Probiotic composition for reducing symptoms associated with drug relapse and uses thereof

Abstract

The present application relates to a probiotic composition for reducing the relapse-related symptoms of drug addiction and uses thereof. The probiotic composition uses Lactobacillus brevis strain GKJOY as an effective ingredient, which can effectively reduce the relapse-related symptoms of drug addiction when continuously administered to a subject for a period of time, thereby serving as an effective ingredient and being used for preparing various compositions.

Description

TECHNICAL FIELD

[0001] The present application relates to a probiotic composition and its use, in particular to a probiotic composition and its use for reducing relapse-related symptoms of drug addiction using probiotics.

[0002] PRIOR ART

[0003] Addiction refers to an extraordinary liking and habit of a person for something, which stimulates the reward system of the central nervous system to feel pleasure or excitement.

[0004] When an individual repeatedly craves for and abuses something uncontrollably, causing adverse consequences to oneself, it is called addiction, which can be divided into behavioural addiction and substance addiction.

[0005] Behavioural addiction includes gambling addiction, mobile phone addiction, sex addiction, shopping addiction, etc., which can cause physical and mental harm to individuals, families, or society, such as affecting work efficiency, property loss, sexually transmitted diseases, or other mental diseases, etc.

[0006] Substance addiction includes smoking addiction, alcohol addiction, and drug addiction, which are extremely harmful to personal health and social problems. Such as physical symptoms such as pneumonia, intestinal leakage, weight loss, and nervous system damage, which can be fatal. Among them, the illegal substance addiction of drug addiction is also a social problem, and drug offenders accounted for 49.9% of the prison population in 2017; among them, many drug-related criminals are also drug addicts.

[0007] Another feature of addiction is withdrawal symptoms, which refers to the physiological or psychological changes that occur when the use of addictive substances is stopped or interrupted, such as anxiety, irritability, emotional instability, lack of concentration, dizziness, insomnia, restlessness, increased appetite, nausea, vomiting, seizures, etc. Although these withdrawal symptoms are temporary (the duration of the phenomenon is less than a few weeks), more than 2 / 3 of individuals cannot tolerate the physical or mental burden brought by these symptoms, and therefore give up on withdrawal and relapse to the state of addiction.

[0008] Drug treatment is one of the ways to treat drug addiction (drug addiction). Traditionally, symptomatic treatment is the main method, such as tranquilizers, antipsychotic drugs, and clonidine. However, tranquilizers also have doubts about causing addiction; the use of antipsychotic drugs has doubts about the side effects of the vertebral canal; clonidine can reduce withdrawal symptoms, but cannot completely eliminate the pain caused by withdrawal.

[0009] Only Opioid, such as Heroin, Cocaine, Opium, Morphine, etc. has effective substitute drugs (such as Methadone, Bupremorphine). The principle of these Opioid substitute drugs is to maintain the addict on this drug to avoid the onset of drug addiction or reduce the pleasure of using drugs and reduce withdrawal symptoms. Because of its similar structure to the drug itself, there is still the possibility of abuse.

[0010] Non-Opioid, such as Amphetamine, Ketamine, etc. Because it is not like Opioid has effective substitute drugs, so there is a need to find a substitute drug or method to prevent relapse during withdrawal.

[0011] Addiction is related to neural regulation of the brain, and illegal drug addiction has been proven to be a brain function disorder that affects individual cognitive function and behavior, and is accompanied by chronic and recurrent course. Studies have found that gut microbes can affect the brain and behavior of mice through the brain-gut axis, for example, in a mouse test of anxiety behavior caused by mother-child separation, giving the mouse Lactobacillus plantarum can reduce the mouse's anxiety behavior. Because there is no particularly effective or side-effect-free treatment for addiction at present, a variety of alternative methods are urgently needed, and probiotics have the potential to improve addiction withdrawal in theory.

