L-theanine composition

Abstract

The L-theanine composition provided by the invention is placed at 60 DEG C for 10 days, the growth rate of pyroglutamic acid impurities is within 3 times, and the quality requirement that the content of the pyroglutamic acid impurities is below 1% is met; the L-theanine composition is prepared from L-theanine, an excipient and magnesium stearate, wherein the mass ratio of the L-theanine is 5%-30%; the excipient comprises one or more of pregelatinized starch, lactose, microcrystalline cellulose, mannitol, colloidal silicon dioxide and / or a pH regulator, and the mass ratio of the excipient is 65%-94.9%; the mass ratio of the magnesium stearate is 0.1%-5%. Therefore, the medicine is endowed with higher stability, so that the L-theanine preparation composition which is good in stability, effectiveness and safety and meets the pharmacopoeia standard is obtained. Meanwhile, related pharmacodynamic experiments are carried out by the inventor, and it is proved that the composition can be used for preparing the medicine for preventing and / or treating vaginitis.

Description

Technical Field

[0001] The present invention relates to a composition, in particular to an L-theanine composition. Background Art

[0002] Theanine is a free amino acid unique to tea leaves. It was first isolated and extracted from green tea in 1950. It belongs to the amide class of compounds and its chemical name is N-ethyl-L-glutamine. The process of extracting L-theanine from tea leaves involves multiple steps, including extraction, purification, and separation of the target substance. Errors in any step may lead to contamination of the target substance or the production of non-target impurities, such as pyroglutamic acid. For example, in the process of converting glutamic acid to theanine by chemical synthesis, side reactions may occur, leading to the production of impurities such as pyroglutamic acid; in the process of synthesizing L-theanine using microorganisms, genetically engineered strains may express other enzymes related to theanine synthesis but not the target product when expressing the target enzyme, which may lead to the production of impurities such as pyroglutamic acid. Therefore, pyroglutamic acid itself will exist as a secondary impurity in the final L-theanine product, thereby reducing the purity and quality of the product.

[0003] Furthermore, since L-theanine is highly soluble in water, it is unstable under both acidic and alkaline conditions and will be hydrolyzed to form the impurity pyroglutamic acid, which will also affect the stability of L-theanine products, causing the quality of the products to deteriorate during long-term storage. At the same time, when its content exceeds certain prescribed standards, it will cause safety issues, such as allergic reactions and digestive system problems.

[0004] At present, L-theanine can be used as a food additive and cosmetic raw material in food, health care products and skin care products, but there is no drug with L-theanine as an active ingredient on the market. After investigation, L-theanine itself has high stability, but its compatibility with most excipients is poor, which will cause the pyroglutamic acid in the preparation to exceed the pharmacopoeia standard, thus affecting its development and listing as a drug. For example, when conducting stability studies on L-theanine preparations, it is necessary to study the influencing factors under conditions of high temperature, high humidity, light, etc. for 10 days. Usually, the development fails because the pyroglutamic acid increases too quickly and exceeds the quality requirements.

[0005] Developing an L-theanine composition that meets pharmacopoeia standards is the key to whether L-theanine can be successfully marketed as a drug and benefit the people, so there is an urgent need to carry out relevant research. Summary of the invention

[0006] In order to overcome the defects of the prior art, the present invention provides an L-theanine composition. The inventors have conducted in-depth exploration, selected specific excipients such as excipients, and carried out relevant ratio studies, and strictly controlled the types of excipients added and the amounts of raw excipients, thereby reducing the effects of the types and amounts of raw excipients on the acidity and alkalinity of the L-theanine preparation composition, avoiding or reducing the generation of impurities, and giving the drug higher stability, thereby obtaining an L-theanine preparation composition with good stability, effectiveness and safety, and meeting the pharmacopoeia standards. At the same time, the inventors carried out relevant pharmacodynamic experiments, confirming that the composition can be used to prepare drugs for preventing and / or treating vaginitis.

