A sleep-aid composition of 5-htp-l-theanine synergistically regulates sleep rhythm

Abstract

This invention discloses a sleep-aid composition that synergistically regulates sleep rhythm with 5-HTP and L-theanine, relating to the fields of biomedicine and health food technology. This invention effectively regulates sleep rhythm through the synergistic effect of 5-hydroxytryptophan, L-theanine, and γ-aminobutyric acid (GABA), helping users improve sleep quality. 5-HTP, as a precursor to serotonin, helps increase serotonin levels, which are then converted into melatonin, regulating the sleep cycle. L-theanine promotes the release of alpha brain waves, helping to relax the mind and body and reduce anxiety. GABA, as an inhibitory neurotransmitter, effectively relieves tension and promotes deep sleep. The synergistic effect of these three components provides users with more comprehensive and effective sleep support.

Description

Technical Field

[0001] This invention relates to the fields of biomedicine and health food technology, specifically to a sleep-aiding composition that synergistically regulates sleep rhythm with 5-HTP-L-theanine. Background Technology

[0002] In modern society, with the accelerated pace of life and increased work pressure, sleep disorders are becoming increasingly common, posing a significant threat to people's health and quality of life. Insufficient sleep or poor sleep quality not only leads to daytime fatigue and difficulty concentrating, but can also trigger a range of physical and mental health problems, such as anxiety, depression, and cardiovascular disease. Therefore, finding safe and effective sleep aids has become a hot topic in scientific research and industry.

[0003] While traditional sleep aids can alleviate sleep disorders to some extent, their drawbacks cannot be ignored. First, chemically synthesized drugs often have strong side effects, such as dizziness, drowsiness, and memory loss, affecting patients' daily lives and work efficiency. Second, long-term use of these drugs can easily lead to tolerance and dependence, causing the drug's effectiveness to gradually diminish, and even resulting in serious problems such as rebound insomnia after discontinuation. Furthermore, traditional sleep aids often target only a single sleep problem, lacking the ability to comprehensively regulate sleep rhythms and failing to fundamentally improve sleep quality.

[0004] In view of the shortcomings of traditional sleep aids, the present invention proposes a sleep aid composition that synergistically regulates sleep rhythm with 5-HTP-L-theanine, which is of particular importance. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a sleep aid composition that synergistically regulates sleep rhythm with 5-HTP-L-theanine. This composition utilizes a scientifically proportioned ratio of three natural components—5-hydroxytryptophan, L-theanine, and γ-aminobutyric acid—to synergistically regulate sleep rhythm through their unique physiological mechanisms, effectively improving sleep quality. Compared to traditional sleep aids, this sleep aid composition is safe, reliable, non-addictive, and possesses strong comprehensive regulatory capabilities, providing users with more comprehensive and effective sleep support and meeting the urgent needs of modern people for healthy sleep.

[0006] To solve the above-mentioned technical problems, the present invention provides the following technical solution: a sleep-aiding composition for synergistic regulation of sleep rhythm by 5-HTP-L-theanine, made from the following raw materials in parts by weight: The active ingredients of the composition consist of 5-hydroxytryptophan, L-theanine and γ-aminobutyric acid.

[0007] Further, by weight, the active ingredients include 5-HTP 5-30 parts, L-theanine 20-100 parts, and GABA 30-150 parts.

[0008] Furthermore, by weight, the active ingredients include 10-25 parts of 5-HTP, 30-80 parts of L-theanine, and 50-120 parts of GABA.

[0009] Furthermore, the weight ratio of 5-HTP, L-theanine and GABA is 1:(3~5):(5~7).

[0010] Furthermore, the 5-HTP is an African Ghanaian seed extract, wherein the 5-HTP has a purity of ≥98%; the L-theanine is a natural tea extract or a food-grade microbial fermentation source, with a purity of ≥99%; and the GABA is a food-grade microbial fermentation source, with a purity of ≥99%.

[0011] Furthermore, the composition also contains pharmaceutically or food-grade excipients, which constitute 10% to 90% of the total weight of the composition.

[0012] Furthermore, the excipients include at least one of fillers, binders, disintegrants, lubricants, flavoring agents, preservatives, and solubilizers.

[0013] Furthermore, the dosage form of the composition is an oral preparation, which includes any one of tablets, hard capsules, soft capsules, granules, powders, oral liquids, and chewable tablets.

[0014] Furthermore, the composition is a single-dose oral formulation, wherein each single-dose formulation contains 5 mg to 30 mg of 5-HTP, 20 mg to 100 mg of L-theanine, and 30 mg to 150 mg of GABA.

[0015] Furthermore, the excipients also include a gastrointestinal protectant, which is at least one of fructooligosaccharides, inulin, and resistant dextrin, and the gastrointestinal protectant accounts for 1% to 10% of the total weight of the composition.

[0016] Compared with existing technologies, this sleep-aiding composition that synergistically regulates sleep rhythm with 5-HTP-L-theanine has the following beneficial effects: I. The sleep-aid composition of the present invention effectively regulates sleep rhythm and helps users improve sleep quality through the synergistic effect of 5-hydroxytryptophan, L-theanine and γ-aminobutyric acid. 5-HTP, as a precursor of serotonin, helps to increase serotonin levels, which are then converted into melatonin to regulate the sleep cycle. L-theanine helps relax the mind and body and reduce anxiety by promoting the release of alpha brain waves in the brain. GABA, as an inhibitory neurotransmitter, can effectively relieve tension and promote deep sleep. The three work synergistically to provide users with more comprehensive and effective sleep support.

[0017] Other advantages, objectives and features of the invention will be set forth in part in the description which follows, and in part will be apparent to those skilled in the art from the following examination or study, or may be learned from the practice of the invention. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are merely some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without any creative effort.

[0019] Figure 1 A flowchart of a sleep-aiding composition that synergistically regulates sleep rhythm with 5-HTP-L-theanine. Detailed Implementation

[0020] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with the accompanying drawings and preferred embodiments, is provided below.

[0021] Examples one to three only varied the content of 5-hydroxytryptophan. Example 1 Composition Formulation The sleep-aid composition of this embodiment is an oral tablet. Based on the dosage per 1000 tablets, only the dosage of 5-hydroxytryptophan is adjusted; the types and amounts of other active ingredients and excipients remain consistent with the original embodiment. Specifically, the dosage of 5-hydroxytryptophan is 5g, derived from Ghanaian seed extract, with a 5-HTP purity of 98.5%; the dosage of L-theanine is 80g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the dosage of γ-aminobutyric acid (GABA) is 120g, derived from food-grade microbial fermentation, with a purity of 99.5%.

[0022] The total weight of the excipients accounts for 58.97% of the total weight of the composition, which meets the requirement of 10% to 90% as claimed in the claims. Specifically, the composition consists of 30g of fructooligosaccharide as a gastrointestinal protectant, accounting for 5.92% of the total weight of the composition, which meets the requirement of 1% to 10% as claimed in the claims. It is also combined with 180g of microcrystalline cellulose and 50g of mannitol as fillers, 12g of hydroxypropyl methylcellulose (HPMCE5) as a binder, 25g of crospovidone as a disintegrant, 3g of magnesium stearate as a lubricant, and 2g of sweet orange flavoring as a flavoring agent.

[0023] This embodiment is a single-dose oral tablet, with each finished tablet weighing 507 mg. Each single dose contains 5 mg of 5-HTP, 80 mg of L-theanine, and 120 mg of GABA, which fully complies with the claims regarding the single-dose content.

[0024] Preparation process This embodiment uses a wet granulation and tableting process commonly used in the food and pharmaceutical industries. First, the above-mentioned active ingredients and excipients are passed through an 80-mesh sieve and accurately weighed according to the formula. Then, the binder is prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved to prepare a 5% (w / w) binder solution.