[0012] However, there are few studies on the use of probiotics to reduce drug relapse, and there is an urgent need to develop a probiotic composition for reducing drug relapse and its use. SUMMARY

[0013] Therefore, one aspect of the present application provides a probiotic composition for reducing drug relapse-related symptoms, which comprises Lactobacillus brevis strain GKJOY as an effective ingredient.

[0014] Secondly, another aspect of the present application provides a probiotic for use in reducing drug relapse-related symptoms, comprising administering an oral composition containing an effective dose of probiotics to a subject for a period of time, and the probiotic comprises strain GKJOY.

[0015] According to the above aspect of the present application, a probiotic composition for reducing relapse-related symptoms of drug addiction is provided. In one embodiment, the probiotic composition for reducing relapse-related symptoms of drug addiction comprises Lactobacillus brevis strain GKJOY as an active ingredient, which was deposited with the National Institute of Technology and Evaluation Patent Microorganisms Depository (Address: 2-5-8, Kamatamachi, Kashiwa, Chiba 292-0818, Japan) on November 6, 2020, under accession number NITE BP-03316.

[0016] In the above embodiment, the aforementioned probiotic composition can be, for example, an oral composition, such as a pharmaceutical composition. In the above example, the aforementioned probiotic composition further comprises a pharmaceutically acceptable carrier, excipient, and / or additive.

[0017] In the above embodiment, the dosage form of the aforementioned probiotic composition can include, for example, a powder, a tablet, a granule, a suppository, a microcapsule, an ampoule, a liquid spray, or a plug.

[0018] According to another aspect of the present application, use of a probiotic for the manufacture of a composition for reducing relapse-related symptoms of Kainite drug addiction is provided, comprising administering an oral composition comprising an effective dose of a probiotic to a subject for at least two weeks, and the probiotic comprises Lactobacillus brevis strain GKJOY, which was deposited with the National Institute of Technology and Evaluation Patent Microorganisms Depository (Address: 2-5-8, Kamatamachi, Kashiwa, Chiba 292-0818, Japan) on November 6, 2020, under accession number NITE BP-03316.

[0019] In the above embodiment, the aforementioned subject can be, for example, an adult, and the effective dose of the aforementioned probiotic for the subject can be, for example, 500 mg / 60 kg body weight / day to 1500 mg / 60 kg body weight / day.

[0020] In the above embodiment, the aforementioned subject can be, for example, a rat, and the effective dose of the aforementioned probiotic for the subject can be, for example, 51.5 mg / kg body weight / day to 155 mg / kg body weight / day.

[0021] The aforementioned probiotic composition for reducing relapse-related symptoms of drug addiction and use thereof according to the present application, which comprises Lactobacillus brevis strain GKJOY as an active ingredient, can effectively reduce the seeking behavior for addictive drugs when administered to a subject for a certain period of time, thereby serving as an active ingredient and being used for the manufacture of various compositions.

[0022] It is to be understood that both the foregoing general description and the following detailed description are merely exemplary and intended to provide further explanation of the application claimed.

[0023] Lactobacillus brevis strain GKJOY is deposited in the National Patent Microorganisms Depositary, National Institute of Technology and Evaluation (NITE), 2-5-8 Kamitsuma-Kamase, 292-0818 Kisarazu-shi, Chiba-ken, Japan, on November 6, 2020, and has the accession number NITEBP-03316, and the survival of the strain was confirmed on November 11, 2020.

[0024] [FIGURE]

[0025] To make the above and other objects, features, advantages and embodiments of the present application more comprehensible, the detailed description of the accompanying drawings is as follows:

[0026] [ Figure 1 ] is a flowchart illustrating the evaluation of the effect of drug addiction withdrawal in test animals according to an embodiment of the present application.

