Heat-not-burn device liquid medicine for restoring consciousness and soothing nerves and preparation method thereof

Abstract

The invention provides heat-not-burn device liquid medicine for restoring consciousness and soothing nerves and a preparation method of the heat-not-burn device liquid medicine, and belongs to the technical field of traditional Chinese medicine. Comprising the following raw materials in parts by weight: 3-5 parts of essence, 7-12 parts of a traditional Chinese medicine extract, 80-90 parts of an atomizing agent, 3-5 parts of a sweetening agent and 0.5-1 part of a bitterness inhibition composition, and the traditional Chinese medicine extract is prepared from traditional Chinese medicines such as ginseng, polygala tenuifolia and rhizoma acori graminei. According to the heat-not-burn device for restoring consciousness and soothing nerves, liquid medicine is added into the heat-not-burn device and atomized under the action of the heater, traditional Chinese medicine extracts are inhaled into the human body, insomnia can be treated, the refreshing effect can be achieved, the effect is fast, both symptoms and root causes are treated, relapse is not likely to happen, and the heat-not-burn device is convenient to use by high-intensity workers and is good in fragrance and taste coordination and not obvious in bitter taste; the mouthfeel is good.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a heat-not-burning medicinal liquid for stimulating the mind and calming the nerves, and its preparation method. Background Technology

[0002] The concept of wakefulness and sleep refers to the vital phenomena of human life. Disorders of wakefulness and sleep are a common clinical condition, encompassing insomnia, hypersomnia, and restless sleep. It can be both a symptom and a disease. The *Huangdi Neijing* (Yellow Emperor's Inner Classic) mentions terms such as "inability to sleep," "eyes unable to close," "inability to lie down," "restless sleep," "frequent sleep," "excessive sleep," and "little sleep." Modern medicine refers to this as "sleep disorder." According to the *Global Sleep Survey: China Regional Survey Report*, 45.4% of the Chinese population suffers from sleep disorders. The *Huangdi Neijing* has developed a relatively systematic theory regarding the physiological mechanisms of wakefulness and sleep, explaining the etiology and pathogenesis of these disorders from multiple perspectives. These theories provide important guidance for the treatment of insomnia and hypersomnia, as well as for daily health maintenance.

[0003] With the increasingly fast pace and fierce competition of modern life, insomnia has become a common ailment. Its main symptoms include difficulty falling asleep, decreased sleep quality, memory loss, decreased attention span, and reduced work capacity, severely impacting people's quality of life. Currently, most medications for treating insomnia are sedative-hypnotic drugs. The elderly, in particular, are highly susceptible to insomnia due to their lifestyle and other factors. While most existing medical treatments utilize Western medicine, which can alleviate insomnia, some Western medications have significant side effects, and insomnia is prone to relapse after discontinuation. Furthermore, the weakened immune systems of the elderly further exacerbate memory and immunity decline when taking Western medications. Meanwhile, heated non-combustible devices have received widespread attention in recent years, but are currently not used in the field of traditional Chinese medicine. With the development of traditional Chinese medicine technology, how to improve the quality and efficacy of Chinese medicine, expand its application scenarios, and advance the research and development of medical devices are important current issues.

[0004] Although traditional Chinese medicine decoctions hold an important place in TCM treatment, they do have shortcomings in practical application. For example, large doses are inconvenient to take, the active ingredients of some drugs are difficult to extract or easily volatilize and dissipate, storage and carrying are difficult, the content of active ingredients is low, preparation is difficult, and further promotion and application are not convenient. These shortcomings may affect patient compliance and treatment efficacy. Therefore, in modern medical practice, how to improve the preparation and administration of traditional Chinese medicine decoctions, and how to better preserve and utilize their traditional advantages, are important issues facing the development of TCM. Traditional sedative-hypnotics are drugs that inhibit the central nervous system. They do have value in relieving patients' tension, anxiety, and insomnia symptoms, as well as in anticonvulsant and antiepileptic effects. However, long-term use of these drugs, such as zolpidem tartrate, estazolam, triazolam, and zopiclone, almost all have varying degrees of adverse effects. Summary of the Invention