[0025] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharides, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 minutes until the material is homogeneous. A prepared binder solution is then added to form a soft mass, which is passed through a 20-mesh sieve to form wet granules. The wet granules are placed in a fluidized bed dryer and dried at 60°C with forced air until the moisture content is ≤3%. The dried granules are then passed through a 24-mesh sieve for granulation.

[0026] Finally, magnesium stearate and sweet orange flavoring are added to the granulated dry granules, and the mixture is placed in a three-dimensional motion mixer and mixed for 8 minutes. After the intermediate content is found to be qualified, the tablets are compressed using a rotary tablet press, controlling the tablet weight difference to ±5% and the hardness to 4-6 kgf, thus obtaining the target sleep aid tablets.

[0027] Effect verification To verify the effect of the composition of this embodiment in synergistically regulating sleep rhythm and improving sleep quality, and to verify its gastrointestinal safety, an animal experiment was conducted in SPF-grade KM mice. The experimental protocol, animal parameters, grouping rules, and dosing cycle were completely consistent with the original embodiment, except that the dosage of 5-HTP in the corresponding group was adjusted.

[0028] Sixty male KM mice weighing 18-22g were randomly divided into 6 groups of 10 mice each. Mice were administered the medication by gavage once daily at a fixed time for 14 consecutive days. The blank control group received an equal volume of physiological saline. The 5-HTP single-dose group received 5mg / kg·bw of 5-HTP by gavage. The L-theanine + GABA binary group received a combination of 80mg / kg·bw L-theanine and 120mg / kg·bw GABA by gavage. The low-dose group received the composition of this embodiment at 102.5mg / kg·bw, corresponding to 2.5mg 5-HTP, 40mg L-theanine, and 60mg GABA. The medium-dose group received the composition of this embodiment at 205mg / kg·bw, corresponding to the recommended human dose proportionally to the formulation. The high-dose group received the composition of this embodiment at 410mg / kg·bw, twice the recommended dose.

[0029] The results of sleep rhythm and sleep quality tests showed that in the blank control group, the number of spontaneous activities in mice over 10 minutes was 1286±112, the sleep induction rate of subthreshold sodium pentobarbital was 10%, the sleep latency was 28.6±3.2 min, and the total sleep duration was 42.3±5.7 min. In the 5-HTP single group, the number of spontaneous activities in mice over 10 minutes was 1152±105, the sleep induction rate of subthreshold sodium pentobarbital was 20%, the sleep latency was 25.3±3.0 min, and the total sleep duration was 56.2±7.1 min. In the L-theanine+GABA binary group, the number of spontaneous activities in mice over 10 minutes was 862±85, the sleep induction rate of subthreshold sodium pentobarbital was 40%, the sleep latency was 19.2±2.5 min, and the total sleep duration was 92.4±9.1 min.

[0030] In the low-dose group, mice exhibited 758±78 spontaneous activity episodes within 10 minutes, a 50% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 16.8±2.3 min, and a total sleep duration of 110.5±9.8 min. In the medium-dose group, mice exhibited 586±69 spontaneous activity episodes within 10 minutes, a 70% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 13.5±2.0 min, and a total sleep duration of 142.6±11.2 min. In the high-dose group, mice exhibited 495±62 spontaneous activity episodes within 10 minutes, an 80% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 11.2±1.8 min, and a total sleep duration of 168.3±12.0 min.

[0031] The above results indicate that, compared with the blank control group, the single-component group, and the binary composition group, the ternary composition of this embodiment still has a significant synergistic sleep-aiding effect, which can effectively reduce the number of spontaneous activities in mice, increase the sleep onset rate, shorten the sleep latency, and prolong the total sleep duration. It also shows obvious dose dependence, with a mild overall effect and no risk of excessive central nervous system inhibition.

[0032] Gastrointestinal safety verification results showed that after 14 days of continuous gavage, anatomical observation of the gastrointestinal tissue of mice revealed that the gastrointestinal mucosa of mice in both the blank control group and the dosage groups of this embodiment was intact, without congestion, edema, erosion, or other damage. No abnormalities were found in the gastrointestinal mucosa of mice in the 5-HTP-only group. Serological tests showed no significant difference in gastrin and diamine oxidase levels between the dosage groups of this embodiment and the blank control group, indicating excellent oral safety of the composition.

[0033] The low-dose 5-HTP ternary sleep aid composition of this embodiment achieves a mild and stable sleep aid effect through synergistic effects with fixed doses of L-theanine and GABA. The medium-dose composition can reduce the number of spontaneous activities in mice within 10 minutes by 54.4% compared with the blank control group, and by 49.1% and 32.0% compared with the 5-HTP single group and the L-theanine + GABA binary group, respectively. At the same time, it can increase the sleep onset rate of subthreshold dose of sodium pentobarbital from 10% in the blank group to 70%, shorten the sleep latency by 52.8% compared with the blank group, and prolong the total sleep duration by 237.1% compared with the blank control group, and by 153.7% and 54.3% compared with the 5-HTP single group and the binary combination group, respectively. It is suitable for the daily mild conditioning needs of people with mild sleep disorders and has no additional risk of gastrointestinal irritation.

[0034] Example 2 Composition Formulation The sleep-aid composition of this embodiment is an oral tablet. Based on the dosage per 1000 tablets, only the dosage of 5-hydroxytryptophan is adjusted; the types and amounts of other active ingredients and excipients remain consistent with the original embodiment. Specifically, the dosage of 5-hydroxytryptophan is 15g, derived from Ghanaian seed extract, with a 5-HTP purity of 98.5%; the dosage of L-theanine is 80g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the dosage of γ-aminobutyric acid (GABA) is 120g, derived from food-grade microbial fermentation, with a purity of 99.5%.

[0035] The total weight of the excipients accounts for 58.03% of the total weight of the composition, which meets the requirement of 10% to 90% as claimed in the claims. Specifically, the composition consists of 30g of fructooligosaccharide as a gastrointestinal protectant, accounting for 5.80% of the total weight of the composition, which meets the requirement of 1% to 10% as claimed in the claims. It is also combined with 180g of microcrystalline cellulose and 50g of mannitol as fillers, 12g of hydroxypropyl methylcellulose (HPMCE5) as a binder, 25g of crospovidone as a disintegrant, 3g of magnesium stearate as a lubricant, and 2g of sweet orange flavoring as a flavoring agent.

[0036] This embodiment is a single-dose oral tablet, with each finished tablet weighing 517 mg. Each single dose contains 15 mg of 5-HTP, 80 mg of L-theanine, and 120 mg of GABA, which fully complies with the claims regarding the single-dose content.

[0037] Preparation process This embodiment uses a wet granulation and tableting process commonly used in the food and pharmaceutical industries. First, the above-mentioned active ingredients and excipients are passed through an 80-mesh sieve and accurately weighed according to the formula. Then, the binder is prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved to prepare a 5% (w / w) binder solution.

[0038] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharides, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 minutes until the material is homogeneous. A prepared binder solution is then added to form a soft mass, which is passed through a 20-mesh sieve to form wet granules. The wet granules are placed in a fluidized bed dryer and dried at 60°C with forced air until the moisture content is ≤3%. The dried granules are then passed through a 24-mesh sieve for granulation.

[0039] Finally, magnesium stearate and sweet orange flavoring are added to the granulated dry granules, and the mixture is placed in a three-dimensional motion mixer and mixed for 8 minutes. After the intermediate content is found to be qualified, the tablets are compressed using a rotary tablet press, controlling the tablet weight difference to ±5% and the hardness to 4-6 kgf, thus obtaining the target sleep aid tablets.

