Medicine for treating heart-spleen deficiency type insomnia and preparation method thereof

Abstract

The invention discloses a medicine for treating heart-spleen deficiency type insomnia and a preparation method thereof. The medicine is prepared from vinegar schisandra chinensis, fried spina date seed, fried white hyacinth bean, wine-processed rhizoma polygonati, vine of multiflower knotweed, rose, gastrodia elata, chrysanthemum, eupatorium and jujube. The traditional Chinese medicine has the effects of calming the heart, soothing the nerves, soothing the liver, relieving depression, strengthening the spleen, harmonizing the stomach, nourishing the blood, promoting the secretion of saliva or removing dampness and heat, and is mainly used for treating insomnia caused by poor physique of the elderly, heart fatigue and nerve injury caused by long-term pressure or qi deficiency and hemophthisis after long-term illness, and the insomnia is shown as non-deep sleep, dreaminess, easy awakening, dizziness, body weakness, listlessness and yellow and dim face. The traditional Chinese medicine is suitable for heart-spleen deficiency insomnia patients. The medicinal materials in the whole formula are medicinal and edible medicinal materials, have small toxic and side effects, are safe to use and can be taken for a long time.

Description

Field of the Invention

[0001] The present invention relates to a drug for treating insomnia of the syndrome of deficiency of both the heart and spleen and its preparation method, belonging to the technical field of pharmaceuticals. Background Art

[0002] Common symptoms of insomnia are difficulty in falling asleep, decreased sleep quality, reduced sleep time, decreased memory and attention, etc. Modern medicine (Western medicine) treats insomnia through methods such as lifestyle conditioning, psychological and behavioral therapy, and drug therapy. Common drug types for relieving insomnia include estazolam tablets, flurazepam hydrochloride capsules, quazepam tablets, etc. Although Western medicine has a certain effect in treating insomnia, taking Western medicine for a long time not only fails to improve the symptoms of insomnia, but may also produce certain side effects, such as gastrointestinal reactions, liver and kidney damage, drug dependence, endocrine disorders, etc., and it is also easy to treat the symptoms rather than the root cause.

[0003] From the perspective of traditional Chinese medicine, insomnia is mainly caused by problems in various organs of the body. Among the types of insomnia, the classification in traditional Chinese medicine is different from that in Western medicine, mainly divided into five aspects, including insomnia of the type of stagnation of liver qi and hyperactivity of liver yang, phlegm-heat type insomnia, yin deficiency and fire hyperactivity type insomnia, deficiency of both the heart and spleen type insomnia, and deficiency of both the heart and gallbladder qi type insomnia. Deficiency of both the heart and spleen type insomnia is more common in the elderly with weak constitutions, caused by overstrain of the mind due to long-term stress or qi deficiency and blood deficiency after a long illness or serious illness, manifested as difficulty in falling into a deep sleep, frequent dreaming and easy waking, dizziness, blurred vision, weakness all over the body, listlessness, and sallow complexion. In contrast, traditional Chinese medicine treats insomnia through the method of syndrome differentiation and treatment to achieve the best therapeutic effect. The treatment of insomnia with traditional Chinese medicine has relatively fewer side effects and less harm to the body compared with Western medicine treatment.

[0004] The drug of the present invention has the effects of calming the mind and tranquilizing the spirit, soothing the liver and relieving depression, strengthening the spleen and regulating the stomach, nourishing blood and promoting the production of body fluid, and dispelling dampness and heat. It is mainly used for treating insomnia caused by overstrain of the mind due to long-term stress or qi deficiency and blood deficiency after a long illness or serious illness in the elderly with weak constitutions, manifested as difficulty in falling into a deep sleep, frequent dreaming and easy waking, dizziness, blurred vision, weakness all over the body, listlessness, and sallow complexion. It is applicable to the population of insomnia patients with the syndrome of deficiency of both the heart and spleen. The prescription of the present invention is safe in medication and has obvious curative effects. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a drug for treating insomnia of the syndrome of deficiency of both the heart and spleen and its preparation method. The present invention has the effects of calming the mind and tranquilizing the spirit, soothing the liver and relieving depression, strengthening the spleen and regulating the stomach, nourishing blood and promoting the production of body fluid, and dispelling dampness and heat, and is applicable to the population of insomnia patients with the syndrome of deficiency of both the heart and spleen. Moreover, all the medicinal materials in the whole formula are both medicinal and edible materials, with small toxic and side effects, safe to use, and can be taken for a long time.

[0006] To solve the above technical problems, the present invention is realized by adopting the following technical solutions:

[0007] A drug for treating insomnia of the syndrome of deficiency of both the heart and spleen, wherein the medicinal effective components are calculated according to weight components: prepared from 200 - 800 parts of Schisandra chinensis Baill. var. chinensis (Turcz.) Baill. processed with vinegar, 200 - 800 parts of Semen Ziziphi Spinosae stir-fried, 200 - 800 parts of Semen Lablab Album stir-fried, 100 - 500 parts of Polygonatum sibiricum Delar. ex Redoute processed with wine, 100 - 500 parts of Caulis Polygoni Multiflori, 100 - 500 parts of Rosa rugosa Thunb., 100 - 500 parts of Gastrodia elata Blume, 50 - 400 parts of Flos Chrysanthemi, 100 - 500 parts of Herba Eupatorii Fortunei and 100 - 500 parts of Fructus Jujubae.