[0005] The purpose of this invention is to provide a heat-not-burning medicinal liquid for stimulating the mind and calming the nerves, and its preparation method. The medicinal liquid is added to the heat-not-burning device and atomized under the action of the heater, so that the Chinese herbal extracts can be inhaled into the human body. It can treat insomnia and refresh the mind, with fast effect, treat both the symptoms and the root cause, and is not easy to relapse. It is convenient for high-intensity workers to use, and has good aroma and taste coordination, with no obvious bitterness and good taste.

[0006] The technical solution of this invention is implemented as follows: This invention provides a liquid medicine for a heat-not-burning device for stimulating the mind and calming the nerves, comprising the following raw materials in parts by weight: 3-5 parts of flavoring, 7-12 parts of traditional Chinese medicine extract, 80-90 parts of atomizing agent, 3-5 parts of sweetener, and 0.5-1 parts of bitterness-inhibiting composition, wherein the traditional Chinese medicine extract includes extracts made from ginseng, polygala, and acorus.

[0007] As a further improvement of the present invention, the herbal extract comprises the following parts by weight of raw materials prepared from the following: 5-10 parts of ginseng, 10-15 parts of polygala tenuifolia, and 10-20 parts of acorus tatarinowii.

[0008] As a further improvement of the present invention, the preparation method of the traditional Chinese medicine extract is as follows: Ginseng, Polygala tenuifolia, and Acorus tatarinowii were washed, mixed, crushed, and added to an ethanol-water solution. The mixture was heated and refluxed for extraction. The extraction was repeated, filtered, and the filtrates were combined. The solvent was recovered under reduced pressure to obtain the Chinese herbal extract.

[0009] As a further improvement of the present invention, the atomizing agent is a mixture of water and propylene glycol in a volume ratio of 1-3:8-10.

[0010] As a further improvement of the present invention, the sweetener is a mixture of sucralose and erythritol in a mass ratio of 4-6:1-2.

[0011] As a further improvement of the present invention, the bitterness-inhibiting composition comprises a γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate and a bitterness inhibitor in a mass ratio of 4-7:1-2, and the structural formula of the bitterness inhibitor is shown in Formula I: ; Formula I.

[0012] As a further improvement of the present invention, the preparation method of the γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate is as follows: γ-aminobutyric acid was added to water, followed by N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The mixture was stirred and activated, then glutamyl peptide was added. The mixture was stirred and reacted, dialyzed, and freeze-dried to obtain the γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate.

[0013] As a further improvement of the present invention, the method for preparing the bitterness inhibitor is as follows: S1. Inosine and phosphorus oxychloride were reacted to prepare intermediate 1, with the following structure: ; S2. Inosine was added to acetic anhydride, sodium acetate was added, and the mixture was heated under reflux to prepare intermediate 2, with the following structural formula: ; S3. Intermediate 1 and intermediate 2 are reacted to obtain intermediate 3, with the following structure: ; S4. Intermediate 3 was reacted with menthol to prepare intermediate 4, with the following structure: ; S5. Intermediate 4 was reacted under pressure in a saturated NH3 / CH3OH solution to obtain intermediate 5, with the following structure: ; S6. React intermediate 5 with phosphorus oxychloride, and neutralize the product with sodium hydroxide to obtain the final product.

[0014] The present invention further protects a medicinal liquid for a heat-not-burning device for stimulating the mind and calming the nerves, wherein a traditional Chinese medicine extract and flavoring are dissolved in an atomizing agent, a sweetener and a bitterness-inhibiting composition are added, the mixture is stirred and mixed evenly, filtered through a 0.22μm microporous membrane, and sterilized to obtain a medicinal liquid for a heat-not-burning device for stimulating the mind and calming the nerves.

