A Jin medicine compound sedative ointment that prolongs deep sleep and has no dependence, and its preparation method.

Abstract

This invention relates to the field of traditional Chinese medicine technology, and more particularly to a Jin medicine compound calming ointment that prolongs deep sleep and is non-addictive, as well as its preparation method. This invention is the first to use prolonging deep sleep duration as the core therapeutic target. The combined use of various herbs in this invention nourishes blood and calms the mind, nourishes yin and clears heat, and harmonizes the heart and kidneys, effectively treating insomnia caused by deficiency of heart and liver blood, disharmony between heart and kidneys, and yin deficiency with excessive fire. Furthermore, this invention, through the synergistic effect of multiple components, can effectively regulate the neurotransmitter GABA receptors, targeting and prolonging deep sleep, reducing the number of nighttime awakenings, fundamentally optimizing sleep structure, and also inhibiting excessive activation of the HPA axis, reducing abnormally elevated cortisol levels, thereby alleviating anxiety, breaking the vicious cycle of anxiety-insomnia, and effectively treating anxiety-related insomnia. Simultaneously, it has antioxidant effects, protects nerve cells, improves cerebral microcirculation, provides sufficient oxygen and nutrients to the brain, and creates a favorable physiological environment for the restoration of normal sleep rhythms.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a Jin medicine compound calming ointment that prolongs deep sleep and is non-addictive, and its preparation method. Background Technology

[0002] Insomnia is a neuropsychiatric disorder characterized by difficulty falling asleep or maintaining sleep under conditions of sufficient sleep time and a suitable environment, leading to daytime dysfunction. Its main symptoms include difficulty falling asleep, frequent awakenings, early awakenings, and non-restorative sleep. Its incidence is increasing year by year with the accelerating pace of modern life. Long-term insomnia can lead to various problems such as anxiety, depression, memory loss, and weakened immunity.

[0003] Traditional treatments for insomnia primarily include medication and behavioral therapy. However, long-term use of sleeping pills can lead to dependence and a range of side effects, such as dependence, morning hangover, daytime sleepiness, poor concentration, and memory loss. Consequently, people are increasingly seeking safer, more natural therapies to improve sleep quality, including traditional Chinese medicine (TCM). However, current TCM treatments often only address difficulty falling asleep without considering the prolongation of deep sleep. Furthermore, while some TCM herbs have shown some clinical efficacy in treating insomnia, they are mostly administered in traditional decoction forms, which suffer from outdated formulations, low retention of active ingredients, and limited effectiveness in improving deep sleep. Summary of the Invention

[0004] Therefore, in view of the shortcomings of the prior art, the present invention provides a compound sedative ointment made with Shanxi medicine, which can not only improve difficulty falling asleep, but also target and prolong deep sleep, and its preparation method.

[0005] The technical solution provided by this invention is as follows: A traditional Chinese medicine compound composition that prolongs deep sleep and is non-addictive, comprising the following ingredients by weight: 30-40 parts of Ziziphus jujuba seed, 20-28 parts of Polygonum multiflorum vine, 10-15 parts of Polygala tenuifolia, 15-20 parts of Lilium brownii, 15-20 parts of Morus alba, 15-20 parts of Poria cocos, 10-15 parts of Anemarrhena asphodeloides, 10-15 parts of Ligusticum chuanxiong, and 5-8 parts of Glycyrrhiza uralensis.

[0006] Furthermore, by weight, it is composed of the following raw materials: The ingredients included 36 parts of Ziziphus jujuba seed, 24 parts of Polygonum multiflorum vine, 12 parts of Polygala tenuifolia, 18 parts of lily bulb, 18 parts of mulberry fruit, 18 parts of Poria cocos, 12 parts of Anemarrhena asphodeloides, 12 parts of Ligusticum chuanxiong, and 6 parts of licorice. Based on the same inventive concept, this invention also provides the application of the aforementioned Jin medicine compound composition that prolongs deep sleep and is non-addictive in the preparation of drugs for treating insomnia.

[0007] Furthermore, the insomnia described is caused by deficiency of heart and liver blood, disharmony between heart and kidney, and yin deficiency with excessive fire.

[0008] Based on the same inventive concept, this invention also provides the application of the aforementioned Jin medicine compound composition that prolongs deep sleep and is non-addictive in the preparation of a drug for treating anxiety-induced insomnia.

[0009] Based on the same inventive concept, this invention also provides the application of the aforementioned Jin medicine compound composition that prolongs deep sleep and is non-addictive in the preparation of a drug for treating insomnia by regulating abnormal function of the neurotransmitter GABA receptor and / or reducing abnormally high levels of cortisol.