[0027] [ Figure 2 ] is a histogram showing the number of times the test animals pressed the lever after relapse behavior was induced by light stimulation after withdrawal of the addictive drug according to an embodiment of the present application. [EMBODIMENT]

[0028] If the definition or usage of a term in a cited document is inconsistent with or contrary to the definition of the term herein, the definition of the term herein is applicable and the definition of the term in the cited document is not applicable. Second, unless the context otherwise requires, a singular term can include a plural, and a plural term can also include a singular.

[0029] As described above, the present application provides a probiotic composition for reducing the symptoms associated with relapse of drug addiction, which, when administered to a subject for a continuous period, can effectively reduce the seeking behavior for addictive drugs.

[0030] In one embodiment, the "probiotic" as referred to herein means Lactobacillus brevis. Lactobacillus brevis is a Gram-positive bacterial species in the genus Lactobacillus, commonly found in fermented foods such as sauerkraut, yogurt, beer, and can also be found in animals, such as the human gut, vagina, feces, etc. The species is recognized as a probiotic for animals, and several strains have been found to have properties such as anti-biofilm formation, antioxidant, or production of gamma-aminobutyric acid (GABA). However, the Lactobacillus brevis strain GKJOY disclosed herein has a new effect of reducing symptoms associated with relapse of drug addiction. The Lactobacillus brevis strain GKJOY was deposited with the National Institute of Technology and Evaluation Patent Microorganisms Depository (address: 2-5-8, Kamitsuma Kayashima, Kisarazu-shi, Chiba-ken, 292-0818, Japan) on November 6, 2020, under accession number NITE BP-03316, and the strain was confirmed to be viable on November 11, 2020. It is noted that the probiotic used in the present application must be selected from a specific strain, and only the resulting probiotic composition can exhibit the effect of reducing symptoms associated with relapse of drug addiction. If the probiotic is not selected from the specific strain, the effect of reducing symptoms associated with relapse of drug addiction cannot be expected.

[0031] The "reducing symptoms associated with relapse of drug addiction" as referred to herein means symptoms associated with relapse of drug addiction, which can include, but is not limited to, craving and seeking behavior for addictive drugs.

[0032] In use, the probiotic composition can be, for example, an oral composition, such as a pharmaceutical composition or a food composition. The Lactobacillus brevis strain GKJOY can be used in various forms, which can include, but are not limited to, fermentation broth, slurry, supernatant, and freeze-dried powder. In the above embodiment, the fermentation broth refers to a product including bacterial cells and culture medium. The slurry refers to a product obtained by removing the supernatant from the fermentation broth. The supernatant refers to a product obtained by removing the slurry from the fermentation broth. The freeze-dried powder refers to a freeze-dried powder prepared from the fermentation broth, the slurry, and / or the supernatant.

[0033] Examples of the pharmaceutical composition can include, but are not limited to, a drug. Examples of the food composition to which the probiotic is applied can include, but are not limited to, general food, health food, beverage, nutritional supplement, dairy product, or feed, etc. In the above examples of the oral composition, the probiotic composition can further optionally include a pharmaceutically and a food acceptable carrier, excipient, and / or additive. In other examples, the dosage form of the probiotic composition can include, but is not limited to, powder, tablet, granule, suppository, microcapsule, ampoule, liquid spray, or plug.

[0034] When the aforementioned probiotics are used to reduce symptoms associated with drug relapse, an oral formulation containing an effective dose of probiotics may be administered to the subject for a continuous period, such as at least two weeks. The effective dose depends on the subject and is not particularly limited. For example, when the subject is an adult, the effective dose of probiotics for adults may be, for example, 500 mg / 60 kg body weight / day to 1500 mg / 60 kg body weight / day, but 750 mg / 60 kg body weight / day to 1250 mg / 60 kg body weight / day is preferred, and approximately 1000 mg / 60 kg body weight / day is even more preferred. In another example, when the subject is a rat, the effective dose of probiotics for this subject may be, for example, 51.5 mg / kg body weight / day to 155 mg / kg body weight / day, but 77.3 mg / kg body weight / day to 129 mg / kg body weight / day is preferred, and approximately 103 mg / kg body weight / day is even more preferred.

