CFU: 1.67X10 6), 3.33g of Thiobacillus cinnabarinus ttys-997), 1g/80ml/d (80 ml purified water containing 0.34g of Lactobacillus rhamnosus TT628 (CFU: 0.34X 10 6), 0.66g of Lactobacillus cinnabarinus ttys-997), 0.1g/80ml/d (80 ml purified water containing 0.034g of Lactobacillus rhamnosus TT628 (CFU: 0.034X 10 6), 0.066g of Thiobacillus cinnabarinus ttys-997), and the Lactobacillus rhamnosus TT628 to be used was spray-dried. Once a day, for 28 consecutive days. The model group was given free feeding.
3 Observation index and detection method
Mouse twitch behavior score: taking out the mice from the rearing cage, putting the mice into an observation cage, starting digital video recording after adapting to the environment, observing the movements of the head and neck of the mice, the movements of the dance patterns rotating up and down and the times of involuntary rotation, grading the notch board behaviors and the exercise behaviors of the mice by selecting grading standards such as Diamond, and laying padding in the cage in a quiet environment to simulate the normal living environment of the mice. The observation was performed by double-blind method to avoid subjective speculation affecting the experimental results.
4 Data analysis
Adopting IBM SPSS22.0 version statistical software to analyze, wherein each numerical value is represented by mean + -standard deviation (M+ -s), and is subjected to normal distribution and uniform variance multi-sample mean comparison, single-factor variance analysis is used, and LSD test is adopted for every two comparisons; the above differences were all statistically significant with P < 0.05. The composition is carried out by adopting GRAPHPAD PRISM.3.0 statistical software, the average comparison of multiple samples which are subjected to normal distribution and have uniform variance is carried out, and the single-factor analysis of variance is used, and the P <0.05 is taken as the difference to have statistical significance.
5 Results
Note that: compared to model group, p <0.05.
After successful modeling (the scores of mice in each group are equal to or greater than 2 points), the mice in each group are comparable before treatment. On day 28 post-intervention treatment, each group of mice with a dry prognosis was compared to the model group of mice, and the low dose group of the composition was compared to the model group of mice with no statistical difference (P > 0.05); the medium and high dose groups showed significant differences in panel performance scores (P < 0.05) compared to the model group. Indicating that the doses and high doses in the composition can improve the notch behavior of tic mice to some extent.
The invention is a successful example for improving tic disorder by adopting the composition of the cinnabar sulfur bacteria ttys-997 and the lactobacillus rhamnosus TT628 for the first time in the world, and has the characteristics of high efficiency and safety.
Finally, it should be noted that the above embodiments are only for illustrating the technical solution of the present invention and not for limiting the scope of the present invention, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solution of the present invention may be modified or substituted equally without departing from the spirit and scope of the technical solution of the present invention.
Claims (10)
1. A pharmaceutical composition for improving tic disorder, comprising rhodosporidium ttys-997 and lactobacillus rhamnosus TT628.
2. The pharmaceutical composition according to claim 1, wherein the ratio of the amount of rhodosporidium ttys-997 to lactobacillus rhamnosus TT628 is 2g:10 6 CFU; preferably, each 3g of the pharmaceutical composition contains 10 6 CFU of lactobacillus rhamnosus TT628 viable bacteria and 2g of thiobacillus cinnabarinus ttys-997.
3. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is an oral formulation.
4. Use of a pharmaceutical composition according to any one of claims 1-3 for the preparation of a medicament for improving tic disorders.
5. A food product comprising rhodosporidium ttys-997 and lactobacillus rhamnosus TT6287.
6. The food product according to claim 1, characterized in that the ratio of the amount of rhodosporidium ttys-997 to lactobacillus rhamnosus TT628 is 2g:10 6 CFU; preferably, each 3g of the food contains 10 6 CFU of lactobacillus rhamnosus TT628 viable bacteria and 2g of thiobacillus cinnabarinus ttys-997.
7. The food product according to claim 1, characterized in that the food product is an oral preparation.
8. A health product is characterized by comprising rhodosporidium ttys-997 and lactobacillus rhamnosus TT6287.
9. The health product according to claim 1, wherein the ratio of the amount of rhodosporidium ttys-997 to lactobacillus rhamnosus TT628 is 2g:10 6 CFU; preferably, each 3g of the health-care product contains 10 6 CFU of lactobacillus rhamnosus TT628 viable bacteria and 2g of cinnabar sulfur bacteria ttys-997.
10. The health product according to claim 1, wherein the health product is an oral preparation.
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| CN202311721111.7A CN117899129A (en) | 2023-12-14 | 2023-12-14 | Pharmaceutical composition for improving tic disorder and application thereof |
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| CN202311721111.7A CN117899129A (en) | 2023-12-14 | 2023-12-14 | Pharmaceutical composition for improving tic disorder and application thereof |
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