Depression-resolving, fire-decreasing and mind-tranquilizing ointment formula and preparation method thereof

Abstract

The invention discloses a depression-relieving, fire-decreasing and mind-tranquilizing ointment formula and a preparation method thereof. The invention discloses a depression-relieving, fire-decreasing and mind-tranquilizing ointment formula. The traditional Chinese medicine composition comprises the following components in parts by weight: 5-15 parts of pericarpium citri reticulatae, 15-45 parts of poria cocos, 10-20 parts of rhizoma pinellinae praeparata, 5-15 parts of fructus aurantii immaturus, 5-15 parts of fructus chebulae, 10-20 parts of fried semen ziziphi spinosae, 3-10 parts of baked ginger, 5-15 parts of schisandra chinensis, 5-20 parts of angelica sinensis, 5-20 parts of raw rhizoma atractylodis macrocephalae, 3-15 parts of mangnolia officinalis, 5-20 parts of agastache rugosus, 3-10 parts of honey-fried licorice root, 5-15 parts of poria with hostwood, 5-15 parts of cassia twig, 5-15 parts of pericarpium citri reticulatae viride, 5-20 parts of rhizoma anemarrhenae, 5-20 parts of The traditional Chinese medicine is prepared from 15-45 parts of oyster, 5-20 parts of rhizoma acori graminei, 10-30 parts of radix ophiopogonis, 5-20 parts of radix salviae miltiorrhizae, 5-30 parts of rhizoma dioscoreae, 5-10 parts of herba menthae, 5-20 parts of radix paeoniae alba, 15-30 parts of light wheat, 5-15 parts of arillus longan and 100-200 parts of honey. The invention further provides a preparation method of the ointment capable of resolving depression, decreasing internal heat and tranquilizing mind. The traditional Chinese medicine composition is used for treating liver depression transforming fire and yin impairment and spleen deficiency, dampness obstruction and qi stagnation syndrome type chronic insomnia, and has the effects of soothing liver-qi stagnation, clearing away heart-fire, tonifying spleen, promoting qi circulation, reducing phlegm, soothing nerves, stabilizing mind and the like.

Description

Technical Field

[0001] The invention relates to a traditional Chinese medicine ointment for relieving depression, reducing internal heat and calming the mind, and in particular to an ointment for relieving depression, reducing internal heat and calming the mind, and a preparation method and application thereof. Background Art

[0002] Chronic insomnia refers to long-term difficulty sleeping that impairs daytime function. It is characterized by difficulty falling asleep, waking easily, waking early, and impaired sleep maintenance. According to statistics, insomnia is the most common sleep disorder worldwide, characterized by sleep disturbances, difficulty falling asleep, and frequent awakenings. Insomnia has become a widespread problem that seriously impacts public health. Its harmful effects not only lead to daytime fatigue, poor concentration, and decreased cognitive function, significantly reducing work and study efficiency and quality of life, but are also a significant risk factor for inducing or exacerbating anxiety, depression, cardiovascular disease, and other conditions.

[0003] Modern medical treatments primarily rely on sedative hypnotics (such as zopiclone, alprazolam, and diazepam) and antidepressants. While these can provide short-term relief for insomnia, long-term use carries significant drawbacks, including drug dependence, tolerance, next-day residual effects (such as drowsiness and dizziness), and cognitive impairment. In contrast, Traditional Chinese Medicine (TCM) demonstrates unique value through its synergistic compatibility, holistic conditioning, and multi-component, multi-target therapeutic approaches. Furthermore, the sustained-release properties of paste formulations enable steady and sustained drug release, effectively avoiding the dependency and withdrawal reactions common with Western medicine.

[0004] The inventors found in previous clinical practice research that there is a type of insomnia patients with liver depression transforming into fire and spleen deficiency causing phlegm obstruction and qi stagnation, which is especially common in Lingnan and Guangdong. Because Lingnan is located in a low-lying area with abundant rainfall, people living there often have spleen deficiency and dampness. In addition, the economy in Lingnan and Guangdong is relatively developed, the pace of life and work is fast, the work intensity is high, and people generally think and worry a lot. Those with liver qi disharmony are particularly common. How to create a safe, effective, easy-to-use, suitable for long-term use and conditioning Chinese medicine preparation for such high-pressure people in the workplace has become a technical problem that needs to be solved urgently. Summary of the Invention

[0005] The first purpose of the present invention is to provide a prescription for relieving depression, reducing fire and tranquilizing the mind for treating chronic insomnia of the type with liver depression transforming into fire and damaging yin, spleen deficiency and dampness blocking qi stagnation, and the prescription has the effects of soothing the liver and relieving depression, clearing the heart and reducing fire, strengthening the spleen and promoting qi and resolving phlegm, and calming the mind and stabilizing the spirit.

[0006] The second object of the present invention is to provide a method for preparing the above-mentioned depression-relieving, fire-reducing and mind-calming ointment.

[0007] To achieve the above object, the present invention adopts the following technical solutions:

[0008] A prescription for relieving depression, reducing fire and calming the mind, comprising the following components by weight: 5-15 parts of dried tangerine peel, 15-45 parts of poria, 10-20 parts of pinellia tuber, 5-15 parts of immature bitter orange, 5-15 parts of terminalia chebula, 10-20 parts of stir-fried spinach seeds, 3-10 parts of roasted ginger, 5-15 parts of schisandra chinensis, 5-20 parts of angelica sinensis, 5-20 parts of raw atractylodes macrocephala, 3-15 parts of magnolia bark, 5-20 parts of patchouli, 3-10 parts of radix scutellariae, 5-15 parts of poria, cassia twig 5-15 parts, 5-15 parts of green peel, 5-15 parts of anemarrhena, 5-20 parts of bupleurum, 10-20 parts of moutan bark, 3-10 parts of gardenia, 15-45 parts of dragon bone, 15-45 parts of oyster, 5-20 parts of calamus, 10-30 parts of ophiopogon, 5-20 parts of salvia miltiorrhiza, 5-30 parts of yam, 5-10 parts of mint, 5-20 parts of white peony root, 15-30 parts of floating wheat, 5-15 parts of longan meat, and 100-200 parts of honey.

[0009] Preferably, the following components are included in parts by weight: 5 parts of dried tangerine peel, 15 parts of Poria cocos, 10 parts of French Pinellia, 5 parts of Citrus aurantium, 5 parts of Terminalia chebula, 10 parts of stir-fried Ziziphus jujuba seeds, 3 parts of roasted ginger, 5 parts of Schisandra chinensis, 5 parts of Angelica sinensis, 5 parts of raw Atractylodes macrocephala, 3 parts of Magnolia officinalis, 5 parts of Patchouli, 3 parts of Radix Glycyrrhizae, 5 parts of Poria, 5 parts of cinnamon twig, 5 parts of Citrus aurantium, 5 parts of Anemarrhena asphodeloides, 5 parts of Bupleurum chinense, 10 parts of Cortex Moutan, 3 parts of Gardenia jasminoides, 15 parts of Dragon Bone, 15 parts of Oyster, 5 parts of Acorus calamus, 10 parts of Ophiopogon japonicus, 5 parts of Salvia miltiorrhiza, 5 parts of Chinese yam, 5 parts of mint, 5 parts of white peony root, 15 parts of floating wheat, 5 parts of longan meat, and 100 parts of honey.

[0010] Preferably, the invention comprises the following components in parts by weight: 10 parts of dried tangerine peel, 30 parts of Poria cocos, 150 parts of French pinellia, 10 parts of immature bitter orange, 10 parts of terminalia chebula, 15 parts of stir-fried spinach seeds, 3 parts of roasted ginger, 10 parts of schisandra chinensis, 10 parts of angelica sinensis, 10 parts of raw atractylodes macrocephala, 10 parts of Magnolia officinalis, 10 parts of Patchouli, 3 parts of roasted ginseng, 10 parts of poria, 10 parts of cinnamon twig, 10 parts of green peel, 15 parts of anemarrhena, 10 parts of bupleurum, 15 parts of moutan bark, 3 parts of gardenia, 30 parts of dragon bone, 30 parts of oyster, 10 parts of calamus, 20 parts of ophiopogon, 10 parts of salvia miltiorrhiza, 15 parts of yam, 5 parts of mint, 10 parts of white peony root, 20 parts of floating wheat, 10 parts of longan meat, and 150 parts of honey.

[0011] Preferably, the following components are included in parts by weight: 7.5 parts of dried tangerine peel, 22.5 parts of Poria cocos, 11.5 parts of French pinellia, 7.5 parts of immature bitter orange, 7.5 parts of terminalia chebula, 11.5 parts of stir-fried spinach seeds, 5 parts of roasted ginger, 7.5 parts of schisandra chinensis, 10 parts of angelica sinensis, 10 parts of raw atractylodes, 7.5 parts of Magnolia officinalis, 10 parts of Patchouli, 5 parts of roasted ginseng, 7.5 parts of Poria, 7.5 parts of cinnamon twig, 7.5 parts of green peel, 10 parts of Anemarrhena asphodeloides, 10 parts of Bupleurum chinense, 11.5 parts of Cortex Moutan, 5 parts of Gardenia jasminoides, 22.5 parts of dragon bone, 22.5 parts of oyster, 10 parts of Acorus calamus, 15 parts of Ophiopogon japonicus, 10 parts of Salvia miltiorrhiza, 12.5 parts of yam, 5 parts of mint, 10 parts of white peony root, 17.5 parts of floating wheat, 7.5 parts of longan meat, and 115 parts of honey.

