A sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and l-theanine

Abstract

The present invention discloses a sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine, relating to the technical field of biomedicine and health foods. Through the synergistic action of 5-hydroxytryptophan, L-theanine, and gamma-aminobutyric acid, the present invention effectively regulates the sleep rhythm and helps users improve sleep quality. As a precursor of serotonin, 5-HTP helps increase the serotonin level and is then converted into melatonin to regulate the sleep cycle. L-theanine promotes the release of alpha brain waves to help relax the body and mind and reduce anxiety. As an inhibitory neurotransmitter, GABA can effectively relieve tension and promote deep sleep. The three components act synergistically to provide users with more comprehensive and more effective sleep support.

Description

[0001] DESCRIPTION

[0002] A sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine TECHNICAL FIELD

[0003] The present invention relates to the technical field of biomedicine and health foods, and in particular to a sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine.

[0004] BACKGROUND ART

[0005] In modern society, as the pace of life accelerates and work pressure increases, sleep disorders have become increasingly common and have become an important factor affecting people's health and quality of life. Insufficient sleep or poor sleep quality not only causes daytime fatigue and lack of concentration, but may also trigger a series of physical and mental health problems, such as anxiety, depression, and cardiovascular diseases. Therefore, finding safe and effective methods for improving sleep has become a hot topic in both research and industry.

[0006] Although conventional sleep-aid drugs can alleviate sleep disorders to some extent, their disadvantages cannot be ignored. First, chemically synthesized drugs often have relatively strong side effects, such as dizziness, drowsiness, and memory decline, which affect patients' daily life and work efficiency. Second, long-term use readily leads to tolerance and dependence, causing the efficacy to gradually weaken and even resulting in severe problems such as rebound insomnia after withdrawal. In addition, traditional sleep-aid methods often target only a single sleep problem and lack the ability to comprehensively regulate the sleep rhythm, making it difficult to fundamentally improve sleep quality.

[0007] In view of the deficiencies of conventional sleep-aid technologies, it is particularly important to provide a sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine.

[0008] SUMMARY OF THE INVENTION DESCRIPTION

[0009] The purpose of the present invention is to overcome the deficiencies of the prior art by providing a sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine. Through the scientific combination of 5 -hydroxytryptophan, L-theanine, and gamma-aminobutyric acid, the composition uses the distinct physiological mechanisms of the three natural ingredients to synergistically regulate the sleep rhythm and effectively improve sleep quality. Compared with conventional sleep-aid drugs, the composition of the present invention is safe and reliable, non-dependent, and capable of comprehensive regulation, thereby providing users with more comprehensive and more effective sleep support and meeting modern consumers' urgent demand for healthy sleep.

[0010] To solve the above technical problems, the present invention provides the following technical solution: a sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine, prepared from the following raw materials in parts by weight:

[0011] The active ingredients of the composition consist of 5 -hydroxytryptophan, L-theanine, and gamma-aminobutyric acid.

[0012] Further, in parts by weight, the active ingredients comprise 5-30 parts of 5-HTP, 20-100 parts of L-theanine, and 30-150 parts of GABA.

[0013] Furthermore, in parts by weight, the active ingredients comprise 10-25 parts of 5-HTP, 30-80 parts of L-theanine, and 50-120 parts of GABA.

[0014] Furthermore, the weight ratio of 5-HTP, L-theanine, and GABA is l:(3-5):(5-7).

[0015] Furthermore, the 5-HTP is derived from Griffonia seed extract from Africa, wherein the purity of 5-HTP is >=98%; the L-theanine is derived from natural tea DESCRIPTION extraction or food-grade microbial fermentation, with a purity of >=99%; and the GABA is derived from food-grade microbial fermentation, with a purity of >=99%.

[0016] Furthermore, the composition further comprises pharmaceutically or food-acceptable excipients, and the weight of the excipients accounts for 10%-90% of the total weight of the composition.

[0017] Furthermore, the excipients comprise at least one selected from the group consisting of a filler, a binder, a disintegrant, a lubricant, a flavoring agent, a preservative, and a solubilizer.

[0018] Furthermore, the composition is an oral preparation, and the oral preparation is any one selected from a tablet, a hard capsule, a soft capsule, a granule, a powder, an oral liquid, and a chewable tablet.

[0019] Furthermore, the composition is a single-dose oral preparation, wherein each single-dose preparation contains 5 mg-30 mg of 5-HTP, 20 mg- 100 mg of L-theanine, and 30 mg- 150 mg of GABA.

[0020] Furthermore, the excipients further comprise a gastrointestinal protectant, wherein the gastrointestinal protectant is at least one selected from fructooligosaccharide, inulin, and resistant dextrin, and the weight of the gastrointestinal protectant accounts for l%-10% of the total weight of the composition.

[0021] Compared with the prior art, the sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine has the following beneficial effects:

[0022] I. Through the synergistic action of 5-hydroxytryptophan, L-theanine, and DESCRIPTION gamma-aminobutyric acid, the sleep-aid composition of the present invention effectively regulates the sleep rhythm and helps users improve sleep quality. As a precursor of serotonin, 5-HTP helps increase the serotonin level and is then converted into melatonin to regulate the sleep cycle. L-theanine promotes the release of alpha brain waves to help relax the body and mind and reduce anxiety. As an inhibitory neurotransmitter, GABA can effectively relieve tension and promote deep sleep. The three components act synergistically to provide users with more comprehensive and more effective sleep support.

[0023] Other advantages, objectives, and features of the present invention will be set forth in part in the following description and in part will become apparent to those skilled in the art upon examination of the following disclosure or may be learned from practice of the invention.

[0024] BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to describe the technical solutions in the embodiments of the present invention or in the prior art more clearly, the drawings required for describing the embodiments or the prior art are briefly introduced below. Obviously, the drawings in the following description merely illustrate certain embodiments of the present invention, and those of ordinary skill in the art can derive other drawings therefrom without inventive effort.

[0026] Figure 1 is a flow chart of the sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine.

[0027] DETAILED DESCRIPTION

[0028] In order to further illustrate the technical means and effects adopted by the present invention to achieve the intended objectives, the specific implementation, structure, features, and effects of the present invention are described in detail below in conjunction with the accompanying drawing and DESCRIPTION preferred embodiments.

[0029] Examples I to III differ only in the content of 5 -hydroxy tryptophan.

[0030] Example I

[0031] Composition formula

[0032] In this example, the sleep-aid composition is an oral tablet. Based on the input quantity for every 1,000 tablets, only the input amount of 5-hydroxytryptophan is adjusted, while the other active ingredients and the types and amounts of excipients remain the same as in the original embodiment. The input amount of 5-hydroxytryptophan is 5 g, derived from Griffonia seed extract from Africa, with a 5-HTP purity of 98.5%; the input amount of L-theanine is 80 g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the input amount of gamma-aminobutyric acid is 120 g, derived from food-grade microbial fermentation, with a purity of 99.5%.