[0010] Based on the same inventive concept, the present invention also provides a Jin medicine compound calming ointment that prolongs deep sleep and is non-addictive, which is made from the aforementioned Jin medicine compound composition that prolongs deep sleep and is non-addictive.

[0011] Based on the same inventive concept, this invention also provides a method for preparing a Jin medicine compound sedative ointment that prolongs deep sleep and is non-addictive, comprising the following steps: ① After crushing Chuanxiong, Yuanzhi and Baihe into powder, mix them together. Then, use 6 to 10 times the weight of the mixed drugs to perform low-temperature steam distillation on the mixed drugs. Collect the condensed distillate and then introduce the distillate for water-oil separation to collect the volatile oil. ② Mix the jujube seed, fleeceflower stem, mulberry, poria, anemarrhena and licorice with the residue after low-temperature steam distillation in step ①, add 8 to 12 times the weight of the mixed drugs in water, extract with ultrasound at 40 to 60°C 2 to 3 times, filter, each time for 30 to 60 minutes, and combine the extracts; ③ The combined extracts were concentrated under reduced pressure to a relative density of 1.15–1.25 g / ml (60℃) to obtain a clear extract; ④ The volatile oil obtained in step ① is encapsulated with β-cyclodextrin to obtain an encapsulated suspension of the volatile oil; ⑤ Add the inclusion suspension and clear extract to the ointment base, stir and mix at a temperature below 60°C, and then collect the ointment.

[0012] Furthermore, the temperature of the low-temperature steam distillation in step ① is less than 100℃.

[0013] Furthermore, the ointment base in step ⑤ is made from refined honey and malt syrup.

[0014] Further, in step ⑤, the paste is reduced to a relative density of 1.30-1.40 g / ml (60℃).

[0015] The beneficial effects achieved by this invention are as follows: This invention employs a rational formulation, with jujube seed as the principal ingredient. It nourishes blood, calms the mind, and tonifies the liver and gallbladder. The liver stores blood, and blood houses the spirit; the heart governs blood, and blood nourishes the spirit. Jujube seed directly enters the heart and liver meridians, nourishing yin and blood to calm the spirit and resolve insomnia, palpitations, and forgetfulness caused by blood deficiency failing to nourish the heart and liver spirit. The other ingredients are fleeceflower stem, polygala root, and lily bulb as assistant ingredients. Both fleeceflower stem and polygala root have the effect of harmonizing the heart and kidneys. Heart fire needs to descend to warm kidney water, and kidney water needs to ascend to nourish heart fire for restful sleep. These two herbs work synergistically to guide the heart... The kidneys are in harmony with the elements of water and fire. Anemarrhena asphodeloides and mulberry are used as adjuvant herbs. Anemarrhena asphodeloides clears deficiency heat and, together with lily bulb, clears the deficiency fire caused by yin deficiency. Mulberry nourishes yin and replenishes blood, assisting the principal herb in enhancing its ability to nourish yin and blood, and also works synergistically with anemarrhena asphodeloides to treat the root cause of yin deficiency. Poria cocos, chuanxiong rhizome, and licorice root are used as guiding herbs. Poria cocos strengthens the spleen and calms the mind. The spleen is the source of qi and blood production; strengthening the spleen helps generate qi and blood, assisting in nourishing blood, and calming the mind directly aids sleep. Chuanxiong rhizome promotes qi and blood circulation, making the entire formula nourishing without being cloying or stagnant. Licorice root harmonizes the other herbs and benefits qi and the middle jiao. The combined effects of these herbs nourish blood and calm the mind, nourish yin and clear heat, and harmonize the heart and kidneys, effectively treating insomnia caused by deficiency of heart and liver blood, disharmony between heart and kidneys, and yin deficiency with excessive fire. Furthermore, this invention, through the synergistic effect of multiple components, can effectively regulate the neurotransmitter GABA receptors, targeting and prolonging deep sleep, reducing the number of nighttime awakenings, fundamentally optimizing sleep structure. It can also inhibit excessive activation of the HPA axis, reduce abnormally elevated cortisol levels, thereby alleviating anxiety, breaking the vicious cycle of anxiety and insomnia, and effectively treating anxiety-related insomnia. Simultaneously, it has antioxidant properties, protects nerve cells, improves cerebral microcirculation, provides the brain with sufficient oxygen and nutrients, and creates a favorable physiological environment for the restoration of normal sleep rhythms.