[0035] It is understood that the specific strains, formulations, dosages, detection methods, viewpoints, examples, and embodiments described below are for illustrative purposes only and are not intended to limit the scope of the invention. The main features of the invention can be used in various embodiments without departing from the spirit and scope thereof. Therefore, those skilled in the art to which this invention pertains can easily identify the essential technical features of this invention and make various modifications and refinements to suit different uses and conditions without departing from the spirit and scope of the invention.

[0036] Example 1

[0037] 1.1 Source of strains

[0038] The bacterial strain used in this embodiment is Lactobacillus brevis strain GKJOY. Lactobacillus brevis strain GKJOY was deposited on November 6, 2020, at the Patent and Microbial Collection Center of the Technical Base for Product Evaluation of Japan (Address: Room 122, 2-5-8 Kamisamaashi, Kisarazu City, Chiba Prefecture, Japan 292-0818), with accession number NITE BP-03316.

[0039] The strain GKJOY was isolated from pickled food used in an indigenous tribe on June 30, 2014. The 16S rDNA nucleotide sequence of the strain GKJOY was subjected to molecular biological identification (date of identification: June 13, 2019) to obtain the 16S rDNA sequence of the strain GKJOY, which is shown as SEQ ID NO: 1. The sequence shown in SEQ ID NO: 1 was subjected to sequence alignment with the database on the NCBI website, and the result showed that the 16S rDNA sequence of the strain GKJOY had a sequence similarity of 100% with that of Lactobacillus brevis, and the strain GKJOY was determined to be Lactobacillus brevis. The strain GKJOY was deposited with the National Institute of Technology and Evaluation, Patent Microorganisms Depository, National Institute of Technology and Evaluation (2-5-8, Kamitsuma Kayashiki, 292-0818, Kisarazu-shi, Chiba-ken, Japan) on November 6, 2020, under the accession number NITE BP-03316, and the survival of the strain was confirmed on November 11, 2020.

[0040] The Lactobacillus brevis strain GKJOY was inoculated into a solid culture medium to activate the strain. In a preferred embodiment, the solid culture medium is MRS agar. After colonies were formed, a single colony was picked and inoculated into a liquid culture medium for liquid culture. In a preferred embodiment, the liquid culture was performed at a temperature of 25°C to 40°C for 16 to 24 hours, preferably 18 hours, under conditions such as a nitrogen gas or carbon dioxide gas flow rate of 0 to 1 vvm and a shaking speed of 250 rpm to 1000 rpm, so that the number of viable cells reached a maximum. The liquid culture medium was MRS (deMan, Rogosa, and Sharpe) liquid culture medium. After the liquid culture was completed, fermentation culture was performed, and the formulation of the fermentation medium is shown in Table 1.

[0041] Table 1

[0042]

[0043] 1.2 Preparation of freeze-dried powder

[0044] After the Lactobacillus brevis strain GKJOY was grown by fermentation culture, the fermentation whole liquid containing the bacterial cells and the culture solution was collected and centrifuged at a speed of 1000 rpm to 15000 rpm to obtain a cell pellet (or bacterial sludge). The obtained cell pellet was mixed with a protective agent (i.e., 6% to 50% by weight of skim milk powder) and freeze-dried.

[0045] The aforementioned freeze-drying is pre-frozen in a gradient setting mode, sequentially stored at 20°C to 0°C for 1 to 4 hours, then stored at 0°C to -20°C for 4 to 8 hours, and then stored at -30°C to -196°C for more than 8 hours. In a preferred embodiment, the temperature and time of freeze-drying are stored at -40°C for 2 hours, then stored at -20°C for 2 hours, then stored at 0°C for 2 hours, and finally stored at 20°C for more than 10 hours. After that, the freeze-dried powder obtained by the aforementioned freeze-drying is placed in low-temperature storage. The temperature of the aforementioned low-temperature storage is -30°C to 4°C. The stored freeze-dried powder is used as a raw material of the probiotic composition to be administered to the test animals in the following animal experiments.