[0033] The total weight of the excipients accounts for 58.97% of the total weight of the composition, meeting the claimed range of 10%-90%. Specifically, the excipients comprise 30 g of fructooligosaccharide as the gastrointestinal protectant, accounting for 5.92% of the total weight of the composition and meeting the claimed range of l%-10%, together with 180 g of microcrystalline cellulose and 50 g of mannitol as fillers, 12 g of hydroxypropyl methylcellulose (HPMC E5) as the binder, 25 g of crospovidone as the disintegrant, 3 g of magnesium stearate as the lubricant, and 2 g of sweet orange flavor as the flavoring agent.

[0034] This example is a single-dose oral tablet. Each finished tablet weighs 507 mg and each single dose contains 5 mg of 5-HTP, 80 mg of L-theanine, and 120 mg of GABA, fully meeting the limitations on single-dose contents set forth in the claims.

[0035] Preparation process

[0036] In this example, the preparation is carried out by a conventional wet DESCRIPTION granulation and tableting process commonly used in the food and pharmaceutical fields. First, the above active ingredients and excipients are each passed through an 80-mesh sieve and accurately weighed according to the formula. A binder is then prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved, thereby preparing a binder solution at a mass concentration of 5%.

[0037] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharide, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 min until uniform. The prepared binder solution is added to form a soft mass, and the soft mass is passed through a 20-mesh sieve to prepare wet granules. The wet granules are dried in a fluidized-bed dryer with forced air at 60 C until the moisture content is <=3%, and the dried granules are passed through a 24-mesh sieve for sizing.

[0038] Finally, magnesium stearate and sweet orange flavor are added to the sized dry granules, which are then blended in a three-dimensional motion mixer for 8 min. After the content of the intermediate is confirmed to be qualified, the mixture is compressed with a rotary tablet press while controlling the tablet weight variation within + / -5% and the hardness at 4-6 kgf, thereby obtaining the target sleep-aid tablets.

[0039] Effect verification

[0040] To verify the effects of the composition of this example on synergistically regulating the sleep rhythm and improving sleep quality, while also verifying gastrointestinal safety, an SPF-grade KM mouse study was conducted. The test protocol, animal parameters, grouping rules, and administration period were identical to those of the original embodiment, except that the dose of 5-HTP was adjusted for the corresponding group.

[0041] Sixty male KM mice weighing 18-22 g were randomly divided into six groups of ten mice each. The mice were intragastrically administered once daily at a fixed time for 14 consecutive days. The blank control group DESCRIPTION received an equal volume of normal saline; the 5-HTP-alone group received 5-HTP at 5 mg / kg bw; the L-theanine + GABA binary group received a composition containing 80 mg / kg bw of L-theanine and 120 mg / kg bw of GABA; the low-dose composition group received 102.5 mg / kg bw of the composition of this example, corresponding to 2.5 mg of 5-HTP, 40 mg of L-theanine, and 60 mg of GABA; the medium-dose composition group received 205 mg / kg bw of the composition of this example, corresponding proportionally to the recommended human dose; and the high-dose composition group received 410 mg / kg bw of the composition of this example, equal to twice the recommended dose.

[0042] The results for sleep rhythm and sleep quality showed that, in the blank control group, the number of spontaneous activities within 10 min was 1286 + / - 112, the sleep onset rate at the subthreshold dose of 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-alone group, the number of spontaneous activities within 10 min was 1152 + / - 105, the sleep onset rate at the subthreshold dose of 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 within 10 min was 862 + / - 85, the sleep onset rate at the subthreshold dose of 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 composition group, the number of spontaneous activities within 10 min was 758 + / - 78, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 50%, the sleep latency was 16.8 + / - 2.3 min, and the total sleep duration was 110.5 + / - 9.8 min. In the medium-dose composition group, the number of spontaneous activities within 10 min was 586 + / - 69, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 70%, the sleep latency was 13.5 + / - 2.0 min, and the total sleep duration was 142.6 DESCRIPTION

[0044] + / - 11.2 min. In the high-dose composition group, the number of spontaneous activities within 10 min was 495 + / - 62, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 80%, the sleep latency was 11.2 + / - 1.8 min, and the total sleep duration was 168.3 + / - 12.0 min.

[0045] 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 example still exhibits a significant synergistic sleep-promoting effect, can effectively reduce spontaneous activity in mice, increase the sleep onset rate, shorten sleep latency, and prolong total sleep duration, and shows an obvious dose-dependent relationship. The overall action is mild, without the risk of excessive central inhibition.

[0046] The gastrointestinal safety results showed that, after 14 consecutive days of intragastric administration, anatomical observation of mouse gastrointestinal tissues revealed intact gastrointestinal mucosa in the blank control group and in all dose groups of this example, without congestion, edema, erosion, or other injuries, and no abnormalities were observed in the gastrointestinal mucosa of the 5-HTP-alone group. Serological tests showed no significant differences in gastrin and diamine oxidase levels between the dose groups of this example and the blank control group, indicating excellent oral safety of the composition.

[0047] The low-dose 5-HTP ternary sleep-aid composition of this example, through synergy with fixed doses of L-theanine and GABA, achieved a mild yet stable sleep-promoting effect. Among them, the medium-dose composition reduced the number of spontaneous activities within 10 min by 54.4% relative to the blank control group and by 49.1% and 32.0%, respectively, relative to the 5-HTP-alone group and the L-theanine + GABA binary group. At the same time, it increased the sleep onset rate at the subthreshold dose of sodium pentobarbital from 10% in the blank group to 70%, shortened the sleep latency by 52.8% relative to the blank group, and prolonged the total sleep DESCRIPTION duration by 237.1% relative to the blank control group and by 153.7% and 54.3%, respectively, relative to the 5-HTP-alone group and the binary composition group. It is therefore suitable for the daily mild conditioning needs of people with mild sleep disorders, without additional gastrointestinal irritation risk.

[0048] Example II

[0049] Composition formula

[0050] In this example, the sleep-aid composition is an oral tablet. Based on the input quantity for every 1,000 tablets, only the input amount of 5-hydroxytryptophan is adjusted, while the other active ingredients and the types and amounts of excipients remain the same as in the original embodiment. The input amount of 5-hydroxytryptophan is 15 g, derived from Griffonia seed extract from Africa, with a 5-HTP purity of 98.5%; the input amount of L-theanine is 80 g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the input amount of gamma-aminobutyric acid is 120 g, derived from food-grade microbial fermentation, with a purity of 99.5%.

[0051] The total weight of the excipients accounts for 58.03% of the total weight of the composition, meeting the claimed range of 10%-90%. Specifically, the excipients comprise 30 g of fructooligosaccharide as the gastrointestinal protectant, accounting for 5.80% of the total weight of the composition and meeting the claimed range of l%-10%, together with 180 g of microcrystalline cellulose and 50 g of mannitol as fillers, 12 g of hydroxypropyl methylcellulose (HPMC E5) as the binder, 25 g of crospovidone as the disintegrant, 3 g of magnesium stearate as the lubricant, and 2 g of sweet orange flavor as the flavoring agent.

