Application of L-theanine in product for preventing and treating irritable bowel syndrome

Abstract

The invention provides an application of L-theanine in a product for preventing and / or treating irritable bowel syndrome. Through continuous exploration, the inventor accidentally finds that the L-theanine can alleviate positive symptoms of patients with irritable bowel syndrome, and further develops related pharmacodynamic tests to explore an effective dose. The traditional Chinese medicine composition not only effectively solves the problems of high occurrence rate of adverse reactions and easy relapse of drugs for treating irritable bowel syndrome in the prior art, but also is non-toxic and harmless, and has a beneficial regulation effect on the body.

Description

Technical Field

[0001] The present invention relates to the application of L-theanine, and in particular to the application of L-theanine in products for preventing and treating irritable bowel syndrome. Background Art

[0002] Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by recurrent abdominal pain and discomfort accompanied by changes in bowel habits and / or stool characteristics. According to the Rome IV criteria, IBS is divided into four subtypes: constipation, diarrhea, mixed, and indeterminate. Among them, diarrhea-predominant IBS (IBS-D) is the most common in clinical practice, accounting for 23.3% to 65.0% of all IBS patients; literature shows that constipation-predominant IBS accounts for 37.4% of all IBS patients. It can be seen that the treatment of diarrhea-predominant and constipation-predominant IBS is of representative significance in the treatment of IBS.

[0003] Although the disease has a high incidence, the pathogenesis is not very clear due to the complexity of pathogenic factors, the lack of good biological markers, and the presence of multiple, overlapping, and non-specific symptoms, which makes diagnosis difficult. The mechanism of intestinal syndrome is unclear, which limits the selection and application of treatment methods. It is currently believed that the physiological and pathological mechanisms of irritable bowel syndrome are closely related to visceral hypersensitivity, intestinal motility abnormalities, intestinal flora disorders, gut-brain axis abnormalities, low-grade intestinal inflammation, mental psychology, genetics and other factors. The treatment methods are very limited. In the past 10 years, almost no new technologies and drugs have been introduced to the clinic. At the same time, for irritable bowel syndrome, the incidence of adverse reactions to current drug treatments is relatively high, which may affect the patient's quality of life and the continuity of treatment; the long-term recurrence rate is high, especially for some traditional Chinese medicine treatments. Although the short-term efficacy is good, the long-term recurrence rate is also relatively high.

[0004] Therefore, patients often suffer from recurrent abdominal symptoms, which seriously affects their work and life, and brings a heavy economic burden due to long-term medical treatment and medication. Currently, more research is needed to explore more effective and safe treatment options. Summary of the invention

[0005] In order to overcome the defects of the prior art, the present invention provides an application of L-theanine in a product for the prevention and treatment of irritable bowel syndrome. Through continuous exploration, the inventor unexpectedly discovered that L-theanine can alleviate the positive symptoms of patients with irritable bowel syndrome, and further carried out relevant pharmacodynamic tests to explore the effective dose. It not only effectively solves the high incidence of adverse reactions and the risk of recurrence in the prior art of drug treatment of irritable bowel syndrome, but is also non-toxic and harmless and has a beneficial regulatory effect on the body.

[0006] The present invention provides an application of L-theanine in a product for preventing and / or treating irritable bowel syndrome. The inventor unexpectedly discovered that administering L-theanine to patients with irritable bowel syndrome (IBS) can reduce symptoms of irritable bowel syndrome (IBS), such as diarrhea and bloating.

[0007] According to the pharmacodynamic study of L-theanine on irritable bowel syndrome (IBS) conducted by the inventor, the results show that L-theanine can improve or reverse the pathological changes in intestinal tissue caused by IBS, such as significantly improving symptoms such as mucosal muscularis infiltration, mucosal thickening, edema, and pathological changes in epithelial cells and crypt structures; at the same time, it significantly improves the positive symptoms of IBS, such as reducing mucus stool in diarrhea-type IBS rats, promoting stool formation, and increasing the number of stool particles in constipation-type IBS rats. Through creative work, the inventor revealed that L-theanine has preventive and therapeutic effects on irritable bowel syndrome (IBS).

[0008] Preferably, the use of L-theanine provided by the present invention in a product for the prevention and / or treatment of irritable bowel syndrome, wherein irritable bowel syndrome includes diarrhea type and / or constipation type. The inventor established an animal model of irritable bowel syndrome and conducted a pharmacodynamic study on the treatment of L-theanine in diarrhea type and constipation type irritable bowel syndrome, respectively. In a study on a rat model of diarrhea type IBS, it was found that after the animals with irritable bowel syndrome were modeled, different doses of L-theanine were given, and a significant increase in the body weight of the rats was observed, while the disease activity index (DAI score) decreased rapidly in a short period of time. There were statistically significant differences between each dose group and the model group, and the difference was dose-dependent. In a study on a rat model of constipation type IBS, it was found that after the animals with irritable bowel syndrome were modeled, different doses of L-theanine were given, and an increase in the number of stool particles was observed. In particular, there were statistically significant differences between the medium and high dose groups and the model group.