[0015] This invention further protects the use of the above-mentioned heat-not-burning device liquid for waking the mind and calming the nerves in the preparation of drugs for treating insomnia and narcolepsy.

[0016] The present invention has the following beneficial effects: This invention selects ginseng, polygala tenuifolia, and acorus tatarinowii to extract their active components. Ginseng has the effects of replenishing qi and improving intelligence, and regulating neurotransmitters and neurotrophic factors. Polygala tenuifolia has the effects of calming the mind and improving intelligence, regulating acetylcholine and anti-inflammatory and antioxidant effects. Acorus tatarinowii has the effects of opening the orifices and refreshing the mind, regulating cerebral blood flow and inhibiting excessive excitation. The combination of the three herbs can synergistically enhance the effect of "awakening the mind and calming the nerves", and has significant effects on treating mental disorders such as forgetfulness, insomnia, anxiety, and depression.

[0017] However, because the medicinal liquid in the heated non-combustible device of this invention contains traditional Chinese medicine extracts, which are rich in bitter substances including alkaloids, glycosides, terpenes, aldehydes, and phenols, the aroma and taste are not well-coordinated. Adding existing sweeteners can only improve the sweetness to a certain extent. This invention uses a compound sweetener, which has advantages such as increasing flavor, improving taste, shortening the taste gap, improving sweetness stability, increasing sweetness while reducing the total amount of sweetener used, and reducing costs. However, it still cannot completely mask the bitterness of the traditional Chinese medicine extracts. Moreover, the sweetener itself also brings a certain degree of bitterness. Therefore, the sensory evaluation of the resulting medicinal liquid for the heated non-combustible device is not good.

[0018] This invention further incorporates a bitterness-inhibiting composition, comprising a γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate and a bitterness inhibitor. The γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate hydrolyzes to produce glutamyl peptide and γ-aminobutyric acid. Glutamic peptide inhibits the human bitterness receptor hTAS2R16, thus suppressing bitterness. γ-aminobutyric acid binds to specific bitterness receptors (TAS2R family), preventing the activation of bitter substances. Simultaneously, the unhydrolyzed conjugate can also act on the transmission of bitterness signals from taste bud cells to nerves, effectively inhibiting bitterness. Furthermore, the bitterness inhibitor molecule has a menthol structure linked to the 6th position of sodium 5'-adenosine monophosphate. This molecule structure is effective in inhibiting or masking bitterness in heated non-combustible device aerosols and bitter substances in traditional Chinese medicine extracts. Moreover, the preparation method is simple, highly efficient, and under mild conditions.

[0019] This invention relates to a heat-not-burning device for stimulating the mind and calming the nerves. The medicinal liquid is added to the device and atomized by a heater, allowing the inhalation of traditional Chinese medicine extracts. This device treats insomnia and refreshes the mind, offering rapid relief, addressing both the symptoms and root cause, with a low recurrence rate. It is suitable for those engaged in high-intensity work, and has a well-balanced aroma and taste with minimal bitterness. Furthermore, this invention expands the application scenarios of traditional Chinese medicine, promotes the improvement of the quality and efficiency of traditional Chinese medicine and medical devices, drives the innovative development of traditional Chinese medicine, and advances the development of innovative traditional Chinese medicine drugs, improved traditional Chinese medicine drugs, and compound preparations of ancient classic prescriptions, thus promoting the development of traditional Chinese medicine technology. Detailed Implementation

[0020] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0021] Preparation Example 1: Extracts from Traditional Chinese Medicine The preparation method is as follows: Wash 5g of ginseng, 10g of polygala tenuifolia and 10g of acorus tatarinowii, mix them, crush them, add them to 300mL of 50wt% ethanol aqueous solution, heat and reflux for 3h, repeat the extraction 3 times, filter, combine the filtrates, and recover the solvent under reduced pressure to obtain the Chinese herbal extract.