[0012] Preferably, the following components are included in parts by weight: 12.5 parts of dried tangerine peel, 37.5 parts of Poria cocos, 17.5 parts of French pinellia, 12.5 parts of immature bitter orange, 12.5 parts of terminalia chebula, 17.5 parts of stir-fried spinach seeds, 7.5 parts of roasted ginger, 12.5 parts of schisandra chinensis, 15 parts of angelica sinensis, 15 parts of raw white atractylodes, 12.5 parts of magnolia bark, 15 parts of patchouli, 7.5 parts of radix scutellariae, and 12.5 parts of poria. , 12.5 parts of cinnamon twig, 12.5 parts of green peel, 15 parts of anemarrhena, 15 parts of bupleurum, 17.5 parts of moutan bark, 7.5 parts of gardenia, 37.5 parts of dragon bone, 37.5 parts of oyster, 15 parts of calamus, 25 parts of ophiopogon, 15 parts of salvia miltiorrhiza, 22.5 parts of yam, 7.5 parts of mint, 15 parts of white peony root, 27.5 parts of floating wheat, 12.5 parts of longan meat, and 190 parts of honey.

[0013] Preferably, the following components are included in parts by weight: 15 parts of dried tangerine peel, 45 parts of Poria cocos, 20 parts of French pinellia, 15 parts of immature bitter orange, 15 parts of Terminalia chebula, 20 parts of stir-fried spinach seeds, 10 parts of roasted ginger, 15 parts of Schisandra chinensis, 20 parts of angelica sinensis, 20 parts of raw Atractylodes macrocephala, 15 parts of Magnolia officinalis, 20 parts of Patchouli, 10 parts of roasted ginseng, 15 parts of Poria, 15 parts of cinnamon twig, 15 parts of Citrus aurantium, 20 parts of Anemarrhena asphodeloides, 20 parts of Bupleurum chinense, 20 parts of Cortex Moutan, 10 parts of Gardenia jasminoides, 45 parts of dragon bone, 45 parts of oyster, 20 parts of Acorus calamus, 30 parts of Ophiopogon japonicus, 20 parts of Salvia miltiorrhiza, 30 parts of Chinese yam, 10 parts of mint, 20 parts of white peony root, 30 parts of floating wheat, 15 parts of longan meat, and 200 parts of honey.

[0014] A method for preparing a prescription for relieving depression, reducing fire and calming the mind paste comprises the following steps:

[0015] 7.1 Weigh tangerine peel, Poria cocos, French pinellia, immature bitter orange, Terminalia chebula, roasted ginger, Schisandra chinensis, Chinese angelica, raw white atractylodes, Magnolia bark, Patchouli, roasted liquorice, Poria, cinnamon twig, green peel, Anemarrhena, Bupleurum, Cortex Moutan, Gardenia, Acorus calamus, Ophiopogon japonicus, Salvia miltiorrhiza, Chinese yam, white peony root, floating wheat, and longan meat together in proportion by weight and soak for 7-9 hours;

[0016] 7.2 Stir-fry the spinach seeds to extract the fat-soluble tranquilizing ingredients. Then, use water to extract the water-soluble ingredients from the filtered medicinal residue for later use.

[0017] 7.3 Crush the keel and oysters to less than 200 mesh and set aside;

[0018] 7.4 Place the soaked Chinese medicinal materials from step 7.1 in a pot together with the crushed dragon bones and oysters from step 7.3. Boil over low heat twice, each time for 1.3-1.7 hours. Add mint 7-13 minutes before the end of the second decoction.

[0019] 7.5 Add the water-soluble ingredients obtained in step 7.2 to the medicinal liquid obtained after decocting in step 7.4, and then filter it 2-3 times. Concentrate the filtrate until it becomes a clear paste in the shape of honeycomb balls. Simmer over low heat and add melted honey. Keep stirring and control the temperature at 70-80℃ until the paste is formed.

[0020] Preferably, the Poria cocos is subjected to vacuum freeze-drying technology before step 7.1 to retain its active ingredients;

[0021] In step 7.1, put dried tangerine peel, Poria cocos, French pinellia, immature bitter orange, Terminalia chebula, roasted ginger, Schisandra chinensis, Chinese angelica, raw white atractylodes, Magnolia bark, Patchouli, roasted liquorice, Poria, cinnamon twig, green peel, Anemarrhena asphodeloides, Bupleurum chinense, Cortex Moutan, Gardenia jasminoides, Acorus calamus, Ophiopogon japonicus, Salvia miltiorrhiza, Chinese yam, white peony root, floating wheat, and longan meat into a cloth bag and soak in purified water 6-8 times the weight of the medicinal materials in this step for 8 hours;

[0022] In step 7.2, a predetermined amount of stir-fried spinach seeds is weighed and subjected to a component extraction process using a combined alcohol extraction-water extraction process, namely, based on different solvent solubilities, first using an ethanol-water solution with a volume ratio of water to ethanol of 70% by volume at 70-80° C., wherein the weight ratio of the stir-fried spinach seeds to the ethanol-water solution is 1:8-10, reflux for 1.9-2.1 hours, and repeated twice, and then concentrated under reduced pressure at 55° C.-65° C. to remove alcohol to obtain the fat-soluble sedative component of the stir-fried spinach seeds; the spinach seeds residue after the fat-soluble sedative component is extracted is filtered and separated, and washed thoroughly with pure water until no ethanol residue is left, and then the spinach seeds residue is decocted with 6-8 times the weight of the spinach seeds residue at normal pressure of 90±2° C. for 1.4-1.6 hours to obtain the water-soluble component of the residue;

[0023] In step 7.3, the dragon bones and oysters were crushed to 200 mesh using ultrafine grinding technology as follows;

[0024] In step 7.4, simmer for 1.5 hours twice, adding mint 10 minutes before the end of the second simmering;

[0025] In step 7.5, filter 2-3 times with a sieve of 80 to 100 mesh. The paste is collected by using the standard of water droplets forming beads and hanging flags. After the paste is collected, it is packaged into sterilized glass bottles while hot and sterilized with high-pressure steam at 115℃-125℃ for 20-30 minutes. After the paste is cooled, it can be sealed.

[0026] The depression-relieving, fire-reducing and mind-calming ointment of the present invention can be used for treating chronic insomnia of liver depression-fire-damaging yin, spleen deficiency-dampness-blocking and qi stagnation syndrome, etc.

[0027] The beneficial effects of the present invention are as follows:

[0028] The Chinese medicine paste of the present invention has suitable medicinal materials and compatibility, conforms to the theories of traditional Chinese medicine and modern medicine, and has the effects of soothing the liver and relieving depression, clearing the heart and reducing fire, strengthening the spleen and promoting qi circulation and resolving phlegm, and calming the mind. In the theory of traditional Chinese medicine, due to imbalance of yin and yang, malnutrition of the mind, combined with spleen deficiency and dampness blocking qi stagnation, liver qi stagnation, emotional stagnation, depression and fire damage to yin, disturbing the mind, and ultimately manifesting as difficulty falling asleep, irritability and dreaminess. Therefore, in the treatment of this syndrome of liver depression turning into fire and damaging yin, spleen deficiency and dampness blocking qi stagnation, it is necessary to regulate the qi mechanism in combination with clearing fire and nourishing yin, strengthening the spleen and removing dampness to calm the mind, and focusing on strengthening the spleen and promoting qi circulation and resolving phlegm, and comprehensively treating the complexity of the pathogenesis to achieve both symptomatic and root cause treatment, which should have a better effect.