[0046] Example 2

[0047] 2.1 Test animals

[0048] The following example uses 8-week-old SD male mice, each weighing about 225 to 250 grams, purchased from BioLASCO (BioLASCO Biotechnology). The mice are raised in conventional cages, the room temperature is maintained at 25±2°C, the humidity is 40 to 70%, the light and dark are set for 12 hours, and the water and standard feed are fully supplied. All animal experiment procedures are reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of the Taiwan Institute of Health Research. After the test animals are acclimated for 1 week, they are randomly divided into a control group and an experimental group, each group having 6 animals.

[0049] 2.2 Experimental design

[0050] Please refer to Figure 1 , which is a flowchart showing the evaluation of the addictive withdrawal effect of test animals according to an embodiment of the present application. In Figure 1 , after the test animals are acclimated, the test animals are trained for food for 3 to 7 days to make the test animals perform a specified action. Then, the test animals are subjected to intravenous catheterization surgery. After recovery, the test animals are subjected to two-stage drug addiction training for 12 to 20 days to induce addictive behavior by allowing the test animals to obtain a reward drug through a specified action. After that, the test animals are subjected to withdrawal, and during the withdrawal period, the probiotic composition of Example 1 (GKJOY experimental group) or double-distilled water (control group) is administered orally. Finally, the test animals are given addictive drug stimulation again, and the recurrence of addictive behavior in the animals is evaluated.

[0051] 2.3 Establishment of a drug addiction system

[0052] The above-mentioned addictive behavior is trained in the test animals in a self-administration mode of intravenous drug to establish a drug addiction system. Briefly, the positive reinforcement of the drug is controlled by certain conditions, and the test animals can obtain certain incentives after performing a specified action, so as to establish the connection between the behavior and the reward of the test animals, so as to simulate the situation of human drug abuse. The specific description of the addiction system is as follows.

[0053] After the test animals adapt to the environment (7 days), the test animals are subjected to food restriction and food training for 3 to 7 days. Before the training starts, the test animals have been subjected to food restriction for 2 days (5g / day). Then, the test animals are placed in a food training experimental box, and only a single lever is provided in the experimental box for the test animals to press, and the specified action is set as pressing the lever. The test animals can obtain one food pellet (45mg, bioseerve) for each time of pressing the lever. Each training time is 1 hour. When the test animals obtain 100 food pellets, the training of the day is completed. The total training process is about 3 to 7 days, and the test animals must press to obtain 100 food pellets within 1 hour in the training time for 3 consecutive days to pass the training plan. During the training period, the test animals are subjected to food restriction of 12g of feed per day.

[0054] The test animals are trained, and then subjected to intravenous catheterization surgery and postoperative recovery for 7 days. In other words, after the test animals are anesthetized with gas (isoflurane, 2% v / v), the intravenous catheterization surgery is performed, that is, a silicone tube (ID = 0.51mm; OD = 0.94mm; Dow Corning Silastic) is inserted into the jugular vein of the rat, and the silicone tube is passed through the subcutaneous tissue to the top of the head. After the surgery, intensive monitoring and care are provided for 3 days, and analgesics, anti-inflammatory drugs (subcutaneous injection of 5mg / ml kentoprofen) and antibiotics (intravenous injection of 5mg / ml baytril dissolved in 50IU / ml heparin saline) are administered, so as to reduce the pain, inflammation, infection of the animals after the surgery and prevent the blockage of the intravenous blood.