[0007] The invention provides an L-theanine composition, wherein the L-theanine composition is placed at 60° C. for 10 days, the growth rate of pyroglutamic acid impurities is within 3 times, and the quality requirement of the pyroglutamic acid impurity content being below 1% is met; the L-theanine composition comprises L-theanine, an excipient, and magnesium stearate; wherein the mass proportion of L-theanine is 5%-30%; the excipient comprises one or more of pregelatinized starch, lactose, microcrystalline cellulose, mannitol, colloidal silicon dioxide and / or a pH regulator, and the mass proportion of the excipient is 65%-94.9%; and the mass proportion of magnesium stearate is 0.1%-5%.

[0008] After in-depth exploration and long-term research, the inventors have found that under the conditions of conducting influencing factor tests in the drug development process of the L-theanine composition, especially when placed at a high temperature of 60°C for 10 days, the growth rate of pyroglutamic acid impurities is more than 3 times, and the quality requirement of the pyroglutamic acid impurity content being below 1% cannot be met. The inventors abandoned the development idea of ​​complex prescriptions, selected specific excipients and composition ratios, and solved the key problems that troubled drug developers and hindered product development in a simpler way, which has outstanding substantive characteristics and significant progress.

[0009] Preferably, the present invention provides an L-theanine composition, wherein the L-theanine composition meets the quality requirement of a pyroglutamic acid impurity content of less than 0.5%, and the excipient is selected from pregelatinized starch, lactose, colloidal silicon dioxide and / or a pH regulator. After further research, the inventors selected specific excipients and screened out an L-theanine composition that has a pyroglutamic acid impurity growth rate of less than 3 times when placed at 60°C for 10 days and meets the high quality standard of a pyroglutamic acid impurity content of less than 0.5%, which has made a breakthrough in the successful listing of the composition.

[0010] Preferably, the present invention provides an L-theanine composition, wherein the pH value of the L-theanine composition is 5 to 7. It is well known that during the prescription screening and proportioning process of the composition, its pH value will vary greatly with the type and quantity of excipients. After long-term exploration, the inventors found that the stability of the L-theanine composition, especially the growth rate of pyroglutamic acid impurities, is highly correlated with the pH value of the composition. When the pH value of the L-theanine composition is 5 to 7, the stability of L-theanine in the composition can be improved, the impurity level is effectively reduced, and the requirements for the pyroglutamic acid impurity content in the present invention are met. At the same time, the phenomenon of increased impurity content after long-term storage is avoided, and it has higher drug stability, storage stability and safety.

[0011] Preferably, the present invention provides an L-theanine composition, wherein the mass proportion of L-theanine in the composition is 7% to 20%, the mass proportion of the excipient is 78% to 92.9%, and the mass proportion of magnesium stearate is 0.1% to 2%. After research, the inventor found that when the mass proportion of L-theanine in the composition is less than 7% or greater than 20%, the impurity content of pyroglutamic acid is relatively high. The ratio of the above-mentioned L-theanine composition can meet the need of the present invention to better control the impurity content of pyroglutamic acid.

[0012] Preferably, the present invention provides an L-theanine composition, wherein the mass proportion of L-theanine in the composition is 10% to 15%, the mass proportion of the excipient is 83.5% to 89.5%, and the mass proportion of magnesium stearate is 0.5% to 1.5%. After further exploration, the inventors have shown through confirmatory studies that this ratio range can fully guarantee the quality requirements of the L-theanine composition in the drug development process, which is of great significance.

[0013] Preferably, the present invention provides an L-theanine composition, wherein the weight ratio of L-theanine to excipient is 1:6-1:8. The present invention further meets the requirements of pH range and impurity content of the composition by selecting the type of excipient and the ratio with the active ingredient.

[0014] Preferably, the present invention provides an L-theanine composition, wherein the L-theanine composition includes solid preparations, liquid preparations, semisolid 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; semisolid preparations include ointments, gels and / or plasters; gas preparations include aerosols, sprays and / or powder sprays.

[0015] Preferably, the present invention provides an L-theanine composition, wherein the L-theanine composition includes pills, tablets, granules, powders and / or capsules. After further screening by the inventors, the above dosage forms can better achieve the purpose of the present invention.