[0029] The paste prescription formed by the above-mentioned Chinese medicine combination of the present invention can soothe the liver, clear away heat, calm the mind and stabilize the spirit, and has both the functions of invigorating the spleen, promoting qi circulation and resolving phlegm and dampness, and is effective in treating insomnia caused by various liver depression, qi stagnation, fire transformation and spleen earth generating phlegm and dampness. Compared with the single liver-clearing and heat-clearing, spleen-invigorating, blood-tonifying and heart-nourishing or heart-kidney-connecting Chinese patent medicines sold on the market, this combination takes into account the pathogenesis of spleen deficiency and dampness obstructing the spirit in Lingnan area of ​​Guangdong Province, and specifically uses dried tangerine peel, Poria cocos, Pinellia ternata, Terminalia chebula, Magnolia officinalis, and Citrus aurantium to invigorate the spleen and promote qi circulation, warm and dry to resolve phlegm and dampness, reduce the interference of phlegm and dampness on the spirit and make it difficult to fall asleep. The monarch medicine in this paste prescription is selected from Bupleurum chinense to soothe the liver and relieve depression, Gardenia jasminoides to clear away the stagnant fire of the triple burner, and Cortex Moutan to clear heat and cool blood, and is combined with Dragon Bone and Oyster to calm the mind, suppress yang and stabilize the spirit, which are the main forces. The auxiliary herbs, stir-fried Ziziphus jujuba seeds, nourish the heart and calm the mind, Poria cocos calms the heart and calms palpitations, and Schisandra chinensis calms the mind and helps the main herb calm the mind; Pinellia ternata dries dampness and resolves phlegm, Acorus gramineus resolves phlegm and opens the orifices, and Citrus aurantium and Citrus aurantium dissolve qi and relieve depression, helping the main herb resolve depression and resolve phlegm. A comprehensive adjuvant system is used: Anemarrhena rhizome nourishes yin and reduces heat, Ophiopogon japonicus moistens dryness and promotes fluid production, and Angelica sinensis and White Peony Root nourish blood and soften the liver to address the root cause. Raw Atractylodes macrocephala and Chinese yam strengthen the spleen and replenish qi to prevent cold and dampness in the middle, Tangerine peel and Magnolia officinalis regulate qi and eliminate dampness, and Patchouli invigorates the spleen and clears turbidity to regulate the middle burner. Roasted ginger and cinnamon warm the middle and protect the stomach, preventing excessive coldness from heat-clearing herbs. Salvia miltiorrhiza activates blood circulation and relieves restlessness, Wheat Flos astringes sweat and eliminates heat, Longan flesh nourishes blood and nourishes the heart, Terminalia chebula astringes the lungs and prevents dryness, and Mentha arvense clears heat and relieves depression, treating both symptoms. The auxiliary herb, roasted licorice, harmonizes the herbs, while honey moisturizes and corrects the flavor, helps the paste form, and harmonizes the medicinal properties. The whole formula works synergistically through multiple targets to relieve liver depression, clear away heat and reduce fire, nourish yin and blood, calm the mind and nourish the heart and soften the liver. It targets the pathogenesis of insomnia caused by liver depression turning into fire and internal disturbance of deficiency heat, and can effectively improve symptoms such as difficulty falling asleep, shallow sleep and easy awakening, frequent dreams, irritability and palpitations.

[0030] In addition, the Chinese medicine composition of the present invention has a safe and reliable formulation of Chinese medicine raw materials, low technical risk, broad market demand, and obvious economic and social benefits. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0032] Figure 1a Schematic diagram of the righting experiment results of the sleep latency of mice in the present invention;

[0033] Figure 1b Schematic diagram of the righting experiment results of the sleep duration of each mouse in the present invention;

[0034] Figure 2a This is a schematic diagram of the open field test analysis of the total distance each mouse enters the central area after drug administration in the present invention;

[0035] Figure 2b This is a schematic diagram of the open field test analysis of the number of times each mouse entered the central area after drug administration in the present invention;

[0036] Figure 2c A schematic diagram of the open field test analysis of the time taken by each mouse to enter the central area after drug administration in the present invention; and

[0037] Figure 3 Schematic diagram of the analysis of the experimental results of novel object recognition by each mouse in the present invention;

[0038] Figure 4 This is a graph comparing the effects of the Jieyu Jianghuo Ningshen ointment of the present invention and the corresponding ancient prescription in a new object recognition experiment in mice after administration;

[0039] Figure 5 This is a graph comparing the effects of the Jieyu Jianghuo Ningshen ointment prescription of the present invention and the corresponding ancient prescription in the experiment of correcting the end latency time of mice after administration;

[0040] Figure 6 This is a comparative diagram of the effects of the Jieyu Jianghuo Ningshen ointment prescription of the present invention and the corresponding ancient prescription on the corrected end-of-sleep time of mice after administration;

[0041] Figure 7 This is a graph comparing the effects of the Jieyu Jianghuo Ningshen ointment of the present invention and the corresponding ancient prescription in an open field test on the number of times mice entered the central area after being administered with the ointment;

[0042] Figure 8 This is a graph comparing the time it takes for mice to enter the central area after being administered the Jieyu Jianghuo Ningshen ointment of the present invention and the corresponding ancient prescription in an open field experiment;

[0043] Figure 9This is a comparative effect diagram of the open field experiment on the total distance mice traveled into the central area after being administered the relieving depression, reducing fire and calming the mind ointment formula of the present invention and the corresponding ancient formula.

[0044] Explanation of the accompanying symbols: * represents P<0.1, ** represents P<0.01, *** represents P<0.001, and **** represents P<0.0001. DETAILED DESCRIPTION

[0045] The following is a clear and complete description of the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0046] A prescription for relieving depression, reducing fire and calming the mind, comprising the following components by weight: 5-15 parts of dried tangerine peel, 15-45 parts of poria, 10-20 parts of pinellia tuber, 5-15 parts of immature bitter orange, 5-15 parts of terminalia chebula, 10-20 parts of stir-fried spinach seeds, 3-10 parts of roasted ginger, 5-15 parts of schisandra chinensis, 5-20 parts of angelica sinensis, 5-20 parts of raw atractylodes macrocephala, 3-15 parts of magnolia bark, 5-20 parts of patchouli, 3-10 parts of radix scutellariae, 5-15 parts of poria, cassia twig 5-15 parts, 5-15 parts of green peel, 5-15 parts of anemarrhena, 5-20 parts of bupleurum, 10-20 parts of moutan bark, 3-10 parts of gardenia, 15-45 parts of dragon bone, 15-45 parts of oyster, 5-20 parts of calamus, 10-30 parts of ophiopogon, 5-20 parts of salvia miltiorrhiza, 5-30 parts of yam, 5-10 parts of mint, 5-20 parts of white peony root, 15-30 parts of floating wheat, 5-15 parts of longan meat, and 100-200 parts of honey.

[0047] A method for preparing a prescription for relieving depression, reducing fire and calming the mind paste comprises the following steps:

[0048] 7.1 Weigh tangerine peel, Poria cocos, French pinellia, immature bitter orange, Terminalia chebula, roasted ginger, Schisandra chinensis, Chinese angelica, raw white atractylodes, Magnolia bark, Patchouli, roasted liquorice, Poria, cinnamon twig, green peel, Anemarrhena, Bupleurum, Cortex Moutan, Gardenia, Acorus calamus, Ophiopogon japonicus, Salvia miltiorrhiza, Chinese yam, white peony root, floating wheat, and longan meat together in proportion by weight and soak for 7-9 hours;

[0049] 7.2 Stir-fry the spinach seeds to extract the fat-soluble tranquilizing ingredients. Then, use water to extract the water-soluble ingredients from the filtered medicinal residue for later use.

[0050] 7.3 Crush the keel and oysters to less than 200 mesh and set aside;

[0051] 7.4 Place the soaked Chinese medicinal materials from step 7.1 in a pot together with the crushed dragon bones and oysters from step 7.3. Boil over low heat twice, each time for 1.3-1.7 hours. Add mint 7-13 minutes before the end of the second decoction.

[0052] 7.5 Add the water-soluble ingredients obtained in step 7.2 to the medicinal liquid obtained after decocting in step 7.4, and then filter it 2-3 times. Concentrate the filtrate until it becomes a clear paste in the shape of honeycomb balls. Simmer over low heat and add melted honey. Keep stirring and control the temperature at 70-80℃ until the paste is formed.

[0053] Preferably, the Poria cocos is subjected to vacuum freeze drying technology before step 7.1 to retain its active ingredients, wherein the vacuum freeze drying technology is used to dehydrate the medicinal material by low-temperature freezing and vacuum sublimation, thereby maximally retaining the active ingredients of the traditional Chinese medicine;

[0054] In step 7.1, put dried tangerine peel, Poria cocos, French pinellia, immature bitter orange, Terminalia chebula, roasted ginger, Schisandra chinensis, Chinese angelica, raw white atractylodes, Magnolia bark, Patchouli, roasted liquorice, Poria, cinnamon twig, green peel, Anemarrhena asphodeloides, Bupleurum chinense, Cortex Moutan, Gardenia jasminoides, Acorus calamus, Ophiopogon japonicus, Salvia miltiorrhiza, Chinese yam, white peony root, floating wheat, and longan meat into a cloth bag and soak in purified water 6-8 times the weight of the medicinal materials in this step for 8 hours;

[0055] In step 7.2, a predetermined amount of stir-fried spinach seeds is weighed and subjected to a component extraction process using an alcohol extraction-water extraction combined process. That is, based on the different solubility of the solvent, an ethanol-water solution having a volume ratio of water to ethanol of 70% is first used for heating and reflux extraction at 70-80° C., wherein the weight ratio of the stir-fried spinach seeds to the ethanol-water solution is 1:8-10, and the process is refluxed for 1.9-2.1 hours, for example, 1.9, 2.0, or 2.1 hours, repeated twice, and then concentrated under reduced pressure at 55° C.-65° C. to remove the alcohol to obtain the fat-soluble sedative component of the stir-fried spinach seeds. , for example: 55℃ or 60℃ or 65℃; after extracting the fat-soluble tranquilizing components, the Chinese jujube seed residue is filtered and separated and fully washed with pure water until no ethanol residue is left, and then the Chinese jujube seed residue is decocted with 6-8 times the weight of pure water of the Chinese jujube seed residue at normal pressure and 90±2℃ for 1.4-1.6 hours to obtain the water-soluble components of the residue, for example: 1.4 or 1.5 or 1.6 hours; wherein, the alcohol extraction-water extraction combined process is adopted, and the effective components of different polarities in the traditional Chinese medicine can be extracted by different solvent solubilities, thereby achieving efficient and comprehensive extraction;

[0056] In step 7.3, dragon bones and oysters are crushed to 200 mesh using ultrafine grinding technology to promote absorption;

[0057] In step 7.4, simmer for 1.5 hours twice, adding mint 10 minutes before the end of the second simmering;

[0058] In step 7.5, filter 2-3 times with a sieve of 80 to 100 mesh, for example 80, 90 or 100 mesh. The paste is collected by using the standards of water droplets forming beads and hanging flags. After the paste is collected, it is packaged into sterilized glass bottles while hot and sterilized by high-pressure steam at 115℃-125℃ for 20-30 minutes. After the paste is cooled, it can be sealed.