[0009] Preferably, the use of L-theanine provided by the present invention in a product for the prevention and / or treatment of irritable bowel syndrome, wherein the prevention and / or treatment product includes medicines, dietary supplements, functional foods, health care medical devices and / or other auxiliary products. Since the source of L-theanine has the property of being both a medicine and a food, it can be widely used in medicines, health care products, foods, and medical devices to produce a preventive and therapeutic effect on irritable bowel syndrome.

[0010] Preferably, the L-theanine provided by the present invention is used in a product for preventing and / or treating irritable bowel syndrome, wherein the product for preventing and / or treating irritable bowel syndrome is a human product and / or a veterinary product.

[0011] Preferably, the use of L-theanine provided by the present invention in a preventive and / or therapeutic product for irritable bowel syndrome, wherein the preventive and / or therapeutic product includes solid preparations, liquid preparations, semisolid preparations and / or gaseous preparations; solid preparations include pills, tablets, granules, powders, capsules, suppositories, films and / or lozenges; liquid preparations include mixtures, syrups, lotions, probes, injections, lotions and / or film coatings; semisolid preparations include ointments, gels and / or patches; gaseous preparations include aerosols, sprays and / or powder sprays.

[0012] Preferably, the use of L-theanine in the prevention and / or treatment products of irritable bowel syndrome provided by the present invention comprises capsules, suppositories, liquid preparations and / or semisolid preparations. Through exploratory research by the inventors, the above application dosage forms of L-theanine can act on the intestines faster and can be used for local administration.

[0013] Preferably, the application of L-theanine provided by the present invention in a product for the prevention and / or treatment of irritable bowel syndrome, wherein the product for the prevention and / or treatment is for anal administration and / or rectal administration. In actual applications, both anal administration and rectal administration are local administration, the difference being that the depth of administration is different, which will affect the circulation and absorption of the drug in the body. For anal administration, the direct absorption rate of the drug is nearly 50% to 75%, which is mainly local absorption; for rectal administration, part of the drug will enter the circulatory system, but the effect on the intestine is also more direct. As a product for the prevention and / or treatment of irritable bowel syndrome, L-theanine can reach the affected area faster using the above two administration methods, and the effect is more obvious.

[0014] Preferably, the use of L-theanine provided by the present invention in a product for the prevention and / or treatment of irritable bowel syndrome, wherein the effective concentration of the product for the prevention and / or treatment is 0.1 w / w% to 5.0 w / w% (calculated as L-theanine, by weight), or 1 mg to 500 mg / day (calculated as L-theanine content).

[0015] After repeated experiments and in-depth research, the inventors explored the effective concentration of L-theanine as a preventive and / or therapeutic product for irritable bowel syndrome, making an outstanding contribution to the widespread application of L-theanine. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0017] Figure 1 The effects of the normal group (A), model group (B), and three dose groups of L-theanine (D. 0.1% L-theanine group; E. 0.5% L-theanine group; F. 5.0% L-theanine group) on the colonic histopathology of rats with diarrhea-type IBS (HE staining, ×200); Figure 2 The changes in the number of stool particles in the normal group, model group, and L-theanine three-dose groups on the 14th and 21st days. DETAILED DESCRIPTION

[0018] In order to further illustrate the present invention, examples are given below. It should be noted that these examples are purely illustrative. The purpose of providing these examples is to fully illustrate the meaning and content of the present invention, but the present invention is not limited to the scope of the embodiments. Example 1

[0019] L-theanine can be used in products for the prevention and / or treatment of irritable bowel syndrome, wherein irritable bowel syndrome includes diarrhea type and / or constipation type. The prevention and / or treatment product can be a medicine, a dietary supplement, a functional food, a health care medical device and / or other auxiliary products, and can also be a human product or a veterinary product.

[0020] L-theanine is used in the prevention and / or treatment of irritable bowel syndrome, which can be solid preparations, liquid preparations, semi-solid preparations and / or gas preparations; solid preparations include pills, tablets, granules, powders, capsules, suppositories, films and / or lozenges; liquid preparations include mixtures, syrups, lotions, probes, injections, lotions and / or film coatings; semi-solid preparations include ointments, gels and / or patches; gas preparations include aerosols, sprays and / or powder sprays.

[0021] In one embodiment, the L-theanine product for preventing and / or treating irritable bowel syndrome is a capsule, a suppository, a liquid preparation or a semisolid preparation.

[0022] In another embodiment, the preventive and / or therapeutic product is administered anally and / or rectally.