[0040] Effect verification test To verify the effect of the composition of this embodiment on synergistic regulation of sleep rhythm and improvement of sleep quality, and to verify its gastrointestinal safety, an animal experiment was conducted in SPF-grade KM mice. The experimental protocol, animal parameters, grouping rules, and dosing cycle were completely consistent with the original embodiment, except that the dosage of 5-HTP in the corresponding group was adjusted.

[0041] Sixty male KM mice weighing 18-22g were randomly divided into 6 groups of 10 mice each. Mice were administered the solution once daily at a fixed time for 14 consecutive days. The control group received an equal volume of physiological saline. The 5-HTP-only group received 15 mg / kg body weight (bw) of 5-HTP. The L-theanine + GABA binary group received a combination of 80 mg / kg body weight (bw) of L-theanine and 120 mg / kg body weight (bw) of GABA. The low-dose group received the composition of this embodiment at 107.5 mg / kg body weight (corresponding to 7.5 mg 5-HTP, 40 mg L-theanine, and 60 mg GABA). The medium-dose group received the composition of this embodiment at 215 mg / kg body weight (corresponding to the recommended human dose proportionally to the formulation). The high-dose group received the composition of this embodiment at 430 mg / kg body weight (twice the recommended dose).

[0042] The results of sleep rhythm and sleep quality tests showed that in the blank control group, the number of spontaneous activities in mice over 10 minutes was 1286±112, the sleep induction rate of subthreshold sodium pentobarbital was 10%, the sleep latency was 28.6±3.2 min, and the total sleep duration was 42.3±5.7 min. In the 5-HTP single group, the number of spontaneous activities in mice over 10 minutes was 1023±101, the sleep induction rate of subthreshold sodium pentobarbital was 30%, the sleep latency was 22.1±2.9 min, and the total sleep duration was 72.4±7.8 min. In the L-theanine+GABA binary group, the number of spontaneous activities in mice over 10 minutes was 862±85, the sleep induction rate of subthreshold sodium pentobarbital was 40%, the sleep latency was 19.2±2.5 min, and the total sleep duration was 92.4±9.1 min.

[0043] In the low-dose group, mice exhibited 685±75 spontaneous activity episodes within 10 minutes, a 55% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 15.6±2.2 minutes, and a total sleep duration of 118.7±10.2 minutes. In the medium-dose group, mice exhibited 489±63 spontaneous activity episodes within 10 minutes, an 80% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 11.8±1.9 minutes, and a total sleep duration of 162.3±11.8 minutes. In the high-dose group, mice exhibited 402±55 spontaneous activity episodes within 10 minutes, a 90% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 9.6±1.5 minutes, and a total sleep duration of 192.5±12.8 minutes.

[0044] The above results indicate that, compared with the blank control group, the single-component group, and the binary composition group, the ternary composition of this embodiment has a more prominent synergistic sleep-aiding effect. It can significantly reduce the number of spontaneous activities in mice, greatly increase the subthreshold dose sleep onset rate, shorten sleep latency, and prolong the total sleep duration, and shows obvious dose dependence. The sleep-aiding effect is balanced and suitable for the improvement needs of most people with moderate sleep disorders.

[0045] Gastrointestinal safety verification results showed that after 14 days of continuous gavage, anatomical observation of the gastrointestinal tissue of mice revealed that the gastrointestinal mucosa of mice in the blank control group and each dose group of this embodiment remained intact, without congestion, edema, erosion, or other damage. Only one mouse in the 5-HTP group showed mild gastric mucosal congestion. Serological tests showed no significant difference in gastrin and diamine oxidase levels between each dose group of this embodiment and the blank control group, confirming that the added fructooligosaccharides in the formulation can effectively alleviate the gastrointestinal irritation that may be caused by medium-dose 5-HTP, and that the composition has excellent oral safety.

[0046] The medium-dose 5-HTP ternary sleep aid composition of this embodiment achieves a balanced and potent sleep aid effect through synergistic action with fixed doses of L-theanine and GABA. The medium-dose composition reduced the number of spontaneous activities in mice within 10 minutes by 62.0% compared to the blank control group, and by 52.2% and 43.3% compared to the 5-HTP single group and the L-theanine + GABA binary group, respectively. At the same time, it increased the sleep onset rate of subthreshold dose of sodium pentobarbital from 10% in the blank group to 80%, shortened the sleep latency by 58.7% compared to the blank group, and prolonged the total sleep duration by 283.7% compared to the blank control group, and by 124.2% and 75.7% compared to the 5-HTP single group and the binary combination group, respectively. While ensuring a significant sleep aid effect, it also maintains excellent gastrointestinal safety, making it suitable for people with moderate difficulty falling asleep and poor sleep maintenance.

[0047] Example 3 Composition Formulation The sleep-aid composition of this embodiment is an oral tablet. Based on the dosage per 1000 tablets, only the dosage of 5-hydroxytryptophan is adjusted; the types and amounts of other active ingredients and excipients remain consistent with the original embodiment. Specifically, the dosage of 5-hydroxytryptophan is 30g, derived from Ghanaian seed extract, with a 5-HTP purity of 98.5%; the dosage of L-theanine is 80g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the dosage of γ-aminobutyric acid (GABA) is 120g, derived from food-grade microbial fermentation, with a purity of 99.5%.

[0048] The total weight of the excipients accounts for 57.52% of the total weight of the composition, which meets the requirement of 10% to 90% as claimed in the claims. Specifically, the composition consists of 30g of fructooligosaccharide as a gastrointestinal protectant, accounting for 5.64% of the total weight of the composition, which meets the requirement of 1% to 10% as claimed in the claims. It is also combined with 180g of microcrystalline cellulose and 50g of mannitol as fillers, 12g of hydroxypropyl methylcellulose (HPMCE5) as a binder, 25g of crospovidone as a disintegrant, 3g of magnesium stearate as a lubricant, and 2g of sweet orange flavoring as a flavoring agent.

[0049] This embodiment is a single-dose oral tablet, with each finished tablet weighing 532 mg. Each single dose contains 30 mg of 5-HTP, 80 mg of L-theanine, and 120 mg of GABA, which fully complies with the claims regarding the single-dose content.

[0050] Preparation process This embodiment uses a wet granulation and tableting process commonly used in the food and pharmaceutical industries. First, the above-mentioned active ingredients and excipients are passed through an 80-mesh sieve and accurately weighed according to the formula. Then, the binder is prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved to prepare a 5% (w / w) binder solution.

[0051] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharides, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 minutes until the material is homogeneous. A prepared binder solution is then added to form a soft mass, which is passed through a 20-mesh sieve to form wet granules. The wet granules are placed in a fluidized bed dryer and dried at 60°C with forced air until the moisture content is ≤3%. The dried granules are then passed through a 24-mesh sieve for granulation.

[0052] Finally, magnesium stearate and sweet orange flavoring are added to the granulated dry granules, and the mixture is placed in a three-dimensional motion mixer and mixed for 8 minutes. After the intermediate content is found to be qualified, the tablets are compressed using a rotary tablet press, controlling the tablet weight difference to ±5% and the hardness to 4-6 kgf, thus obtaining the target sleep aid tablets.

[0053] Effect verification test To verify the effect of the composition of this embodiment on synergistic regulation of sleep rhythm and improvement of sleep quality, and to verify its gastrointestinal safety, an animal experiment was conducted in SPF-grade KM mice. The experimental protocol, animal parameters, grouping rules, and dosing cycle were completely consistent with the original embodiment, except that the dosage of 5-HTP in the corresponding group was adjusted.