[0022] Preparation Example 2: Traditional Chinese Medicine Extracts The preparation method is as follows: Wash 10g of ginseng, 15g of polygala tenuifolia and 20g of acorus tatarinowii, mix them, crush them, add them to 300mL of 50wt% ethanol aqueous solution, heat and reflux for 3h, repeat the extraction 3 times, filter, combine the filtrates, and recover the solvent under reduced pressure to obtain the Chinese herbal extract.

[0023] Preparation Example 3: Traditional Chinese Medicine Extracts The preparation method is as follows: Wash 8g of ginseng, 12g of polygala tenuifolia and 15g of acorus tatarinowii, mix them, crush them, add them to 300mL of 50wt% ethanol aqueous solution, heat and reflux for 3h, repeat the extraction 3 times, filter, combine the filtrates, and recover the solvent under reduced pressure to obtain the Chinese herbal extract.

[0024] Comparative Preparation Example 1 The difference compared to Preparation Example 3 is that ginseng was not added.

[0025] The preparation method is as follows: Wash 12g of Polygala tenuifolia and 15g of Acorus tatarinowii, mix them, crush them, add them to 300mL of 50wt% ethanol aqueous solution, heat and reflux for 3h, repeat the extraction 3 times, filter, combine the filtrates, and recover the solvent under reduced pressure to obtain the Chinese herbal extract.

[0026] Comparative Preparation Example 2 The difference compared to Preparation Example 3 is that Polygala tenuifolia was not added.

[0027] The preparation method is as follows: Wash 8g of ginseng and 15g of acorus tatarinowii, mix them, crush them, add them to 300mL of 50wt% ethanol aqueous solution, heat and reflux for 3h, repeat the extraction 3 times, filter, combine the filtrates, and recover the solvent under reduced pressure to obtain the Chinese herbal extract.

[0028] Comparative preparation example 3 The difference compared to Preparation Example 3 is that no Acorus tatarinowii was added.

[0029] The preparation method is as follows: Wash 8g of ginseng and 12g of polygala, mix them, crush them, add them to 300mL of 50wt% ethanol aqueous solution, heat and reflux for 3h, repeat the extraction 3 times, filter, combine the filtrates, and recover the solvent under reduced pressure to obtain the Chinese herbal extract.

[0030] Preparation Example 4: γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate The preparation method is as follows: 2g of γ-aminobutyric acid was added to water, along with 0.2g of N-hydroxysuccinimide and 0.5g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The mixture was stirred and activated at 0℃ for 30min. Then, 5g of γ-L-glutamyl-L-alanine was added, and the mixture was stirred and reacted for 12h. The mixture was dialyzed using a dialysis bag with a pore size of 1000Da for 24h and then freeze-dried to obtain the γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate.

[0031] Preparation Example 5: Bitterness Inhibitor Synthesis route: ; The preparation method is as follows: S1. 13.6 g of hypoxanthine, 120 mL of phosphorus oxychloride, and 50 mL of N,N-dimethylformamide were added to a reaction flask and heated under reflux for 3 h. The solvent was removed under reduced pressure, 200 mL of dichloromethane was added, and HCl gas was passed through at 0 °C. The mixture was filtered, and the product was recrystallized from ethanol to obtain intermediate 1 with a yield of 89%. ESI-MS calculated value: C5H4ClN4(M+H) + 155.56, Measured value: 155.6; NMR result: 1 H NMR (300MHz, CDCl3) δ11.0 (br, 1H), 9.22 (s, 1H), 8.57 (s, 1H).

[0032] S2. 26.8 g of inosine was added to 80 mL of acetic anhydride, followed by 5 g of sodium acetate. The mixture was heated under reflux for 3 h, the solvent was removed under reduced pressure, the product was poured into ice water, filtered, and recrystallized from solid ethyl acetate to obtain intermediate 2, yield 87%; ESI-MS calculated value: C 13 H 19 O9(M+H) + 319.28, measured value: 319.3; NMR result: 1 H NMR (300MHz, CDCl3) δ4.7-4.8 (m, 5H), 4.2-4.3 (m, 1H), 2.0-2.2 (m, 12H).