[0055] After the post-surgical wound of the test animal is healed, the test animal is subjected to drug addiction training. First, the other end of the silicone tube connected to the vein of the test animal is connected to the stainless steel cannula (infusion harness, CH95 Instech Laboratories, Inc) worn by the animal. The other end of the stainless steel cannula is then connected to the syringe containing the drug and fixed to the pump. The test animal is placed in the drug addiction training experimental box described above, which contains the pressure rod device. Unlike the food training experimental box described above, the drug addiction training experimental box has two pressure rods on both sides to provide the test animal with test levers, wherein the left pressure rod is the active lever and the right pressure rod is the inactive lever, and has an additional light device.

[0056] Afterwards, the test animal is subjected to drug addiction training for 3 hours per day. When the test animal presses the left pressure rod (active lever), the injection pump switch is turned on, and the drug is automatically injected into the animal for 4 seconds, and the light device beside the device is turned on to provide a cue light for about 20 seconds. When the test animal presses the right pressure rod (inactive lever), no drug is injected into the test animal, and no light is activated. If the test animal presses the left pressure rod again during the light stimulation, the test animal will not continuously receive drug injection (i.e. will not receive drug reward), and will have to wait until the light is turned off before pressing the left pressure rod again to receive drug injection. In the drug addiction training, the test animal will not receive food pellets regardless of whether the test animal presses the left pressure rod or the right pressure rod. By the experience of the test animal in the food training described above, the drug addiction training can induce the test animal to seek drug behavior using similar devices to establish the addiction of the test animal to the drug.

[0057] The drug addiction training described above is divided into two stages. In the first stage (T1) of addiction training, the test animal receives one dose of injection for each time the test animal presses the active lever. When the average number of times the test animal presses the lever for 3 consecutive days is less than 20% deviation, the second stage (T2) of addiction training is performed.

[0058] In the second stage (T2) of addiction training, the test animal needs to press the active lever twice to receive one dose of injection. The dose of injection is 0.5 mg per kg of body weight (0.5 mg / kg B.W., i.e. training dose) each time. When the average number of times the test animal presses the lever per day for 3 consecutive days has no significant statistical difference, it is considered that the stable standard is reached (i.e. the animal is defined to have addiction to the drug, and the desire for the drug reaches the upper limit of stability), and the training is ended.

[0059] This example uses ketamine as the addictive drug for the drug addiction system, i.e. the drug injected as described above.

[0060] 2.4 Post-withdrawal cue-induced drug-seeking behavior test

[0061] 2.4.1 Extinction phase

[0062] After the test animals were trained for 12 to 20 days and developed drug addiction through self-administration, the test animals entered the extinction phase, in which the test animals did not receive drug reward or light stimulation when stepping on the pressure bar. When the number of effective pressure on the pressure bar reached the extinction standard (i.e. 20% of the number of pressure during the addiction training) for two consecutive days, the drug test of cue-induced relapse was performed.

[0063] In the extinction phase, the test animals in the experimental group were given the strain GKJOY freeze-dried powder at a dose of about 103mg / kg of rat body weight per day (equivalent to 1 gram of bacterial powder per day for a 60 kg adult human); the test animals in the control group were given double distilled water (ddH2O) instead. After about 14 days of withdrawal (i.e. after two weeks of continuous administration of the strain GKJOY to the experimental group), the drug test of cue-induced relapse was performed.

[0064] 2.4.2 Drug test of cue-induced relapse

[0065] The drug test of cue-induced relapse is described as follows. The test animals were placed in the aforementioned addiction training experimental box, and the number of times the test animals voluntarily pulled the lever in this space and in the unstimulated state was recorded as the initial baseline value. The light in the box was then periodically stimulated, and when the light cue was given, the number of times the test animals pressed the pressure bar after being stimulated was recorded. When the test animals made the response of pressing the pressure bar, it was considered as the relapse of the seeking behavior for the addictive drug, and the results are shown in Figure 2 .