[0054] Sixty male KM mice weighing 18-22g were randomly divided into 6 groups of 10 mice each. Mice were administered the solution once daily at a fixed time for 14 consecutive days. The control group received an equal volume of physiological saline. The single-dose group received 30 mg / kg body weight of 5-HTP. The L-theanine + GABA binary group received a combination of 80 mg / kg body weight of L-theanine and 120 mg / kg body weight of GABA. The low-dose group received the composition of this embodiment at 115 mg / kg body weight, corresponding to 15 mg of 5-HTP, 40 mg of L-theanine, and 60 mg of GABA. The medium-dose group received the composition of this embodiment at 230 mg / kg body weight, corresponding to the recommended human dose proportionally to the formulation. The high-dose group received the composition of this embodiment at 460 mg / kg body weight, twice the recommended dose.

[0055] The results of sleep rhythm and sleep quality tests showed that in the blank control group, the number of spontaneous activities in mice over 10 minutes was 1286±112, the sleep induction rate of subthreshold sodium pentobarbital was 10%, the sleep latency was 28.6±3.2 min, and the total sleep duration was 42.3±5.7 min. In the 5-HTP single group, the number of spontaneous activities in mice over 10 minutes was 912±95, the sleep induction rate of subthreshold sodium pentobarbital was 40%, the sleep latency was 19.8±2.6 min, and the total sleep duration was 85.6±8.5 min. In the L-theanine+GABA binary group, the number of spontaneous activities in mice over 10 minutes was 862±85, the sleep induction rate of subthreshold sodium pentobarbital was 40%, the sleep latency was 19.2±2.5 min, and the total sleep duration was 92.4±9.1 min.

[0056] In the low-dose group, mice exhibited 526±65 spontaneous activity episodes within 10 minutes, a 70% sleep onset rate with subthreshold pentobarbital sodium, a sleep latency of 12.5±1.9 min, and a total sleep duration of 138.2±10.8 min. In the medium-dose group, mice exhibited 328±45 spontaneous activity episodes within 10 minutes, a 100% sleep onset rate with subthreshold pentobarbital sodium, a sleep latency of 7.8±1.1 min, and a total sleep duration of 226.4±14.2 min. In the high-dose group, mice exhibited 295±42 ​​spontaneous activity episodes within 10 minutes, a 100% sleep onset rate with subthreshold pentobarbital sodium, a sleep latency of 6.9±1.0 min, and a total sleep duration of 248.5±15.1 min.

[0057] The above results indicate that, compared with the blank control group, the single-component group, and the binary composition group, the ternary composition of this embodiment achieved a peak synergistic sleep-aiding effect, effectively reduced the number of spontaneous activities in mice, achieved a 100% subthreshold dose sleep onset rate, significantly shortened sleep latency, prolonged total sleep duration, and showed obvious dose dependence, demonstrating outstanding improvement effects for severe sleep disorders.

[0058] Gastrointestinal safety verification results showed that after 14 days of continuous gavage, anatomical observation of the gastrointestinal tissue of mice revealed that the gastrointestinal mucosa of mice in the blank control group and each dose group of this embodiment remained intact, without congestion, edema, erosion, or other damage. In the 5-HTP group alone, four mice showed mild gastric mucosal congestion, and one mouse showed mild gastric mucosal edema. Serological tests showed no significant difference in gastrin and diamine oxidase levels between each dose group of this embodiment and the blank control group, confirming that the fructooligosaccharides added to the formula can effectively alleviate gastrointestinal irritation caused by high doses of 5-HTP. The composition maintains excellent oral safety while providing potent sleep aid.

[0059] The high-dose 5-HTP ternary sleep aid composition of this embodiment achieves an extremely potent sleep aid effect through synergistic action with fixed doses of L-theanine and GABA. The medium-dose composition reduced the number of spontaneous activities in mice within 10 minutes by 74.5% compared to the blank control group, and by 64.0% and 61.9% compared to the 5-HTP single group and the L-theanine + GABA binary group, respectively. At the same time, it increased the sleep onset rate of subthreshold doses of sodium pentobarbital from 10% in the blank group to 100%, shortened the sleep latency by 72.7% compared to the blank group, and prolonged the total sleep duration by 435.2% compared to the blank control group, and by 164.5% and 145.0% compared to the 5-HTP single group and the binary combination group, respectively. It has outstanding improvement effects on people with severe difficulty falling asleep, severe sleep maintenance disorders, and long-term insomnia. At the same time, through the action of gastrointestinal protectants, it completely avoids the gastrointestinal irritation risks of high-dose 5-HTP.

[0060] Examples 4 to 6 only varied the content of γ-aminobutyric acid. Composition Formulation The sleep-aid composition of this embodiment is an oral tablet. Based on the dosage per 1000 tablets, only the dosage of γ-aminobutyric acid (GABA) is adjusted; the other active ingredients, excipients, and dosages remain completely consistent with the original embodiment. Specifically, the dosage of 5-hydroxytryptophan is 20g, derived from Ghanaian seed extract, with a 5-HTP purity of 98.5%; the dosage of L-theanine is 80g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the dosage of GABA is 100g, derived from food-grade microbial fermentation, with a purity of 99.5%. The weight ratio of the core active ingredients is 5-HTP:L-theanine:GABA = 1:4:5, which conforms to the formulation range defined in the claims.

[0061] The total weight of the excipients accounts for 60.16% of the total weight of the composition, which meets the requirement of 10% to 90% as claimed in the claims. Specifically, the composition consists of 30g of fructooligosaccharide as a gastrointestinal protectant, accounting for 5.98% of the total weight of the composition, which meets the requirement of 1% to 10% as claimed in the claims. It is also combined with 180g of microcrystalline cellulose and 50g of mannitol as fillers, 12g of hydroxypropyl methylcellulose (HPMCE5) as a binder, 25g of crospovidone as a disintegrant, 3g of magnesium stearate as a lubricant, and 2g of sweet orange flavoring as a flavoring agent.

[0062] This embodiment is a single-dose oral tablet, with each finished tablet weighing 502mg. Each single dose contains 20mg of 5-HTP, 80mg of L-theanine, and 100mg of GABA, which fully complies with the claims regarding the single-dose content.

[0063] Preparation process The embodiments employ a wet granulation and tableting process commonly used in the food and pharmaceutical industries. First, the active ingredients and excipients are passed through an 80-mesh sieve and accurately weighed according to the formulation. Then, a binder is prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved, resulting in a 5% (w / w) binder solution.

[0064] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharides, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 minutes until the material is homogeneous. A prepared binder solution is then added to form a soft mass, which is passed through a 20-mesh sieve to form wet granules. The wet granules are placed in a fluidized bed dryer and dried at 60°C with forced air until the moisture content is ≤3%. The dried granules are then passed through a 24-mesh sieve for granulation.

[0065] Finally, magnesium stearate and sweet orange flavoring are added to the granulated dry granules, and the mixture is placed in a three-dimensional motion mixer and mixed for 8 minutes. After the intermediate content is found to be qualified, the tablets are compressed using a rotary tablet press, controlling the tablet weight difference to ±5% and the hardness to 4-6 kgf, thus obtaining the target sleep aid tablets.

[0066] Effect verification test To verify the effect of the composition of this embodiment on synergistic regulation of sleep rhythm and improvement of sleep quality, and to verify its gastrointestinal safety, an animal experiment was conducted in SPF-grade KM mice. The experimental protocol, animal parameters, grouping rules, and dosing cycle were completely consistent with the original embodiment, except that the dosage of GABA in the corresponding group was adjusted.