[0016] This invention is the first to use "prolonging deep sleep duration" as the core therapeutic target, making up for the shortcomings of existing Chinese medicine in improving sleep structure.

[0017] The formula of this invention is composed entirely of mild Chinese herbs, and it works through overall conditioning, avoiding the dependence, withdrawal reactions and hangover effects commonly found in chemical sleeping pills, making it suitable for long-term use.

[0018] This invention employs different graded extraction methods tailored to the characteristics of different drugs. For volatile oil active ingredients such as Ligusticum chuanxiong, Polygala tenuifolia, and Lilium brownii, low-temperature steam distillation is used, and β-cyclodextrin is used to encapsulate the volatile oil, which greatly improves the stability and solubility of the volatile oil in the preparation, ensuring the persistence and uniformity of the therapeutic effect. The residue after steam distillation is mixed with other drugs and then extracted by ultrasound, and the most effective components are extracted again, maximizing the retention of all kinds of effective components in the whole formula. Detailed Implementation

[0019] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, 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.

[0020] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods; the experiments used in the following embodiments... Unless otherwise specified, all materials were purchased from commercial channels.

[0021] Example 1: A Jin medicine compound sedative ointment that prolongs deep sleep and has no dependence, the raw materials for which are prepared by weight are as follows: The ingredients included 36 parts of Ziziphus jujuba seed, 24 parts of Polygonum multiflorum vine, 12 parts of Polygala tenuifolia, 18 parts of lily bulb, 18 parts of mulberry fruit, 18 parts of Poria cocos, 12 parts of Anemarrhena asphodeloides, 12 parts of Ligusticum chuanxiong, and 6 parts of licorice.

[0022] In practical applications, the jujube seed, fleeceflower stem, polygala root, lily bulb, mulberry, poria cocos, anemarrhena rhizome, chuanxiong rhizome, and licorice root are all sourced from Shanxi Province.

[0023] Its specific preparation includes the following steps: ① After crushing Chuanxiong, Yuanzhi and Baihe into powder, pass them through a 10-20 mesh sieve and mix them. Use water with 10 times the weight of the mixed drugs to perform low-temperature steam distillation on the mixed drugs. After collecting the condensed distillate, introduce the distillate for water-oil separation and collect the volatile oil. Operation of low-temperature steam distillation: Lay a layer of gauze on the sieve plate of the extraction tank, spread the crushed medicinal materials on it, and stack them loosely to ensure that the steam can penetrate the entire material layer evenly. Add drinking water at a volume 10 times the weight of the mixed herbs to the bottom of the extraction tank. Heat the water to boiling, generating steam. The rising steam passes through the herb layer, carrying volatile components out. Control the distillate flow rate by adjusting the heating power, ideally to 1-2 drops per second. After condensation in a condenser, the distillate is introduced into an oil-water separator. Since volatile oils are generally less dense than water, they will float on the top layer. After standing for a sufficient time (at least 30 minutes), separate and collect the upper layer of volatile oil. Reserve the lower water layer and the herb residue.

[0024] ② After pulverizing the jujube seed, fleeceflower stem, mulberry, poria cocos, anemarrhena asphodeloides and licorice into powder and passing them through a 10-20 mesh sieve, mix them with the residue from the low-temperature steam distillation in step ①, add 12 times the weight of the mixed drugs in water (part of which is the lower layer of water separated in step ①), and extract three times with ultrasonic assistance at 50℃ (frequency 35 kHz, power 300 W), filter, 45 min each time, and combine the three extracts; ③ The combined extracts were concentrated under reduced pressure at 55℃ and -0.07MPa to a relative density of 1.2g / ml (60℃) to obtain a clear extract; ④ The volatile oil, oil and β-cyclodextrin obtained in step ① are included in a saturated aqueous solution by means of a 1:8 ratio (g / g) to obtain an inclusion suspension of volatile oil; ⑤ After adding the inclusion suspension to the clear paste and stirring evenly, add the refined honey and stir continuously at 55℃ until evenly mixed. Continue to concentrate and stir at low temperature until the relative density of the paste reaches 1.35g / ml at 60℃, then stop heating. After cooling to room temperature, dispense into 10g / sachet composite film bags to obtain the oral sedative paste.

[0025] The sedative ointment prepared above is a thick paste ranging from brown to dark brown, with a slightly fragrant odor and a sweet and slightly bitter taste.

[0026] Seal and store in a cool, dry place.

