Use of a combination of a composition and sodium pentobarbital in the manufacture of a medicament for improving sleep and a combination for improving sleep

Abstract

The application belongs to the field of pharmaceutical preparations, and specifically discloses a composition combined with sodium pentobarbital for use in the preparation of a sleep-improving medicine and a sleep-improving combined medicine. The composition is prepared from raw materials including the following components in mass parts: 100-150 parts of a yellow-fin-tube enzymatic extract, 50-75 parts of a polygonatum extract, 50-75 parts of a semen ziziphi spinozae extract, 50-75 parts of a poria cocos extract, and 250-375 parts of a Naqu 4580 probiotic. The composition combined with sodium pentobarbital can improve sleep, can significantly help sleep without reaching the clinical effective dose of sodium pentobarbital, and can make the sleep-aiding effect more stable and more in line with human physiological laws. The effect is close to that of a commonly used clinical medicine but has no dependency side effects, highlights the core advantages of "safety and high efficiency", and has practical popularization and application value.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparations, specifically relating to the use of a composition in combination with sodium pentobarbital in the preparation of a drug for improving sleep, and the combined use of the drug for improving sleep. Background Technology

[0002] Sleep is a crucial process for the body's repair and recovery. During sleep, the body undergoes cell repair, tissue growth, and the removal of metabolic waste. Insufficient sleep can lead to poor concentration, impaired judgment, increased error rates and accident risks, and negatively impact work efficiency and productivity. Studies have shown that chronic sleep deprivation increases the risk of various chronic diseases, such as heart disease, stroke, and diabetes. Sleep deprivation can also affect metabolic function, increasing the risk of weight gain and obesity. With the fast pace of modern life and increased mental stress, the incidence of sleep disorders is rising year by year. Currently, while commonly used hypnotic drugs can quickly improve sleep, long-term use can easily lead to side effects such as dependence and memory loss. For example, sodium pentobarbital has sedative, hypnotic, and anticonvulsant effects, but it can cause drowsiness, fatigue, and memory loss. Therefore, finding natural, safe, and effective sleep-aiding ingredients has become a research hotspot.

[0003] Traditional Chinese medicine (TCM) offers certain benefits in improving sleep, particularly in regulating the nervous system, improving sleep quality, and overall well-being. For example, components of TCM such as jujube seed and schisandra fruit can regulate neurotransmitters and improve sleep disorders; while wolfberry and angelica can help adjust the biological clock and promote a normal sleep-wake cycle. However, current research on TCM's ability to improve sleep largely relies on subjective evaluations, lacking standardized objective indicators to assess efficacy. Furthermore, the diversity of TCM formulas and combinations of different prescriptions and herbs can lead to significant differences in efficacy. Therefore, it is necessary to provide a TCM composition with a clearly defined sleep-aiding effect and mechanism of action for highly effective sleep promotion. Summary of the Invention

[0004] To achieve the above objectives, the present invention provides the use of a composition in combination with sodium pentobarbital in the preparation of a drug for improving sleep, wherein the mass ratio of the composition to sodium pentobarbital is 750:33~50;

[0005] The composition is prepared from raw materials comprising the following parts by weight:

[0006] 100-150 parts of Polygonatum odoratum enzymatic hydrolysis extract, 50-75 parts of Polygonatum odoratum extract, 50-75 parts of Ziziphus jujuba var. spinosa extract, 50-75 parts of Poria cocos extract, and 250-375 parts of Nagqu 4580 probiotics.

[0007] The enzymatic hydrolysis extract of Polygonatum is obtained by sequentially hydrolyzing Polygonatum in water with a compound enzyme, an alkaline protease, and a neutral protease.

[0008] The Polygonatum odoratum extract is an aqueous extract of Polygonatum odoratum.

[0009] The jujube seed extract is an aqueous extract of jujube seed.

[0010] The Poria cocos extract is an aqueous extract of Poria cocos.

[0011] Furthermore, the composition is prepared from raw materials comprising the following parts by weight:

[0012] 150 parts of Polygonatum odoratum enzymatic hydrolysis extract, 75 parts of Polygonatum odoratum extract, 75 parts of Ziziphus jujuba var. spinosa extract, 75 parts of Poria cocos extract, and 375 parts of Nagqu 4580 probiotics.

[0013] Furthermore, the composition further includes 250-375 parts of protein peptides;

[0014] The protein peptides are casein hydrolysate peptides and / or fish collagen peptides.