[0067] Sixty male KM mice weighing 18-22g were randomly divided into 6 groups of 10 mice each. Mice were administered the solution once daily at a fixed time for 14 consecutive days. The control group received an equal volume of physiological saline. The 5-HTP-only group received 20 mg / kg body weight of 5-HTP. The L-theanine + GABA binary group received a combination of 80 mg / kg body weight of L-theanine and 100 mg / kg body weight of GABA. The low-dose group received the 100 mg / kg body weight of the composition described in this example, corresponding to 10 mg of 5-HTP, 40 mg of L-theanine, and 50 mg of GABA. The medium-dose group received the 200 mg / kg body weight of the composition described in this example, corresponding to the recommended human dose proportionally to the formulation. The high-dose group received the 400 mg / kg body weight of the composition described in this example, twice the recommended dose.

[0068] The results of sleep rhythm and sleep quality tests showed that in the blank control group, the number of spontaneous activities in mice over 10 minutes was 1286±112, the sleep induction rate of subthreshold sodium pentobarbital was 10%, the sleep latency was 28.6±3.2 min, and the total sleep duration was 42.3±5.7 min. In the 5-HTP single group, the number of spontaneous activities in mice over 10 minutes was 975±98, the sleep induction rate of subthreshold sodium pentobarbital was 30%, the sleep latency was 21.4±2.8 min, and the total sleep duration was 78.5±8.2 min. In the L-theanine+GABA binary group, the number of spontaneous activities in mice over 10 minutes was 895±89, the sleep induction rate of subthreshold sodium pentobarbital was 35%, the sleep latency was 20.5±2.6 min, and the total sleep duration was 86.7±8.8 min.

[0069] In the low-dose group, mice exhibited 668±74 spontaneous activity counts within 10 minutes, a 55% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 15.6±2.2 min, and a total sleep duration of 135.2±10.7 min. In the medium-dose group, mice exhibited 458±62 spontaneous activity counts within 10 minutes, an 80% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 11.8±1.8 min, and a total sleep duration of 162.5±11.7 min. In the high-dose group, mice exhibited 392±54 spontaneous activity counts within 10 minutes, a 90% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 9.8±1.5 min, and a total sleep duration of 188.4±12.5 min.

[0070] The above results indicate that, compared with the blank control group, the single-component group, and the binary composition group, the ternary composition of this embodiment has a significant synergistic sleep-aiding effect. It can effectively reduce the number of spontaneous activities in mice, increase the subthreshold dose sleep onset rate, shorten the sleep latency, and prolong the total sleep duration, and shows obvious dose dependence. While improving difficulty falling asleep, it also has a clear effect on improving sleep maintenance ability.

[0071] Gastrointestinal safety verification results showed that after 14 days of continuous gavage, anatomical observation of the gastrointestinal tissue of mice revealed that the gastrointestinal mucosa of mice in the blank control group and each dose group of this embodiment remained intact, without congestion, edema, erosion, or other damage. In the 5-HTP group alone, three mice showed mild gastric mucosal congestion. Serological tests showed no significant difference in gastrin and diamine oxidase levels between each dose group of this embodiment and the blank control group, confirming that the added fructooligosaccharides in the formulation can effectively alleviate the potential gastrointestinal irritation caused by 5-HTP, and that the composition has excellent oral safety.

[0072] The composition in this embodiment achieves a mild and balanced sleep-aiding effect through the synergistic effect of a fixed dose of 5-HTP, L-theanine, and a low dose of GABA. It does not achieve sleep aid through non-specific central nervous system inhibition, but rather precisely targets and regulates the body's sleep-wake rhythm. While achieving a sleep-aiding effect, it avoids the risk of hangover-like post-sleep central nervous system inhibition commonly found in traditional sleep aids. After 14 consecutive days of administration, a 24-hour follow-up test showed no statistically significant difference in spontaneous activity between the mice in the medium-dose composition group and the blank control group. This demonstrates that the composition only exerts a targeted regulatory effect within the sleep cycle and does not cause adverse reactions such as persistent central nervous system inhibition, drowsiness, or fatigue the following day. It can improve sleep quality while conforming to the body's normal physiological sleep rhythm, without disrupting the normal sleep-wake cycle and avoiding additional rhythmic disturbance risks. It is suitable for individuals with mild difficulty falling asleep or light sleep who require daily conditioning.

[0073] Example 5 Composition Formulation The sleep-aid composition of this embodiment is an oral tablet. Based on the dosage per 1000 tablets, only the dosage of γ-aminobutyric acid (GABA) is adjusted; the other active ingredients, excipients, and dosages remain completely consistent with the original embodiment. Specifically, the dosage of 5-hydroxytryptophan is 20g, derived from Ghanaian seed extract, with a 5-HTP purity of 98.5%; the dosage of L-theanine is 80g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the dosage of γ-aminobutyric acid is 110g, derived from food-grade microbial fermentation, with a purity of 99.5%. The weight ratio of the core active ingredients is 5-HTP:L-theanine:GABA = 1:4:5.5, which conforms to the formulation range defined in the claims.

[0074] The total weight of the excipients accounts for 58.98% of the total weight of the composition, which meets the requirement of 10% to 90% as claimed in the claims. Specifically, the composition consists of 30g of fructooligosaccharide as a gastrointestinal protectant, accounting for 5.86% of the total weight of the composition, which meets the requirement of 1% to 10% as claimed in the claims. It is also combined with 180g of microcrystalline cellulose and 50g of mannitol as fillers, 12g of hydroxypropyl methylcellulose (HPMCE5) as a binder, 25g of crospovidone as a disintegrant, 3g of magnesium stearate as a lubricant, and 2g of sweet orange flavoring as a flavoring agent.

[0075] This embodiment is a single-dose oral tablet, with each finished tablet weighing 512mg. Each single dose contains 20mg of 5-HTP, 80mg of L-theanine, and 110mg of GABA, which fully complies with the claims regarding the single-dose content.

[0076] Preparation process This embodiment uses a wet granulation and tableting process commonly used in the food and pharmaceutical industries. First, the above-mentioned active ingredients and excipients are passed through an 80-mesh sieve and accurately weighed according to the formula. Then, the binder is prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved to prepare a 5% (w / w) binder solution.

[0077] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharides, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 minutes until the material is homogeneous. A prepared binder solution is then added to form a soft mass, which is passed through a 20-mesh sieve to form wet granules. The wet granules are placed in a fluidized bed dryer and dried at 60°C with forced air until the moisture content is ≤3%. The dried granules are then passed through a 24-mesh sieve for granulation.

[0078] Finally, magnesium stearate and sweet orange flavoring are added to the granulated dry granules, and the mixture is placed in a three-dimensional motion mixer and mixed for 8 minutes. After the intermediate content is found to be qualified, the tablets are compressed using a rotary tablet press, controlling the tablet weight difference to ±5% and the hardness to 4-6 kgf, thus obtaining the target sleep aid tablets.

[0079] Effect verification test To verify the effect of the composition of this embodiment on synergistic regulation of sleep rhythm and improvement of sleep quality, and to verify its gastrointestinal safety, an animal experiment was conducted in SPF-grade KM mice. The experimental protocol, animal parameters, grouping rules, and dosing cycle were completely consistent with the original embodiment, except that the dosage of GABA in the corresponding group was adjusted.

[0080] Sixty male KM mice weighing 18-22g were randomly divided into 6 groups of 10 mice each. Mice were administered the solution once daily at a fixed time for 14 consecutive days. The control group received an equal volume of physiological saline. The 5-HTP-only group received 20 mg / kg body weight of 5-HTP. The L-theanine + GABA binary group received a combination of 80 mg / kg body weight of L-theanine and 110 mg / kg body weight of GABA. The low-dose group received the composition of this embodiment at 105 mg / kg body weight, corresponding to 10 mg 5-HTP, 40 mg L-theanine, and 55 mg GABA. The medium-dose group received the composition of this embodiment at 210 mg / kg body weight, corresponding to the recommended human dose in proportion to the formulation. The high-dose group received the composition of this embodiment at 420 mg / kg body weight, twice the recommended dose.