[0027] When using the calming ointment prepared above: take orally, one packet (10g) at a time, once or twice a day, and it is recommended to take it 30 to 60 minutes before bedtime.

[0028] Comparative Example 1: A Jin medicine compound sedative ointment that prolongs deep sleep and is non-addictive, the raw materials for which are prepared by weight are as follows: The ingredients are: 60 parts of Ziziphus jujuba seed, 12 parts of Polygala tenuifolia root, 18 parts of Lilium brownii bulb, 18 parts of Morus alba fruit, 18 parts of Poria cocos, 12 parts of Anemarrhena asphodeloides rhizome, 12 parts of Ligusticum chuanxiong rhizome, and 6 parts of Glycyrrhiza uralensis root.

[0029] Compared to Example 1, this comparative example replaces Polygonum multiflorum vine with the same weight of Ziziphus jujuba seed.

[0030] Everything else is the same as in Example 1.

[0031] Comparative Example 2: A Jin medicine compound sedative ointment that prolongs deep sleep and is non-addictive, the raw materials for which are prepared by weight are as follows: 36 parts of jujube seed, 24 parts of Polygonum multiflorum vine, 12 parts of Polygala tenuifolia, 18 parts of lily bulb, 18 parts of mulberry fruit, 18 parts of Poria cocos, 12 parts of Anemarrhena asphodeloides, 12 parts of Ligusticum chuanxiong and 6 parts of licorice.

[0032] The preparation of the sedative ointment in this comparative example includes the following steps: ① After taking the raw materials according to the proportion, pulverize them separately and pass them through a 10-20 mesh sieve. Add water with a weight of 12 times the weight of the mixed drugs, and extract three times with ultrasonic assistance at 50℃. Filter and extract for 45 minutes each time. Combine the three extracts. ② The combined extracts were concentrated under reduced pressure at 55℃ and -0.07MPa to a relative density of 1.2g / ml (60℃) to obtain a clear extract; ③ Add the clear paste to the refined honey, and stir continuously at 55℃ until evenly mixed. Continue to concentrate and stir at low temperature until the relative density of the paste reaches 1.35g / ml at 60℃, then stop heating. After cooling to room temperature, dispense into 10g / sachet composite film bags to obtain the oral tranquilizing paste.

[0033] Compared to Example 1, this comparative example only uses ultrasonic extraction to extract the active ingredients.

[0034] Comparative Example 3: A Jin medicine compound sedative ointment that prolongs deep sleep and is non-addictive, the raw materials for which are prepared by weight are as follows: 36 parts of jujube seed, 24 parts of Polygonum multiflorum vine, 12 parts of Polygala tenuifolia, 18 parts of lily bulb, 18 parts of mulberry fruit, 18 parts of Poria cocos, 12 parts of Anemarrhena asphodeloides, 12 parts of Ligusticum chuanxiong and 6 parts of licorice.

[0035] The preparation of the sedative ointment in this comparative example includes the following steps: ① Pulverize the jujube seed, fleeceflower stem, mulberry, poria, anemarrhena and licorice separately, pass them through a 10-20 mesh sieve and mix them. Use water with 10 times the weight of the mixed drugs to perform low-temperature steam distillation on the mixed drugs. Collect the condensed distillate and introduce it into the water-oil separation to collect the volatile oil. Operation of low-temperature steam distillation: Lay a layer of gauze on the sieve plate of the extraction tank, spread the crushed medicinal materials on it, and stack them loosely to ensure that the steam can penetrate the entire material layer evenly. Add drinking water at a volume 10 times the weight of the mixed herbs to the bottom of the extraction tank. Heat the water to boiling, generating steam. The steam rises, passes through the herb layer, and carries volatile components out. Control the distillate flow rate by adjusting the heating power, ideally to 1-2 drops per second. After condensation in a condenser, the distillate is introduced into an oil-water separator. Since volatile oils are generally less dense than water, they will float on the top layer. After standing for a sufficient time (e.g., more than 30 minutes), separate and collect the upper layer of volatile oil, keep the lower water layer for later use, and keep the herb residue for later use.