[0052] This example is a single-dose oral tablet. Each finished tablet weighs 517 mg and each single dose contains 15 mg of 5-HTP, 80 mg of L-theanine, and 120 mg of GABA, fully meeting the limitations on single-dose contents set DESCRIPTION forth in the claims.

[0053] Preparation process

[0054] In this example, the preparation is carried out by a conventional wet granulation and tableting process commonly used in the food and pharmaceutical fields. First, the above active ingredients and excipients are each passed through an 80-mesh sieve and accurately weighed according to the formula. A binder is then prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved, thereby preparing a binder solution at a mass concentration of 5%.

[0055] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharide, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 min until uniform. The prepared binder solution is added to form a soft mass, and the soft mass is passed through a 20-mesh sieve to prepare wet granules. The wet granules are dried in a fluidized-bed dryer with forced air at 60 C until the moisture content is <=3%, and the dried granules are passed through a 24-mesh sieve for sizing.

[0056] Finally, magnesium stearate and sweet orange flavor are added to the sized dry granules, which are then blended in a three-dimensional motion mixer for 8 min. After the content of the intermediate is confirmed to be qualified, the mixture is compressed with a rotary tablet press while controlling the tablet weight variation within + / -5% and the hardness at 4-6 kgf, thereby obtaining the target sleep-aid tablets.

[0057] Effect verification test

[0058] To verify the effects of the composition of this example on synergistically regulating the sleep rhythm and improving sleep quality, while also verifying gastrointestinal safety, an SPF-grade KM mouse study was conducted. The test protocol, animal parameters, grouping rules, and administration period were identical to those of the original embodiment, except that the dose of 5-HTP was adjusted for the corresponding group. io DESCRIPTION

[0059] Sixty male KM mice weighing 18-22 g were randomly divided into six groups of ten mice each. The mice were intragastrically administered once daily at a fixed time for 14 consecutive days. The blank control group received an equal volume of normal saline; the 5-HTP-alone group received 5-HTP at 15 mg / kg bw; the L-theanine + GABA binary group received a composition containing 80 mg / kg bw of L-theanine and 120 mg / kg bw of GABA; the low-dose composition group received 107.5 mg / kg bw of the composition of this example, corresponding to 7.5 mg of 5-HTP, 40 mg of L-theanine, and 60 mg of GABA; the medium-dose composition group received 215 mg / kg bw of the composition of this example, corresponding proportionally to the recommended human dose; and the high-dose composition group received 430 mg / kg bw of the composition of this example, equal to twice the recommended dose.

[0060] The results for sleep rhythm and sleep quality showed that, in the blank control group, the number of spontaneous activities within 10 min was 1286 + / - 112, the sleep onset rate at the subthreshold dose of 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-alone group, the number of spontaneous activities within 10 min was 1023 + / - 101, the sleep onset rate at the subthreshold dose of 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 within 10 min was 862 + / - 85, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 40%, the sleep latency was 19.2 + / - 2.5 min, and the total sleep duration was 92.4 + / - 9.1 min.

[0061] In the low-dose composition group, the number of spontaneous activities within 10 min was 685 + / - 75, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 55%, the sleep latency was 15.6 + / - 2.2 min, and the total sleep duration was 118.7 + / - 10.2 min. In the medium-dose composition n DESCRIPTION group, the number of spontaneous activities within 10 min was 489 + / - 63, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 80%, the sleep latency was 11.8 + / - 1.9 min, and the total sleep duration was 162.3 + / - 11.8 min. In the high-dose composition group, the number of spontaneous activities within 10 min was 402 + / - 55, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 90%, the sleep latency was 9.8 + / - 1.5 min, and the total sleep duration was 188.5 + / - 12.6 min.

[0062] 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 example exhibits a more prominent synergistic sleep-promoting effect, can significantly reduce spontaneous activity in mice, markedly increase the sleep onset rate at the subthreshold dose, shorten sleep latency, and prolong total sleep duration, and shows an obvious dose-dependent relationship. The sleep-promoting effect is balanced and is suitable for the needs of most people with moderate sleep disorders.

[0063] The gastrointestinal safety results showed that, after 14 consecutive days of intragastric administration, anatomical observation of mouse gastrointestinal tissues revealed intact gastrointestinal mucosa in the blank control group and in all dose groups of this example, without congestion, edema, erosion, or other injuries, while mild gastric mucosal congestion was observed in one mouse in the 5-HTP-alone group. Serological tests showed no significant differences in gastrin and diamine oxidase levels between the dose groups of this example and the blank control group, confirming that the added fructooligosaccharide in the formula can effectively alleviate the gastrointestinal irritation that may be caused by a medium dose of 5-HTP, and that the composition has excellent oral safety.

[0064] The medium-dose 5-HTP ternary sleep-aid composition of this example, through synergy with fixed doses of L-theanine and GABA, achieved a balanced and potent sleep-promoting effect. Among them, the medium-dose DESCRIPTION composition reduced the number of spontaneous activities within 10 min by 62.0% relative to the blank control group and by 52.2% and 43.3%, respectively, relative to the 5-HTP-alone group and the L-theanine + GABA binary group. At the same time, it increased the sleep onset rate at the subthreshold dose of sodium pentobarbital from 10% in the blank group to 80%, shortened the sleep latency by 58.7% relative to the blank group, and prolonged the total sleep duration by 283.7% relative to the blank control group. It therefore provides a balanced and strong effect appropriate for the core improvement needs of most people with moderate sleep disorders.

[0065] Example III

[0066] Composition formula

[0067] In this example, the sleep-aid composition is an oral tablet. Based on the input quantity for every 1,000 tablets, only the input amount of 5-hydroxytryptophan is adjusted, while the other active ingredients and the types and amounts of excipients remain the same as in the original embodiment. The input amount of 5-hydroxytryptophan is 30 g, derived from Griffonia seed extract from Africa, with a 5-HTP purity of 98.5%; the input amount of L-theanine is 80 g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the input amount of gamma-aminobutyric acid is 120 g, derived from food-grade microbial fermentation, with a purity of 99.5%.

[0068] The total weight of the excipients accounts for 57.52% of the total weight of the composition, meeting the claimed range of 10%-90%. Specifically, the excipients comprise 30 g of fructooligosaccharide as the gastrointestinal protectant, accounting for 5.64% of the total weight of the composition and meeting the claimed range of l%-10%, together with 180 g of microcrystalline cellulose and 50 g of mannitol as fillers, 12 g of hydroxypropyl methylcellulose (HPMC E5) as the binder, 25 g of crospovidone as the disintegrant, 3 g of magnesium stearate as the lubricant, DESCRIPTION and 2 g of sweet orange flavor as the flavoring agent.

[0069] This example is a single-dose oral tablet. Each finished tablet weighs 532 mg and each single dose contains 30 mg of 5-HTP, 80 mg of L-theanine, and 120 mg of GABA, fully meeting the limitations on single-dose contents set forth in the claims.