[0015] Furthermore, it is prepared from the following parts by weight of raw materials:

[0016] 100 parts of Polygonatum odoratum enzymatic hydrolysis extract, 50 parts of Polygonatum odoratum extract, 50 parts of Ziziphus jujuba var. spinosa extract, 50 parts of Poria cocos extract, 250 parts of Nagqu 4580 probiotics, 187.5 parts of casein hydrolyzed peptides, and 62.5 parts of fish collagen peptides.

[0017] Furthermore, the enzymatic hydrolysis extract of Polygonatum is obtained by hydrolyzing Polygonatum that has been steamed and sun-dried six times with a compound enzyme at 4% of its weight in water at 50°C and pH 5 for 3 hours, followed by hydrolysis with alkaline protease at 4% of its weight in water at 45°C and pH 8.5 for 3 hours, and finally hydrolysis with neutral protease at 4% of its weight in water at 30-45°C for 3 hours. After heating to 90°C and holding for 30 minutes to inactivate the enzyme, the extract is filtered, the supernatant is concentrated, and then freeze-dried under vacuum.

[0018] The complex enzyme consists of cellulase and pectinase in a mass ratio of 1:1.

[0019] The Polygonatum odoratum extract is obtained by extracting Polygonatum odoratum with water, concentrating the extract into an extract equivalent to 3g of raw medicinal material per gram, and spray drying the extract.

[0020] The jujube seed extract is obtained by extracting jujube seeds with water, concentrating the extract into an extract equivalent to 20g of raw medicinal material per gram, and then spray drying the extract.

[0021] The Poria cocos extract is obtained by extracting Poria cocos with water, concentrating the extract into an extract equivalent to 10g of raw medicinal material per gram, and then spray drying the extract.

[0022] The present invention also provides a combination drug for improving sleep, comprising a composition for simultaneous or separate administration and a packet of sodium pentobarbital;

[0023] The mass ratio of the composition to sodium pentobarbital is 750:33~50;

[0024] The composition is prepared from raw materials comprising the following parts by weight:

[0025] 100-150 parts of Polygonatum odoratum enzymatic hydrolysis extract, 50-75 parts of Polygonatum odoratum extract, 50-75 parts of Ziziphus jujuba var. spinosa extract, 50-75 parts of Poria cocos extract, and 250-375 parts of Nagqu 4580 probiotics.

[0026] The enzymatic hydrolysis extract of Polygonatum is obtained by sequentially hydrolyzing Polygonatum in water with a compound enzyme, an alkaline protease, and a neutral protease.

[0027] The Polygonatum odoratum extract is an aqueous extract of Polygonatum odoratum.

[0028] The jujube seed extract is an aqueous extract of jujube seed.

[0029] The Poria cocos extract is an aqueous extract of Poria cocos.

[0030] Furthermore, the composition is prepared from raw materials comprising the following parts by weight:

[0031] 150 parts of Polygonatum odoratum enzymatic hydrolysis extract, 75 parts of Polygonatum odoratum extract, 75 parts of Ziziphus jujuba var. spinosa extract, 75 parts of Poria cocos extract, and 375 parts of Nagqu 4580 probiotics.

[0032] Furthermore, the composition further includes 250-375 parts of protein peptides;

[0033] The protein peptides are casein hydrolysate peptides and / or fish collagen peptides.

[0034] Furthermore, it is prepared from the following parts by weight of raw materials:

[0035] 100 parts of Polygonatum odoratum enzymatic hydrolysis extract, 50 parts of Polygonatum odoratum extract, 50 parts of Ziziphus jujuba var. spinosa extract, 50 parts of Poria cocos extract, 250 parts of Nagqu 4580 probiotics, 187.5 parts of casein hydrolyzed peptides, and 62.5 parts of fish collagen peptides.

[0036] The complex enzyme consists of cellulase and pectinase in a mass ratio of 1:1.

[0037] The Polygonatum odoratum extract is obtained by extracting Polygonatum odoratum with water, concentrating the extract into an extract equivalent to 3g of raw medicinal material per gram, and spray drying the extract.

[0038] The jujube seed extract is obtained by extracting jujube seeds with water, concentrating the extract into an extract equivalent to 20g of raw medicinal material per gram, and then spray drying the extract.

[0039] The Poria cocos extract is obtained by extracting Poria cocos with water, concentrating the extract into an extract equivalent to 10g of raw medicinal material per gram, and then spray drying the extract.

[0040] Furthermore, the combined medication is an injectable and / or oral formulation; the oral formulation includes solutions, powders, granules, tablets, pills, and ointments.