[0066] Please refer to Figure 2 , which shows the histogram of the number of times the test animals pressed the pressure bar after relapse behavior was stimulated by light after withdrawal of the addictive drug according to an embodiment of the present application. As shown in Figure 2 , there was no significant difference between the test animals in the experimental group and the control group in the number of times the test animals pressed the lever of the experimental box after withdrawal without stimulation (p>0.05). However, after withdrawal and light stimulation, the number of times the test animals in the control group pressed the lever after light stimulation was significantly higher than the number of times they pressed the lever before light stimulation, indicating that the light cue successfully induced the relapse of the addictive behavior after withdrawal. In contrast, after receiving light stimulation, the number of times the test animals in the experimental group pressed the lever of the experimental box was significantly lower than that of the control group (p<0.01), indicating that the administration of the strain GKJOY to the test animals in the experimental group during withdrawal indeed effectively reduced the relapse of the cue-induced addictive behavior.

[0067] 2.5 Data Statistics

[0068] The values described herein are expressed in mean ± standard deviation (mean ± SD) and analyzed by two-way mixed measure analysis of variance and commercially available software, with statistical significant differences indicated by asterisks (* represents p < 0.05; ** represents p < 0.01).

[0069] In summary, the present application uses a specific strain, a specific formulation, a specific dosage, a specific detection method, or a specific evaluation method only to illustrate the probiotic composition of the present application for reducing the relapse-related symptoms of drug addiction. However, those skilled in the art should understand that other strains, other formulations, other dosages, other detection methods, or other evaluation methods can also be used in the probiotic composition of the present application for reducing the relapse-related symptoms of drug addiction without departing from the spirit and scope of the present application, and are not limited to the above. For example, the effective dose of strain GKJOY in the above-mentioned probiotic composition can be more or less, depending on the subject. For example, for an adult weighing 60 kg, the effective dose of strain GKJOY in the above-mentioned probiotic composition can be 500 mg / 60 kg body weight / day to 1500 mg / 60 kg body weight / day, or 750 mg / 60 kg body weight / day to 1250 mg / 60 kg body weight / day. For example, for a rat, the effective dose of strain GKJOY in the above-mentioned probiotic composition can be 51.5 mg / kg body weight / day to 155 mg / kg body weight / day, or 77.3 mg / kg body weight / day to 129 mg / kg body weight / day. The above-mentioned probiotic composition can be, for example, a pharmaceutical composition or a food composition, and can optionally contain pharmaceutically and food acceptable carriers, excipients and / or additives, and can be formulated into powders, tablets, granules, suppositories, microcapsules, ampoules, liquid sprays or plugs, etc.

[0070] According to the above-mentioned embodiments, the probiotic composition of the present application for reducing the relapse-related symptoms of drug addiction has the advantage that the probiotic composition contains Lactobacillus brevis strain GKJOY as an effective ingredient, which can effectively reduce the seeking behavior for addictive drugs when administered to a subject for a continuous period of time, and can be used as an effective ingredient for preparing various compositions in the future.