[0070] Preparation process

[0071] In this example, the preparation is carried out by a conventional wet granulation and tableting process commonly used in the food and pharmaceutical fields. First, the above active ingredients and excipients are each passed through an 80-mesh sieve and accurately weighed according to the formula. A binder is then prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved, thereby preparing a binder solution at a mass concentration of 5%.

[0072] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharide, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 min until uniform. The prepared binder solution is added to form a soft mass, and the soft mass is passed through a 20-mesh sieve to prepare wet granules. The wet granules are dried in a fluidized-bed dryer with forced air at 60 C until the moisture content is <=3%, and the dried granules are passed through a 24-mesh sieve for sizing.

[0073] Finally, magnesium stearate and sweet orange flavor are added to the sized dry granules, which are then blended in a three-dimensional motion mixer for 8 min. After the content of the intermediate is confirmed to be qualified, the mixture is compressed with a rotary tablet press while controlling the tablet weight variation within + / -5% and the hardness at 4-6 kgf, thereby obtaining the target sleep-aid tablets.

[0074] Effect verification test

[0075] To verify the effects of the composition of this example on synergistically regulating the sleep rhythm and improving sleep quality, while DESCRIPTION also verifying gastrointestinal safety, an SPF-grade KM mouse study was conducted. The test protocol, animal parameters, grouping rules, and administration period were identical to those of the original embodiment, except that the dose of 5-HTP was adjusted for the corresponding group.

[0076] Sixty male KM mice weighing 18-22 g were randomly divided into six groups of ten mice each. The mice were intragastrically administered once daily at a fixed time for 14 consecutive days. The blank control group received an equal volume of normal saline; the 5-HTP-alone group received 5-HTP at 30 mg / kg bw; the L-theanine + GABA binary group received a composition containing 80 mg / kg bw of L-theanine and 120 mg / kg bw of GABA; the low-dose composition group received 115 mg / kg bw of the composition of this example, corresponding to 15 mg of 5-HTP, 40 mg of L-theanine, and 60 mg of GABA; the medium-dose composition group received 230 mg / kg bw of the composition of this example, corresponding proportionally to the recommended human dose; and the high-dose composition group received 460 mg / kg bw of the composition of this example, equal to twice the recommended dose.

[0077] The results for sleep rhythm and sleep quality showed that, in the blank control group, the number of spontaneous activities within 10 min was 1286 + / - 112, the sleep onset rate at the subthreshold dose of 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-alone group, the number of spontaneous activities within 10 min was 912 + / - 95, the sleep onset rate at the subthreshold dose of 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 within 10 min was 862 + / - 85, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 40%, the sleep latency was 19.2 + / - 2.5 min, and the total sleep duration was 92.4 + / - 9.1 min. DESCRIPTION

[0078] In the low-dose composition group, the number of spontaneous activities within 10 min was 526 + / - 65, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 70%, the sleep latency was 12.5 + / - 1.9 min, and the total sleep duration was 138.2 + / - 10.8 min. In the medium-dose composition group, the number of spontaneous activities within 10 min was 328 + / - 45, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 100%, the sleep latency was 7.8 + / - 1.1 min, and the total sleep duration was 226.4 + / - 14.2 min. In the high-dose composition group, the number of spontaneous activities within 10 min was 295 + / - 42, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 100%, the sleep latency was 6.9 + / - 1.0 min, and the total sleep duration was 248.3 + / - 15.0 min.

[0079] 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 example reaches a peak synergistic sleep-promoting effect, can powerfully reduce spontaneous activity in mice, achieve a 100% sleep onset rate at the subthreshold dose, markedly shorten sleep latency, and prolong total sleep duration, with an obvious dose-dependent relationship, thereby showing outstanding improvement for severe sleep disorders.

[0080] The gastrointestinal safety results showed that, after 14 consecutive days of intragastric administration, anatomical observation of mouse gastrointestinal tissues revealed intact gastrointestinal mucosa in the blank control group and in all dose groups of this example, without congestion, edema, erosion, or other injuries, while mild gastric mucosal congestion was observed in four mice and mild gastric mucosal edema in one mouse in the 5-HTP-alone group. Serological tests showed no significant differences in gastrin and diamine oxidase levels between the dose groups of this example and the blank control group, confirming that the added fructooligosaccharide in the formula can effectively alleviate the gastrointestinal irritation caused by high-dose 5-HTP, and that the composition still maintains excellent oral DESCRIPTION safety while providing a potent sleep-promoting effect.

[0081] The high-dose 5-HTP ternary sleep-aid composition of this example, through synergy with fixed doses of L-theanine and GABA, achieved an extremely potent sleep-promoting effect. Among them, the medium-dose composition reduced the number of spontaneous activities within 10 min by 74.5% relative to the blank control group and by 64.0% and 61.9%, respectively, relative to the 5-HTP-alone group and the L-theanine + GABA binary group. At the same time, it increased the sleep onset rate at the subthreshold dose of sodium pentobarbital from 10% in the blank group to 100%, shortened the sleep latency by 72.7% relative to the blank group, and prolonged the total sleep duration by 435.2% relative to the blank control group, demonstrating particularly prominent improvement for severe sleep disorders.

[0082] Examples IV to VI differ only in the content of gamma-aminobutyric acid.

[0083] Composition formula

[0084] In this example, the sleep-aid composition is an oral tablet. Based on the input quantity for every 1,000 tablets, only the input amount of gamma-aminobutyric acid is adjusted, while all other active ingredients, excipients, and amounts remain completely the same as in the original embodiment. The input amount of 5-hydroxytryptophan is 20 g, derived from Griffonia seed extract from Africa, with a 5-HTP purity of 98.5%; the input amount of L-theanine is 80 g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the input amount of gamma-aminobutyric acid is 100 g, 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.

[0085] The total weight of the excipients accounts for 60.16% of the total weight of the composition, meeting the claimed range of 10%-90%. Specifically, the DESCRIPTION excipients comprise 30 g of fructooligosaccharide as the gastrointestinal protectant, accounting for 5.98% of the total weight of the composition and meeting the claimed range of l%-10%, together with 180 g of microcrystalline cellulose and 50 g of mannitol as fillers, 12 g of hydroxypropyl methylcellulose (HPMC E5) as the binder, 25 g of crospovidone as the disintegrant, 3 g of magnesium stearate as the lubricant, and 2 g of sweet orange flavor as the flavoring agent.

[0086] This example is a single-dose oral tablet. Each finished tablet weighs 502 mg and each single dose contains 20 mg of 5-HTP, 80 mg of L-theanine, and 100 mg of GABA, fully meeting the limitations on single-dose contents set forth in the claims.

[0087] Preparation process

[0088] This example adopts a conventional wet granulation and tableting process commonly used in the food and pharmaceutical fields. First, the above active ingredients and excipients are each passed through an 80-mesh sieve and accurately weighed according to the formula. A binder is then prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved, thereby preparing a binder solution at a mass concentration of 5%.

[0089] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharide, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 min until uniform. The prepared binder solution is added to form a soft mass, and the soft mass is passed through a 20-mesh sieve to prepare wet granules. The wet granules are dried in a fluidized-bed dryer with forced air at 60 C until the moisture content is <=3%, and the dried granules are passed through a 24-mesh sieve for sizing.