[0016] Preferably, the present invention provides an L-theanine composition, wherein the L-theanine composition is used to prepare a drug for preventing and / or treating vaginitis. The present invention conducts a comparative study through rigorous animal experiments and uses a metronidazole vaginal gel group as a positive control group to verify the effect of the L-theanine composition on the vaginal pH value of a mixed vaginitis model in rats, the effect on vaginal Gram bacteria, vaginal cleanliness, vaginal Gardnerella, and vaginal Lactobacillus in a mixed vaginitis model in rats, etc., all of which produce unexpected positive effects, while maintaining high stability and high safety, and are comparable to the prevention and treatment effects of currently marketed chemical drugs. Therefore, the L-theanine composition can be used to prepare a drug for preventing and / or treating vaginitis.

[0017] Preferably, the present invention provides an L-theanine composition, wherein the L-theanine composition is for vaginal administration. The inventors have found that the L-theanine composition is for vaginal administration, and can fully exert its preventive and / or therapeutic effects on vaginitis and the like only through local administration. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] 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.

[0019] Figure 1 A comparison chart of the effect of the L-theanine composition provided by the present invention on the vaginal pH value of a rat mixed vaginitis model before administration; Figure 2 A comparison chart showing the effect of the L-theanine composition provided by the present invention on the vaginal pH value of a rat mixed vaginitis model on the 7th day after administration; Figure 3 This is a comparison chart of the effect of the L-theanine composition provided by the present invention on the vaginal pH value of a rat mixed vaginitis model on the 14th day of administration. DETAILED DESCRIPTION

[0020] 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

[0021] The present invention provides an L-theanine composition, wherein the L-theanine composition is placed at 60°C for 10 days, and the growth rate of pyroglutamic acid impurities is within 3 times, meeting the quality requirement of pyroglutamic acid impurity content below 1%. The L-theanine composition comprises L-theanine, excipients, and magnesium stearate. Among them, the mass proportion of L-theanine is 5% to 30%; the excipients include one or more of pregelatinized starch, lactose, microcrystalline cellulose, mannitol, colloidal silicon dioxide and / or pH regulators, and the mass proportion of the excipients is 65% to 94.9%; the mass proportion of magnesium stearate is 0.1% to 5%. The pH value of the L-theanine composition is 5 to 7, and the weight ratio of L-theanine to excipients can be 1:6-1:8.

[0022] In one embodiment, the L-theanine composition meets the quality requirement that the pyroglutamic acid impurity content is below 0.5%, and the excipient is selected from pregelatinized starch, lactose, colloidal silicon dioxide and / or a pH regulator.

[0023] In another embodiment, L-theanine accounts for 7% to 20% by weight in the composition, the excipient accounts for 78% to 92.9% by weight, and magnesium stearate accounts for 0.1% to 2% by weight.

[0024] In yet another embodiment, L-theanine accounts for 10% to 15% by weight of the composition, the excipient accounts for 83.5% to 89.5% by weight, and magnesium stearate accounts for 0.5% to 1.5% by weight.

[0025] In one embodiment, the L-theanine composition may include 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 plasters; gas preparations include aerosols, sprays and / or powder sprays. In another embodiment, the L-theanine composition includes pills, tablets, granules, powders and / or capsules.

[0026] In one embodiment, the L-theanine composition can be used to prepare a medicament for preventing and / or treating vaginitis, and the L-theanine composition can be used for vaginal administration. Embodiment 2 to Embodiment 9

[0027] Impurity detection method: Chromatographic column: Star Spectrum Technology ArtChorm WP NH2 (4.6×250mm, 5μm); Column temperature: 25°C; Flow rate: 1.0ml / min; Injection volume: 10 μl; Detection wavelength: 200nm; Mobile phase: Mobile phase A: 25mmol phosphate buffered saline (pH3.0), mobile phase B: acetonitrile; Elution conditions: gradient elution, as shown in Table 1.

[0028]

[0029] The active ingredient L-theanine and various excipients were weighed according to the prescription in Table 2 and placed in a clean vial. They were mixed using a capillary tube and sealed and placed at 60° C. for 10 days.