[0059] In addition, the quality control standards are as follows (relative density: tonic pastes ≥1.40 (25°C): heat-clearing pastes ≥1.35; microbial limits: total colony count ≤100CFU / g, mold and yeast ≤10CFU / g, no pathogenic bacteria shall be detected; heavy metals and pesticide residues: lead ≤5mg / kg, cadmium ≤0.3mg / kg, pesticide residues shall comply with the requirements of the "Quality Management Standards for the Production of Chinese Medicinal Materials"). After passing the standards, they can be stored.

[0060] The depression-relieving, fire-reducing and mind-calming ointment of the present invention can be used for treating chronic insomnia of liver depression, fire-transforming and yin-damaging syndrome, spleen deficiency, dampness-blocking and qi stagnation syndrome and the like.

[0061] Among them, the present invention has a 5 preferred formulas of a remedy for relieving depression, reducing fire and calming the mind. The preferred formulas and preparation methods are as follows:

[0062] Preferred formula 1, a prescription for relieving depression, reducing fire and tranquilizing the mind, weighed by weight: 5 parts of dried tangerine peel, 15 parts of Poria cocos, 10 parts of French Pinellia, 5 parts of Citrus aurantium, 5 parts of Terminalia chebula, 10 parts of stir-fried Ziziphus jujuba seeds, 3 parts of roasted ginger, 5 parts of Schisandra chinensis, 5 parts of Angelica sinensis, 5 parts of raw Atractylodes macrocephala, 3 parts of Magnolia officinalis, 5 parts of Patchouli, 3 parts of roasted Glycyrrhiza uralensis, 5 parts of Poria, 5 parts of cinnamon twig, 5 parts of Citrus aurantium, 5 parts of Anemarrhena asphodeloides, 5 parts of Bupleurum chinense, 10 parts of Cortex Moutan, 3 parts of Gardenia jasminoides, 15 parts of Dragon Bone, 15 parts of Oyster, 5 parts of Acorus calamus, 10 parts of Ophiopogon japonicus, 5 parts of Salvia miltiorrhiza, 5 parts of Chinese yam, 5 parts of mint, 5 parts of white peony root, 15 parts of floating wheat, 5 parts of longan meat, and 100 parts of honey.

[0063] The preparation method is as follows:

[0064] Except for the stir-fried sour jujube seeds, dragon bones, oysters, mint and honey, weigh the remaining herbs in proportion and put them into a cloth bag. Add 6-8 times the weight of the herbs in purified water and soak for 8 hours. Extract the stir-fried sour jujube seeds with 70% alcohol and then with water. Bag the mint separately for later use.

[0065] After soaking, decoct the herbs (including ultra-finely ground dragon bones and oysters) twice (about 1.5 hours each time, over a gentle heat). Add the mint 10 minutes before the end of the second decoction. Filter the combined liquid three times through an 80- to 100-mesh sieve, such as an 80-, 90-, or 100-mesh sieve, until it becomes a clear, honeycomb-like paste. Reduce heat to a gentle simmer and add melted honey (control the temperature below 80°C). The paste should be thick enough to form beads or a flag-like consistency.

[0066] While hot, divide the mixture into sterilized bottles, sterilize under high pressure at 121℃ for 30 minutes, cool and seal, and store after passing quality inspection.

[0067] Preferred formula 2, a prescription for relieving depression, reducing fire and tranquilizing the mind, weighed by weight: 10 parts of dried tangerine peel, 30 parts of Poria cocos, 150 parts of French pinellia, 10 parts of immature bitter orange, 10 parts of Terminalia chebula, 15 parts of stir-fried spinach seeds, 3 parts of roasted ginger, 10 parts of Schisandra chinensis, 10 parts of Angelica sinensis, 10 parts of raw Atractylodes macrocephala, 10 parts of Magnolia officinalis, 10 parts of Patchouli, 3 parts of roasted ginseng, 10 parts of Poria, 10 parts of cinnamon twig, 10 parts of Citrus aurantium, 15 parts of Anemarrhena asphodeloides, 10 parts of Bupleurum chinense, 15 parts of Cortex Moutan, 3 parts of Gardenia jasminoides, 30 parts of Dragon Bone, 30 parts of Oyster, 10 parts of Acorus calamus, 20 parts of Ophiopogon japonicus, 10 parts of Salvia miltiorrhiza, 15 parts of Chinese yam, 5 parts of mint, 10 parts of white peony root, 20 parts of floating wheat, 10 parts of longan meat, and 150 parts of honey.

[0068] The preparation method is as follows:

[0069] Except for the stir-fried sour jujube seeds, dragon bones, oysters, mint and honey, weigh the remaining herbs in proportion and put them into a cloth bag. Add 6-8 times the weight of the herbs in purified water and soak for 8 hours. Extract the stir-fried sour jujube seeds with 70% alcohol and then with water. Bag the mint separately for later use.

[0070] After soaking, decoct the herbs (including ultra-finely ground dragon bones and oysters) twice (about 1.5 hours each time, over a gentle heat). Add the mint 10 minutes before the end of the second decoction. Filter the combined liquid through an 80- to 100-mesh sieve three times until it becomes a honeycomb-like paste. Simmer the mixture over a gentle heat (control the temperature below 80°C) and add the melted honey. Set the paste until it forms beads or resembles a flag.

[0071] While hot, divide the mixture into sterilized bottles, sterilize under high pressure at 121℃ for 30 minutes, cool and seal, and store after passing quality inspection.

[0072] Preferred formula 3, a prescription for relieving depression, reducing fire and tranquilizing the mind, weighed in parts by weight: 7.5 parts of dried tangerine peel, 22.5 parts of Poria cocos, 11.5 parts of French pinellia, 7.5 parts of immature bitter orange, 7.5 parts of terminalia chebula, 11.5 parts of stir-fried spinach seeds, 5 parts of roasted ginger, 7.5 parts of schisandra chinensis, 10 parts of raw atractylodes, 7.5 parts of Magnolia officinalis, 10 parts of Patchouli, 5 parts of roasted ginseng, 7.5 parts of Poria, 7.5 parts of cinnamon twig, 7.5 parts of green peel, 10 parts of Anemarrhena asphodeloides, 10 parts of Bupleurum chinense, 11.5 parts of Cortex Moutan, 5 parts of Gardenia jasminoides, 22.5 parts of dragon bone, 22.5 parts of oyster, 10 parts of Acorus calamus, 15 parts of Ophiopogon japonicus, 10 parts of Salvia miltiorrhiza, 12.5 parts of yam, 5 parts of mint, 10 parts of white peony root, 17.5 parts of floating wheat, 7.5 parts of longan meat, and 115 parts of honey.

[0073] The preparation method is as follows:

[0074] Except for the stir-fried sour jujube seeds, dragon bones, oysters, mint and honey, weigh the remaining herbs in proportion and put them into a cloth bag. Add 6-8 times the weight of the herbs in purified water and soak for 8 hours. Extract the stir-fried sour jujube seeds with 70% alcohol and then with water. Bag the mint separately for later use.

[0075] After soaking, decoct the herbs (including ultra-finely ground dragon bones and oysters) twice (about 1.5 hours each time, over a gentle heat). Add the mint 10 minutes before the end of the second decoction. Filter the combined liquid through an 80- to 100-mesh sieve three times, concentrating it into a honeycomb-like paste. Simmer the mixture over a gentle heat (control the temperature below 80°C) and add the melted honey. Set the paste until it forms beads or resembles a flag.

[0076] While hot, divide the mixture into sterilized bottles, sterilize under high pressure at 121℃ for 30 minutes, cool and seal, and store after passing quality inspection.

[0077] Preferred formula 4, a relieving depression, reducing fire and calming the mind ointment prescription, weighed according to weight: 12.5 parts of dried tangerine peel, 37.5 parts of Poria cocos, 17.5 parts of French pinellia, 12.5 parts of immature bitter orange, 12.5 parts of terminalia chebula, 17.5 parts of stir-fried spinach seeds, 7.5 parts of roasted ginger, 12.5 parts of schisandra chinensis, 15 parts of angelica, 15 parts of raw white atractylodes, 12.5 parts of Magnolia officinalis, 15 parts of Patchouli, 7.5 parts of roasted ginseng, Poria 12.5 parts of Chinese wolfberry, 12.5 parts of cinnamon twig, 12.5 parts of green peel, 15 parts of anemarrhena, 15 parts of bupleurum, 17.5 parts of moutan bark, 7.5 parts of gardenia, 37.5 parts of dragon bone, 37.5 parts of oyster, 15 parts of calamus, 25 parts of ophiopogon, 15 parts of salvia miltiorrhiza, 22.5 parts of yam, 7.5 parts of mint, 15 parts of white peony root, 27.5 parts of floating wheat, 12.5 parts of longan meat, and 190 parts of honey.