[0090] Finally, magnesium stearate and sweet orange flavor are added to the sized dry granules, which are then blended in a three-dimensional motion mixer for 8 min. After the content of the intermediate is confirmed to be DESCRIPTION qualified, the mixture is compressed with a rotary tablet press while controlling the tablet weight variation within + / -5% and the hardness at 4-6 kgf, thereby obtaining the target sleep-aid tablets.

[0091] Effect verification test

[0092] To verify the effects of the composition of this example on synergistically regulating the sleep rhythm and improving sleep quality, while also verifying gastrointestinal safety, an SPF-grade KM mouse study was conducted. The test protocol, animal parameters, grouping rules, and administration period were identical to those of the original embodiment, except that the dose of GABA was adjusted for the corresponding group.

[0093] Sixty male KM mice weighing 18-22 g were randomly divided into six groups of ten mice each. The mice were intragastrically administered once daily at a fixed time for 14 consecutive days. The blank control group received an equal volume of normal saline; the 5-HTP-alone group received 5-HTP at 20 mg / kg bw; the L-theanine + GABA binary group received a composition containing 80 mg / kg bw of L-theanine and 100 mg / kg bw of GABA; the low-dose composition group received 100 mg / kg bw of the composition of this example, corresponding to 10 mg of 5-HTP, 40 mg of L-theanine, and 50 mg of GABA; the medium-dose composition group received 200 mg / kg bw of the composition of this example, corresponding proportionally to the recommended human dose; and the high-dose composition group received 400 mg / kg bw of the composition of this example, equal to twice the recommended dose.

[0094] The results for sleep rhythm and sleep quality showed that, in the blank control group, the number of spontaneous activities within 10 min was 1286 + / - 112, the sleep onset rate at the subthreshold dose of 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-alone group, the number of spontaneous activities within 10 min was 975 + / - 98, the sleep onset rate at the DESCRIPTION subthreshold dose of 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 within 10 min was 810 + / - 82, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 40%, the sleep latency was 18.7 + / - 2.4 min, and the total sleep duration was 88.6 + / - 8.9 min.

[0095] In the low-dose composition group, the number of spontaneous activities within 10 min was 668 + / - 74, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 55%, the sleep latency was 15.6 + / - 2.2 min, and the total sleep duration was 135.2 + / - 10.7 min. In the medium-dose composition group, the number of spontaneous activities within 10 min was 458 + / - 62, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 80%, the sleep latency was 11.8 + / - 1.8 min, and the total sleep duration was 162.5 + / - 11.7 min. In the high-dose composition group, the number of spontaneous activities within 10 min was 392 + / - 54, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 90%, the sleep latency was 10.1 + / - 1.5 min, and the total sleep duration was 186.8 + / - 12.4 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 example exhibits a significant synergistic sleep-promoting effect, can effectively reduce spontaneous activity in mice, increase the sleep onset rate at the subthreshold dose, shorten sleep latency, and prolong total sleep duration, and shows an obvious dose-dependent relationship. While improving difficulty in falling asleep, it also clearly enhances sleep maintenance.

[0097] The gastrointestinal safety results showed that, after 14 consecutive days of intragastric administration, anatomical observation of mouse gastrointestinal tissues revealed intact gastrointestinal mucosa in the blank control group and in all dose groups of this example, without congestion, DESCRIPTION edema, erosion, or other injuries, while mild gastric mucosal congestion was observed in three mice in the 5-HTP-alone group. Serological tests showed no significant differences in gastrin and diamine oxidase levels between the dose groups of this example and the blank control group, confirming that the added fructooligosaccharide in the formula can effectively alleviate the gastrointestinal irritation that may be caused by 5-HTP, and that the composition has excellent oral safety.

[0098] Through synergy among fixed doses of 5-HTP and L-theanine together with low-dose GABA, the composition of this example achieved a mild and balanced sleep-promoting effect. The sleep-promoting effect is not produced through non-specific central inhibition, but through precise targeted regulation of the sleep-wake rhythm. While achieving a sleep-promoting effect, it avoids the hangover-like residual central inhibition commonly associated with conventional sleep-aid ingredients. Measurement at 24 h after withdrawal following continuous administration for 14 days showed no statistically significant difference in spontaneous activity between the medium-dose composition group and the blank control group, demonstrating that the composition exerts targeted regulation only during the sleep cycle and does not cause continuous inhibition on the next day.

[0099] Example V

[0100] Composition formula

[0101] In this example, the sleep-aid composition is an oral tablet. Based on the input quantity for every 1,000 tablets, only the input amount of gamma-aminobutyric acid is adjusted, while all other active ingredients, excipients, and amounts remain completely the same as in the original embodiment. The input amount of 5-hydroxytryptophan is 20 g, derived from Griffonia seed extract from Africa, with a 5-HTP purity of 98.5%; the input amount of L-theanine is 80 g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the input amount of gamma-aminobutyric acid is DESCRIPTION

[0102] 110 g, 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.

[0103] The total weight of the excipients accounts for 58.98% of the total weight of the composition, meeting the claimed range of 10%-90%. Specifically, the excipients comprise 30 g of fructooligosaccharide as the gastrointestinal protectant, accounting for 5.86% of the total weight of the composition and meeting the claimed range of l%-10%, together with 180 g of microcrystalline cellulose and 50 g of mannitol as fillers, 12 g of hydroxypropyl methylcellulose (HPMC E5) as the binder, 25 g of crospovidone as the disintegrant, 3 g of magnesium stearate as the lubricant, and 2 g of sweet orange flavor as the flavoring agent.

[0104] This example is a single-dose oral tablet. Each finished tablet weighs 512 mg and each single dose contains 20 mg of 5-HTP, 80 mg of L-theanine, and 110 mg of GABA, fully meeting the limitations on single-dose contents set forth in the claims.

[0105] Preparation process

[0106] In this example, the preparation is carried out by a conventional wet granulation and tableting process commonly used in the food and pharmaceutical fields. First, the above active ingredients and excipients are each passed through an 80-mesh sieve and accurately weighed according to the formula. A binder is then prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved, thereby preparing a binder solution at a mass concentration of 5%.

[0107] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharide, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 min until uniform. The prepared binder solution is added to form a soft mass, and the soft mass is passed through a 20-mesh sieve to prepare wet granules. The wet granules are dried DESCRIPTION in a fluidized-bed dryer with forced air at 60 C until the moisture content is <=3%, and the dried granules are passed through a 24-mesh sieve for sizing.

[0108] Finally, magnesium stearate and sweet orange flavor are added to the sized dry granules, which are then blended in a three-dimensional motion mixer for 8 min. After the content of the intermediate is confirmed to be qualified, the mixture is compressed with a rotary tablet press while controlling the tablet weight variation within + / -5% and the hardness at 4-6 kgf, thereby obtaining the target sleep-aid tablets.