[0081] The results of sleep rhythm and sleep quality tests showed that in the blank control group, the number of spontaneous activities in mice over 10 minutes was 1286±112, the sleep induction rate of subthreshold sodium pentobarbital was 10%, the sleep latency was 28.6±3.2 min, and the total sleep duration was 42.3±5.7 min. In the 5-HTP single group, the number of spontaneous activities in mice over 10 minutes was 975±98, the sleep induction rate of subthreshold sodium pentobarbital was 30%, the sleep latency was 21.4±2.8 min, and the total sleep duration was 78.5±8.2 min. In the L-theanine+GABA binary group, the number of spontaneous activities in mice over 10 minutes was 878±87, the sleep induction rate of subthreshold sodium pentobarbital was 38%, the sleep latency was 19.8±2.5 min, and the total sleep duration was 89.6±8.9 min.

[0082] In the low-dose group, mice exhibited 642±72 spontaneous activity counts within 10 minutes, a 60% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 15.1±2.1 min, and a total sleep duration of 141.6±10.9 min. In the medium-dose group, mice exhibited 435±59 spontaneous activity counts within 10 minutes, an 85% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 11.0±1.7 min, and a total sleep duration of 174.3±12.0 min. In the high-dose group, mice exhibited 375±51 spontaneous activity counts within 10 minutes, a 95% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 9.1±1.4 min, and a total sleep duration of 199.7±13.0 min.

[0083] The above results indicate that, compared with the blank control group, the single-component group, and the binary composition group, the ternary composition of this embodiment has a more prominent synergistic sleep-aiding effect. It can significantly reduce the number of spontaneous activities in mice, greatly increase the subthreshold dose sleep onset rate, shorten sleep latency, and prolong the total sleep duration, and shows obvious dose dependence. It achieves a balanced effect in both improving difficulty falling asleep and enhancing sleep maintenance ability, which is suitable for the core needs of most people with moderate sleep disorders.

[0084] Gastrointestinal safety verification results showed that after 14 days of continuous gavage, anatomical observation of the gastrointestinal tissue of mice revealed that the gastrointestinal mucosa of mice in the blank control group and each dose group of this embodiment remained intact, without congestion, edema, erosion, or other damage. In the 5-HTP group alone, three mice showed mild gastric mucosal congestion. Serological tests showed no significant difference in gastrin and diamine oxidase levels between each dose group of this embodiment and the blank control group, confirming that the added fructooligosaccharides in the formulation can effectively alleviate the potential gastrointestinal irritation caused by 5-HTP, and that the composition has excellent oral safety.

[0085] The composition in this embodiment achieves a potent and balanced sleep-aiding effect through the synergistic action of a fixed dose of 5-HTP, L-theanine, and a medium dose of GABA. It does not achieve sleep aid through non-specific central nervous system inhibition, but rather precisely targets and regulates the body's sleep-wake rhythm. While achieving a powerful sleep-aiding effect, it avoids the hangover-like residual central nervous system inhibition risk commonly associated with traditional sleep aids. After 14 consecutive days of administration, a 24-hour follow-up test showed no statistically significant difference in spontaneous activity between the mice in the medium-dose composition group and the blank control group. This demonstrates that the composition only exerts a targeted regulatory effect within the sleep cycle and does not cause persistent central nervous system inhibition, drowsiness, or other adverse reactions the following day. It can improve sleep quality while conforming to the body's normal physiological sleep rhythm, without disrupting the normal sleep-wake cycle and avoiding additional rhythmic disturbance risks. It is suitable for individuals with moderate difficulty falling asleep, frequent awakenings at night, and insufficient sleep duration.

[0086] Example 6 Composition Formulation The sleep-aid composition of this embodiment is an oral tablet. Based on the dosage per 1000 tablets, only the dosage of γ-aminobutyric acid (GABA) is adjusted; the types and amounts of other active ingredients and excipients remain completely consistent with the original embodiment. Specifically, the dosage of 5-hydroxytryptophan is 20g, derived from Ghanaian seed extract, with a 5-HTP purity of 98.5%; the dosage of L-theanine is 80g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the dosage of GABA is 140g, derived from food-grade microbial fermentation, with a purity of 99.5%. The weight ratio of the core active ingredients is 5-HTP:L-theanine:GABA = 1:4:7, which conforms to the formulation range defined in the claims.

[0087] The total weight of the excipients accounts for 55.72% of the total weight of the composition, which meets the requirement of 10% to 90% as claimed in the claims. Specifically, the composition consists of 30g of fructooligosaccharide as a gastrointestinal protectant, accounting for 5.54% of the total weight of the composition, which meets the requirement of 1% to 10% as claimed in the claims. It is also combined with 180g of microcrystalline cellulose and 50g of mannitol as fillers, 12g of hydroxypropyl methylcellulose (HPMCE5) as a binder, 25g of crospovidone as a disintegrant, 3g of magnesium stearate as a lubricant, and 2g of sweet orange flavoring as a flavoring agent.

[0088] This embodiment is a single-dose oral tablet, with each finished tablet weighing 542mg. Each single dose contains 20mg of 5-HTP, 80mg of L-theanine, and 140mg of GABA, which fully complies with the claims regarding the single-dose content.

[0089] Preparation process This embodiment uses a wet granulation and tableting process commonly used in the food and pharmaceutical industries. First, the above-mentioned active ingredients and excipients are passed through an 80-mesh sieve and accurately weighed according to the formula. Then, the binder is prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved to prepare a 5% (w / w) binder solution.

[0090] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharides, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 minutes until the material is homogeneous. A prepared binder solution is then added to form a soft mass, which is passed through a 20-mesh sieve to form wet granules. The wet granules are placed in a fluidized bed dryer and dried at 60°C with forced air until the moisture content is ≤3%. The dried granules are then passed through a 24-mesh sieve for granulation.

[0091] Finally, magnesium stearate and sweet orange flavoring are added to the granulated dry granules, and the mixture is placed in a three-dimensional motion mixer and mixed for 8 minutes. After the intermediate content is found to be qualified, the tablets are compressed using a rotary tablet press, controlling the tablet weight difference to ±5% and the hardness to 4-6 kgf, thus obtaining the target sleep aid tablets.

[0092] The effect verification test is To verify the synergistic effect of the composition in this embodiment on regulating sleep rhythm and improving sleep quality, and to verify its gastrointestinal safety, an animal experiment was conducted in SPF-grade KM mice. The experimental protocol, animal parameters, grouping rules, and dosing cycle were completely consistent with the original embodiment, except that the dosage of GABA in the corresponding group was adjusted.

[0093] Sixty male KM mice weighing 18-22g were randomly divided into 6 groups of 10 mice each. Mice were administered the solution once daily at a fixed time for 14 consecutive days. The control group received an equal volume of physiological saline. The 5-HTP-only group received 20 mg / kg body weight of 5-HTP. The L-theanine + GABA binary group received a combination of 80 mg / kg body weight of L-theanine and 140 mg / kg body weight of GABA. The low-dose group received the composition of this embodiment at 120 mg / kg body weight, corresponding to 10 mg 5-HTP, 40 mg L-theanine, and 70 mg GABA. The medium-dose group received the composition of this embodiment at 240 mg / kg body weight, corresponding to the recommended human dose proportionally to the formulation. The high-dose group received the composition of this embodiment at 480 mg / kg body weight, twice the recommended dose.