[0041] This invention relates to a composition that improves sleep. By combining specific proportions of enzymatically hydrolyzed extracts of Polygonatum sibiricum, Polygonatum odoratum, Ziziphus jujuba var. spinosa, and Poria cocos with probiotics and protein peptides, this composition, when used in conjunction with sodium pentobarbital, achieves a synergistic sleep-aiding effect. This composition, combined with sodium pentobarbital, significantly promotes sleep even before the effective dose is reached. It avoids the physiological risks associated with direct sodium pentobarbital inducing sleep, such as drowsiness, dizziness, nausea, and long-term addiction. Furthermore, through a synergistic effect ("1+1>2" or "1+1+1>3"), the sleep-aiding effect is more stable and more aligned with human physiological rhythms. Compared to single-ingredient formulations, this approach significantly improves sleep onset and prolongs sleep duration, achieving effects close to clinical drugs without the side effects of dependence. This highlights its core advantages of "safety and high efficiency," making it worthy of practical application.

[0042] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0043] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Detailed Implementation

[0044] The raw materials and equipment used in the specific embodiments of this invention are all known products, obtained by purchasing commercially available products. Among them, Viger brand melatonin tablets are provided by Bestway Beauty and Health Products (Shanghai) Co., Ltd.

[0045] Nagqu 4580 Probiotics: It is made by fermenting and then inactivating three bacteria: Lactobacillus paracasei L578, Lactobacillus helveticus L551, and Streptococcus salivarius subsp. thermophilus S709. It is specifically provided by Hebei Yiran Biotechnology Co., Ltd.

[0046] Casein hydrolyzed peptides: provided by Hangzhou Kangyuan Food Technology Co., Ltd.

[0047] Fish collagen peptides: provided by Liaoning Taiai Peptide Biotechnology Co., Ltd.

[0048] The preparation method of Polygonatum odoratum enzymatic hydrolysis extract is as follows:

[0049] Take six-steamed and six-dried Polygonatum rhizome, add 10 times the volume (v / w) of water, adjust the pH to 5 at 50℃, then add 4% (w / w) of enzyme (cellulase: pectinase = 1:1) by weight of Polygonatum rhizome, react for 3 hours, then at 45℃, maintain the pH to 8.5, add 4% (w / w) of alkaline protease by weight of Polygonatum rhizome, react for 3 hours, then at 30-45℃, add 4% (w / w) of neutral protease by weight of Polygonatum rhizome, react for 3 hours, then heat to 90℃ and keep warm for 30 minutes to inactivate the enzyme, filter, take the supernatant and concentrate under reduced pressure at 50℃ with a vacuum degree of 0.08 MPa, and finally freeze dry to obtain the product;

[0050] The six-steamed and six-dried Polygonatum was prepared according to the method disclosed in Example 1 of Patent ZL201810049671.5, a method for processing steamed Polygonatum; cellulase (100,000 U / g) and pectinase (50,000 U / g) were purchased from Shandong Yaqiu Biotechnology Co., Ltd.; alkaline protease (200 U / mg) and neutral protease (50 U / mg) were purchased from Beijing Aoboxing Biotechnology Co., Ltd.

[0051] Preparation method of Polygonatum odoratum extract: Weigh Polygonatum odoratum slices, add 10 times the amount (v / w) of water and extract twice, 1 hour each time, concentrate to an extract equivalent to 3g of raw medicinal material per gram, spray dry to obtain the extract;

[0052] Preparation method of jujube seed extract: Weigh jujube seed slices, add 10 times the amount (v / w) of water and extract twice, 1 hour each time, concentrate to an extract equivalent to 20g of raw medicinal material per gram, spray dry to obtain the extract;

[0053] Preparation method of Poria cocos extract: Take the Chinese herbal medicine Poria cocos slices, add 10 times the amount (v / w) of water and extract twice, 1 hour each time, concentrate to an extract equivalent to 10g of raw medicinal material per gram, spray dry to obtain the extract.

[0054] Example 1: Preparation of the composition of the present invention

[0055] Formula: 150 parts of Polygonatum odoratum enzymatic hydrolysis extract, 75 parts of Polygonatum odoratum extract, 75 parts of Ziziphus jujuba var. spinosa extract, 75 parts of Poria cocos extract, and 375 parts of Nagqu 4580 probiotics.

[0056] Preparation method: Weigh the above raw materials according to the ratio, add the excipients acceptable for pharmaceuticals or food, and mix to obtain the final product.

