Compound composition for improving sleep disorder and oral mucosa preparation

Abstract

The invention discloses a compound composition for improving sleep disorders, which is characterized by comprising the following components: an inhibitory neurotransmitter component, melatonin and a nano-lipid carrier, the nano-lipid carrier comprises phospholipid and cholesterol, the weight ratio of phospholipid to cholesterol is (1-6): 1, the weight ratio of phospholipid to cholesterol is (1-6): 1, and the weight ratio of melatonin to cholesterol is (1-6): 1. The inhibitory neurotransmitter component is wrapped in the nano-lipid carrier to form lipid nanoparticles, and the weight ratio of the inhibitory neurotransmitter component to the nano-lipid carrier is 1: (1-15). The compound composition can be prepared into a compound oral mucosa preparation, can be rapidly disintegrated when encountering saliva in the oral cavity, is good in patient compliance and small in side effect, all the components play a synergistic effect from different mechanisms through multiple target points, and the compound oral mucosa preparation can improve the sleep quality, prolong the sleep time and shorten the sleep latency; and patients with sleep disorders are helped to improve insomnia from the pathologic root.

Description

Technical Field

[0001] This application relates to the field of compound preparation technology, and in particular to a compound composition for improving sleep disorders and an oral mucosal preparation. Background Technology

[0002] The "Guidelines for the Diagnosis and Treatment of Insomnia in Chinese Adults" defines insomnia as follows: Insomnia is a subjective experience characterized by dissatisfaction with sleep duration and / or quality despite adequate sleep opportunities and environment, which affects daytime function or causes physical discomfort. Insomnia is one of the most common sleep problems. Long-term insomnia affects an individual's normal life and work, increasing the risk of various health problems.

[0003] Oral dissolving films (ODF), also known as oral mucosal preparations, oral dispersible films, or oral fast-dissolving films, are a novel drug delivery system. They do not require water; instead, they disintegrate and disperse the active ingredient in the mouth with the help of saliva. A small portion is absorbed through the oral mucosa, while the majority is absorbed through the gastrointestinal tract after swallowing. For drugs with short biological half-lives, this allows for rapid efficacy and improves bioavailability. They also feature small size, portability, ease of administration, and good compliance.

[0004] Currently, there are some reports on technologies that promote sleep, such as:

[0005] CN114831983A discloses a melatonin oral sublingual fast-dissolving composition and its preparation method. Simply supplementing with exogenous melatonin is only suitable for working people who are jet-lagged, have disrupted day and night cycles, or have altered their biological clocks. It is not entirely suitable for people with insomnia caused by long-term mental stress, emotional anxiety, or other problems, and it does not fundamentally improve the insomnia problem of people with sleep disorders.

[0006] CN103110709 B discloses a composition for improving sleep and its preparation method. By using the inhibitory neurotransmitter GABA in combination with the traditional Chinese medicine extract of jujube seed, it effectively improves sleep in mice and shows a dose-response relationship. However, long-term use of the inhibitory neurotransmitter can cause gastrointestinal discomfort and produce side effects such as nausea, vomiting, and decreased blood pressure.

[0007] CN118845719A discloses a melatonin / buspirone hydrochloride oral instant-dissolving film and its preparation method. The patent only examines the mechanical properties and in vitro release quality attributes of the prepared oral film, and does not provide sufficient data to support that this compound preparation has a good effect on improving sleep.

[0008] CN117398435A discloses a sleep-aiding composition, a sleep-aiding microneedle preparation, a microneedle patch, and a preparation method thereof. The use of the microneedle preparation may damage the integrity of the skin, and there is a risk that the needles may break and remain in the skin, causing pain and inconvenience to the user.