[0033] S3. 32.8 g of intermediate 1, 7.7 g of intermediate 2, and 7.5 g of SnCl4 were added to 150 mL of N,N-dimethylformamide, heated to 120 °C, and stirred for 3 h. The solvent was removed under reduced pressure, and the mixture was recrystallized from ethanol to obtain intermediate 3, with a yield of 79%. ESI-MS calculated value: C 16 H 18 ClN4O7(M+H) + 413.78, Measured value: 413.8; NMR result: 1 H NMR (300MHz, CDCl3) δ9.22 (s, 1H), 8.75 (s, 1H), 6.54 (d, 1H), 4.8-4.9 (m, 4H), 4.2-4.3 (m, 1H), 2.09 (s, 9H).

[0034] S4. 20.6 g of intermediate 3, 8 g of menthol, and 15 g of triethylamine were added to 300 mL of acetonitrile. The mixture was heated under reflux and stirred for 4 h. The solvent was removed under reduced pressure, and the mixture was recrystallized from ethyl acetate to obtain intermediate 4, with a yield of 85%. ESI-MS calculated value: C 26 H 37 N4O8(M+H) + 533.59, measured value: 533.6; NMR result: 1 H NMR (300MHz, CDCl3) δ8.72 (s, 1H), 8.65 (s, 1H), 6.51 (d, 1H), 4.8-4.9 (m, 4H), 4.16-4.2 7 (m, 1H), 3.65 (m, 1H), 2.05 (s, 9H), 1.7-1.9 (m, 4H), 1.4-1.6 (m, 5H), 1.02-1.09 (m, 9H).

[0035] S5. 26.6 g of intermediate 4 was placed in 100 mL of saturated NH3 / CH3OH solution, pressurized to 2.5 MPa, and reacted for 7 h. The solvent was recovered, and the product was recrystallized from a 50% aqueous ethanol solution to obtain intermediate 5, with a yield of 99%. ESI-MS calculated value: C 20 H 31 N4O5(M+H) + 407.48, measured value: 407.5; NMR result: 1 H NMR (300MHz, CDCl3) δ8.66-8.72 (m, 2H), 6.05 (d, 1H), 3.6-3.9 (m, 6H), 1.7-2.1 (m, 7H), 1.4-1.6 (m, 5H), 1.02-1.05 (m, 9H).

[0036] S6. Dissolve 20.3 g of intermediate 5, 10 mL of water, and 90 mL of triethyl phosphate in a mixture. Cool to -15°C, and add 15 g of phosphorus oxychloride dropwise, controlling the reaction temperature not to exceed 0°C. After the addition is complete, continue stirring for 10 hours. Add the product to ice water, allow it to separate into layers, and add sodium hydroxide to the organic layer to adjust the pH to 5.5. Concentrate under reduced pressure, filter, and allow the solid to cool and crystallize to obtain the product with a yield of 80%. ESI-MS calculated value: C 20 H 31 N4NaO8P(M+H) + 509.44, measured value: 509.4; NMR result: 1 H NMR (300MHz, CDCl3) δ 8.69-8.72 (m, 2H), 6.07 (d, 1H), 4.1-4.2 (d, 2H), 3.6-3.8 (m, 4H), 1.9-2.1 (m, 7H), 1.4-1.6 (m, 5H), 1.02-1.09 (m, 9H). Example 1

[0037] This embodiment provides a liquid medicine for a heat-not-burning device for stimulating the mind and calming the nerves, comprising the following raw materials in parts by weight: 3 parts of flavoring, 7 parts of the traditional Chinese medicine extract prepared in Preparation Example 1, 80 parts of atomizing agent, 3 parts of sweetener, and 0.5 parts of bitterness-inhibiting composition.