[0078] The preparation method is as follows:

[0079] Except for the stir-fried sour jujube seeds, dragon bones, oysters, mint and honey, weigh the remaining herbs in proportion and put them into a cloth bag. Add 6-8 times the weight of the herbs in purified water and soak for 8 hours. Extract the stir-fried sour jujube seeds with 70% alcohol and then with water. Bag the mint separately for later use.

[0080] After soaking, decoct the herbs (including ultra-finely ground dragon bones and oysters) twice (about 1.5 hours each time, over a gentle heat). Add the mint 10 minutes before the end of the second decoction. Filter the combined liquid through an 80- to 100-mesh sieve three times, concentrating it into a honeycomb-like paste. Simmer the mixture over a gentle heat (control the temperature below 80°C) and add the melted honey. Set the paste until it forms beads or resembles a flag.

[0081] While hot, divide the mixture into sterilized bottles, sterilize under high pressure at 121℃ for 30 minutes, cool and seal, and store after passing quality inspection.

[0082] Preferred formula 5, a prescription for relieving depression, reducing fire and tranquilizing the mind, weighed by weight: 15 parts of dried tangerine peel, 45 parts of Poria cocos, 20 parts of French pinellia, 15 parts of immature bitter orange, 15 parts of Terminalia chebula, 20 parts of stir-fried spinach seeds, 10 parts of roasted ginger, 15 parts of Schisandra chinensis, 20 parts of angelica sinensis, 20 parts of raw Atractylodes macrocephala, 15 parts of Magnolia officinalis, 20 parts of Patchouli, 10 parts of roasted ginseng, 15 parts of Poria, 15 parts of cinnamon twig, 15 parts of Citrus aurantium, 20 parts of Anemarrhena asphodeloides, 20 parts of Bupleurum chinense, 20 parts of Cortex Moutan, 10 parts of Gardenia jasminoides, 45 parts of dragon bones, 45 parts of oyster, 20 parts of Acorus calamus, 30 parts of Ophiopogon japonicus, 20 parts of Salvia miltiorrhiza, 30 parts of Chinese yam, 10 parts of mint, 20 parts of white peony root, 30 parts of floating wheat, 15 parts of longan meat, and 200 parts of honey.

[0083] The preparation method is as follows:

[0084] Except for the stir-fried sour jujube seeds, dragon bones, oysters, mint and honey, weigh the remaining herbs in proportion and put them into a cloth bag. Add 6-8 times the weight of the herbs in purified water and soak for 8 hours. Extract the stir-fried sour jujube seeds with 70% alcohol and then with water. Bag the mint separately for later use.

[0085] After soaking, decoct the herbs (including ultra-finely ground dragon bones and oysters) twice (about 1.5 hours each time, over a gentle heat). Add the mint 10 minutes before the end of the second decoction. Filter the combined liquid through an 80- to 100-mesh sieve three times, concentrating it into a honeycomb-like paste. Simmer the mixture over a gentle heat (control the temperature below 80°C) and add the melted honey. Set the paste until it forms beads or resembles a flag.

[0086] While hot, divide the mixture into sterilized bottles, sterilize under high pressure at 121℃ for 30 minutes, cool and seal, and store after passing quality inspection.

[0087] Typical Case 1

[0088] The intervention and effects of the Jieyu Jianghuo Ningshen ointment of the present invention on insomnia model mice are as follows:

[0089] 1 Materials and Methods

[0090] 1.1 Experimental Animals

[0091] Sixty healthy, SPF-grade, male C57BL / 6J mice (18 ± 2 g), aged 4-6 weeks, were housed at 24 ± 2°C and 50%-65% relative humidity. They were housed in cages with free access to food and water throughout the study, and maintained on a 12-hour light / dark cycle. The animals were acclimated for 7 days before the experiment. This study was approved by the Shenzhen Zhongxun Precision Medicine Research Institute.

[0092] 1.2 Investigational Drugs

[0093] The depression-relieving, fire-reducing and mind-calming ointment of the present invention is prepared according to the method described in the preferred formula 2. When administered, it is prepared into a solution with purified water.

[0094] Depression-relieving, fire-reducing and tranquilizing ointment: 10 parts of dried tangerine peel, 30 parts of Poria cocos, 150 parts of French pinellia, 10 parts of immature bitter orange, 10 parts of terminalia chebula, 15 parts of stir-fried spinach seeds, 3 parts of roasted ginger, 10 parts of schisandra chinensis, 10 parts of angelica sinensis, 10 parts of raw atractylodes macrocephala, 10 parts of magnolia bark, 10 parts of patchouli, 3 parts of roasted scutellaria baicalensis, 10 parts of poria, 10 parts of cinnamon twig, 10 parts of green peel, 15 parts of anemarrhena, 10 parts of bupleurum, 15 parts of moutan bark, 3 parts of gardenia, 30 parts of dragon bone, 30 parts of oyster, 10 parts of calamus, 20 parts of ophiopogon, 10 parts of salvia miltiorrhiza, 15 parts of yam, 5 parts of mint, 10 parts of white peony root, 20 parts of floating wheat, 10 parts of longan meat, and 150 parts of honey.

[0095] Weigh the remaining medicinal ingredients, except for the stir-fried spinach seeds, dragon bones, oysters, mint, and honey, in appropriate proportions and place them in a cloth bag. Soak the bag in purified water (6-8 times the weight of the ingredients) for 8 hours. Extract the stir-fried spinach seeds separately with 70% alcohol and then with water. Bag the mint separately for later use. After soaking, decoct the ingredients twice, adding the mint 10 minutes before the end of the second decoction. Filter the combined solution three times through an 80- to 100-mesh sieve and concentrate it into a honeycomb-like paste. Reduce heat to low and add the melted honey to dissolve the paste. Prepare the solution with purified water for administration.

[0096] 1.3 Grouping and modeling

[0097] Ten mice were randomly selected as the normal group, and the rest were model groups. The mice were randomly divided into the following three groups, with 10 mice in each group: model group, diazepam group, and Jieyujianghuoningao group.

[0098] This study used a modified chlorophenylalanine combined with chronic unpredictable mild stress model to establish an insomnia mouse model. Adaptive feeding was performed for 7 days. After the adaptation period, starting on the 8th day, all model group mice were exposed to chronic unpredictable mild stress stimulation for 6 weeks. One of the following stimulation methods was performed daily, including forced swimming, wet bedding, food and water deprivation, strong light stroboscopic stimulation, and light-dark reversal cycle. Starting from the 49th day, except for the normal group, all groups of mice were intraperitoneally injected with PCPA (350 mg / kg) every morning for 3 consecutive days. The normal group of mice was placed in the home cage and raised normally to ensure adequate sleep conditions. During the modeling period, all rats had free access to basic feed and distilled water. When the model mice showed typical characteristics such as curling up, lack of security, listlessness, withered fur, reduced food and water intake, and obvious stress response when grasping, it indicated that the model was successful.

[0099] 1.4 Administration

[0100] On the 52nd day, the mice in the Jieyujianghuoningshen ointment group and the diazepam group were given the designated dose for 7 days, and the control group and the model group received an equal amount of normal saline by gavage.

[0101] 1.5 Behavioral testing

[0102] (1) Righting experiment

[0103] After modeling, mice in each group were intraperitoneally injected with 30 mg / kg sodium pentobarbital. Mice were placed on a flat surface with their abdomen facing upward and their bodies held vertically. The time from the time of intraperitoneal injection to the loss of the righting reflex was considered sleep latency. If the mouse turned over more than twice within 60 seconds, the righting reflex was considered recovered. The time from the loss of the righting reflex to the recovery of the righting reflex was considered sleep duration.

[0104] (2) Open field test

[0105] Place the mouse in the center square of an open box (the size of the open box is 100 cm long x 100 cm wide x 40 cm high), use a counter to manually count the number of squares each mouse crosses horizontally within 5 minutes, record the time and number of times the mouse enters the central area, and calculate the total distance the mouse travels.

[0106] (3) New object recognition experiment

[0107] Two objects, A and B, of different shapes and colors, were placed in a chamber, 25 cm apart. On the first day, mice were allowed to acclimate to the chamber for 20 minutes. The two objects were identical (both objects were A). One hour later, object A on the left side was replaced with object B, and the time the mice spent in contact with A and B within a 5-minute period was recorded. After 24 hours, object A on the right side was replaced with object B, and the time the mice spent in contact with A and B within a 5-minute period was recorded.

[0108] 1.6 Statistical methods

[0109] SPSS 23.0 statistical software was used for data processing, and one-way analysis of variance was used to compare data among the groups. P < 0.05 was considered statistically significant.

[0110] 2 Results

[0111] 2.1 Results of the Reversal Experiment

[0112] See Figure 1a-Figure 1b The results of the righting test showed that compared with the control group, the sleep latency time of the mice in the model group was prolonged and the sleep time was shortened, and the differences were statistically significant (P < 0.05). After taking the medicine, the latency time of the mice in the Jieyu Jianghuo Ningshen Paste group and the diazepam group was significantly shortened, and the difference was statistically significant (P < 0.05); the sleep time was also significantly prolonged, and the difference was statistically significant (P < 0.05), indicating that the Jieyu Jianghuo Ningshen Paste prescription has a sedative and tranquilizing effect.