[0030] The impurity detection method as above was used to detect the pyroglutamic acid impurity content on the 0th day and the 10th day of high temperature.

[0031]

[0032] As can be seen from Table 2, the L-theanine composition may include L-theanine, excipients, and magnesium stearate.

[0033] Among them, when the excipient is selected from one or more of pregelatinized starch, lactose, microcrystalline cellulose, mannitol, colloidal silicon dioxide and / or pH regulator, and the mass proportion of L-theanine is 5% to 30%, the mass proportion of the excipient is 65% to 94.9%, and the mass proportion of magnesium stearate is 0.1% to 5%, the pH value of the L-theanine composition is 5 to 7. The L-theanine composition is placed at 60°C for 10 days, and the growth rate of pyroglutamic acid impurities is within 3 times, meeting the quality requirement of pyroglutamic acid impurity content below 1%.

[0034] When the excipient is selected from pregelatinized starch, lactose, colloidal silicon dioxide and / or a pH regulator, the mass proportion of L-theanine in the composition is 7% to 20%, the mass proportion of the excipient is 78% to 92.9%, and the mass proportion of magnesium stearate is 0.1% to 2%; more preferably, the mass proportion of L-theanine in the composition is 10% to 15%, the mass proportion of the excipient is 83.5% to 89.5%, and the mass proportion of magnesium stearate is 0.5% to 1.5%; especially when the weight ratio of L-theanine to excipient is 1:6-1:8, the pH value of the L-theanine composition is 5 to 7. The L-theanine composition is placed at 60°C for 10 days, and the growth rate of pyroglutamic acid impurities is within 3 times, and the quality requirement of pyroglutamic acid impurity content below 0.5% can be met. Example 10

[0035] The L-theanine composition can be used to prepare solid preparations, liquid preparations, semi-solid preparations and / or gas preparations by conventional preparation methods; 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 plasters; gas preparations include aerosols, sprays and / or powder sprays.

[0036] The L-theanine composition is particularly suitable for preparing pills, tablets, granules, powders and / or capsules.

[0037] The following is only an example of the preparation method of capsules to illustrate how the L-theanine composition is used in the preparation of corresponding preparations. It is worth noting that this method is only illustrative in nature, and the actual preparation method is not limited thereto.

[0038] For example, capsules are prepared according to the prescription in Table 2: 1) Weigh the prescribed amount of L-theanine, excipient 1, and magnesium stearate respectively for later use; 2) premixing the prescribed amount of L-theanine with 1 / 10 to 1 / 3 of the prescribed amount of excipient 1 to obtain a mixture I; 3) The mixture I is sieved through a granulator (1.57 mm aperture sieve, rotation speed 1000 rpm), the sieved material is collected and mixed with another 1 / 10 to 1 / 3 of the excipient 1 to obtain a mixture II; 4) Add mixture II and the remaining excipient 1 into a universal mixer and mix evenly. Then add the sieved magnesium stearate and the prescribed amount of excipient 2 (pH adjuster). Mix at 10 rpm for 5 min to prepare capsule powder. 5) The capsule powder prepared in step 4) is added into capsule shells for filling to obtain capsules. Embodiment 11

[0039] Effects of L-theanine preparation on vaginal pH and vaginal bacterial colonization in a mixed vaginitis model in rats 1. Experimental methods: A mixed vaginitis model was established in rats (150 female SPF-grade pathogen-free SD rats, weighing 180-220 g) by bilateral ovariectomy and mixed bacterial infection (Fusobacterium nucleatum, Mobiluncus, and Gardnerella vaginalis). The effect of L-theanine preparation on the mixed vaginitis model in rats was studied to provide an experimental basis for clinical research.