[0009] Therefore, developing a formulation composition that is faster, more effective, and addresses the root cause of insomnia in users has broad market value and clinical application prospects. Summary of the Invention

[0010] To address the shortcomings of existing technologies, this invention provides a compound composition and an oral mucosal preparation for improving sleep disorders. This compound composition, through multiple mechanisms of regulation, helps maintain stable melatonin concentration and effectively avoids adverse reactions such as nausea and vomiting caused by gastrointestinal irritation from traditional oral preparations.

[0011] The present invention provides a compound composition for improving sleep disorders, characterized in that it comprises the following components: an inhibitory neurotransmitter component, melatonin, and a nanolipid carrier, wherein the nanolipid carrier comprises phospholipids and cholesterol, the weight ratio of phospholipids to cholesterol being (1-6):1, wherein the inhibitory neurotransmitter component is encapsulated in the nanolipid carrier to form lipid nanoparticles, and the weight ratio of the inhibitory neurotransmitter component to the nanolipid carrier is 1:(1-15).

[0012] In one embodiment, the weight ratio of the inhibitory neurotransmitter component to the nanolipid carrier is 1:(2-5).

[0013] Melatonin is an endogenous hormone secreted by the pineal gland in the brain. Also known as melatonin, it plays a role in inducing sleep and regulating the body's circadian rhythms. However, in clinical applications, excessive melatonin often produces side effects such as amnesia the next day or melatonin hangover. Users may wake up easily after 3-4 hours of sleep and be unable to fall back asleep. Long-term high-dose use of melatonin can lead to dependence.

[0014] In one embodiment, the inhibitory neurotransmitter components include, but are not limited to, gamma-aminobutyric acid (γ-GABA), 5-hydroxytryptophan (5-HTP), serotonin (5-HT), or glycine (Gly). Inhibitory neurotransmitter components play an important regulatory role in the central nervous system, reducing tension and anxiety, and helping to improve sleep quality. However, directly taking inhibitory neurotransmitter supplements orally may present some problems. For example, GABA has a blood-brain barrier issue; orally administered GABA cannot directly cross the blood-brain barrier to exert its effects, resulting in low bioavailability. Furthermore, 5-HTP, 5-HT, or glycine have poor chemical stability and are easily oxidized / degraded under acidic gastric conditions, leading to low bioavailability when taken directly. Excessive use of these inhibitory neurotransmitter components may also trigger a series of side effects, such as gastrointestinal side effects, long-term dependence, and liver and kidney damage.

[0015] In one embodiment, the phospholipids include, but are not limited to, one or more of hydrogenated soybean lecithin, soybean lecithin, myristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearyl phosphatidylcholine, dioleoyl phosphatidylcholine, or dilauroyl phosphatidylcholine.

[0016] In one embodiment, the compound composition further comprises extracts of traditional Chinese medicinal materials.

[0017] In one embodiment, the herbal extracts include, but are not limited to, jujube seed extract, valerian extract, Ganoderma lucidum extract, green tea extract, lemon verbena extract, arborvitae seed extract, passionflower extract, gastrodia elata extract, or saffron extract. Extracts from valerian, Ganoderma lucidum, passionflower, and other herbal extracts can promote or induce the natural secretion of melatonin, thereby improving sleep patterns and sleep quality. Clinical observations show no significant adverse reactions with long-term or high-dose use. Theanine in green tea extract can cross the blood-brain barrier, stimulate the synthesis and release of GABA, increase GABA levels in the brain, synergistically shorten sleep onset time, promote dopamine secretion, regulate serotonin metabolism, relieve tension, and improve insomnia caused by mood disorders.

[0018] The compound composition of the present invention can be used in pharmaceuticals, food, or health products. Depending on the requirements, the compound composition can be formulated into fast-dissolving tablets, oral mucosal preparations, or oral solutions, etc.

[0019] In one embodiment, the compound composition comprises, by weight percentage, 0.1%-40% inhibitory neurotransmitter lipid nanoparticles, 0.01%-5% melatonin, and 0-40% extracts of traditional Chinese medicine.