[0071] Although the present application has been disclosed above with several specific embodiments, other embodiments are also possible. Therefore, the spirit and scope of the appended claims of the present application should not be limited to the embodiments described herein. SEQUENCE LISTING <110> Portwine Biotech Co., Ltd. <120> Probiotic composition for reducing relapse-related symptoms of drug addiction and uses thereof <130> none <160> 1 <210> 1 <211> 1050 <212> DNA <213> Lactobacillus brevis GKJOY <400> 1 ggggtggact gcctatactg catgtcgaac gagcttccgt tgaatgacgt gcttgcactg 60 atttaaacaa tgaagcgagt ggcgaactgg tgagtaacac gtgggaaatc tgcccagaag 120 caggggataa cacttggaaa caggtgctaa taccgtataa caacaaaatc cgcatggatt 180 ttgtttgaaa ggtggcttcg gctatcactt ctggatgatc ccgcggcgta ttagttagtt 240 ggtgaggtaa aggcccacca agacgatgat acgtagccga cctgagaggg taatcggcca 300 cattgggact gagacacggc ccaaactcct acgggaggca gcagtaggga atcttccaca 360 atggacgaaa gtctgatgga gcaatgccgc gtgagtgaag aagggtttcg gctcgtaaaa 420 ctctgttgtt aaagaagaac acctttgaga gtaactgttc aagggttgac ggtatttaac 480 cagaaagcca cggctaacta cgtgccagca gccgcggtaa tacgtaggtg gcaagcgttg 540 tccggattta ttgggcgtaa agcgagcgca ggcggttttt taagtctgat gtgaaagcct 600 TCGGCTTAACC GGAGAAGTGC ATCGGAAACT GGGAGACTTG AGTGCAGAAG AGGACAGTG 660 GAAC TCC ATG TG T AGCGGT G GAAT GC G T AG AT AT AT GG AAGA AC C C AGT GGC G AAGGC G 720 GCTGTCTAGTCTGTAACGCTGCTGAGGCTCGAAAGCATGGGTAGCGACAGGATTAGAT 780 ACCCTGGTAGTCCATGCCGTAAACGATGAGTGCTAAGTTGTTGGAGGGTTTCGC CCCTTCA 840 GTGCTGCAGCTAACGCATTAAGC ACTCCGCCTGGGGAGTACGACC GCAAG GTTG AAAC TC 900 AAAGGAATTGACGGGGGCCCGCACAGCGGTGGAGCATGTGTTTAATTCGAAGCTA CGC GA 960 GACTTACCAGTCTGACATCTCTGCA TCT AG AG AT AG AC GT CCCTC GGG AC G ATG AC AGT G 1020 TGCA T GT GT C GT C AGCTC GT GT CT G AAT GT 1050

Claims

1. A probiotic composition for reducing symptoms associated with drug addiction relapse, characterized in that, The active ingredient is Lactobacillus brevis strain GKJOY, which was deposited on November 6, 2020, at the Patent and Microbial Collection Center of the Japan Institute for Product Evaluation Technology (Address: Room 122, 2-5-8 Kazusa-Kamazu, Kisarazu City, Chiba Prefecture, Japan 292-0818, Japan), with accession number NIT EB P-03316.

2. The probiotic composition for reducing drug addiction relapse-related symptoms as described in claim 1, characterized in that, The probiotic component is an oral component.

3. The probiotic composition for reducing drug addiction relapse-related symptoms as described in claim 2, characterized in that, The probiotic component is a pharmaceutical component.

4. The probiotic composition for reducing drug addiction relapse-related symptoms as described in claim 2, characterized in that, It also includes pharmaceutically acceptable carriers, excipients and / or additives.

5. The probiotic composition for reducing drug addiction relapse-related symptoms as described in claim 1, characterized in that, The dosage forms of the probiotic components include powders, tablets, granules, suppositories, microcapsules, ampoules, liquid sprays, or plugs.

6. The use of a probiotic in the preparation of a pharmaceutical composition for reducing drug-seeking behavior associated with relapse of ketamine addiction, characterized in that, This includes administering an oral composition containing an effective dose of the probiotic to the subject for at least two consecutive weeks, wherein the probiotic contains Lactobacillus brevis strain GKJOY, with accession number NIT EB P-03316.

7. The use of the probiotic as described in claim 6 in the preparation of a pharmaceutical composition for reducing drug-seeking behavior associated with relapse of ketamine addiction, characterized in that, The pharmaceutical composition is an oral composition.

8. The use of the probiotic as described in claim 6 in the preparation of a pharmaceutical composition for reducing drug-seeking behavior associated with relapse of ketamine addiction, characterized in that, The pharmaceutical composition further includes pharmaceutically acceptable carriers, excipients, and / or additives.

9. The use of the probiotic as described in claim 6 in the preparation of a pharmaceutical composition for reducing drug-seeking behavior associated with relapse of ketamine addiction, characterized in that, The dosage forms of the pharmaceutical composition include powders, tablets, granules, suppositories, microcapsules, ampoules, liquid sprays, or plugs.

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