[0040] 112 rats with successful model were selected and randomly divided into model control group, blank vaginal capsule group, metronidazole vaginal gel group (positive control group), and vaginal capsule experimental group, wherein the vaginal capsule experimental group was constructed using the capsule prepared by the method of Example 10, with vaginal capsule dosages 1, 2, 3, and 4 groups (containing 0.25 mg, 0.5 mg, 1.25 mg, and 2.5 mg L-theanine / capsule, respectively), with 16 rats in each group, for a total of 7 groups. Among them, the sham operation group (normal rats without modeling) and the model control group were not treated, the blank vaginal capsule group was given blank vaginal capsules vaginally; the vaginal capsule experimental group was given the corresponding dose of drugs vaginally, 1 / capsule / rat, once / day, for 14 consecutive days; the metronidazole vaginal gel group was given metronidazole vaginal gel vaginally, 0.1 g / rat, once / day, for 7 consecutive days.

[0041] 2. Results of the experiment on the effect of L-theanine preparation on vaginal pH value in the mixed vaginitis model of rats Vaginal pH was tested (using precision pH test paper) before administration and 24 hours after administration on the 7th day and 24 hours after administration on the 14th day. The results are shown in Table 3. Figures 1 to 3 shown.

[0042] Compared with the sham operation group (equivalent to the normal rat group), the vaginal pH values ​​of the rats in the model control group and the blank vaginal capsule group (blank capsules without active ingredients) were significantly increased before administration, on the 7th day, and on the 14th day after administration (P≤0.01).

[0043] Compared with the model control group, there was no significant difference in the vaginal pH value of the rats in the blank vaginal capsule group before administration and on the 14th day after administration; compared with the model control group, the vaginal pH value of the rats in the blank vaginal capsule group, vaginal capsule dose groups 1, 2, 3, 4, and metronidazole vaginal gel group was significantly decreased on the 7th day after administration (P≤0.01); compared with the model control group, the vaginal pH value of the rats in vaginal capsule dose groups 1, 2, 3, 4, and metronidazole vaginal gel group was significantly decreased on the 14th day after administration (P≤0.01).

[0044] Compared with the blank vaginal capsule group, the vaginal pH values ​​of rats in vaginal capsule dose groups 1 and 3 were significantly decreased after 7 days of administration (P≤0.01); after 14 days of administration, the vaginal pH values ​​of rats in the metronidazole vaginal gel group and vaginal capsule dose groups 1, 2, 3, and 4 were significantly decreased (P≤0.01).

[0045] Compared with the metronidazole vaginal gel group, the vaginal pH value of rats in vaginal capsule dose group 3 was significantly decreased after 7 days of administration (P≤0.01); and the vaginal pH value of rats in vaginal capsule dose groups 2 and 4 was significantly increased after 14 days of administration (P≤0.01).

[0046]

[0047] 3. Results of the experiment on the effect of L-theanine preparation on vaginal bacterial colonization in a mixed vaginitis model in rats Before administration, 24 hours after administration on the 7th day, and 24 hours after administration on the 14th day, the vaginal lavage fluid of each group of rats was collected with a sterile cotton swab (strictly quantified during the operation), smeared on the screening culture medium (sterile operation), and cultured in a 37°C incubator. After 24 hours, the colonies were counted and photographed.

[0048] 1) Comparison of the number of vaginal Gram bacteria in the vaginitis model As shown in Table 4, before administration: compared with the sham operation group, the number of vaginal Gram bacteria in the model control group and blank vaginal capsule group was significantly increased (P≤0.01); compared with the model control group, no significant difference was found between the groups before administration; compared with the blank vaginal capsule group, no significant difference was found between the groups before administration. Compared with the metronidazole vaginal gel group, no significant difference was found between the groups.

[0049] On the 7th day of administration: compared with the sham operation group, the number of vaginal Gram bacteria in the rats in the model control group and the blank vaginal capsule group was significantly increased (P≤0.01); compared with the model control group, the number of vaginal Gram bacteria in the rats in the vaginal capsule dose 3 group and the metronidazole vaginal gel group was significantly decreased (P≤0.05); compared with the blank vaginal capsule group, the number of vaginal Gram bacteria in the rats in the vaginal capsule dose 3 group and the metronidazole vaginal gel group was significantly decreased (P≤0.05).