[0020] Another aspect of the present invention provides an oral mucosal preparation for improving sleep disorders, comprising the above-mentioned compound composition, film-forming material and pharmaceutically acceptable excipients, wherein, based on the total weight of the oral mucosal preparation, the content of inhibitory neurotransmitter lipid nanoparticles is 10%-40%, the content of melatonin is 0.1%-5%, the content of traditional Chinese medicine extract is 0-40%, the content of film-forming material is 20%-70%, and the remainder is excipients.

[0021] In one embodiment, the film-forming material includes, but is not limited to, at least one of hydroxypropyl methylcellulose (such as HPMC E15, HPMC E5), hydroxypropyl cellulose (such as L-HPC), polyvinyl alcohol, starch, inulin, hyaluronic acid, pullulan, povidone, or polyoxyethylene.

[0022] In one embodiment, the excipients comprise at least one of plasticizers, saliva stimulants, sweeteners, colorants, flavorings, or surfactants.

[0023] In one embodiment, the plasticizer is used to increase the plasticity of the film, including but not limited to glycerol, polyethylene glycol, diethyl phthalate, ethyl citrate, glyceryl triacetate, or propylene glycol.

[0024] In one embodiment, the saliva stimulant is used to increase saliva secretion to facilitate swallowing by the user, and includes, but is not limited to, vitamin C, citric acid, tartaric acid, malic acid, or lactic acid.

[0025] In one embodiment, the sweetener includes, but is not limited to, sucralose, steviol, aspartame, maltose, sucrose, starch sugar, mogroside, xylitol, erythritol, or cyclamate.

[0026] In one embodiment, the colorant includes, but is not limited to, natural plant-derived pigments in the form of turmeric or orange.

[0027] In one embodiment, the flavorings include, but are not limited to, strawberry flavoring, orange flavoring, blueberry flavoring, menthol, peppermint oil, eucalyptus oil, lemon essential oil, green tea essential oil, lavender essential oil, osmanthus flavoring, clove essential oil, or lime flavoring.

[0028] In one embodiment, the surfactant is used to promote the disintegration and dispersion of the film agent, including but not limited to sodium dodecyl sulfate, poloxamer, polysorbate, or sucrose ester.

[0029] In one embodiment, the content of plasticizer is 0-20%, saliva stimulant is 0-10%, surfactant is 0-10%, sweetener is 0-1.0%, colorant is 0-1.0%, and flavoring is 0-2%, based on the total weight of the oral mucosa preparation.

[0030] The compound oral mucosal preparation of this invention rapidly disintegrates upon contact with saliva in the oral cavity. It contains the following synergistic active components: exogenous melatonin, after absorption through the gastrointestinal tract, rapidly compensates for insufficient pineal gland secretion, promoting rapid sleep onset; liposome-encapsulated inhibitory neurotransmitter components (such as γ-aminobutyric acid / GABA) reduce nerve excitability by targeting receptors, alleviating anxiety and muscle tension, thus establishing a physiological basis for sleep. Liposome technology significantly improves compound stability, blood-brain barrier penetration, and bioavailability, while reducing the risk of adverse reactions at high doses; active extracts of traditional Chinese medicine (such as jujube seed extract) synergistically promote endogenous melatonin secretion and enhance the in vivo synthesis and release of neurotransmitter components. These multiple mechanisms work together to maintain stable plasma melatonin concentrations in patients, and the oral mucosal preparation dosage form avoids gastrointestinal irritation reactions (such as nausea and vomiting) associated with traditional oral preparations.

[0031] The beneficial effects of this invention are reflected in:

[0032] 1. Enhanced stability and bioavailability of inhibitory neurotransmitters, reducing side effects: Utilizing liposome encapsulation technology significantly improves the stability and oral bioavailability of inhibitory neurotransmitters (such as GABA and 5-HT), effectively reducing side effects caused by high doses. Simultaneously, this technology features sustained-release properties, maintaining a stable melatonin concentration and helping users achieve more complete and higher-quality sleep.