[0109] Effect verification test

[0110] To verify the effects of the composition of this example on synergistically regulating the sleep rhythm and improving sleep quality, while also verifying gastrointestinal safety, an SPF-grade KM mouse study was conducted. The test protocol, animal parameters, grouping rules, and administration period were identical to those of the original embodiment, except that the dose of GABA was adjusted for the corresponding group.

[0111] Sixty male KM mice weighing 18-22 g were randomly divided into six groups of ten mice each. The mice were intragastrically administered once daily at a fixed time for 14 consecutive days. The blank control group received an equal volume of normal saline; the 5-HTP-alone group received 5-HTP at 20 mg / kg bw; the L-theanine + GABA binary group received a composition containing 80 mg / kg bw of L-theanine and 110 mg / kg bw of GABA; the low-dose composition group received 105 mg / kg bw of the composition of this example, corresponding to 10 mg of 5-HTP, 40 mg of L-theanine, and 55 mg of GABA; the medium-dose composition group received 210 mg / kg bw of the composition of this example, corresponding proportionally to the recommended human dose; and the high-dose composition group received 420 mg / kg bw of the composition of this example, equal to twice the recommended dose.

[0112] The results for sleep rhythm and sleep quality showed that, in the blank DESCRIPTION control group, the number of spontaneous activities within 10 min was 1286 + / - 112, the sleep onset rate at the subthreshold dose of 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-alone group, the number of spontaneous activities within 10 min was 975 + / - 98, the sleep onset rate at the subthreshold dose of 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 within 10 min was 830 + / - 84, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 45%, the sleep latency was 18.2 + / - 2.4 min, and the total sleep duration was 95.8 + / - 9.3 min.

[0113] In the low-dose composition group, the number of spontaneous activities within 10 min was 642 + / - 72, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 60%, the sleep latency was 15.1 + / - 2.1 min, and the total sleep duration was 141.6 + / - 10.9 min. In the medium-dose composition group, the number of spontaneous activities within 10 min was 435 + / - 59, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 85%, the sleep latency was 11.0 + / - 1.7 min, and the total sleep duration was 174.3 + / - 12.0 min. In the high-dose composition group, the number of spontaneous activities within 10 min was 375 + / - 51, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 95%, the sleep latency was 9.4 + / - 1.4 min, and the total sleep duration was 201.7 + / - 12.8 min.

[0114] 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 example exhibits a more prominent synergistic sleep-promoting effect, can significantly reduce spontaneous activity in mice, markedly increase the sleep onset rate at the subthreshold dose, shorten sleep latency, and prolong total sleep duration, and shows an obvious dose-dependent relationship. It provides balanced improvement both in DESCRIPTION difficulty falling asleep and in sleep maintenance, and is suitable for the core needs of most people with moderate sleep disorders.

[0115] The gastrointestinal safety results showed that, after 14 consecutive days of intragastric administration, anatomical observation of mouse gastrointestinal tissues revealed intact gastrointestinal mucosa in the blank control group and in all dose groups of this example, without congestion, edema, erosion, or other injuries, while mild gastric mucosal congestion was observed in three mice in the 5-HTP-alone group. Serological tests showed no significant differences in gastrin and diamine oxidase levels between the dose groups of this example and the blank control group, confirming that the added fructooligosaccharide in the formula can effectively alleviate the gastrointestinal irritation that may be caused by 5-HTP, and that the composition has excellent oral safety.

[0116] Through synergy among fixed doses of 5-HTP and L-theanine together with medium-dose GABA, the composition of this example achieved a potent and balanced sleep-promoting effect. The sleep-promoting effect is not produced through non-specific central inhibition, but through precise targeted regulation of the sleep-wake rhythm. While achieving a potent sleep-promoting effect, it avoids the hangover-like residual central inhibition commonly associated with conventional sleep-aid ingredients. Measurement at 24 h after withdrawal following continuous administration for 14 days showed no statistically significant difference in spontaneous activity between the medium-dose composition group and the blank control group, demonstrating that the composition exerts targeted regulation only during the sleep cycle and does not cause next-day continuous suppression.

[0117] Example VI

[0118] Composition formula

[0119] In this example, the sleep-aid composition is an oral tablet. Based on the input quantity for every 1,000 tablets, only the input amount of DESCRIPTION gamma-aminobutyric acid is adjusted, while all other active ingredients, excipients, and amounts remain completely the same as in the original embodiment. The input amount of 5-hydroxytryptophan is 20 g, derived from Griffonia seed extract from Africa, with a 5-HTP purity of 98.5%; the input amount of L-theanine is 80 g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the input amount of gamma-aminobutyric acid is 140 g, 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.

[0120] The total weight of the excipients accounts for 55.72% of the total weight of the composition, meeting the claimed range of 10%-90%. Specifically, the excipients comprise 30 g of fructooligosaccharide as the gastrointestinal protectant, accounting for 5.54% of the total weight of the composition and meeting the claimed range of l%-10%, together with 180 g of microcrystalline cellulose and 50 g of mannitol as fillers, 12 g of hydroxypropyl methylcellulose (HPMC E5) as the binder, 25 g of crospovidone as the disintegrant, 3 g of magnesium stearate as the lubricant, and 2 g of sweet orange flavor as the flavoring agent.

[0121] This example is a single-dose oral tablet. Each finished tablet weighs 542 mg and each single dose contains 20 mg of 5-HTP, 80 mg of L-theanine, and 140 mg of GABA, fully meeting the limitations on single-dose contents set forth in the claims.

[0122] Preparation process

[0123] In this example, the preparation is carried out by a conventional wet granulation and tableting process commonly used in the food and pharmaceutical fields. First, the above active ingredients and excipients are each passed through an 80-mesh sieve and accurately weighed according to the formula. A binder is then prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved, DESCRIPTION thereby preparing a binder solution at a mass concentration of 5%.

[0124] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharide, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 min until uniform. The prepared binder solution is added to form a soft mass, and the soft mass is passed through a 20-mesh sieve to prepare wet granules. The wet granules are dried in a fluidized-bed dryer with forced air at 60 C until the moisture content is <=3%, and the dried granules are passed through a 24-mesh sieve for sizing.

[0125] Finally, magnesium stearate and sweet orange flavor are added to the sized dry granules, which are then blended in a three-dimensional motion mixer for 8 min. After the content of the intermediate is confirmed to be qualified, the mixture is compressed with a rotary tablet press while controlling the tablet weight variation within + / -5% and the hardness at 4-6 kgf, thereby obtaining the target sleep-aid tablets.

[0126] Effect verification test

[0127] To verify the effects of the composition of this example on synergistically regulating the sleep rhythm and improving sleep quality, while also verifying gastrointestinal safety, an SPF-grade KM mouse study was conducted. The test protocol, animal parameters, grouping rules, and administration period were identical to those of the original embodiment, except that the dose of GABA was adjusted for the corresponding group.