[0113] 2.2 Open field test results

[0114] See Figure 2a 、 Figure 2b 、 Figure 2cThe results of the exercise showed that the total distance traveled, the number of times the mice entered the central area, and the time they stayed in the central area in the model group were significantly lower than those in the control group. The total distance traveled by the mice in the Jieyu Jianghuo Ningshen Paste group and the diazepam group was significantly increased (P < 0.05). The number of times the mice in the Jieyu Jianghuo Ningshen Paste group entered the central area was significantly increased (P < 0.05); the time the mice in the Jieyu Jianghuo Ningshen Paste group spent in the central area was significantly increased (P < 0.05). Compared with the model group, the total distance traveled, the number of times the mice entered the central area, and the time they stayed in the central area in the Jieyu Jianghuo Ningshen Paste group were significantly increased, indicating that the Jieyu Jianghuo Ningshen Paste formula can increase the spontaneous activity of mice and relieve their anxiety.

[0115] 2.3 Experimental results of new object recognition

[0116] See Figure 3 The results of the novel object recognition experiment showed that the novel object recognition index of mice in the model group was significantly lower than that in the control group, while the novel object recognition index in the Jieyu Jianghuo Ningshen Paste and diazepam groups was significantly higher (P < 0.05). The novel object recognition index of the Jieyu Jianghuo Ningshen Paste and diazepam groups was higher than that in the model group, indicating that the Jieyu Jianghuo Ningshen Paste prescription helps improve learning and recognition abilities.

[0117] In summary, the effects and advantages of the present invention are as follows:

[0118] (1) The present invention provides a paste formula for treating insomnia of the liver depression transforming into fire and damaging yin, spleen deficiency and dampness blocking qi stagnation type.

[0119] (2) The paste formula of the present invention has a unique effect: the main medicine is selected from Bupleurum chinense to relieve liver depression, Gardenia jasminoides to clear away triple-burner fire, and Cortex moutan to clear heat and cool blood, and Dragon Bone and Oyster to calm the mind and suppress yang, which are the main ingredients. The auxiliary medicines are stir-fried Ziziphus jujuba seeds to nourish the heart and calm the mind, Poria cocos to calm the heart and calm palpitations, and Schisandra chinensis to calm the soul and calm the mind, which help the main medicine to calm the mind; Pinellia ternata to dry dampness and resolve phlegm, Acorus gramineus to resolve phlegm and open the mind, and Citrus aurantium and Citrus aurantium to break up qi and eliminate depression, which help the main medicine to resolve depression and resolve phlegm. The adjuvant system is meticulously designed: Anemarrhena nourishes yin and reduces internal heat, Ophiopogon japonicus moistens dryness and promotes fluid production, while Angelica sinensis and White Peony Root nourish blood and soften the liver to address the underlying cause. Raw Atractylodes macrocephala and Chinese yam strengthen the spleen and replenish qi, preventing cold and dampness-induced damage to the middle burner. Tangerine peel and Magnolia officinalis regulate qi and eliminate dampness, while Patchouli invigorates the spleen, clears turbidity, and regulates the middle burner. Roasted ginger and cinnamon twig warm the middle burner and protect the stomach, preventing excessive coldness from heat-clearing drugs. Salvia miltiorrhiza activates blood circulation and relieves restlessness, while Wheat Flos astringes sweat, consolidates and eliminates heat. Longan flesh nourishes blood and nourishes the heart, Terminalia chebula astringes the lungs and prevents dryness, while Mentha penetrates heat, relieves depression, and treats concurrent symptoms. Roasted licorice root harmonizes the various herbs, while honey moistens dryness, corrects the flavor, aids in the paste's formation, and harmonizes the medicinal properties. The formula, through its multi-targeted synergistic actions of soothing the liver and relieving depression, nourishing yin, clearing heat, and reducing internal heat, strengthening the spleen and resolving phlegm, and nourishing blood and calming the mind, addresses the pathogenesis of insomnia caused by liver stagnation transforming into internal heat, internal disturbances of deficiency-heat, and spleen deficiency and dampness, effectively improving symptoms such as difficulty falling asleep, shallow sleep, frequent dreams, irritability, and palpitations.

[0120] (3) Animal experiments show that the prescription of the present invention has the effects of significantly shortening the time to fall asleep, prolonging the sleep duration, improving cognitive function, improving anxiety symptoms, and relieving fatigue in insomnia model mice. The effect is remarkable. It is precisely because the present invention has the effects of soothing the liver and relieving depression, clearing the heart and reducing fire, strengthening the spleen and promoting qi and resolving phlegm, and calming the mind that the prescription of the present invention has the effects of significantly shortening the time to fall asleep, prolonging the sleep duration, improving cognitive function, improving anxiety symptoms, and relieving fatigue in insomnia model mice.

[0121] (4) The paste formula of the present invention is highly safe, has no toxic side effects, is easy to take, does not require decocting, is easy to store and carry, is suitable for long-term use, and has the effect of conditioning the body.

[0122] Typical Case 2

[0123] The results of the comparison of the intervention and effect of the Jieyu Jianghuo Ningshen ointment of the present invention on insomnia model mice with the intervention and effect of traditional Chinese medicine prescriptions such as Danzhi Xiaoyao Pills, Chaihu Shugan Pills, and Yueju Pills on insomnia model mice are as follows:

[0124] 1 Materials and Methods

[0125] 1.1 Experimental Animals

[0126] Sixty healthy, SPF-grade, male C57BL / 6J mice (18 ± 2 g), aged 4-6 weeks, were housed at 24 ± 2°C and 50%-65% relative humidity. They were housed in cages with free access to food and water throughout the study, and maintained on a 12-hour light / dark cycle. The animals were acclimated for 7 days before the experiment. This study was approved by the Shenzhen Zhongxun Precision Medicine Research Institute.

[0127] 1.2 Investigational Drugs

[0128] The relieving depression, reducing fire and tranquilizing the mind paste of the present invention is prepared according to the method described in Example 1. Purified water is used to prepare a solution for administration.

[0129] Depression-relieving, fire-reducing and tranquilizing ointment: 10 parts of dried tangerine peel, 30 parts of Poria cocos, 15 parts of French pinellia, 10 parts of immature bitter orange, 15 parts of stir-fried spinach seeds, 6.5 parts of roasted ginger, 10 parts of Schisandra chinensis, 12.5 parts of Chinese angelica, 12.5 parts of raw Atractylodes macrocephala, 9 parts of Magnolia officinalis, 12.5 parts of Patchouli, 6.5 parts of roasted Licorice root, 10 parts of Poria, 10 parts of cinnamon twig, 10 parts of Citrus aurantium, 12.5 parts of Anemarrhena asphodeloides, 12.5 parts of Bupleurum chinense, 15 parts of Cortex Moutan, 6.5 parts of Gardenia jasminoides, 30 parts of Dragon Bone, 30 parts of Oyster, 7.5 parts of Menthol, 12.5 parts of White Peony Root, 30 parts of Raw Rehmannia glutinosa, and 150 parts of honey.

[0130] Weigh the remaining herbs, except for the stir-fried sour jujube seeds, dragon bones, oysters, mint, and honey, in appropriate proportions and place them in a cloth bag. Soak in purified water (6-8 times the weight of the herbs) for 8 hours. Extract the stir-fried sour jujube seeds separately with 70% alcohol and then with water. Bag the mint separately for later use. After soaking, decoct the herbs twice, adding the mint 10 minutes before the end of the second decoction. Filter the combined solution three times through an 80- to 100-mesh sieve and concentrate to a honeycomb-like paste. Reduce heat and add the melted honey to dissolve the paste. Prepare the solution with purified water for administration.

[0131] Danzhi Xiaoyao Pills: An ancient recipe from the "Chinese Pharmacopoeia", it is composed of the following components by weight: 100g of peony bark, 100g of gardenia (fried and charred), 150g of bupleurum (made with wine), 150g of white peony root (fried with wine), 150g of angelica, 150g of poria, 150g of atractylodes (fried in earth), 30g of mint, and 120g of licorice (roasted with honey).

[0132] In this typical case, Danzhi Xiaoyao Pills were purchased from Xiamen Traditional Chinese Medicine Factory Co., Ltd., with the national medicine approval number: Z20043203, and specifications: each 12 pills weigh approximately 1 gram; each bag contains 6 grams.

[0133] Chaihu Shugan Pills: An ancient prescription from the "Chinese Pharmacopoeia", which is composed of the following components in parts by weight: 100g of Poria cocos, 50g of stir-fried Citrus aurantium with bran, 40g of cardamom, 50g of white peony root with wine, 50g of liquorice, 75g of Cyperus rotundus with vinegar, 50g of dried tangerine peel, 50g of Platycodon grandiflorum, 50g of Magnolia officinalis with ginger, 50g of stir-fried Crataegus pinnatifida, 50g of Saposhnikovia divaricata, 50g of Liushenqu (stir-fried), 75g of Bupleurum chinense, 50g of Scutellaria baicalensis, 50g of Mentha piperita, 75g of Perilla stem, 25g of costus root, 75g of stir-fried Areca catechu, 50g of vinegar Trillium gracile, 50g of wine-soaked Rhubarb, 50g of Citrus aurantium (stir-fried), 50g of Angelica sinensis, 75g of Pinellia ternata with ginger, 50g of Lindera scutellariae, and 50g of vinegar-soaked Curcuma zedoaria.