[0038] The atomizing agent is a mixture of water and propylene glycol in a volume ratio of 1:8.

[0039] The sweetener is a mixture of sucralose and erythritol in a mass ratio of 4:1.

[0040] The bitterness-inhibiting composition comprises the γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate prepared in Preparation Example 4 and the bitterness inhibitor prepared in Preparation Example 5, in a mass ratio of 4:1.

[0041] The preparation method includes: dissolving traditional Chinese medicine extracts and fragrances in an atomizing agent, adding a sweetener and a bitterness-inhibiting composition, stirring and mixing evenly, filtering through a 0.22μm microporous membrane, and sterilizing by irradiation to obtain a medicinal liquid for a heat-not-burning device used for waking the mind and calming the nerves. Example 2

[0042] This embodiment provides a liquid medicine for a heat-not-burning device for stimulating the mind and calming the nerves, comprising the following raw materials in parts by weight: 5 parts of flavoring, 12 parts of the traditional Chinese medicine extract obtained in Preparation Example 2, 90 parts of atomizing agent, 5 parts of sweetener, and 1 part of bitterness-inhibiting composition.

[0043] The atomizing agent is a mixture of water and propylene glycol in a volume ratio of 3:10.

[0044] The sweetener is a mixture of sucralose and erythritol in a mass ratio of 6:2.

[0045] The bitterness-inhibiting composition comprises the γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate prepared in Preparation Example 4 and the bitterness inhibitor prepared in Preparation Example 5, with a mass ratio of 7:2.

[0046] The preparation method includes: dissolving traditional Chinese medicine extracts and fragrances in an atomizing agent, adding a sweetener and a bitterness-inhibiting composition, stirring and mixing evenly, filtering through a 0.22μm microporous membrane, and sterilizing by irradiation to obtain a medicinal liquid for a heat-not-burning device used for waking the mind and calming the nerves. Example 3

[0047] This embodiment provides a liquid medicine for a heat-not-burning device for stimulating the mind and calming the nerves, comprising the following raw materials in parts by weight: 4 parts of flavoring, 10 parts of the traditional Chinese medicine extract obtained in Preparation Example 3, 85 parts of atomizing agent, 4 parts of sweetener, and 0.7 parts of bitterness-inhibiting composition.

[0048] The atomizing agent is a mixture of water and propylene glycol in a volume ratio of 2:9.

[0049] The sweetener is a mixture of sucralose and erythritol in a mass ratio of 5:1.5.

[0050] The bitterness-inhibiting composition comprises the γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate prepared in Preparation Example 4 and the bitterness inhibitor prepared in Preparation Example 5, with a mass ratio of 5.5:1.5.

[0051] The preparation method includes: dissolving traditional Chinese medicine extracts and fragrances in an atomizing agent, adding a sweetener and a bitterness-inhibiting composition, stirring and mixing evenly, filtering through a 0.22μm microporous membrane, and sterilizing by irradiation to obtain a medicinal liquid for a heat-not-burning device used for waking the mind and calming the nerves. Example 4

[0052] The difference from Example 3 is that the sweetener is sucralose alone. Example 5

[0053] The difference from Example 3 is that the sweetener is a single type of erythritol. Example 6

[0054] The difference from Example 3 is that the bitterness-inhibiting composition is a single γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate prepared in Preparation Example 4. Example 7

[0055] The difference from Example 3 is that the bitterness-inhibiting composition is a single bitterness inhibitor prepared in Preparation Example 5.

[0056] Comparative Example 1 The difference compared to Example 3 is that no bitterness-inhibiting composition was added.

[0057] Comparative Example 2 The difference from Example 3 is that the herbal extract was prepared by Comparative Preparation Example 1.

[0058] Comparative Example 3 The difference from Example 3 is that the herbal extract was prepared by Comparative Preparation Example 2.

[0059] Comparative Example 4 The difference from Example 3 is that the herbal extract was prepared by Comparative Preparation Example 3.