[0033] 2. Improved user experience and patient compliance: The compound composition of this invention is convenient to take, especially the oral mucosal preparation, which has good patient compliance and can effectively avoid adverse reactions such as nausea and vomiting caused by gastrointestinal irritation of traditional oral preparations.

[0034] 3. Synergistic effect of multiple components to comprehensively improve sleep: Through the scientific combination of inhibitory neurotransmitter components, melatonin and Chinese herbal extracts, the three types of components work synergistically to significantly improve sleep quality, prolong sleep time and shorten sleep latency, helping patients with sleep disorders to improve insomnia from the root cause. Detailed Implementation

[0035] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0036] Unless otherwise specified, all raw materials used in this invention are commercially available products in the field.

[0037] Example 1: Preparation of liposomes

[0038] Inhibitory neurotransmitter components were sonicated and dissolved in PBS buffer solution (pH=7.4), which was used as the aqueous phase. Phospholipids and cholesterol were added to anhydrous ethanol and sonicated to dissolve, which was used as the organic phase. The aqueous phase was heated to 50-60℃, and the organic phase was slowly added while stirring, allowing the organic phase to gradually evaporate, thus forming crude liposomes. The crude liposomes were injected into a microfluidic high-pressure homogenizer for homogenization. The pressure of the microfluidic high-pressure homogenizer was controlled at 10-30 Mbar, and the homogenizer was cycled 3-6 times to obtain liposomes with uniform particle size.

[0039] The ingredients and their dosage (by weight) are shown in Table 1 below.

[0040] Table 1

[0041]

[0042] Example 2: Preparation of oral mucosal preparations

[0043] Melatonin, the liposomes obtained in Example 1, the film-forming material, and excipients were sequentially added to distilled water, heated to 50°C, and stirred until completely dissolved to obtain a gel. The gel was then placed in a vacuum degassing device to eliminate air bubbles. The defoamed gel was evenly coated onto a release film using a coating machine, dried at 60-80°C, and cut into suitable sizes to obtain the corresponding oral mucosa preparation. Approximately 1333-2666 oral mucosa tablets can be obtained from 1 kg of gel.

[0044] The components and their amounts (percentage content) in oral mucosal preparations are shown in Table 2 below.

[0045] Table 2

[0046]

[0047]

[0048]

[0049]

[0050] Example 3: Preparation of oral solution

[0051] Melatonin, the liposomes obtained in Example 1, and excipients were added sequentially to distilled water, heated to 50°C, and stirred until completely dissolved. The solution was then filtered through a 0.45 μm microporous membrane to obtain a clear and transparent solution. The solution was sealed in a glass bottle and sterilized with ultraviolet light to obtain the corresponding oral solution.

[0052] The ingredients and their dosages (percentage content) in the prescription are shown in Table 3 below.

[0053] Table 3

[0054]

[0055]

[0056] Example 4: Preparation of Tablets

[0057] The compound composition and excipients are pulverized and passed through an 80-mesh sieve, then mixed evenly in a three-dimensional motion mixer. An appropriate amount of binder is added to the mixed powder to form a soft material, which is then passed through a 10-20 mesh sieve to form wet granules. After drying and pressing, the granules are obtained.

[0058] The ingredients and their amounts (percentage content) are shown in Table 4 below.

[0059] Table 4

[0060]

[0061] Example 5: Preparation of Comparative Formulas 1-4

[0062] The active ingredients, film-forming materials, and excipients are added to distilled water, heated to 50°C, and stirred until completely dissolved to obtain a gel. The gel is then placed in a vacuum degassing device to eliminate air bubbles. The defoamed gel is evenly coated onto a release film using a coating machine, dried at 60-80°C, and cut into suitable sizes to obtain the oral mucosal preparations of comparative formulations 1-4.