[0050] On the 14th day of administration: compared with the sham operation group, the number of vaginal Gram bacteria in the model control group was significantly increased (P≤0.05); compared with the model control group, the number of vaginal Gram bacteria in the rats in the vaginal capsule dose 2, 3, and 4 groups was significantly decreased (P≤0.05); compared with the blank vaginal capsule group, no significant difference was found among the groups; compared with the metronidazole vaginal gel group, no significant difference was found among the groups.

[0051]

[0052] As described above, the L-theanine composition can significantly reduce the number of vaginal Gram bacteria in mixed vaginitis, and its effect is comparable to that of the current mainstream therapeutic drug metronidazole vaginal gel.

[0053] 2) Comparison of vaginal cleanliness levels in vaginitis models As shown in Table 5, compared with the sham operation group, the vaginal cleanliness levels of the rats in the model control group and the blank vaginal capsule group before administration, on the 7th and 14th days after administration were significantly increased (P≤0.01); compared with the model control group, on the 14th day after administration, the vaginal cleanliness levels of the rats in the vaginal capsule dose groups 3 and 4 were significantly decreased (P≤0.05); compared with the blank vaginal capsule group, the vaginal cleanliness levels of the rats in the vaginal capsule dose groups 1, 2, 3, 4 and the metronidazole vaginal gel group were significantly decreased (P≤0.05 or P≤0.01); compared with the metronidazole vaginal gel group, no significant differences were found among the groups.

[0054]

[0055] As described above, the L-theanine composition may reduce the level of vaginal cleanliness in mixed vaginitis, which is comparable to the current mainstream treatment drug metronidazole vaginal gel.

[0056] 3) Comparison of vaginal Gardnerella counts in vaginitis models As shown in Table 6, before administration: compared with the sham operation group, the number of vaginal Gardnerella in the model control group and the blank vaginal capsule group was significantly increased (P≤0.01); compared with the model control group, no significant difference was found between the groups; compared with the blank vaginal capsule group, no significant difference was found between the groups; compared with the metronidazole vaginal gel group, no significant difference was found between the groups.

[0057] On the 7th day of administration: compared with the sham operation group, the number of vaginal Gardnerella in the model control group and blank vaginal capsule group was significantly increased (P≤0.01); compared with the model control group, the number of vaginal Gardnerella in the rats in vaginal capsule dose 1, 3, 4 groups and metronidazole vaginal gel group was significantly decreased (P≤0.05 or P≤0.01); compared with the blank vaginal capsule group, the number of vaginal Gardnerella in the rats in vaginal capsule dose 3 group and metronidazole vaginal gel group was significantly decreased (P≤0.05 or P≤0.01).

[0058] On the 14th day of administration: compared with the sham operation group, the number of vaginal Gardnerella in the rats in the model control group and blank vaginal capsule group was significantly increased (P≤0.01); compared with the model control group, the number of vaginal Gardnerella in the rats in vaginal capsule dose 2, 3, 4 groups and metronidazole vaginal gel group was significantly decreased (P≤0.05 or P≤0.01); compared with the blank vaginal capsule group, the number of vaginal Gardnerella in the rats in vaginal capsule dose 1, 2, 3, 4 groups and metronidazole vaginal gel group was significantly decreased (P≤0.05 or P≤0.01); compared with the metronidazole vaginal gel group, the number of vaginal Gardnerella in the rats in vaginal capsule dose 2 and 3 groups was significantly decreased (P≤0.05 or P≤0.01).

[0059]

[0060] As described above, the L-theanine composition can significantly reduce the number of vaginal Gardnerella in mixed vaginitis, and the effect is more likely to be better than the current mainstream therapeutic drug metronidazole vaginal gel.

[0061] 4) Comparison of the number of vaginal lactobacilli As shown in Table 7, before administration: compared with the sham operation group, the number of vaginal lactobacilli in the model control group and the blank vaginal capsule group was significantly reduced (P≤0.05); compared with the model control group, no significant difference was found between the groups; compared with the blank vaginal capsule group, no significant difference was found between the groups; compared with the metronidazole vaginal gel group, no significant difference was found between the groups.