[0023] In another embodiment, the effective concentration of the preventive and / or therapeutic product is 0.1 w / w% to 5.0 w / w% (calculated as L-theanine, by weight), or 1 mg to 500 mg / day (calculated as L-theanine content). Example 2

[0024] The pharmacodynamics study of L-theanine was conducted in the diarrhea-type IBS rat model: This example adopts the administration in the form of a solution to demonstrate the main pharmacodynamic effect of the active ingredient L-theanine, but does not limit the preventive and / or therapeutic product to a solution.

[0025] Experimental methods: Trinitrobenzene sulfonic acid (TNBS) was used to induce the establishment of an IBS rat model: 70 SPF-grade male SD rats with a weight of 180-220 g were selected, and 8 rats were selected as the normal control group. The remaining rats were fasted but not watered for 18 h, and anesthetized and given 0.28 mL 50% ethanol + 0.02 mL TNBS enema. Two weeks after the end of the enema, restraint stress was applied for 3 h every morning for 3 consecutive weeks.

[0026] The disease activity index (DAI score) of the rats was performed 24 hours after modeling. According to the DAI score and body weight, the rats with successful modeling were randomly divided into 5 groups: normal control group, model control group and experimental group. The experimental groups included 0.1% L-theanine group, 0.5% L-theanine group and 5.0% L-theanine group, with 8 rats in each group.

[0027] In the normal control group and the model control group, rats were given 0.9% sodium chloride injection; in the experimental group, L-theanine solution of the corresponding concentration group was given; the administration volume was 1.0 mL / rat, once a day, for 14 consecutive days. The rats in each group were weighed on the 1st, 3rd, 5th, 7th, and 14th day after modeling, and the disease activity index (DAI score) of the mice was observed and recorded. Among them, the disease activity index scoring standard is shown in Table 1:

[0028] After the last administration, the rats were killed and the colon was dissected and separated. The colon tissue was fixed in 10% neutral formalin solution, embedded in paraffin, and stained with HE to observe the intestinal crypts, villus cells, atypical hyperplasia of intestinal epithelium and intestinal epithelial exfoliation. The colon tissue was examined and scored for pathological examination. The scoring criteria are shown in Table 2. AB-PAS staining was also performed to observe the changes in the number of goblet cells in the rat colon.

[0029]

[0030] Test results: 1) As shown in Table 3, compared with the normal control group, the body weight of the rats in the model control group was significantly reduced from the 0th to the 14th day of administration (P≤0.01). Compared with the model control group, the body weight of the rats in the 5.0% L-theanine group was significantly increased from the 3rd to the 7th day of administration (P≤0.01).

[0031] This indicates that L-theanine can significantly alleviate the symptoms of weight loss caused by diarrhea-type IBS.

[0032]

[0033] 2) As shown in Table 4, compared with the normal control group, the disease activity index of the model control group was significantly increased from day 0 to day 14 of drug administration (P ≤ 0.01).

[0034] Compared with the model control group, the disease activity index of the rats in the 0.5% L-theanine group and the 5.0% L-theanine group was significantly reduced on the 3rd day of administration (P≤0.01); the disease activity index of the rats in the 5.0% L-theanine group was significantly reduced on the 5th day of administration (P≤0.01); the disease activity index of the rats in the 0.1% L-theanine group, the 0.5% L-theanine group, and the 5.0% L-theanine group was significantly reduced on the 14th day of administration (P≤0.01).

[0035] This shows that L-theanine can significantly reduce the disease activity index caused by diarrhea-type IBS and improve the typical positive symptoms of IBS.

[0036]

[0037] 3) As shown in Table 5 and Figure 1 As shown in the figure, compared with the normal control group, rats in the model control group had inflammatory cell infiltration at the base of the crypts, infiltration of the muscularis mucosa, thickening of the mucosa, and edema, and epithelial cells were significantly reduced, the crypts were enlarged or some crypts disappeared (P≤0.01), and the colon histopathological score was significantly increased (P≤0.01). Compared with the model control group, rats in the 0.5% L-theanine group had significantly reduced inflammatory cell infiltration at the base of the crypts, and the inflammatory infiltration score was significantly reduced (P≤0.05). Rats in the 0.5% L-theanine group and the 5.0% L-theanine group had significantly improved symptoms of infiltration of the muscularis mucosa, thickening of the mucosa, and edema, and the epithelial cells and crypt structure were significantly improved (P≤0.05 or P≤0.01).

[0038] This suggests that L-theanine can significantly improve or reverse the pathological changes in intestinal tissue caused by IBS, thereby producing a preventive and therapeutic effect.