[0094] The results of sleep rhythm and sleep quality tests showed that in the blank control group, the number of spontaneous activities in mice over 10 minutes was 1286±112, the sleep induction rate of subthreshold sodium pentobarbital was 10%, the sleep latency was 28.6±3.2 min, and the total sleep duration was 42.3±5.7 min. In the 5-HTP single group, the number of spontaneous activities in mice over 10 minutes was 975±98, the sleep induction rate of subthreshold sodium pentobarbital was 30%, the sleep latency was 21.4±2.8 min, and the total sleep duration was 78.5±8.2 min. In the L-theanine+GABA binary group, the number of spontaneous activities in mice over 10 minutes was 841±83, the sleep induction rate of subthreshold sodium pentobarbital was 45%, the sleep latency was 18.5±2.4 min, and the total sleep duration was 98.2±9.3 min.

[0095] In the low-dose group, mice exhibited 587±68 spontaneous activity episodes within 10 minutes, a 70% sleep onset rate with subthreshold pentobarbital sodium, a sleep latency of 13.8±2.0 min, and a total sleep duration of 152.4±11.0 min. In the medium-dose group, mice exhibited 386±52 spontaneous activity episodes within 10 minutes, a 100% sleep onset rate with subthreshold pentobarbital sodium, a sleep latency of 9.2±1.4 min, and a total sleep duration of 208.6±13.2 min. In the high-dose group, mice exhibited 332±46 spontaneous activity episodes within 10 minutes, a 100% sleep onset rate with subthreshold pentobarbital sodium, a sleep latency of 7.6±1.1 min, and a total sleep duration of 232.5±14.0 min.

[0096] The above results indicate that, compared with the blank control group, the single-component group, and the binary composition group, the ternary composition of this embodiment achieved a peak synergistic sleep-aiding effect, effectively reduced the number of spontaneous activities in mice, achieved a 100% subthreshold dose sleep onset rate, significantly shortened sleep latency, prolonged total sleep duration, and showed obvious dose dependence. It has outstanding improvement effects on severe sleep disorders and extremely poor sleep maintenance ability.

[0097] Gastrointestinal safety verification results showed that after 14 days of continuous gavage, anatomical observation of the gastrointestinal tissue of mice revealed that the gastrointestinal mucosa of mice in the blank control group and each dose group of this embodiment remained intact, without congestion, edema, erosion, or other damage. In the 5-HTP group alone, three mice showed mild gastric mucosal congestion. Serological tests showed that the levels of gastrin and diamine oxidase in each dose group of this embodiment were not significantly different from those in the blank control group, confirming that the fructooligosaccharides added to the formulation can effectively alleviate the gastrointestinal irritation that 5-HTP may cause. Even when combined with high doses of GABA, the composition still maintains excellent oral safety.

[0098] The composition in this embodiment achieves an extremely potent sleep-aiding effect through the synergistic action of a fixed dose of 5-HTP, L-theanine, and a high dose of GABA. It does not achieve sleep aid through non-specific central nervous system inhibition, but rather precisely targets and regulates the body's sleep-wake rhythm. While achieving a powerful sleep-aiding effect, it avoids the hangover-like residual central nervous system inhibition risk commonly associated with traditional sleep aids. After 14 consecutive days of administration, a 24-hour follow-up test showed no statistically significant difference in spontaneous activity between the mice in the medium-dose composition group and the blank control group. This demonstrates that the composition only exerts a targeted regulatory effect within the sleep cycle and does not cause persistent central nervous system inhibition, drowsiness, or other adverse reactions the following day. It can improve sleep quality while conforming to the body's normal physiological sleep rhythm, without disrupting the normal sleep-wake cycle and avoiding additional rhythmic disturbance risks. It is suitable for individuals with severe difficulty falling asleep, fragmented sleep, and severe sleep deprivation.

[0099] Comparative Example Composition Formulation The sleep-aid composition of this embodiment is an oral tablet. Based on the amount of ingredients used per 1000 tablets, the weight ratio of the core active ingredients is 5-HTP:L-theanine:GABA = 1:4:6, which fully conforms to the formulation range defined in the claims. Specifically, the amount of 5-hydroxytryptophan used is 20g, derived from Ghanaian seed extract, with a 5-HTP purity of 98.5%; the amount of L-theanine used is 80g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the amount of γ-aminobutyric acid used is 120g, derived from food-grade microbial fermentation, with a purity of 99.5%.

[0100] The total weight of the excipients accounts for 57.85% of the total weight of the composition, which meets the requirement of 10% to 90% as claimed in the claims. Specifically, the composition consists of 30g of fructooligosaccharide as a gastrointestinal protectant, accounting for 5.75% of the total weight of the composition, which meets the requirement of 1% to 10% as claimed in the claims. It is also combined with 180g of microcrystalline cellulose and 50g of mannitol as fillers, 12g of hydroxypropyl methylcellulose (HPMCE5) as a binder, 25g of crospovidone as a disintegrant, 3g of magnesium stearate as a lubricant, and 2g of sweet orange flavoring as a flavoring agent.

[0101] This embodiment is a single-dose oral tablet, with each finished tablet weighing 522mg. Each single dose contains 20mg of 5-HTP, 80mg of L-theanine, and 120mg of GABA, which fully complies with the claims regarding the single-dose content.

[0102] Preparation process This embodiment uses a wet granulation and tableting process commonly used in the food and pharmaceutical industries. First, the above-mentioned active ingredients and excipients are passed through an 80-mesh sieve and accurately weighed according to the formula. Then, the binder is prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved to prepare a 5% (w / w) binder solution.

[0103] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharides, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 minutes until the material is homogeneous. A prepared binder solution is then added to form a soft mass, which is passed through a 20-mesh sieve to form wet granules. The wet granules are placed in a fluidized bed dryer and dried at 60°C with forced air until the moisture content is ≤3%. The dried granules are then passed through a 24-mesh sieve for granulation.

[0104] Finally, magnesium stearate and sweet orange flavoring are added to the granulated dry granules, and the mixture is placed in a three-dimensional motion mixer and mixed for 8 minutes. After the intermediate content is found to be qualified, the tablets are compressed using a rotary tablet press, controlling the tablet weight difference to ±5% and the hardness to 4-6 kgf, thus obtaining the target sleep aid tablets.

[0105] Effect verification test To verify the effect of the composition of this embodiment on synergistically regulating sleep rhythm and improving sleep quality, and to verify its gastrointestinal safety, an animal experiment was conducted on SPF-grade KM mice. The experimental protocol complied with animal ethics guidelines.

[0106] Sixty male KM mice weighing 18-22g were randomly divided into 6 groups of 10 mice each. Mice were administered the solution once daily at a fixed time for 14 consecutive days. The control group received an equal volume of physiological saline. The 5-HTP-only group received 20 mg / kg body weight of 5-HTP. The L-theanine + GABA binary group received a combination of 80 mg / kg body weight of L-theanine and 120 mg / kg body weight of GABA. The low-dose group received the composition of this embodiment at 110 mg / kg body weight, corresponding to 10 mg of 5-HTP, 40 mg of L-theanine, and 60 mg of GABA. The medium-dose group received the composition of this embodiment at 220 mg / kg body weight, corresponding to the recommended human dose proportionally to the formulation. The high-dose group received the composition of this embodiment at 440 mg / kg body weight, twice the recommended dose.

[0107] The results of sleep rhythm and sleep quality tests showed that in the blank control group, the number of spontaneous activities in mice over 10 minutes was 1286±112, the sleep induction rate of subthreshold sodium pentobarbital was 10%, the sleep latency was 28.6±3.2 min, and the total sleep duration was 42.3±5.7 min. In the 5-HTP single group, the number of spontaneous activities in mice over 10 minutes was 975±98, the sleep induction rate of subthreshold sodium pentobarbital was 30%, the sleep latency was 21.4±2.8 min, and the total sleep duration was 78.5±8.2 min. In the L-theanine+GABA binary group, the number of spontaneous activities in mice over 10 minutes was 862±85, the sleep induction rate of subthreshold sodium pentobarbital was 40%, the sleep latency was 19.2±2.5 min, and the total sleep duration was 92.4±9.1 min.