[0057] Example 2 Preparation of the composition of the present invention

[0058] Formula: 100 parts of Polygonatum odoratum enzymatic hydrolysis extract, 50 parts of Polygonatum odoratum extract, 50 parts of Ziziphus jujuba var. spinosa extract, 50 parts of Poria cocos extract, 250 parts of Nagqu 4580 probiotics, 187.5 parts of casein peptide, and 62.5 parts of fish collagen peptide.

[0059] Preparation method: Weigh the above raw materials according to the ratio, add the excipients acceptable for pharmaceuticals or food, and mix to obtain the final product.

[0060] Example 3: Combined Drugs of the Present Invention

[0061] Formulation: 750 parts of the composition prepared in Example 1, and 33 parts of sodium pentobarbital;

[0062] Preparation method: Weigh the above raw materials according to the ratio, package them separately, and then package them together to obtain the final product.

[0063] Example 4: Combined Drugs of the Present Invention

[0064] Formulation: 750 parts of the composition prepared in Example 1, and 50 parts of sodium pentobarbital;

[0065] Preparation method: Weigh the above raw materials according to the ratio, package them separately, and then package them together to obtain the final product.

[0066] Example 5: Combined Drugs of the Present Invention

[0067] Formulation: 750 parts of the composition prepared in Example 2, and 50 parts of sodium pentobarbital;

[0068] Preparation method: Weigh the above raw materials according to the ratio, package them separately, and then package them together to obtain the final product.

[0069] Example 6: Combined Drugs of the Present Invention

[0070] Formulation: 750 parts of the composition prepared in Example 2, and 33 parts of sodium pentobarbital;

[0071] Preparation method: Weigh the above raw materials according to the ratio, package them separately, and then package them together to obtain the final product.

[0072] The following experimental examples illustrate the beneficial effects of the present invention.

[0073] Experimental Example 1: Experimental Study on the Sleep Improvement of the Composition of the Invention

[0074] 1. Method

[0075] 1.1 Materials

[0076] 1.1.1 Reagents and Test Chemicals

[0077] Weigel Brand Miannadoning Tablets; The traditional Chinese medicine extract consists of the following extracts: 0.2 grams of polygonatum enzymolysis extract, 0.1 grams of polygonatum odoratum extract, 0.1 grams of spina date extract, and 0.1 grams of poria cocos extract; Mixed probiotics: Naqu 4580 probiotics; Protein peptide combination: 0.3 grams of casein peptide and 0.1 grams of fish collagen peptide.

[0078] 1.1.2 Experimental animals

[0079] SPF-grade KM male mice, with a body weight between 18 and 20 g, were purchased from Beijing Speyford Biotechnology Co., Ltd. The experimental animal use license is SCXK (Beijing) 2019-0010. The environmental temperature is 15°C - 25°C, and the humidity is 20 - 40%.

[0080] 1.1.3 Dose setting

[0081] Each batch of animals was randomly divided into 9 groups according to body weight: A: Negative control group (distilled water); B: Positive control group (miannadoning 267 mg / kg); C: Traditional Chinese medicine extract group (polygonatum enzymolysis extract: polygonatum odoratum extract: spina date extract: poria cocos extract = 2:1:1:1; 300, 150, 150, 150 mg / kg); D: Mixed probiotics group (750 mg / kg); E: Protein peptide group (casein hydrolyzate: fish collagen peptide = 3:2; 450, 300 mg / kg); F: Traditional Chinese medicine extract + mixed probiotics group (1:1; 375, 375 mg / kg); G: Traditional Chinese medicine extract + protein peptide group (1:1; 375, 375 mg / kg); H: Protein peptide + mixed probiotics group (1:1; 375, 375 mg / kg); I: Traditional Chinese medicine extract + mixed probiotics group + protein peptide group (1:1:1; 250, 250, 250 mg / kg).

[0082] 1.2 Experimental methods

[0083] 1.2.1 General observation

[0084] Observe the hair color, behavior, and mental state of the mice every day, analyze for abnormalities, and weigh them before and after each experiment: Observe the changes in body weight.