[0039]

[0040] Therefore, L-theanine products, especially at an effective concentration or dosage of 0.1w / w% to 5.0w / w% (calculated as L-theanine, weight percentage), or 1mg to 500mg / day (calculated as L-theanine content), have a significant improvement effect on diarrhea-type irritable bowel syndrome and can be used as a preventive and / or therapeutic product for irritable bowel syndrome. The product can be a medicine, dietary supplement, functional food, health care medical device and / or other auxiliary product, or a human or veterinary product.

[0041] Meanwhile, the preventive and / or therapeutic product can be in various preparation forms, and is particularly suitable for capsules, suppositories, liquid preparations or semisolid preparations, and is preferably administered anally and / or rectally. Example 3

[0042] The pharmacodynamics study of L-theanine was conducted in the constipation-type IBS rat model: This example adopts the administration in the form of a solution to demonstrate the main pharmacodynamic effect of the active ingredient L-theanine, but does not limit the preventive and / or therapeutic product to a solution.

[0043] Experimental methods: After 7 days of adaptive feeding, the rats were randomly divided into a normal control group, a model group, and an experimental group. The experimental group included 0.1% L-theanine group, 0.5% L-theanine group, and 5.0% L-theanine group, with 6 rats in each group. Except for the normal control group, the rats in the other groups were modeled by ice water gavage, that is, ice water (0℃ ice water mixture) was given 2mL / rat every day, once / day, for 14 consecutive days to establish the IBS-C model. The normal control group was given 2mL / rat of normal temperature saline (26-28℃), once / day, for 14 consecutive days. Except for gavage, the animals in each group were free to eat and drink water.

[0044] The next day after modeling, that is, from the 15th day, except for the normal control group, the experimental groups were given anal enema (0.1% L-theanine, 0.5% L-theanine, 5.0% L-theanine solution), and the model group was given an equal dose of normal temperature saline for 7 consecutive days. During the entire experiment, the general condition of the rats was observed regularly; all rats were kept in cages with stainless steel mesh trays on the bottom plate, and double-layer absorbent filter paper was placed on the tray. The number of fecal particles of rats in each group was collected and calculated regularly every day, and the difference in the number of fecal particles on the 14th and 21st days was evaluated.

[0045] Test results: As shown in Table 6 and Figure 2As shown in the figure, compared with the normal group, the number of stool particles in the model group and the experimental group after modeling was significantly reduced. Compared with the model group, the number of stool particles in each dose group of the experimental group increased on the 21st day (D21), and the difference between the 0.5% L-theanine group and the 5.0% L-theanine group and the model group was statistically significant. This shows that L-theanine can significantly improve symptoms such as constipation caused by constipation-type IBS.

[0046]

[0047] Therefore, L-theanine products, especially at an effective concentration or dosage of 0.1w / w% to 5.0w / w% (calculated as L-theanine, weight percentage), or 1mg to 500mg / day (calculated as L-theanine content), have a significant improvement effect on constipation-type irritable bowel syndrome and can be used as a preventive and / or therapeutic product for irritable bowel syndrome. The product can be a medicine, dietary supplement, functional food, health care medical device and / or other auxiliary product, or a human or veterinary product.

[0048] Meanwhile, the preventive and / or therapeutic product can be in various preparation forms, and is particularly suitable for capsules, suppositories, liquid preparations or semisolid preparations, and is preferably administered anally and / or rectally.

[0049] The above are only specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art who is familiar with the technical field can easily think of changes or substitutions within the technical scope disclosed by the present invention, which should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. Use of L-theanine in products for the prevention and / or treatment of irritable bowel syndrome.

2. The use according to claim 1, characterized in that The irritable bowel syndrome includes diarrhea type and / or constipation type.

3. The use according to claim 1, characterized in that The preventive and / or therapeutic products include medicines, dietary supplements, functional foods, health care medical devices and / or other auxiliary products.

4. The use according to claim 1, characterized in that The preventive and / or therapeutic product is for human use and / or veterinary use.

5. The use according to claim 1, characterized in that The preventive and / or therapeutic products include solid preparations, liquid preparations, semisolid preparations and / or gas preparations; the solid preparations include pills, tablets, granules, powders, capsules, suppositories, films and / or lozenges; the liquid preparations include mixtures, syrups, lotions, probes, injections, lotions and / or film coatings; the semisolid preparations include ointments, gels and / or patches; the gas preparations include aerosols, sprays and / or powder sprays.

6. The use according to claim 5, characterized in that The preventive and / or therapeutic products include capsules, suppositories, liquid preparations and / or semisolid preparations.

7. The use according to claim 1, characterized in that The preventive and / or therapeutic product is for anal and / or rectal administration.

8. The use according to claim 1, characterized in that The effective concentration of the preventive and / or therapeutic product is 0.1 w / w% to 5.0 w / w% (calculated as L-theanine, by weight), or 1 mg to 500 mg / day (calculated as L-theanine content).

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