[0063] The components and dosages (percentage content) of prescriptions 1-4 are shown in Table 5 below.

[0064] Table 5

[0065]

[0066] Example 6: Experiment investigating the effects of different samples on mouse sleep

[0067] 1. Materials and Methods

[0068] 1.1 Experimental test samples

[0069] Test sample A: The ingredients are in the same proportion as formulation 4, the tablet weight is 143mg, containing 2mg of melatonin and 45mg of γ-GABA lipid nanoparticles (equivalent to 15mg of γ-GABA).

[0070] Test sample B: The ingredients are in the same proportion as prescription 11, with a tablet weight of 143mg, containing 2mg of melatonin, 45mg of γ-GABA lipid nanoparticles (equivalent to 15mg of γ-GABA), and 30mg of traditional Chinese medicine extract.

[0071] Test sample C: The ingredients are in the same proportion as prescription 17, each vial has a volume of 10mL, containing 2mg of melatonin, 45mg of γ-GABA lipid nanoparticles (equivalent to 15mg of γ-GABA), and 30mg of traditional Chinese medicine extract.

[0072] Test sample D: The ingredients are in the same proportion as prescription 19, the tablet weight is 230mg, containing 2mg of melatonin, 45mg of γ-GABA lipid nanoparticles (equivalent to 15mg of γ-GABA), and 30mg of traditional Chinese medicine extract.

[0073] Test Sample E: Contains the same ingredients as Comparative Formula 1, with a tablet weight of 143 mg, including 2 mg of melatonin and 15 mg of γ-GABA. Test Sample F: Contains the same ingredients as Comparative Formula 2, with a tablet weight of 143 mg, including 2 mg of melatonin and 75 mg of γ-GABA. Test Sample G: Contains the same ingredients as Comparative Formula 3, with a tablet weight of 143 mg, including 2 mg of melatonin, 15 mg of γ-GABA, and 30 mg of traditional Chinese medicine extract.

[0074] Test sample H: The composition ratio is the same as that of the control formulation 4, the tablet weight is 143mg, and it contains 5mg of melatonin and 45mg of γ-GABA lipid nanoparticles (equivalent to 15mg of γ-GABA).

[0075] Control group sample: physiological saline.

[0076] 1.2 Laboratory Animals

[0077] Healthy male ICR mice weigh 15-18g.

[0078] 1.3 Dosage and Grouping

[0079] Three batches of mice were used for the following experiments: (1) sodium pentobarbital sleep duration prolongation experiment; (2) sodium barbital subthreshold dose hypnotic experiment; (3) sodium barbital sleep latency experiment. Mice in each experiment were randomly divided into 9 groups according to their body weight, with 10 mice in each group. Except for test sample C, the other test samples (one tablet each) were processed and dissolved in a small amount of physiological saline to prepare solutions of the same volume. Test sample C (one tablet) was concentrated to the same volume as the above solution before use. The gavage volume for mice was 20 mL / kg, and the gavage was performed continuously for 15 days. The direct sleep effect was observed in one batch of mice on the 14th day after gavage.

[0080] 1.4 Experimental Methods

[0081] 1.4.1 Direct Sleep Experiment

[0082] Each group of mice was administered the corresponding test sample via gavage, while the control group received the same volume of physiological saline. The disappearance of the righting reflex was used as the criterion for falling asleep, and the recovery of the righting reflex was used as the criterion for awakening. Sleep time was defined as the time difference between the recovery of the righting reflex and the disappearance of the righting reflex.

[0083] 1.4.2 Experiment on sodium pentobarbital prolonging sleep time

[0084] The intraperitoneal injection dose of sodium pentobarbital, determined in preliminary experiments, was 43 mg / kg. This dose caused the righting reflex to disappear in animals (as an indicator of sleep onset). Mice were administered the drug by gavage for 15 consecutive days, and 15 minutes after the last administration, sodium pentobarbital (43 mg / kg) was injected intraperitoneally. The sleep duration of mice in each group was observed and compared.