[0036] ② After pulverizing Chuanxiong, Yuanzhi and Baihe into powder and passing them through a 10-20 mesh sieve, mix them with the residue from the low-temperature steam distillation in step ①, add 12 times the weight of the mixed drugs in water (part of which is the lower layer of water separated in step ①), and extract three times with ultrasonic assistance at 50℃ (frequency 35 kHz, power 300 W), filter, 45 min each time, and combine the three extracts; ③ The combined extracts were concentrated under reduced pressure at 55℃ and -0.07MPa to a relative density of 1.2g / ml (60℃) to obtain a clear extract; ④ The volatile oil, oil and β-cyclodextrin obtained in step ① are included in a saturated aqueous solution by means of a 1:8 ratio (g / g) to obtain an inclusion suspension of volatile oil; ⑤ Add the inclusion suspension to the clear paste and then to the refined honey. Stir continuously at 55℃ until the mixture is homogeneous. Continue to concentrate and stir at low temperature until the relative density of the paste reaches 1.35 g / ml at 60℃, then stop heating. After cooling to room temperature, dispense into 10 g / sachet composite film bags to obtain the oral sedative paste.

[0037] Compared to Example 1, the drugs extracted by steam distillation in this comparative example were replaced by Ligusticum chuanxiong, Polygala tenuifolia, and Lilium brownii with Ziziphus jujuba var. spinosa, Polygonum multiflorum vine, Morus alba, Poria cocos, Anemarrhena asphodeloides, and Glycyrrhiza uralensis. In other words, Ligusticum chuanxiong, Polygala tenuifolia, and Lilium brownii were not extracted by steam distillation.

[0038] Comparative Example 4: A Jin medicine compound sedative ointment that prolongs deep sleep and is non-addictive, the raw materials for which are prepared by weight are as follows: 36 parts of jujube seed, 24 parts of Polygonum multiflorum vine, 12 parts of Polygala tenuifolia, 18 parts of lily bulb, 18 parts of mulberry fruit, 18 parts of Poria cocos, 12 parts of Anemarrhena asphodeloides, 12 parts of Ligusticum chuanxiong and 6 parts of licorice.

[0039] The preparation of the sedative ointment in this comparative example includes the following steps: ① After crushing Chuanxiong, Yuanzhi and Baihe into powder, pass them through a 10-20 mesh sieve and mix them. Use water with 10 times the weight of the mixed drugs to perform low-temperature steam distillation on the mixed drugs. After collecting the condensed distillate, introduce the distillate for water-oil separation and collect the volatile oil. Operation of low-temperature steam distillation: Lay a layer of gauze on the sieve plate of the extraction tank, spread the crushed medicinal materials on it, and stack them loosely to ensure that the steam can penetrate the entire material layer evenly. Add drinking water at a volume 10 times the weight of the mixed herbs to the bottom of the extraction tank. Heat the water to boiling, generating steam. The steam rises, passes through the herb layer, and carries volatile components out. Control the distillate flow rate by adjusting the heating power, ideally to 1-2 drops per second. After condensation in a condenser, the distillate is introduced into an oil-water separator. Since volatile oils are generally less dense than water, they will float on the top layer. After standing for a sufficient time (e.g., more than 30 minutes), separate and collect the upper layer of volatile oil, keep the lower water layer for later use, and keep the herb residue for later use.

[0040] ② After pulverizing the jujube seed, fleeceflower stem, mulberry, poria cocos, anemarrhena asphodeloides and licorice into powder and passing them through a 10-20 mesh sieve, mix them with the residue from the low-temperature steam distillation in step ①, add 12 times the weight of the mixed drugs in water (part of which is the lower layer of water separated in step ①), and extract three times with ultrasonic assistance at 50℃ (frequency 35 kHz, power 300 W), filter, 45 min each time, and combine the three extracts; ③ The combined extracts were concentrated under reduced pressure at 55℃ and -0.07MPa to a relative density of 1.2g / ml (60℃) to obtain a clear extract; ④ Add the volatile oil to the clear paste, stir well, then add the refined honey. Stir continuously at 55℃ until well mixed, continue to concentrate and stir at low temperature until the relative density of the paste reaches 1.35g / ml at 60℃, then stop heating. After cooling to room temperature, dispense into 10g / bag composite film bags to obtain the oral tranquilizing paste.

[0041] Compared to Example 1, this comparative example omits the step of encapsulating the volatile oil.

[0042] Comparative Example 5: A Jin medicine compound sedative ointment that prolongs deep sleep and is non-addictive, the raw materials for which are prepared by weight are as follows: 36 parts of jujube seed, 24 parts of Polygonum multiflorum vine, 12 parts of Polygala tenuifolia, 18 parts of lily bulb, 18 parts of mulberry fruit, 18 parts of Poria cocos, 12 parts of Anemarrhena asphodeloides, 12 parts of Ligusticum chuanxiong and 6 parts of licorice.