[0128] Sixty male KM mice weighing 18-22 g were randomly divided into six groups of ten mice each. The mice were intragastrically administered once daily at a fixed time for 14 consecutive days. The blank control group received an equal volume of normal saline; the 5-HTP-alone group received 5-HTP at 20 mg / kg bw; the L-theanine + GABA binary group received a composition containing 80 mg / kg bw of L-theanine and 140 mg / kg bw of GABA; the low-dose composition group received 120 mg / kg bw of the composition of this example, corresponding to 10 mg of 5-HTP, 40 mg of DESCRIPTION

[0129] L-theanine, and 70 mg of GABA; the medium-dose composition group received 240 mg / kg bw of the composition of this example, corresponding proportionally to the recommended human dose; and the high-dose composition group received 480 mg / kg bw of the composition of this example, equal to twice the recommended dose.

[0130] The results for sleep rhythm and sleep quality showed that, in the blank control group, the number of spontaneous activities within 10 min was 1286 + / - 112, the sleep onset rate at the subthreshold dose of 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-alone group, the number of spontaneous activities within 10 min was 975 + / - 98, the sleep onset rate at the subthreshold dose of 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 within 10 min was 850 + / - 86, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 50%, the sleep latency was 17.6 + / - 2.3 min, and the total sleep duration was 103.2 + / - 9.7 min.

[0131] In the low-dose composition group, the number of spontaneous activities within 10 min was 587 + / - 68, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 70%, the sleep latency was 13.8 + / - 2.0 min, and the total sleep duration was 152.4 + / - 11.0 min. In the medium-dose composition group, the number of spontaneous activities within 10 min was 386 + / - 52, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 100%, the sleep latency was 9.2 + / - 1.4 min, and the total sleep duration was 208.6 + / - 13.2 min. In the high-dose composition group, the number of spontaneous activities within 10 min was 332 + / - 46, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 100%, the sleep latency was 8.0 + / - 1.2 min, and the total sleep duration was 236.1 + / - 14.0 min.

[0132] The above results indicate that, compared with the blank control group, DESCRIPTION the single-component group, and the binary composition group, the ternary composition of this example reaches a peak synergistic sleep-promoting effect, can powerfully reduce spontaneous activity in mice, achieve a 100% sleep onset rate at the subthreshold dose, markedly shorten sleep latency, and prolong total sleep duration, with an obvious dose-dependent relationship, thereby showing outstanding improvement for severe sleep disorders and extremely poor sleep maintenance.

[0133] The gastrointestinal safety results showed that, after 14 consecutive days of intragastric administration, anatomical observation of mouse gastrointestinal tissues revealed intact gastrointestinal mucosa in the blank control group and in all dose groups of this example, without congestion, edema, erosion, or other injuries, while mild gastric mucosal congestion was observed in three mice in the 5-HTP-alone group. Serological tests showed no significant differences in gastrin and diamine oxidase levels between the dose groups of this example and the blank control group, confirming that the added fructooligosaccharide in the formula can effectively alleviate the gastrointestinal irritation that may be caused by 5-HTP, and that the composition still maintains excellent oral safety even when combined with a high dose of GABA.

[0134] Through synergy among fixed doses of 5-HTP and L-theanine together with high-dose GABA, the composition of this example achieved an extremely potent sleep-promoting effect. The sleep-promoting effect is not produced through non-specific central inhibition, but through precise targeted regulation of the sleep- wake rhythm. While achieving a potent effect, it avoids the hangover-like residual central inhibition commonly associated with conventional sleep-aid ingredients. Measurement at 24 h after withdrawal following continuous administration for 14 days showed no statistically significant difference in spontaneous activity between the medium-dose composition group and the blank control group, demonstrating that the DESCRIPTION composition exerts targeted regulation only during the sleep cycle and does not cause next-day continuous suppression.

[0135] Comparative example

[0136] Composition formula

[0137] In this comparative example, the sleep-aid composition is an oral tablet. Based on the input quantity for every 1,000 tablets, the weight ratio of the core active ingredients is 5-HTP:L-theanine:GABA = 1:4:6, fully meeting the claimed range. The input amount of 5-hydroxytryptophan is 20 g, derived from Griffonia seed extract from Africa, with a 5-HTP purity of 98.5%; the input amount of L-theanine is 80 g, derived from food-grade microbial fermentation, with a purity of 99.2%; and the input amount of gamma-aminobutyric acid is 120 g, derived from food- grade microbial fermentation, with a purity of 99.5%.

[0138] The total weight of the excipients accounts for 57.85% of the total weight of the composition, meeting the claimed range of 10%-90%. Specifically, the excipients comprise 30 g of fructooligosaccharide as the gastrointestinal protectant, accounting for 5.75% of the total weight of the composition and meeting the claimed range of l%-10%, together with 180 g of microcrystalline cellulose and 50 g of mannitol as fillers, 12 g of hydroxypropyl methylcellulose (HPMC E5) as the binder, 25 g of crospovidone as the disintegrant, 3 g of magnesium stearate as the lubricant, and 2 g of sweet orange flavor as the flavoring agent.

[0139] This comparative example is a single-dose oral tablet. Each finished tablet weighs 522 mg and each single dose contains 20 mg of 5-HTP, 80 mg of L-theanine, and 120 mg of GABA, fully meeting the limitations on single-dose contents set forth in the claims.

[0140] Preparation process

[0141] This example adopts a conventional wet granulation and tableting process commonly used in the food and pharmaceutical fields. First, the above DESCRIPTION active ingredients and excipients are each passed through an 80-mesh sieve and accurately weighed according to the formula. A binder is then prepared by adding hydroxypropyl methylcellulose to purified water and stirring until completely dissolved, thereby preparing a binder solution at a mass concentration of 5%.

[0142] After pretreatment, 5-HTP, L-theanine, GABA, fructooligosaccharide, microcrystalline cellulose, mannitol, and crospovidone are placed in a wet mixing granulator and premixed for 10 min until uniform. The prepared binder solution is added to form a soft mass, and the soft mass is passed through a 20-mesh sieve to prepare wet granules. The wet granules are dried in a fluidized-bed dryer with forced air at 60 C until the moisture content is <=3%, and the dried granules are passed through a 24-mesh sieve for sizing.

[0143] Finally, magnesium stearate and sweet orange flavor are added to the sized dry granules, which are then blended in a three-dimensional motion mixer for 8 min. After the content of the intermediate is confirmed to be qualified, the mixture is compressed with a rotary tablet press while controlling the tablet weight variation within + / -5% and the hardness at 4-6 kgf, thereby obtaining the target sleep-aid tablets.

[0144] Effect verification test

[0145] To verify the effects of the composition of this comparative example on synergistically regulating the sleep rhythm and improving sleep quality, while also verifying gastrointestinal safety, an SPF-grade KM mouse study was conducted, and the protocol complied with animal ethics requirements.