[0085] 1.2.2 Effects of different doses of pentobarbital sodium on the sleep incidence and sleep time of mice

[0086] Sixty male KM mice, 10 in each group. Inject pentobarbital sodium solution into the mice intraperitoneally at gradient doses of 3, 5, 40, 45, 50, 55 mg / kg respectively, and measure the effects of pentobarbital sodium on the incidence and sleep time of mice at different doses

[0087] 1.2.3 Effects of different groups on the direct sleep of mice

[0088] Ninety male KM mice were randomly divided into nine groups (grouping as described in section 1.1.3), with ten mice in each group. Each group was administered a different drug solution via gavage once daily at a dose of 0.1 ml / 10 g for 30 consecutive days. Daily food intake was recorded, and the mice were weighed every seven days with free access to food and water. The presence of sleep was observed after drug administration. Sleep was defined as the disappearance of the righting reflex; if the mouse could not right itself for more than 60 seconds, the righting reflex was considered absent, confirming sleep. The return of the righting reflex indicated awakening. The period from the disappearance to the return of the righting reflex was considered sleep time. The number of mice falling asleep and the duration of sleep were recorded for each group. Sleep latency was calculated by subtracting the injection time from the onset of sleep, and sleep duration was calculated by subtracting the onset time from the end of sleep.

[0089] 1.2.4 Effects of different groups on sleep latency and sleep duration in mice taking subthreshold doses of sodium pentobarbital

[0090] Following the grouping criteria in 1.1.3 and the intraperitoneal injection of 33 mg / kg sodium pentobarbital 30 min after the last administration, the number of animals falling asleep in each group was recorded to observe the effect of each group on the incidence of sleep in mice with subthreshold doses of sodium pentobarbital.

[0091] 1.2.5 Effects of different groups on the sleep latency and sleep duration of sodium pentobarbital

[0092] Following the grouping and administration guidelines in 1.1.3, mice were intraperitoneally injected with 50 mg / kg sodium pentobarbital 1 hour after the last administration. The injection time of sodium pentobarbital, the time of onset of sleep, and the time of end of sleep were recorded to observe the effects of each group on the sleep latency and sleep duration of mice.

[0093] 1.3 Results

[0094] 1.3.1 Effect of the test substance on mouse body weight

[0095] In each experimental group, there were no abnormalities in coat color, behavior, or mental state of the mice in each dosage group. See Table 1.

[0096] Table 1 Mouse body weight

[0097]

[0098] 1.3.2 Effects of different doses of sodium pentobarbital on the incidence and duration of sleep in mice

[0099] The optimal dose of sodium pentobarbital was determined by inducing 100% sleep in mice; the threshold dose determined in this experiment was 50 mg / kg. The maximum subthreshold dose of sodium pentobarbital is the sedative dose at which 80%-90% of mice do not lose their righting reflex; the maximum subthreshold dose determined in this experiment was 33 mg / kg. See Table 2.

[0100] Table 2. Effects of different doses of sodium pentobarbital on the incidence and duration of sleep in mice (n = 10, x ± s)

[0101]

[0102] 1.3.3 Effects of different groups on direct sleep in mice

[0103] The experimental results showed that none of the mice in the direct sleep experiment fell asleep, indicating that none of the test substances and combinations had a direct hypnotic effect, as shown in Table 3.

[0104] Table 3 Direct Sleep Experiments in Different Groups

[0105]

[0106] 1.3.4 Subthreshold dose hypnotic experiment with sodium pentobarbital

[0107] In the subthreshold dose experiment of sodium pentobarbital, when the sodium pentobarbital dosage was 33 mg / kg, the positive control group (Group B) had the highest sleep onset rate (70%), followed by the combination group of three (Group I) (60%), the traditional Chinese medicine + probiotic group (Group F) had 50%, the traditional Chinese medicine extract group (Group C) and the mixed probiotic group (Group D) both had 40%, and the sleep onset rate of the remaining groups was low (20%-30%), as shown in Table 4.

[0108] Further analysis of the data in Table 4 reveals that, compared to the blank control group (Group A), the sleep onset rate of the Chinese herbal extract group (Group C) and the mixed probiotic group (Group D) both increased by 20%. However, the sleep onset rate of the Chinese herbal extract + probiotic group (Group F) increased by 30% at the same dosage, indicating that the combination of Chinese herbal extract and probiotics produced a 1+1>2 effect. The sleep onset rate of the protein peptide group (Group E) remained unchanged compared to Group A, but the sleep onset rate of the Chinese herbal extract + probiotics + protein peptide group (Group I) increased by 40% at the same dosage, indicating that the combination of Chinese herbal extract, probiotics and protein peptides produced a 1+1+1>3 effect.