[0043] The preparation of the sedative ointment in this comparative example includes the following steps: ① After taking the raw materials according to the proportion, crush them separately, pass them through a 10-20 mesh sieve, and then mix them. Use water with 10 times the weight of the mixed drugs to perform low-temperature steam distillation on the mixed drugs. After collecting the condensed distillate, introduce the distillate for water-oil separation and collect the volatile oil. Operation of low-temperature steam distillation: Lay a layer of gauze on the sieve plate of the extraction tank, spread the crushed medicinal materials on it, and stack them loosely to ensure that the steam can penetrate the entire material layer evenly. Add drinking water at a volume 10 times the weight of the mixed herbs to the bottom of the extraction tank. Heat the water to boiling, generating steam. The steam rises, passes through the herb layer, and carries volatile components out. Control the distillate flow rate by adjusting the heating power, ideally to 1-2 drops per second. After condensation in a condenser, the distillate is introduced into an oil-water separator. Since volatile oils are generally less dense than water, they will float on the top layer. After standing for a sufficient time (e.g., more than 30 minutes), separate and collect the upper layer of volatile oil, keep the lower water layer for later use, and keep the herb residue for later use.

[0044] ② Add the residue to 12 times its own weight of water (part of which is the lower water layer after separation in step ①), and extract three times with ultrasonic assistance at 50℃ (frequency 35 kHz, power 300 W). Filter, each time for 45 minutes, and combine the three extracts. ③ The combined extracts were concentrated under reduced pressure at 55℃ and -0.07MPa to a relative density of 1.2g / ml (60℃) to obtain a clear extract; ④ The volatile oil, oil and β-cyclodextrin obtained in step ① are included in a saturated aqueous solution by means of a 1:8 ratio (g / g) to obtain an inclusion suspension of volatile oil; ⑤ After adding the inclusion suspension to the clear paste and stirring evenly, add the refined honey and stir continuously at 55℃ until evenly mixed. Continue to concentrate and stir at low temperature until the relative density of the paste reaches 1.35g / ml at 60℃, then stop heating. After cooling to room temperature, dispense into 10g / sachet composite film bags to obtain the oral sedative paste.

[0045] Compared to Example 1, in this comparative example, all the drugs were extracted by steam distillation and then by ultrasonic extraction.

[0046] Mouse insomnia experiment C57BL / 6J mice, purchased from Beijing Vital River Technology Co., Ltd., were 6 weeks old, weighing approximately 20g, and in good health. After one week of acclimatization, 100 mice were randomly selected and injected intraperitoneally with 400mg / kg PCPA (dissolved in physiological saline) at a dose of 0.1mL / 10g for 3 consecutive days. The mouse insomnia model was successfully established when the mice exhibited loss of circadian rhythm, increased aggression, disheveled fur, and weight loss. Sixty mice were randomly selected from these mice and divided into 6 groups: the model group, the example group, and the corresponding control group. Ten mice were randomly selected as the blank control group without any treatment.

[0047] Seventy mice were randomly selected and randomly divided into seven groups: a blank control group, an experimental group, and a corresponding control group.

[0048] The tranquilizing ointments prepared in the example group and the corresponding comparative group were respectively mixed with distilled water to prepare a 10 mg / ml solution.

[0049] The example group and the corresponding comparative group were respectively administered the drug of the example or the comparative group by gavage, with a gavage volume of 20 ml / kg. The blank control group was administered the same distilled water by gavage. After three consecutive days of administration, the sleep patterns of the mice were recorded by a polysomnography instrument, and the sleep onset time (from entering a resting state to the start of sleep), sleep duration (total sleep duration), deep sleep ratio, etc. were calculated. The results are shown in Table 1.