[0134] In this typical case, Chaihu Shugan Pills were purchased from Huatuo National Pharmaceutical Co., Ltd., with the national medicine approval number: Z34020960, and the specification: each pill weighs 10 grams.

[0135] Yueju Pills are derived from an ancient recipe in the "Chinese Pharmacopoeia". They are composed of the following components in parts by weight: 200g of vinegar-soaked Cyperus rotundus, 200g of Chuanxiong, 200g of stir-fried Gardenia jasminoides, 200g of stir-fried Atractylodes lancea, and 200g of stir-fried Liushenqu. The above five ingredients are crushed into fine powder, sieved, mixed, made into pills with water, and dried.

[0136] In this typical case, Yueju Pills were purchased from Beijing Tongrentang Pharmaceutical Co., Ltd., with the national drug approval number: Z11020511, and specifications: 6 grams per 100 pills.

[0137] When administering the drug, grind Danzhi Xiaoyao Pills, Chaihu Shugan Pills and Yueju Pills into fine powder (pass through a 200-mesh sieve), add physiological saline solution containing 0.5% sodium carboxymethyl cellulose (CMC-Na), mix thoroughly and set aside.

[0138] 1.3 Grouping and modeling

[0139] Ten mice were randomly selected as the control group, and the rest were the model group. The mice were randomly divided into the following four groups, with 10 mice in each group: model group, Danzhi Xiaoyao pill group, Chaihu Shugan pill group, Yueju pill group, and Jieyu Jianghuo Ningshen paste group.

[0140] This study used a modified chlorophenylalanine combined with chronic unpredictable mild stress model to establish an insomnia mouse model. Adaptive feeding was performed for 7 days. After the adaptation period, starting on the 8th day, all model group mice were exposed to chronic unpredictable mild stress stimulation for 6 weeks. One of the following stimulation methods was performed daily, including forced swimming, wet bedding, food and water deprivation, strong light stroboscopic stimulation, and light-dark reversal cycle. Starting from the 49th day, except for the normal group, all groups of mice were intraperitoneally injected with PCPA (350 mg / kg) every morning for 3 consecutive days. The normal group of mice was placed in the home cage and raised normally to ensure adequate sleep conditions. During the modeling period, all rats had free access to basic feed and distilled water. When the model mice showed typical characteristics such as curling up, lack of security, listlessness, withered fur, reduced food and water intake, and obvious stress response when grasping, it indicated that the model was successful.

[0141] 1.4 Administration

[0142] On the 52nd day, the mice in the Danzhi Xiaoyao Pills group, Chaihu Shugan Pills group, Yueju Pills group, and Jieyu Jianghuo Ningshen Paste group were given medication according to the designated clinical equivalent dose for 7 days, and the control group and model group received an equal amount of normal saline by gavage.

[0143] 1.5 Behavioral testing

[0144] (1) Righting experiment

[0145] After modeling, mice in each group were intraperitoneally injected with 30 mg / kg sodium pentobarbital. Mice were placed on a flat surface with their abdomen facing upward and their bodies held vertically. The time from the time of intraperitoneal injection to the loss of the righting reflex was considered sleep latency. If the mouse turned over more than twice within 60 seconds, the righting reflex was considered recovered. The time from the loss of the righting reflex to the recovery of the righting reflex was considered sleep duration.

[0146] (2) Open field test

[0147] Place the mouse in the center square of an open box (the size of the open box is 100 cm long x 100 cm wide x 40 cm high), use a counter to manually count the number of squares each mouse crosses horizontally within 5 minutes, record the time and number of times the mouse enters the central area, and calculate the total distance the mouse travels.

[0148] (3) New object recognition experiment

[0149] Two objects, A and B, of different shapes and colors, were placed in a chamber, 25 cm apart. On the first day, mice were allowed to acclimate to the chamber for 20 minutes. The two objects were identical (both objects were A). One hour later, object A on the left side was replaced with object B, and the time the mice spent in contact with A and B within a 5-minute period was recorded. After 24 hours, object A on the right side was replaced with object B, and the time the mice spent in contact with A and B within a 5-minute period was recorded.

[0150] 2 Results

[0151] 2.1 Results of the Reversal Experiment

[0152] Figures 5 and 6 Results of the reversal experiment showed that compared with the control group, the model group mice had prolonged sleep latency and shortened sleep duration. After medication, mice in the Danzhi Xiaoyao Pill, Chaihu Shugan Pill, Yueju Pill, and Jieyu Jianghuo Ningshen Paste groups showed significantly shorter sleep latency and longer sleep duration. The Jieyu Jianghuo Ningshen Paste group showed the most significant reduction in sleep latency and the greatest increase in sleep duration, indicating that the Jieyu Jianghuo Ningshen Paste has a more potent sedative and tranquilizing effect.

[0153] 2.2 Open field test results

[0154] Figures 7 to 9 The results of exercise showed that the total distance traveled by the model group mice (e.g. Figure 9 ), the number of times entering the central area (such as Figure 7 ) and the time spent in the central area (e.g. Figure 8 ) was significantly lower than that of the control group. The total distance of movement of mice in the Danzhi Xiaoyao Pills, Chaihu Shugan Pills, Yueju Pills, and Jieyu Jianghuo Ningshen Paste groups increased; the number of times the mice in the Danzhi Xiaoyao Pills, Chaihu Shugan Pills, Yueju Pills, and Jieyu Jianghuo Ningshen Paste groups entered the central area increased; the time the mice in the Danzhi Xiaoyao Pills, Chaihu Shugan Pills, Yueju Pills, and Jieyu Jianghuo Ningshen Paste groups entered the central area increased. Among them, the total distance of movement, the number of times the mice entered the central area, and the time they stayed in the central area increased most significantly in the Jieyu Jianghuo Ningshen Paste group compared with the Danzhi Xiaoyao Pills, Chaihu Shugan Pills, and Yueju Pills groups, indicating that the Jieyu Jianghuo Ningshen Paste can increase the spontaneous activity of mice and is more effective in relieving the anxiety of mice.

[0155] 2.3 Experimental results of new object recognition

[0156] Figure 4The results of the novel object recognition experiment showed that the novel object recognition index of mice in the model group was significantly lower than that of the control group, while the novel object recognition index of mice in the Danzhi Xiaoyao Pills, Chaihu Shugan Pills, Yueju Pills, and Jieyu Jianghuo Ningshen Paste groups all increased. Among them, the Jieyu Jianghuo Ningshen Paste group showed the greatest increase in novel object recognition index compared to the Danzhi Xiaoyao Pills, Chaihu Shugan Pills, and Yueju Pills groups, indicating that Jieyu Jianghuo Ningshen Paste has the greatest effect on improving learning and recognition abilities.

[0157] In summary, from the comparison results, it can be seen that the efficacy of the Jieyu Jianghuo Ningshen ointment of the present invention is significantly better than that of ancient prescriptions such as Danzhi Xiaoyao Pills, Chaihu Shugan Pills, and Yueju Pills.

[0158] The above describes the preferred embodiments of the present invention. It should be understood that the present invention is not limited to the above-mentioned specific embodiments, and the devices and structures that are not described in detail should be understood to be implemented in a common manner in the art; any technician familiar with the art can use the above-mentioned disclosed methods and technical contents to make many possible changes and modifications to the technical solutions of the present invention without departing from the scope of the technical solutions of the present invention, or modify them into equivalent embodiments of equivalent changes, which does not affect the essential content of the present invention. Therefore, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention that do not depart from the content of the technical solutions of the present invention are still within the scope of protection of the technical solutions of the present invention.

Claims

1. A prescription for relieving depression, reducing fire and calming the mind, characterized in that: The ingredients include the following by weight: 5-15 parts of dried tangerine peel, 15-45 parts of Poria cocos, 10-20 parts of French pinellia, 5-15 parts of immature bitter orange, 5-15 parts of terminalia chebula, 10-20 parts of stir-fried spinach seeds, 3-10 parts of roasted ginger, 5-15 parts of schisandra chinensis, 5-20 parts of angelica sinensis, 5-20 parts of raw atractylodes macrocephala, 3-15 parts of magnolia bark, 5-20 parts of patchouli, 3-10 parts of radix scutellariae, 5-15 parts of poria, and 5-15 parts of cassia twig. , 5-15 parts of green peel, 5-20 parts of Anemarrhena, 5-20 parts of Bupleurum, 10-20 parts of Cortex Moutan, 3-10 parts of Gardenia, 15-45 parts of Dragon Bone, 15-45 parts of Oyster, 5-20 parts of Acorus calamus, 10-30 parts of Ophiopogon japonicus, 5-20 parts of Salvia miltiorrhiza, 5-30 parts of Chinese yam, 5-10 parts of mint, 5-20 parts of white peony root, 15-30 parts of floating wheat, 5-15 parts of longan meat, and 100-200 parts of honey.