[0085] 1.4.3 Subthreshold dose hypnotic experiment with sodium pentobarbital

[0086] The subthreshold intraperitoneal injection dose of sodium pentobarbital, determined in preliminary experiments, was 38 mg / kg. This dose prevented the loss of the righting reflex (i.e., not falling asleep) in 90%-100% of animals, and was used to observe the sleep rate. Mice were administered the drug by gavage for 15 consecutive days, and 15 minutes after the last administration, sodium pentobarbital (38 mg / kg) was injected intraperitoneally. The number of mice whose righting reflex remained absent for ≥1 minute within 30 minutes after injection was recorded, and the sleep rate was calculated.

[0087] 1.4.4 Sodium barbital sleep latency test

[0088] The intraperitoneal injection dose of sodium pentobarbital, determined in preliminary experiments, was 290 mg / kg. This dose induced sleep in all animals, with a moderate sleep duration (20-40 minutes), suitable for observing sleep latency. The disappearance (as an indicator of sleep onset) and recurrence (as an indicator of wakefulness) of the righting reflex were used as observation endpoints. After 15 consecutive days of oral administration, mice were intraperitoneally injected with sodium pentobarbital (290 mg / kg) 15 minutes after the last administration. Sleep latency was defined as the time interval from the completion of sodium pentobarbital injection to the disappearance of the righting reflex (lasting 1 minute).

[0089] 1.4 Statistical Methods

[0090] Analysis of variance and χ² were used to analyze the experimental results. 2 test.

[0091] 2. Experimental Results

[0092] 2.1 Direct Sleep Effect

[0093] The results of the direct sleep study showed that the mice in the control group had normal activity, while the mice in each group of the test samples showed varying degrees of reduced spontaneous activity, but no sleep was observed during the entire process, and the number of animals that fell asleep was 0, indicating that the test samples did not have a significant direct sleep effect.

[0094] 2.2 Results of pentobarbital sodium prolongation of sleep time

[0095] Table 6. Results of each test sample's effect on prolonging sleep time with sodium pentobarbital.

[0096]

[0097]

[0098] As shown in Table 6 above, all tested sample groups significantly prolonged the sleep time induced by sodium pentobarbital, with a significant difference compared to the control group (P<0.05).

[0099] 2.3 Hypnotic Results of Subthreshold Doses of Sodium Pentobarbital

[0100] Table 7. Hypnotic effects of subthreshold doses of sodium pentobarbital on each test sample.

[0101]

[0102] As shown in Table 7, all tested sample groups enhanced the hypnotic effect of sodium pentobarbital, and the difference was significant compared with the control group (P<0.05).

[0103] 2.4 Results of sodium barbital sleep latency

[0104] Table 8 Results of sleep latency of barbiturate sodium for each test sample

[0105]

[0106] As shown in Table 8, all tested sample groups effectively shortened the sleep latency of sodium barbital, and the difference was significant compared with the control group (P<0.05).

[0107] In summary, as shown in Tables 6-8: ① The sleep duration, sleep onset rate, and sleep latency of the tested mice were all superior to those of the control group, demonstrating a significant effect in improving sleep disorders in mice; ② Among all tested samples, sample B had the longest sleep duration, the highest sleep onset rate, and the shortest sleep latency, followed by samples C and D; ③ Comparing tested samples A with samples E and F, and tested samples B with sample G, highlights that lipid nanoparticle treatment of the inhibitory neurotransmitter γ-GABA can significantly improve its bioavailability, increase sleep duration and sleep onset rate, and shorten sleep latency in mice; ④ Comparing tested samples B, C, and D with tested sample H indicates that the added traditional Chinese medicine extract can effectively promote the secretion of endogenous melatonin, reducing the side effects of high-dose melatonin intake, increasing sleep duration and sleep onset rate, and shortening sleep latency; ⑤ Comparing tested samples B with tested samples C and D, different formulation types can effectively improve sleep duration and sleep onset rate and shorten sleep latency in mice.