[0050] Table 1: Sleep patterns of mice in each group

[0051] As shown in the table above, PCPA successfully induced insomnia in the model group, manifested as extreme difficulty falling asleep, short sleep duration, and very shallow sleep. Compared to the model group, Example 1 showed the best effect in improving insomnia, with its sleep onset time, sleep duration, and deep sleep time being closest to the blank control group. The comparative examples showed a worse improvement effect on insomnia mice compared to Example 1, which was analyzed because the substitution of Ziziphus jujuba seed for Polygonum multiflorum disrupted the compatibility relationship and affected the overall efficacy. Comparative examples 2 and 3 showed poor sleep improvement effects. In Comparative Example 2, all medicinal materials were extracted using ultrasound, with no extraction of volatile oils. Analysis revealed that the lost volatile oils contained key components regulating neurotransmitters, resulting in minimal improvement in difficulty falling asleep and deep sleep. Comparative Example 3 used ultrasound extraction only for Ligusticum chuanxiong, Polygala tenuifolia, and Lilium brownii, without steam distillation. Similar to Comparative Example 2, key components in the volatile oils were lost. Distillation of herbs like Ziziphus jujuba var. spinosa may destroy their components, affecting efficacy. While Comparative Example 4 showed less improvement in insomnia in mice than Example 1, it was superior to Comparative Examples 2 and 3. This may be because the extracted volatile oils were not encapsulated with β-cyclodextrin, leading to reduced volatile oil content in later sleep. During the preparation process, a large amount of substances were released and oxidized, resulting in low bioavailability. In Comparative Example 5, all medicinal materials were first distilled and then extracted using ultrasound, but the effect was lower than that of Example 1. Analysis showed that the heat-sensitive components of medicinal materials such as Ziziphus jujuba seed and Anemarrhena asphodeloides may have been damaged during distillation, resulting in a lower overall synergistic efficiency of the components compared to Example 1, which used targeted graded extraction. As can be seen from the above, in the preparation process of the ointment of the present invention, different extraction methods are used for different medicinal materials. In particular, for volatile substances containing key components such as Ligusticum chuanxiong, Polygala tenuifolia, and Lilium brownii, steam distillation is first used, and then the residue is extracted together with other medicinal materials using ultrasound. The ointment prepared in this way has the best effect on improving insomnia.

[0052] Three mice were randomly selected from each group, and blood was collected from the submandibular vein. The cortisol content was detected by ELISA. Three mice from each group were also randomly selected and sacrificed. The hypothalamus of the rats was removed, and the contents of 5-hydroxytryptamine (5-HT) and GABA in the hypothalamus tissue of each group were determined by enzyme-linked immunosorbent assay. The results are shown in Table 2.

[0053] Table 2:

[0054] As shown in the table above, the PCPA insomnia model in the model group showed a significant decrease in neurotransmitter levels (5-HT, GABA), activation of the stress system (HPA axis), and an increase in cortisol. GABA and cortisol levels are core indicators related to resisting anxiety and promoting deep sleep. Compared with the model group, the GABA level in Example 1 was significantly increased, and the cortisol level was significantly decreased. The analysis showed that the oils of Ligusticum chuanxiong, Polygala tenuifolia, and Lilium brownii were first distilled and encapsulated with β-cyclodextrin. The residue and other medicinal materials were then extracted by ultrasound, which maximized the preservation and stabilization of the components that regulate GABA receptors (volatile oils of Ligusticum chuanxiong and Polygala tenuifolia) and nourish blood and calm the mind (such as Ziziphus jujuba var. spinosa). Comparative Example 1 lacked Polygonum multiflorum, and its indicators were all lower than those of Example 1. Comparative Example 2 was only extracted by ultrasound and did not extract the volatile oils of Ligusticum chuanxiong, Polygala tenuifolia, and Lilium brownii at all, thus losing the core substances that regulate the GABA system. Therefore, the GABA level was almost unimproved, the cortisol level decreased only slightly, and 5-HT was slightly increased due to the effects of other components, making it one of the worst-performing examples. In Comparative Example 3, distillation of non-volatile medicinal materials such as Ziziphus jujuba var. spinosa may destroy their heat-sensitive components, while the volatile oils of medicinal materials that should be distilled, such as Ligusticum chuanxiong, were not extracted. The effect of Comparative Example 4 was far less than that of Example 1, but better than Comparative Example 2 and Comparative Example 3 (because a trace amount of volatile oil still had an effect). The effect of Comparative Example 5 was inferior to that of Example 1.

[0055] Specific applications: Twenty-three patients, aged 37-56 years, were diagnosed by traditional Chinese medicine consultation as having insomnia caused by deficiency of heart and liver blood, disharmony between heart and kidney, and yin deficiency with fire excess. Among them, there were 9 males and 14 females. All patients with insomnia were treated with the calming ointment of Example 1, one packet per day, taken before going to bed. After 7 consecutive days of treatment, the efficacy was statistically analyzed.

[0056] Efficacy criteria (drafted with reference to the efficacy criteria for insomnia in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines"): Clinical cure: Sleep duration returns to normal or nighttime sleep duration is ≥6 hours, sleep is deep, and one feels energetic upon waking.

[0057] Significant effect: Sleep improved significantly, sleep time increased by 3 hours, sleep depth increased, but total sleep time was less than 6 hours.

[0058] Effective: Symptoms were relieved, and sleep increased by less than 3 hours compared to before.