[0109] Table 4. Incidence of hypnosis in mice induced by subthreshold doses of sodium pentobarbital in different groups

[0110]

[0111] 1.3.5 Effects of suprathreshold doses of sodium pentobarbital on sleep latency and sleep duration in mice

[0112] In the suprathreshold dose experiment of sodium pentobarbital, when the sodium pentobarbital dosage was 50 mg / kg, compared with the blank control group (Group A), the sleep latency of Groups B, C, E, G, H, and I was significantly shortened (P < 0.05), and the sleep time of Groups B, C, G, H, and I was significantly prolonged (P < 0.05). Among them, Group B had the longest sleep time (218.45 ± 80.62 min), followed by Group I (205.68 ± 78.35 min), and Group C had a sleep time of 189.57 ± 82.46 min. This indicates that the extract of traditional Chinese medicine alone or in combination with other components (especially the combination of the three) has a good hypnotic effect, and the effect of the combination of the three is close to that of the positive drug, as shown in Table 5.

[0113] Table 5. Effects of different groups on hypnotic latency and sleep duration induced by sodium pentobarbital in mice.

[0114]

[0115] Compared with the blank control group (distilled water): 1) P < 0.05

[0116] 2. Discussion

[0117] Sodium pentobarbital is a barbiturate drug with sedative, hypnotic, and anticonvulsant effects. However, it may cause central nervous system depression symptoms such as drowsiness, fatigue, and memory loss, and its hypnotic effect weakens with long-term use. Therefore, it is mainly used clinically for short-term treatment of insomnia. Using subthreshold doses of sodium pentobarbital can reduce side effects, but the corresponding efficacy is poor. To reduce the dosage of sodium pentobarbital while improving efficacy, this invention systematically explored the sleep-aiding potential of traditional Chinese medicine extracts (such as Polygonatum sibiricum and Polygonatum odoratum), mixed probiotics, and protein peptides, both alone and in combination, using SPF-grade KM male mice.

[0118] Animal experiments showed that the composition of this invention exhibited a significant synergistic sleep-aiding effect when used in combination with sodium pentobarbital. Specifically, the combination of the traditional Chinese medicine composition and probiotics resulted in a higher sleep onset rate in mice compared to either ingredient alone, producing a synergistic effect greater than the sum of its parts (1+1>2). Furthermore, the addition of protein peptides, which had no effect on sleep onset rate, further increased the sleep onset rate at the same dosage, demonstrating that the combination of the traditional Chinese medicine composition, probiotics, and protein peptides produced a synergistic effect greater than the sum of its parts (1+1+1>3). In the subthreshold dose experiment, the combination of the traditional Chinese medicine composition, probiotics, and protein peptides achieved a sleep onset rate of 60%, close to the positive control group (70%). In the suprathreshold dose experiment, this combination not only significantly shortened the sleep latency but also extended the sleep duration to 205.68±78.35 min, an effect close to that of the positive control drug melatonin (218.45±80.62 min).

[0119] The mechanism of action of the composition of this invention is analyzed as follows: This invention is a natural ingredient combination composed of traditional Chinese medicine extracts, mixed probiotics, and protein peptides. Its core competitiveness lies in its breakthrough of traditional hypnotic logic: it does not rely on a forced intervention mode that directly inhibits the central nervous system, but rather exerts its effect through the synergistic regulation of multiple components. Specifically, the traditional Chinese medicine extracts may lay the foundation for sleep by regulating the balance of neurotransmitters (such as serotonin and gamma-aminobutyric acid); the mixed probiotics optimize the central nervous environment through the "gut-brain axis"; and the protein peptides assist in the transmission of nerve signals—the three form a multi-target synergistic effect, which not only avoids the physiological risks that may be brought about by direct hypnosis, but also makes the sleep-aiding effect more stable and more in line with the human body's physiological rhythms through synergistic doubling effect. Compared with single components, this mode can improve the sleep onset rate and prolong the sleep time, and the effect is close to that of clinical drugs but without the side effects of dependence, highlighting the core advantages of "safety and high efficiency".

Claims

1. The use of a composition in combination with sodium pentobarbital in the preparation of a medicament for improving sleep, characterized in that: The mass ratio of the composition to sodium pentobarbital is 750:33~50; The composition is prepared from the following raw materials in parts by weight: 100-150 parts of Polygonatum odoratum enzymatic hydrolysis extract, 50-75 parts of Polygonatum odoratum extract, 50-75 parts of Ziziphus jujuba var. spinosa extract, 50-75 parts of Poria cocos extract, and 250-375 parts of Nagqu 4580 probiotics. The enzymatic hydrolysis extract of Polygonatum is obtained by sequentially hydrolyzing Polygonatum in water with a compound enzyme, an alkaline protease, and a neutral protease. The complex enzyme consists of cellulase and pectinase in a mass ratio of 1:

1. The Polygonatum odoratum extract is an aqueous extract of Polygonatum odoratum. The jujube seed extract is an aqueous extract of jujube seed. The Poria cocos extract is an aqueous extract of Poria cocos.