[0146] Sixty male KM mice weighing 18-22 g were randomly divided into six groups of ten mice each. The mice were intragastrically administered once daily at a fixed time for 14 consecutive days. The blank control group received an equal volume of normal saline; the 5-HTP-alone group received 5-HTP at 20 mg / kg bw; the L-theanine + GABA binary group received a composition containing 80 mg / kg bw of L-theanine and 120 mg / kg bw of DESCRIPTION

[0147] GABA; the low-dose composition group received 110 mg / kg bw of the composition of this comparative example, corresponding to 10 mg of 5-HTP, 40 mg of L-theanine, and 60 mg of GABA; the medium-dose composition group received 220 mg / kg bw of the composition of this comparative example, corresponding proportionally to the recommended human dose; and the high-dose composition group received 440 mg / kg bw of the composition of this comparative example, equal to twice the recommended dose.

[0148] The results for sleep rhythm and sleep quality showed that, in the blank control group, the number of spontaneous activities within 10 min was 1286 + / - 112, the sleep onset rate at the subthreshold dose of 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-alone group, the number of spontaneous activities within 10 min was 975 + / - 98, the sleep onset rate at the subthreshold dose of 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 within 10 min was 842 + / - 85, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 45%, the sleep latency was 18.0 + / - 2.4 min, and the total sleep duration was 98.4 + / - 9.5 min.

[0149] In the low-dose composition group, the number of spontaneous activities within 10 min was 624 + / - 71, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 60%, the sleep latency was 14.7 + / - 2.1 min, and the total sleep duration was 126.8 + / - 10.5 min. In the medium-dose composition group, the number of spontaneous activities within 10 min was 412 + / - 56, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 90%, the sleep latency was 10.3 + / - 1.6 min, and the total sleep duration was 185.2 + / - 12.3 min. In the high-dose composition group, the number of spontaneous activities within 10 min was 358 + / - 48, the sleep onset rate at the subthreshold dose of sodium pentobarbital was 95%, the sleep latency was 8.8 DESCRIPTION

[0150] + / - 1.3 min, and the total sleep duration was 214.6 + / - 13.5 min.

[0151] 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 comparative example can significantly reduce spontaneous activity in mice, increase the sleep onset rate at the subthreshold dose, markedly shorten sleep latency, and prolong total sleep duration, and shows an obvious dose-dependent relationship, confirming that 5-HTP, L-theanine, and GABA have a significant synergistic sleep-promoting effect and can effectively regulate the sleep rhythm and improve difficulties in falling asleep and insufficient sleep duration.

[0152] The gastrointestinal safety results showed that, after 14 consecutive days of intragastric administration, anatomical observation of mouse gastrointestinal tissues revealed intact gastrointestinal mucosa in the blank control group and in all dose groups of this comparative example, without congestion, edema, erosion, or other injuries, while mild gastric mucosal congestion was observed in three mice in the 5-HTP-alone group. Serological tests showed no significant differences in gastrin and diamine oxidase levels between the dose groups of this comparative example and the blank control group, confirming that the added fructooligosaccharide in the formula can effectively alleviate the gastrointestinal irritation that may be caused by 5-HTP, and that the composition has excellent oral safety.

[0153] The specific contents are shown in the table below: DESCRIPTION

[0154] Examples I to III achieved graded and differentiated sleep-promoting effects by adjusting the single-dose content of 5-HTP (5 mg, 15 mg, and 30 mg) while keeping the amounts of L-theanine and GABA and all other parameters fixed, and all verified the synergistic sleep-promoting effect of 5-HTP with L-theanine and GABA while maintaining excellent oral safety. The sleep-promoting effect of the three examples increased significantly in a dose-dependent manner with increasing 5-HTP content. Among them, the 5 mg low-dose 5-HTP example provided a mild and stable sleep-promoting effect suitable for daily conditioning in people with mild sleep disorders; the 15 mg medium-dose 5-HTP example provided a balanced and strong sleep-promoting effect suitable for the core needs of most people with moderate sleep disorders; and the 30 mg high-dose 5-HTP example provided an extremely potent sleep-promoting effect suitable for people with severe sleep disorders.

[0155] Examples IV to VI adjusted the input amount of gamma-aminobutyric acid while keeping all other raw-material parameters, preparation processes, and test protocols fully consistent with the original embodiment, and all examples were within the ranges defined by the claims. As the GABA content increased stepwise, the synergistic sleep-promoting effect of the ternary composition also increased significantly in a dose-dependent manner. The improvements in sleep onset rate and shortening of sleep latency were steadily DESCRIPTION optimized, while the enhancement in prolonging total sleep duration and improving sleep maintenance was particularly prominent, fully verifying the core role of GABA in sleep maintenance and deep-sleep regulation within the composition, as well as its important synergistic value when combined with 5-HTP and L-theanine.

[0156] The foregoing description is merely of the preferred embodiments of the present invention and does not limit the present invention in any form. Although the present invention has been disclosed above with preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art may, without departing from the scope of the technical solutions of the present invention, make certain changes or modifications to the disclosed technical content so as to obtain equivalent embodiments. Any simple modification, equivalent change, or modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solutions of the present invention shall still fall within the scope of the technical solutions of the present invention.

Claims

CLAIMS1. A sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine, characterized in that the composition is prepared from the following raw materials in parts by weight:The active ingredients of the composition consist of 5 -hydroxy tryptophan, L-theanine, and gamma-aminobutyric acid.

2. The sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine according to claim 1, characterized in that, in parts by weight, the active ingredients comprise 5-30 parts of 5-HTP, 20-100 parts of L-theanine, and 30-150 parts of GABA.

3. The sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine according to claim 2, characterized in that, in parts by weight, the active ingredients comprise 10-25 parts of 5-HTP, 30-80 parts of L-theanine, and 50-120 parts of GABA.

4. The sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and 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-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine according to claim 1, characterized in that the 5-HTP is derived from Griffonia seed extract from Africa, wherein the purity of 5-HTP is >=98%; the L-theanine is derived from natural tea extraction or food-grade microbial fermentation, with a purity of >=99%; and the GABA is derived from food-grade microbial fermentation, with a purity of >=99%.

6. The sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine according to claim 1, characterized in that the composition further comprises pharmaceutically or food-acceptable excipients, and the weight of the excipients accounts for 10%-90% of the total weight of the composition.

7. The sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine according to claim 6, characterized in thatCLAIMS the excipients comprise at least one selected from the group consisting of a filler, a binder, a disintegrant, a lubricant, a flavoring agent, a preservative, and a solubilizer.

8. The sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine according to claim 1, characterized in that the composition is an oral preparation, and the oral preparation is any one selected from a tablet, a hard capsule, a soft capsule, a granule, a powder, an oral liquid, and a chewable tablet.

9. The sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine according to claim 1, characterized in that the composition is a single-dose oral preparation, wherein each single-dose preparation contains 5 mg-30 mg of 5-HTP, 20 mg-100 mg of L-theanine, and 30 mg-150 mg of GABA.

10. The sleep-aid composition for synergistically regulating the sleep rhythm with 5-HTP and L-theanine according to claim 1, characterized in that the excipients further comprise a gastrointestinal protectant, wherein the gastrointestinal protectant is at least one selected from fructooligosaccharide, inulin, and resistant dextrin, and the weight of the gastrointestinal protectant accounts for 1%-10% of the total weight of the composition.

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