[0060] Test Example 1 Add 1g of the heat-not-burning device liquid prepared in Examples 1-7 or Comparative Example 1 to each cartridge, and label the heat-not-burning device. Organize 10 experts with sensory evaluation qualifications to conduct sensory quality evaluation of the heat-not-burning device liquid samples.

[0061] The sensory quality of the liquid medicine in the heated non-combustible device was evaluated using six indicators (Table 1): smoke volume, aroma, harmony, irritation, off-flavors, and aftertaste. Each item was scored in units of 0.5; the weighted average score for each item was calculated separately, accurate to 0.01; the total sensory quality score was expressed as the sum of the weighted average scores of each item, accurate to 0.1.

[0062] Table 1

[0063] The results are shown in Table 2.

[0064] Table 2 Sensory evaluation results (unit: points)

[0065] As can be seen from the table above, the heat-not-burning device liquid prepared in Examples 1-3 of the present invention has a high sensory score, and the score for impurities (bitterness) is also high.

[0066] Test Example 2 After SPF-grade SD rats were acclimatized for 7 days, they were randomly divided into a normal control group, a model group, Example 1-3 groups, and Comparative Example 2-4 groups, with 6 rats in each group. Except for the normal control group, the rats in the other groups were intraperitoneally injected with 300 mg / kg of p-chlorophenylalanine via gavage at a dose of 10 mL / kg once daily from 8:00 to 8:30 AM for 2 consecutive days. The normal control group received an intraperitoneal injection of the same volume of weakly alkaline 0.9% sodium chloride injection as the p-chlorophenylalanine. After successful replication of the rat insomnia model, the heat-not-burning device solution prepared in Example 1-3 and Comparative Example 2-4 was heated and atomized using a heater and introduced into the environment where the rats were housed. The rats were kept in a sealed environment to prevent rapid smoke dissipation. Each atomization was 6 g of the heat-not-burning device solution, 10 times daily. The normal control group and the model group used deionized water for atomization. The administration was continuous for 7 days. The rats were fasted for 12 hours before the last administration (day 7). After the last administration, spontaneous activity was observed. 60 min after administration, rat brains were collected after intraperitoneal injection of 10% chloral hydrate at a dose of 0.3 g / kg for analysis. The results are shown in Table 3.

[0067] Table 3

[0068] Note: # indicates that compared with the normal control group, P<0.05; # indicates that compared with the model group, P<0.05.

[0069] As shown in the table above, the heat-not-burning liquid medicine prepared in Examples 1-3 of the present invention for stimulating the mind and calming the nerves can significantly reduce the dopamine content in the rat brain and increase the content of γ-aminobutyric acid and serotonin.

[0070] The open field test was used to evaluate rats' anxiety, autonomy, and exploratory behavior in a new environment. The open field test chamber was 50 cm high and 50 cm long at the base. The interior area of ​​the open field was divided into 4×4 squares, with the four inner squares forming the central area and the outer squares forming the peripheral area. The open field was placed directly under an incandescent light bulb, and the camera was positioned directly above the open field. The open field test was conducted in a quiet environment. The experimenters placed the animals at a uniform angle into the center of the chamber's bottom surface and then filmed and timed the event. The rats' activities were spontaneously recorded by the camera. Each rat was tested for 10 minutes. After the test, the open field was cleaned, and the inner walls and bottom of the test chamber were washed to prevent the retention of odors and excrement. Test indicators included: total distance traveled by the rat in the open field, number of times the rat stopped in the center of the open field, and duration of the stop. The results are shown in Table 4.

[0071] Table 4

[0072] Note: # indicates that compared with the normal control group, P<0.05; # indicates that compared with the model group, P<0.05.

[0073] As shown in the table above, the heat-not-burning liquid medicine for waking up the mind and calming the nerves prepared in Examples 1-3 of the present invention can significantly improve the anxiety of rats in the open field caused by insomnia.