2. The use according to claim 1, characterized in that: The composition is prepared from the following raw materials in parts by weight: 150 parts of Polygonatum odoratum enzymatic hydrolysis extract, 75 parts of Polygonatum odoratum extract, 75 parts of Ziziphus jujuba var. spinosa extract, 75 parts of Poria cocos extract, and 375 parts of Nagqu 4580 probiotics.

3. The use of a composition in combination with sodium pentobarbital in the preparation of a medicament for improving sleep, characterized in that: The mass ratio of the composition to sodium pentobarbital is 750:33~50; The composition is prepared from the following raw materials in parts by weight: 100-150 parts of Polygonatum odoratum enzymatic hydrolysis extract, 50-75 parts of Polygonatum odoratum extract, 50-75 parts of Ziziphus jujuba var. spinosa extract, 50-75 parts of Poria cocos extract, 250-375 parts of Nagqu 4580 probiotics, and 250-375 parts of protein peptides. The protein peptides are casein hydrolysate peptides and / or fish collagen peptides. The enzymatic hydrolysis extract of Polygonatum is obtained by sequentially hydrolyzing Polygonatum in water with a compound enzyme, an alkaline protease, and a neutral protease. The complex enzyme consists of cellulase and pectinase in a mass ratio of 1:

1. The Polygonatum odoratum extract is an aqueous extract of Polygonatum odoratum. The jujube seed extract is an aqueous extract of jujube seed. The Poria cocos extract is an aqueous extract of Poria cocos.

4. The use according to claim 3, characterized in that: The composition is prepared from the following raw materials in parts by weight: 100 parts of Polygonatum odoratum enzymatic hydrolysis extract, 50 parts of Polygonatum odoratum extract, 50 parts of Ziziphus jujuba var. spinosa extract, 50 parts of Poria cocos extract, 250 parts of Nagqu 4580 probiotics, 187.5 parts of casein hydrolyzed peptides, and 62.5 parts of fish collagen peptides.

5. The use according to claim 1 or 3, characterized in that: The enzymatic hydrolysis extract of Polygonatum sibiricum is obtained by hydrolyzing Polygonatum sibiricum that has been steamed and sun-dried six times with a compound enzyme at 4% of its weight in water at 50°C and pH 5 for 3 hours, followed by hydrolysis with alkaline protease at 4% of its weight in water at 45°C and pH 8.5 for 3 hours, and finally hydrolysis with neutral protease at 4% of its weight in water at 30-45°C for 3 hours. After heating to 90°C and holding for 30 minutes to inactivate the enzymes, the extract is filtered, the supernatant is concentrated, and then freeze-dried under vacuum. The Polygonatum odoratum extract is obtained by extracting Polygonatum odoratum with water, concentrating the extract into an extract equivalent to 3g of raw medicinal material per gram, and spray drying the extract. The jujube seed extract is obtained by extracting jujube seeds with water, concentrating the extract into an extract equivalent to 20g of raw medicinal material per gram, and then spray drying the extract. The Poria cocos extract is obtained by extracting Poria cocos with water, concentrating the extract into an extract equivalent to 10g of raw medicinal material per gram, and then spray drying the extract.

6. A combination drug for improving sleep, characterized in that: It is a combination for simultaneous or separate administration and a packet containing sodium pentobarbital; The mass ratio of the composition to sodium pentobarbital is 750:33~50; The composition is prepared from the following raw materials in parts by weight: 100-150 parts of Polygonatum odoratum enzymatic hydrolysis extract, 50-75 parts of Polygonatum odoratum extract, 50-75 parts of Ziziphus jujuba var. spinosa extract, 50-75 parts of Poria cocos extract, and 250-375 parts of Nagqu 4580 probiotics. The enzymatic hydrolysis extract of Polygonatum is obtained by sequentially hydrolyzing Polygonatum in water with a compound enzyme, an alkaline protease, and a neutral protease. The complex enzyme consists of cellulase and pectinase in a mass ratio of 1:

1. The Polygonatum odoratum extract is an aqueous extract of Polygonatum odoratum. The jujube seed extract is an aqueous extract of jujube seed. The Poria cocos extract is an aqueous extract of Poria cocos.