[0108] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

Claims

1. A compound composition for improving sleep disorders, characterized in that, It comprises the following components: an inhibitory neurotransmitter component, melatonin, and a nanolipid carrier, wherein the nanolipid carrier includes phospholipids and cholesterol, with a weight ratio of phospholipids to cholesterol of (1-6):1, wherein the inhibitory neurotransmitter component is encapsulated in the nanolipid carrier to form lipid nanoparticles, with a weight ratio of inhibitory neurotransmitter component to nanolipid carrier of 1:(1-15).

2. The compound composition according to claim 1, characterized in that, The weight ratio of the inhibitory neurotransmitter component to the nanolipid carrier is 1:(2-5).

3. The compound composition according to claim 1, characterized in that, The inhibitory neurotransmitter component is selected from γ-aminobutyric acid, 5-hydroxytryptophan, 5-hydroxytryptamine, or glycine; the phospholipid is selected from one or more of hydrogenated soybean lecithin, soybean lecithin, myristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearyl phosphatidylcholine, dioleoyl phosphatidylcholine, or dilauroyl phosphatidylcholine.

4. The compound composition according to claim 1, characterized in that, The compound composition includes extracts of traditional Chinese medicinal materials, which are selected from extracts of jujube seed, valerian, ganoderma, green tea, lemon verbena, cypress seed, passionflower, gastrodia, or saffron.

5. The compound composition according to any one of claims 1-4, characterized in that, The compound composition comprises, by weight percentage, 0.1%-40% inhibitory neurotransmitter lipid nanoparticles, 0.01%-5% melatonin, and 0-40% extracts of traditional Chinese medicine.

6. An oral mucosal preparation for improving sleep disorders, characterized in that, The formulation includes the compound composition according to any one of claims 1-5, the film-forming material, and the pharmaceutically acceptable excipients, wherein, based on the total weight of the oral mucosal preparation, the content of inhibitory neurotransmitter lipid nanoparticles is 10%-40%, the content of melatonin is 0.1%-5%, the content of traditional Chinese medicine extract is 0-40%, the content of film-forming material is 20%-70%, and the remainder is excipients.

7. The oral mucosa preparation according to claim 6, characterized in that, The film-forming material is selected from at least one of hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, starch, inulin, hyaluronic acid, pullulan, povidone, or polyoxyethylene.

8. The oral mucosa preparation according to claim 6, characterized in that, The excipients include at least one of plasticizers, saliva stimulants, sweeteners, colorants, flavorings, or surfactants.

9. The oral mucosa preparation according to claim 8, characterized in that, The plasticizer is selected from glycerin, polyethylene glycol, diethyl phthalate, ethyl citrate, glyceryl triacetate, or propylene glycol; the salivary stimulant is selected from vitamin C, citric acid, tartaric acid, malic acid, or lactic acid; the sweetener is selected from sucralose, steviol, aspartame, maltose, sucrose, starch sugar, mogroside, xylitol, erythritol, or cyclamate; the colorant is selected from natural plant extracts of turmeric or orange-yellow; the fragrance is selected from strawberry flavoring, orange flavoring, blueberry flavoring, menthol, peppermint oil, eucalyptus oil, lemon essential oil, green tea essential oil, lavender essential oil, osmanthus flavoring, clove essential oil, or lime flavoring; and the surfactant is selected from sodium lauryl sulfate, poloxamer, polysorbate, or sucrose ester.

10. The oral mucosa preparation according to claim 8, characterized in that, Based on the total weight of the oral mucosal preparation, the content of plasticizer is 0-20%, saliva stimulant is 0-10%, surfactant is 0-10%, sweetener is 0-1.0%, colorant is 0-1.0%, and flavoring is 0-2%.

Images