[0074] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A heatable, non-flammable liquid medicine for stimulating the mind and calming the nerves, characterized in that, The raw materials include the following parts by weight: 3-5 parts of flavoring, 7-12 parts of traditional Chinese medicine extract, 80-90 parts of atomizing agent, 3-5 parts of sweetener, and 0.5-1 parts of bitterness-inhibiting composition, wherein the traditional Chinese medicine extract includes extracts made from ginseng, polygala, and acorus.

2. The medicinal liquid for the heating and non-combustible device for stimulating the mind and calming the nerves according to claim 1, characterized in that, The herbal extract comprises the following parts by weight of raw materials: 5-10 parts ginseng, 10-15 parts polygala, and 10-20 parts acorus.

3. The medicinal liquid for the heating and non-combustible device for stimulating the mind and calming the nerves according to claim 2, characterized in that, The preparation method of the traditional Chinese medicine extract is as follows: Ginseng, Polygala tenuifolia, and Acorus tatarinowii were washed, mixed, crushed, and added to an ethanol-water solution. The mixture was heated and refluxed for extraction. The extraction was repeated, filtered, and the filtrates were combined. The solvent was recovered under reduced pressure to obtain the Chinese herbal extract.

4. The medicinal liquid for the heating and non-combustible device for stimulating the mind and calming the nerves according to claim 1, characterized in that, The atomizing agent is a mixture of water and propylene glycol in a volume ratio of 1-3:8-10.

5. The medicinal liquid for the heating and non-combustible device for stimulating the mind and calming the nerves according to claim 1, characterized in that, The sweetener is a mixture of sucralose and erythritol in a mass ratio of 4-6:1-2.

6. The medicinal liquid for the heating and sedation device according to claim 1, characterized in that, The bitterness-inhibiting composition comprises a γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate and a bitterness inhibitor in a mass ratio of 4-7:1-2, and the structural formula of the bitterness inhibitor is shown in Formula I: ; Formula I.

7. The medicinal liquid for the heating and non-combustible device for stimulating the mind and calming the nerves according to claim 6, characterized in that, The preparation method of the γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate is as follows: γ-aminobutyric acid was added to water, followed by N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The mixture was stirred and activated, then glutamyl peptide was added. The mixture was stirred and reacted, dialyzed, and freeze-dried to obtain the γ-L-glutamyl-L-alanine / γ-aminobutyric acid conjugate.

8. The medicinal liquid for the heating and sedation device according to claim 6, characterized in that, The method for preparing the bitterness inhibitor is as follows: S1. Inosine and phosphorus oxychloride were reacted to prepare intermediate 1, with the following structure: ; S2. Inosine was added to acetic anhydride, sodium acetate was added, and the mixture was heated under reflux to prepare intermediate 2, with the following structural formula: ; S3. Intermediate 1 and intermediate 2 are reacted to obtain intermediate 3, with the following structure: ; S4. Intermediate 3 was reacted with menthol to prepare intermediate 4, with the following structure: ; S5. Intermediate 4 was reacted under pressure in a saturated NH3 / CH3OH solution to obtain intermediate 5, with the following structure: ; S6. React intermediate 5 with phosphorus oxychloride, and neutralize the product with sodium hydroxide to obtain the final product.

9. A method for preparing a heat-not-burning medicinal liquid for a mind-awakening and calming device as described in any one of claims 1-8, characterized in that, Traditional Chinese medicine extracts and flavorings are dissolved in an atomizing agent, and a sweetener and a bitterness-inhibiting composition are added. The mixture is stirred and mixed evenly, filtered through a 0.22μm microporous membrane, and sterilized to obtain a medicinal liquid for a heat-not-burning device used for waking the mind and calming the nerves.

10. The use of a heat-not-burning liquid medicine for stimulating the mind and calming the nerves as described in any one of claims 1-8 in the preparation of a medicine for treating insomnia and narcolepsy.

Images