7. The combination drug according to claim 6, characterized in that: The composition is prepared from the following raw materials in parts by weight: 150 parts of Polygonatum odoratum enzymatic hydrolysis extract, 75 parts of Polygonatum odoratum extract, 75 parts of Ziziphus jujuba var. spinosa extract, 75 parts of Poria cocos extract, and 375 parts of Nagqu 4580 probiotics. The enzymatic hydrolysis extract of Polygonatum sibiricum is obtained by hydrolyzing Polygonatum sibiricum that has been steamed and sun-dried six times with a compound enzyme at 4% of its weight in water at 50°C and pH 5 for 3 hours, followed by hydrolysis with alkaline protease at 4% of its weight in water at 45°C and pH 8.5 for 3 hours, and finally hydrolysis with neutral protease at 4% of its weight in water at 30-45°C for 3 hours. After heating to 90°C and holding for 30 minutes to inactivate the enzymes, the extract is filtered, the supernatant is concentrated, and then freeze-dried under vacuum. The Polygonatum odoratum extract is obtained by extracting Polygonatum odoratum with water, concentrating the extract into an extract equivalent to 3g of raw medicinal material per gram, and spray drying the extract. The jujube seed extract is obtained by extracting jujube seeds with water, concentrating the extract into an extract equivalent to 20g of raw medicinal material per gram, and then spray drying the extract. The Poria cocos extract is obtained by extracting Poria cocos with water, concentrating the extract into an extract equivalent to 10g of raw medicinal material per gram, and then spray drying the extract.

8. A combination drug for improving sleep, characterized in that: It is a combination for simultaneous or separate administration and a packet containing sodium pentobarbital; The composition is prepared from the following raw materials in parts by weight: 100-150 parts of Polygonatum odoratum enzymatic hydrolysis extract, 50-75 parts of Polygonatum odoratum extract, 50-75 parts of Ziziphus jujuba var. spinosa extract, 50-75 parts of Poria cocos extract, 250-375 parts of Nagqu 4580 probiotics, and 250-375 parts of protein peptides. The protein peptides are casein hydrolysate peptides and / or fish collagen peptides. The enzymatic hydrolysis extract of Polygonatum is obtained by sequentially hydrolyzing Polygonatum in water with a compound enzyme, an alkaline protease, and a neutral protease. The complex enzyme consists of cellulase and pectinase in a mass ratio of 1:

1. The Polygonatum odoratum extract is an aqueous extract of Polygonatum odoratum. The jujube seed extract is an aqueous extract of jujube seed. The Poria cocos extract is an aqueous extract of Poria cocos.

9. The combination drug according to claim 8, characterized in that: The composition is prepared from the following raw materials in parts by weight: 100 parts of Polygonatum odoratum enzymatic hydrolysis extract, 50 parts of Polygonatum odoratum extract, 50 parts of Ziziphus jujuba var. spinosa extract, 50 parts of Poria cocos extract, 250 parts of Nagqu 4580 probiotics, 187.5 parts of casein hydrolyzed peptides, and 62.5 parts of fish collagen peptides. The enzymatic hydrolysis extract of Polygonatum sibiricum is obtained by hydrolyzing Polygonatum sibiricum that has been steamed and sun-dried six times with a compound enzyme at 4% of its weight in water at 50°C and pH 5 for 3 hours, followed by hydrolysis with alkaline protease at 4% of its weight in water at 45°C and pH 8.5 for 3 hours, and finally hydrolysis with neutral protease at 4% of its weight in water at 30-45°C for 3 hours. After heating to 90°C and holding for 30 minutes to inactivate the enzymes, the extract is filtered, the supernatant is concentrated, and then freeze-dried under vacuum. The Polygonatum odoratum extract is obtained by extracting Polygonatum odoratum with water, concentrating the extract into an extract equivalent to 3g of raw medicinal material per gram, and spray drying the extract. The jujube seed extract is obtained by extracting jujube seeds with water, concentrating the extract into an extract equivalent to 20g of raw medicinal material per gram, and then spray drying the extract. The Poria cocos extract is obtained by extracting Poria cocos with water, concentrating the extract into an extract equivalent to 10g of raw medicinal material per gram, and then spray drying the extract.

10. The combination drug according to claim 6, characterized in that: The combined medication is sodium pentobarbital injection and an oral formulation of the combination; the oral formulation includes solutions, powders, granules, tablets, pills, and ointments.

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