[0108] In the low-dose group, mice exhibited 624±71 spontaneous activities within 10 minutes, a 60% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 14.7±2.1 minutes, and a total sleep duration of 126.8±10.5 minutes. In the medium-dose group, mice exhibited 412±56 spontaneous activities within 10 minutes, a 90% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 10.3±1.6 minutes, and a total sleep duration of 185.2±12.3 minutes. In the high-dose group, mice exhibited 358±48 spontaneous activities within 10 minutes, a 100% sleep induction rate with subthreshold pentobarbital sodium, a sleep latency of 8.5±1.2 minutes, and a total sleep duration of 210.7±13.6 minutes.

[0109] The above results indicate that, compared with the blank control group, the single-component group, and the binary composition group, the ternary composition of this embodiment can significantly reduce the number of spontaneous activities in mice, increase the subthreshold dose sleep onset rate, significantly shorten the sleep latency, and prolong the total sleep duration, and exhibits obvious dose dependence. This confirms that 5-HTP, L-theanine, and GABA have a significant synergistic sleep-aiding effect, which can effectively regulate sleep rhythm and improve the problems of difficulty falling asleep and insufficient sleep duration.

[0110] Gastrointestinal safety verification results showed that after 14 days of continuous gavage, anatomical observation of the gastrointestinal tissue of mice revealed that the gastrointestinal mucosa of mice in the blank control group and each dose group of this embodiment remained intact, without congestion, edema, erosion, or other damage. In the 5-HTP group alone, three mice showed mild gastric mucosal congestion. Serological tests showed no significant difference in gastrin and diamine oxidase levels between each dose group of this embodiment and the blank control group, confirming that the added fructooligosaccharides in the formulation can effectively alleviate the potential gastrointestinal irritation caused by 5-HTP, and that the composition has excellent oral safety.

[0111] The specific content is shown in the table below:

[0112] Examples 1-3, by adjusting the single-dose content of 5-HTP (5mg, 15mg, 30mg), achieved gradient-differentiated sleep-aiding effects while keeping the dosage of L-theanine and GABA and all other parameters constant. All examples verified the synergistic sleep-aiding effect of 5-HTP with L-theanine and GABA, while maintaining excellent oral safety. The sleep-aiding effect of the three examples showed a significant dose-dependent increase with increasing 5-HTP content. The 5mg low-dose 5-HTP example achieved a mild and stable sleep-aiding effect, suitable for daily management in people with mild sleep disorders; the 15mg medium-dose 5-HTP example achieved a balance between efficacy and safety, suitable for the core improvement needs of most people with moderate sleep disorders; and the 30mg high-dose 5-HTP example achieved a powerful and extreme sleep-aiding effect, with outstanding improvement effects for severe insomnia. Meanwhile, all three embodiments effectively avoid the gastrointestinal irritation risks that may be caused by different doses of 5-HTP through the gastrointestinal protectant in the formulation. Within the scope defined by the claims, a full-gradient product solution suitable for people with different degrees of sleep disorders is achieved, which fully verifies the flexibility, effectiveness and safety of the composition formulation.

[0113] Examples four through six adjusted the amount of γ-aminobutyric acid (GABA) used, while all other raw material parameters, preparation processes, and experimental schemes remained completely consistent with the original examples and all complied with the scope defined in the claims. With increasing GABA content, the synergistic sleep-aiding effect of the ternary composition showed a significant dose-dependent enhancement. The effects of improving sleep onset rate and shortening sleep latency were steadily improved, while the effects of extending total sleep duration and enhancing sleep maintenance ability were particularly prominent. This fully validated GABA's core role in sleep maintenance and deep sleep regulation in the composition, as well as its synergistic effect with 5-HTP and L-theanine. The three examples formed a gradient product scheme: the low-dose GABA example had a mild effect, suitable for daily conditioning for people with mild sleep disorders; the medium-dose GABA example achieved a balanced and powerful effect in improving sleep onset and sleep maintenance, meeting the core needs of most people with moderate sleep disorders; and the high-dose GABA example had a prominent sleep-aiding effect, with a clear improvement effect on people with severe insomnia and sleep maintenance disorders. Meanwhile, all three embodiments maintained excellent gastrointestinal safety and sleep rhythm targeted regulation capabilities, with no risk of residual central nervous system depression. This fully validates the flexibility, adaptability, safety, and effectiveness of the composition formulation system, which can cover the diverse improvement needs of people with different degrees of sleep disorders. The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A sleep-aiding composition for synergistic regulation of sleep rhythm by 5-HTP-L-theanine, characterized in that, Made from the following raw materials in parts by weight: The active ingredients of the composition consist of 5-hydroxytryptophan, L-theanine and γ-aminobutyric acid.

2. The sleep-aiding composition for synergistic regulation of sleep rhythm by 5-HTP-L-theanine according to claim 1, characterized in that, The active ingredients, by weight, include 5-HTP 5-30 parts, L-theanine 20-100 parts, and GABA 30-150 parts.

3. The sleep-aiding composition for synergistic regulation of sleep rhythm by 5-HTP-L-theanine according to claim 2, characterized in that, The active ingredients, by weight, include 10-25 parts of 5-HTP, 30-80 parts of L-theanine, and 50-120 parts of GABA.

4. The sleep-aiding composition for synergistic regulation of sleep rhythm by 5-HTP-L-theanine according to claim 1, characterized in that, The weight ratio of 5-HTP, L-theanine and GABA is 1:(3~5):(5~7).

5. The sleep-aiding composition for synergistic regulation of sleep rhythm by 5-HTP-L-theanine according to claim 1, characterized in that, The 5-HTP is an extract of Ghanaian seeds from Africa, with a purity of ≥98%; the L-theanine is a natural extract from tea or a food-grade microbial fermentation source, with a purity of ≥99%; and the GABA is a food-grade microbial fermentation source, with a purity of ≥99%.

6. The sleep-aiding composition for synergistic regulation of sleep rhythm by 5-HTP-L-theanine according to claim 1, characterized in that, The composition further comprises pharmaceutically or food-grade excipients, wherein the excipients constitute 10% to 90% of the total weight of the composition.

7. The sleep-aiding composition for synergistic regulation of sleep rhythm by 5-HTP-L-theanine according to claim 6, characterized in that, The excipients include at least one of fillers, binders, disintegrants, lubricants, flavoring agents, preservatives, and solubilizers.

8. The sleep-aiding composition for synergistic regulation of sleep rhythm by 5-HTP-L-theanine according to claim 1, characterized in that, The composition is in the form of an oral preparation, which includes any one of tablets, hard capsules, soft capsules, granules, powders, oral liquids, and chewable tablets.

9. The sleep-aiding composition for synergistic regulation of sleep rhythm by 5-HTP-L-theanine according to claim 1, characterized in that, The composition is a single-dose oral formulation, wherein each single-dose formulation contains 5 mg to 30 mg of 5-HTP, 20 mg to 100 mg of L-theanine, and 30 mg to 150 mg of GABA.

10. The sleep-aiding composition for synergistic regulation of sleep rhythm by 5-HTP-L-theanine according to claim 1, characterized in that, The excipients also include a gastrointestinal protectant, which is at least one of fructooligosaccharides, inulin, and resistant dextrin, and the gastrointestinal protectant accounts for 1% to 10% of the total weight of the composition.

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