[0059] Ineffective: No significant improvement or worsening of sleep after treatment.

[0060] Effectiveness rate = (clinically cured + significantly effective + effective) * 100% / total number of people.

[0061] The results showed that 2 patients were clinically cured, 7 patients showed significant improvement, 11 patients showed improvement, and 3 patients showed no improvement, with an effectiveness rate of 91.3%.

[0062] The present invention and its embodiments have been described above. This description is not restrictive, and the embodiments shown are only one of the embodiments of the present invention. The actual structure is not limited to this. In conclusion, if those skilled in the art are inspired by this description and design similar structures and embodiments without departing from the spirit of the present invention, they should all fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine compound composition that prolongs deep sleep and is non-addictive, characterized in that, By weight, it consists of the following raw materials: 30-40 parts of Ziziphus jujuba seed, 20-28 parts of Polygonum multiflorum vine, 10-15 parts of Polygala tenuifolia, 15-20 parts of Lilium brownii, 15-20 parts of Morus alba, 15-20 parts of Poria cocos, 10-15 parts of Anemarrhena asphodeloides, 10-15 parts of Ligusticum chuanxiong, and 5-8 parts of Glycyrrhiza uralensis.

2. The Jin medicine compound composition for prolonging deep sleep and without dependence according to claim 1, characterized in that, By weight, it consists of the following raw materials: The ingredients included 36 parts of Ziziphus jujuba seed, 24 parts of Polygonum multiflorum vine, 12 parts of Polygala tenuifolia, 18 parts of lily bulb, 18 parts of mulberry fruit, 18 parts of Poria cocos, 12 parts of Anemarrhena asphodeloides, 12 parts of Ligusticum chuanxiong, and 6 parts of licorice.

3. A Jin medicine compound composition for prolonging deep sleep and without dependence according to claim 1 or 2, characterized in that, The ingredients mentioned above, including jujube seed, fleeceflower stem, polygala root, lily bulb, mulberry, poria cocos, anemarrhena rhizome, chuanxiong rhizome, and licorice root, all originate from Shanxi Province.

4. The use of the Jin medicine compound composition according to claims 1 to 3, which prolongs deep sleep and is non-addictive, in the preparation of a drug for treating insomnia.

5. The application according to claim 4, characterized in that, The insomnia mentioned is caused by deficiency of heart and liver blood, disharmony between heart and kidney, yin deficiency and fire excess, and / or anxiety insomnia.

6. The use of the Jin medicine compound composition according to claims 1 to 3, which prolongs deep sleep and is non-addictive, in the preparation of a drug for treating insomnia by regulating abnormal function of the neurotransmitter GABA receptor and / or reducing abnormally high levels of cortisol.

7. A Jin medicine compound sedative ointment that prolongs deep sleep and is non-addictive, characterized in that... It is made from a Jin medicine compound composition that prolongs deep sleep and is non-addictive, as described in claim 1 or 2.

8. The preparation method of the Jin medicine compound sedative ointment that prolongs deep sleep and is non-addictive, as described in claim 7, is characterized in that... Includes the following steps: ① After crushing Chuanxiong, Yuanzhi and Baihe into powder, mix them together. Then, use 6 to 10 times the weight of the mixed drugs to perform low-temperature steam distillation on the mixed drugs. Collect the condensed distillate and then introduce the distillate for water-oil separation to collect the volatile oil. ② Mix the jujube seed, fleeceflower stem, mulberry, poria, anemarrhena and licorice with the residue after low-temperature steam distillation in step ①, add 8 to 12 times the weight of the mixed drugs in water, extract with ultrasound at 40 to 60°C 2 to 3 times, filter, each time for 30 to 60 minutes, and combine the extracts; ③ The combined extracts were concentrated under reduced pressure to a relative density of 1.15–1.25 g / ml (60℃) to obtain a clear extract; ④ The volatile oil obtained in step ① is encapsulated with β-cyclodextrin to obtain an encapsulated suspension of the volatile oil; ⑤ Add the inclusion suspension and clear ointment to the ointment base, stir and mix at a temperature below 60°C, and then collect the ointment.

9. The preparation method of the Jin medicine compound sedative ointment that prolongs deep sleep and is non-addictive according to claim 7, characterized in that, The temperature of the low-temperature steam distillation in step ① is less than 100℃.

10. The preparation method of the Jin medicine compound sedative ointment that prolongs deep sleep and is non-addictive according to claim 7, characterized in that, The ointment base in step ⑤ is made from refined honey and malt syrup.

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