[0062] On the 7th day of administration: compared with the sham operation group, the number of vaginal Lactobacillus in the model control group and blank vaginal capsule groups was significantly decreased (P≤0.05); compared with the model control group, the number of vaginal Lactobacillus in the rats in vaginal capsule dose 1, 2, 3, and 4 groups was significantly increased (P≤0.05); compared with the blank vaginal capsule group, the number of vaginal Lactobacillus in the rats in vaginal capsule dose 1, 2, 3, and 4 groups was significantly increased (P≤0.05); compared with the metronidazole vaginal gel group, the number of vaginal Lactobacillus in the rats in vaginal capsule dose 1, 2, 3, and 4 groups was significantly increased (P≤0.05).

[0063] On the 14th day of administration: compared with the sham operation group, the number of vaginal Lactobacillus in the model control group and blank vaginal capsule group was significantly decreased (P≤0.05); compared with the model control group, the number of vaginal Lactobacillus in the rats in vaginal capsule dose 2, 3, and 4 groups was significantly increased (P≤0.05 or P≤0.01); compared with the blank vaginal capsule group, the number of vaginal Lactobacillus in the rats in vaginal capsule dose 3 and 4 groups was significantly increased (P≤0.05); compared with the metronidazole vaginal gel group, the number of vaginal Lactobacillus in the rats in vaginal capsule dose 4 group was significantly increased (P≤0.05).

[0064]

[0065] As described above, the L-theanine composition can significantly increase the number of beneficial bacteria vaginal lactobacilli in mixed vaginitis, and the effect is more likely to be better than the current mainstream therapeutic drug metronidazole vaginal gel.

[0066] Therefore, according to the experimental results of Example 11, the L-theanine composition provided by the present invention can improve the pH value and bacterial colony distribution of the vagina, and can be used to prepare a drug for preventing and / or treating vaginitis. The administration method of the L-theanine composition can be vaginal administration.

[0067] 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. An L-theanine composition, characterized in that The L-theanine composition is placed at 60° C. for 10 days, and the growth rate of pyroglutamic acid impurities is within 3 times, meeting the quality requirement of pyroglutamic acid impurity content being below 1%; The L-theanine composition comprises L-theanine, excipients, and magnesium stearate; Wherein, the mass proportion of L-theanine is 5% to 30%; The excipients include one or more of pregelatinized starch, lactose, microcrystalline cellulose, mannitol, colloidal silicon dioxide and / or a pH adjuster, and the mass proportion of the excipients is 65% to 94.9%; The magnesium stearate accounts for 0.1% to 5% by mass.

2. The L-theanine composition according to claim 1, characterized in that The L-theanine composition meets the quality requirement that the pyroglutamic acid impurity content is below 0.5%, and the excipient is selected from pregelatinized starch, lactose, colloidal silicon dioxide and / or a pH regulator.

3. The L-theanine composition according to claim 1, wherein The pH value of the L-theanine composition is 5-7.

4. The L-theanine composition according to claim 1, characterized in that The L-theanine accounts for 7% to 20% by weight in the composition, the excipient accounts for 78% to 92.9% by weight, and the magnesium stearate accounts for 0.1% to 2% by weight.

5. The L-theanine composition according to claim 1, characterized in that The L-theanine accounts for 10% to 15% by weight in the composition, the excipient accounts for 83.5% to 89.5% by weight, and the magnesium stearate accounts for 0.5% to 1.5% by weight.

6. The L-theanine composition according to claim 1, characterized in that The weight ratio of the L-theanine to the excipient is 1:6-1:

8.

7. The L-theanine composition according to claim 1, wherein The L-theanine composition includes 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 plasters; the gas preparations include aerosols, sprays and / or powder sprays.

8. The L-theanine composition according to claim 7, characterized in that The L-theanine composition includes pills, tablets, granules, powders and / or capsules.

9. The L-theanine composition according to claim 1, wherein The L-theanine composition is used for preparing a medicine for preventing and / or treating vaginitis.

10. The L-theanine composition according to claim 1, characterized in that The L-theanine composition is used for vaginal administration.

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