2. A prescription for relieving depression, reducing fire and calming the mind according to claim 1, characterized in that: The ingredients include: 5 parts of dried tangerine peel, 15 parts of Poria cocos, 10 parts of French pinellia, 5 parts of immature bitter orange, 5 parts of Terminalia chebula, 10 parts of stir-fried spinach seeds, 3 parts of roasted ginger, 5 parts of Schisandra chinensis, 5 parts of Angelica sinensis, 5 parts of raw Atractylodes macrocephala, 3 parts of Magnolia officinalis, 5 parts of Patchouli, 3 parts of roasted ginseng, 5 parts of Poria, 5 parts of cinnamon twig, 5 parts of Citrus aurantium, 5 parts of Anemarrhena asphodeloides, 5 parts of Bupleurum chinense, 10 parts of Cortex Moutan, 3 parts of Gardenia jasminoides, 15 parts of Dragon Bone, 15 parts of oyster, 5 parts of Acorus calamus, 10 parts of Ophiopogon japonicus, 5 parts of Salvia miltiorrhiza, 5 parts of Chinese yam, 5 parts of mint, 5 parts of white peony root, 15 parts of floating wheat, 5 parts of longan meat, and 100 parts of honey.

3. The prescription for relieving depression, reducing fire and calming the mind according to claim 1, characterized in that: The invention comprises the following components in parts by weight: 10 parts of dried tangerine peel, 30 parts of poria, 150 parts of French pinellia, 10 parts of immature bitter orange, 10 parts of terminalia chebula, 15 parts of stir-fried spinach seeds, 3 parts of roasted ginger, 10 parts of schisandra chinensis, 10 parts of angelica sinensis, 10 parts of raw atractylodes macrocephala, 10 parts of magnolia bark, 10 parts of patchouli, 3 parts of roasted ginseng, 10 parts of poria, 10 parts of cinnamon twig, 10 parts of green peel, 15 parts of anemarrhena, 10 parts of bupleurum, 15 parts of moutan bark, 3 parts of gardenia, 30 parts of dragon bone, 30 parts of oyster, 10 parts of calamus, 20 parts of ophiopogon, 10 parts of salvia miltiorrhiza, 15 parts of yam, 5 parts of mint, 10 parts of white peony root, 20 parts of floating wheat, 10 parts of longan meat, and 150 parts of honey.

4. The prescription for relieving depression, reducing fire and calming the mind according to claim 1, characterized in that: The invention comprises the following components in parts by weight: 7.5 parts of dried tangerine peel, 22.5 parts of poria, 11.5 parts of ternate ternate, 7.5 parts of immature citrus aurantium, 7.5 parts of terminalia chebula, 11.5 parts of stir-fried jujube seeds, 5 parts of roasted ginger, 7.5 parts of schisandra chinensis, 10 parts of angelica sinensis, 10 parts of raw atractylodes macrocephala, 7.5 parts of magnolia bark, 10 parts of patchouli, 5 parts of roasted ginseng, 7.5 parts of poria, 7.5 parts of cinnamon twig, 7.5 parts of green peel, 10 parts of anemarrhena, 10 parts of bupleurum, 11.5 parts of moutan bark, 5 parts of gardenia, 22.5 parts of dragon bone, 22.5 parts of oyster, 10 parts of calamus, 15 parts of ophiopogon, 10 parts of salvia miltiorrhiza, 12.5 parts of yam, 5 parts of mint, 10 parts of white peony root, 17.5 parts of floating wheat, 7.5 parts of longan meat, and 115 parts of honey.

5. The prescription for relieving depression, reducing fire and calming the mind according to claim 1, characterized in that: The invention comprises the following components in parts by weight: 12.5 parts of dried tangerine peel, 37.5 parts of poria, 17.5 parts of French pinellia, 12.5 parts of immature bitter orange, 12.5 parts of terminalia chebula, 17.5 parts of stir-fried spinach seeds, 7.5 parts of roasted ginger, 12.5 parts of schisandra chinensis, 15 parts of angelica sinensis, 15 parts of raw atractylodes, 12.5 parts of magnolia bark, 15 parts of patchouli, 7.5 parts of roasted ginseng, 12.5 parts of poria, 12.5 parts of cinnamon twig, 12.5 parts of green peel, 15 parts of anemarrhena, 15 parts of bupleurum, 17.5 parts of moutan bark, 7.5 parts of gardenia, 37.5 parts of dragon bone, 37.5 parts of oyster, 15 parts of calamus, 25 parts of ophiopogon, 15 parts of salvia miltiorrhiza, 22.5 parts of yam, 7.5 parts of mint, 15 parts of white peony root, 27.5 parts of floating wheat, 12.5 parts of longan meat, and 190 parts of honey.

6. The prescription for relieving depression, reducing fire and calming the mind according to claim 1, characterized in that: The invention comprises the following components in parts by weight: 15 parts of dried tangerine peel, 45 parts of poria, 20 parts of ternate ternate, 15 parts of immature citrus aurantium, 15 parts of terminalia chebula, 20 parts of stir-fried jujube seeds, 10 parts of roasted ginger, 15 parts of schisandra chinensis, 20 parts of raw atractylodes macrocephala, 15 parts of magnolia bark, 20 parts of patchouli, 10 parts of roasted ginseng, 15 parts of poria, 15 parts of cinnamon twig, 15 parts of green peel, 20 parts of anemarrhena, 20 parts of bupleurum, 20 parts of moutan bark, 10 parts of gardenia, 45 parts of dragon bone, 45 parts of oyster, 20 parts of calamus, 30 parts of ophiopogon, 20 parts of salvia miltiorrhiza, 30 parts of yam, 10 parts of mint, 20 parts of white peony root, 30 parts of floating wheat, 15 parts of longan meat, and 200 parts of honey.

7. A method for preparing the prescription for relieving depression, reducing fire and calming the mind according to any one of claims 1 to 6, characterized in that: It includes the following steps: 7.1 Weigh tangerine peel, Poria cocos, French pinellia, immature bitter orange, Terminalia chebula, roasted ginger, Schisandra chinensis, Chinese angelica, raw white atractylodes, Magnolia bark, Patchouli, roasted liquorice, Poria, cinnamon twig, green peel, Anemarrhena, Bupleurum, Cortex Moutan, Gardenia, Acorus calamus, Ophiopogon japonicus, Salvia miltiorrhiza, Chinese yam, white peony root, floating wheat, and longan meat together in proportion by weight and soak for 7-9 hours; 7.2 Stir-fry the spinach seeds to extract the fat-soluble tranquilizing ingredients. Then, use water to extract the water-soluble ingredients from the filtered medicinal residue for later use. 7.3 Crush the keel and oysters to less than 200 mesh and set aside; 7.4 Place the soaked Chinese medicinal materials from step 7.1 in a pot together with the crushed dragon bones and oysters from step 7.

3. Boil over low heat twice, each time for 1.3-1.7 hours. Add mint 7-13 minutes before the end of the second decoction. 7.5 Add the water-soluble ingredients obtained in step 7.2 to the medicinal liquid obtained after decocting in step 7.4, and then filter it 2-3 times. Concentrate the filtrate until it becomes a clear paste in the shape of honeycomb balls. Simmer over low heat and add melted honey. Keep stirring and control the temperature at 70-80℃ until the paste is formed.

8. The preparation method of the prescription for relieving depression, reducing fire and calming the mind according to claim 7, characterized in that: Poria cocos was freeze-dried using vacuum technology before step 7.1 to preserve its active ingredients; In step 7.1, put dried tangerine peel, Poria cocos, French pinellia, immature bitter orange, Terminalia chebula, roasted ginger, Schisandra chinensis, Chinese angelica, raw white atractylodes, Magnolia bark, Patchouli, roasted liquorice, Poria, cinnamon twig, green peel, Anemarrhena asphodeloides, Bupleurum chinense, Cortex Moutan, Gardenia jasminoides, Acorus calamus, Ophiopogon japonicus, Salvia miltiorrhiza, Chinese yam, white peony root, floating wheat, and longan meat into a cloth bag and soak in purified water 6-8 times the weight of the medicinal materials in this step for 8 hours; In step 7.2, a predetermined amount of stir-fried spinach seeds is weighed and subjected to a component extraction process using a combined alcohol extraction-water extraction process, namely, based on different solvent solubilities, first using an ethanol-water solution with a volume ratio of water to ethanol of 70% by volume at 70-80° C., wherein the weight ratio of the stir-fried spinach seeds to the ethanol-water solution is 1:8-10, reflux for 1.9-2.1 hours, and repeated twice, and then concentrated under reduced pressure at 55° C.-65° C. to remove alcohol to obtain the fat-soluble sedative component of the stir-fried spinach seeds; the spinach seeds residue after the fat-soluble sedative component is extracted is filtered and separated, and washed thoroughly with pure water until no ethanol residue is left, and then the spinach seeds residue is decocted with 6-8 times the weight of the spinach seeds residue at normal pressure of 90±2° C. for 1.4-1.6 hours to obtain the water-soluble component of the residue; In step 7.3, the dragon bones and oysters were crushed to 200 mesh using ultrafine grinding technology as follows; In step 7.4, simmer for 1.5 hours twice, adding mint 10 minutes before the end of the second simmering; In step 7.5, filter 2-3 times with a sieve of 80 to 100 mesh. The paste is collected by using the standard of water droplets forming beads and hanging flags. After the paste is collected, it is packaged into sterilized glass bottles while hot and sterilized with high-pressure steam at 115℃-125℃ for 20-30 minutes. After the paste is cooled, it can be sealed.

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