[0008] The aforementioned drug for treating insomnia of the syndrome of deficiency of both the heart and spleen, wherein the medicinal effective components are calculated according to weight components: prepared from 400 - 600 parts of Schisandra chinensis Baill. var. chinensis (Turcz.) Baill. processed with vinegar, 400 - 600 parts of Semen Ziziphi Spinosae stir-fried, 400 - 600 parts of Semen Lablab Album stir-fried, 200 - 400 parts of Polygonatum sibiricum Delar. ex Redoute processed with wine, 200 - 400 parts of Caulis Polygoni Multiflori, 200 - 400 parts of Rosa rugosa Thunb., 200 - 400 parts of Gastrodia elata Blume, 100 - 300 parts of Flos Chrysanthemi, 200 - 400 parts of Herba Eupatorii Fortunei and 200 - 400 parts of Fructus Jujubae.

[0009] Specifically, the aforementioned drug for treating insomnia of the syndrome of deficiency of both the heart and spleen, wherein the medicinal effective components are calculated according to weight components: prepared from 500 parts of Schisandra chinensis Baill. var. chinensis (Turcz.) Baill. processed with vinegar, 500 parts of Semen Ziziphi Spinosae stir-fried, 500 parts of Semen Lablab Album stir-fried, 300 parts of Polygonatum sibiricum Delar. ex Redoute processed with wine, 300 parts of Caulis Polygoni Multiflori, 300 parts of Rosa rugosa Thunb., 300 parts of Gastrodia elata Blume, 200 parts of Flos Chrysanthemi, 300 parts of Herba Eupatorii Fortunei and 300 parts of Fructus Jujubae.

[0010] The preparation method of the aforementioned drug for treating insomnia of the syndrome of deficiency of both the heart and spleen is to weigh all the medicinal materials in the formula according to the proportion and process them according to the conventional preparation method to make the corresponding pharmaceutical preparations.

[0011] The aforementioned pharmaceutical preparations include powder, capsule, tablet, extract, granule, decoction or pill.

[0012] The aforementioned powder is prepared as follows: weigh each medicinal material according to the prescription proportion, add 6 times the amount of water and boil for reflux extraction 2 times, each time for 0.5 h, combine the two extraction liquids, filter while it is hot, concentrate to an extract with a relative density of 1.10 - 1.30 at 70 °C, dry the extract at 70 - 85 °C to obtain a dry extract, pulverize it into fine powder, pass through a 100-mesh sieve, sterilize and then package, and that's it.

[0013] The aforementioned capsule is prepared as follows: weigh each medicinal material according to the prescription proportion, add 8 times the amount of water and boil for reflux extraction 3 times, each time for 1 h, combine the three extraction liquids, mix well, concentrate to 65% of the original medicinal liquid, filter while it is hot, concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70 °C, dry the extract at 70 - 85 °C to obtain a dry extract, pulverize it into fine powder, add 10% of the starch of the finished product amount and 1% of magnesium stearate and mix evenly, granulate with 90% ethanol, dry at 70 °C, size the granules, fill the capsules, and that's it.

[0014] The foregoing tablets are prepared as follows: Weigh each medicinal material according to the prescription ratio, add 10 times the amount of water, boil under reflux for 2 times, each time for 0.5 h. Combine the two extraction liquids, mix well, concentrate to 65% of the original medicinal liquid, filter while it is hot, concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70 °C. Dry the extract at 70 - 85 °C to obtain a dry extract, and pulverize it into fine powder to obtain the dry extract. Take the dry extract, add 1% talcum powder and 1% sodium carboxymethylcellulose, granulate with 10% starch paste, dry at 70 °C, press tablets, and perform film coating to obtain the tablets.

[0015] The foregoing extractum cinnamomi is prepared as follows: Weigh each medicinal material according to the prescription ratio, add 6 times the amount of water, boil under reflux for 3 times, each time for 1 h. Combine the three extraction liquids, mix well, concentrate to 65% of the original medicinal liquid, filter while it is hot, concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70 °C. Separately take 40% of the refined honey by weight of the above extract, slowly add it to the above extract, stir evenly, continue to heat and collect the extract with a gentle fire. When a little can be pulled into filaments horizontally, or when dropped on paper without water marks, fill it into a sterile bottle and seal it to obtain the extractum cinnamomi.

[0016] The foregoing granules are prepared as follows: Weigh each medicinal material according to the prescription ratio, add 12 times the amount of water, boil under reflux for 2 times, each time for 1.5 h. Combine the two extraction liquids, mix well, concentrate to 65% of the original medicinal liquid, filter while it is hot, concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70 °C. Dry the extract at 70 - 85 °C and pulverize it into fine powder to obtain the dry extract. Take 1 part of the dry extract, 0.5 part of sucrose and 0.5 part of dextrin, prepare granules by wet method with 60% ethanol. After making the granules, dry them at 80 - 90 °C, sieve through a 14 - mesh sieve once, and separate the fine powder with a 60 - mesh sieve to obtain the granules.

[0017] The foregoing decoction is prepared as follows: Weigh each medicinal material according to the prescription ratio, add 6 times the amount of water, boil under reflux for 2 times, each time for 0.5 h. Combine the two extraction liquids, filter while it is hot, sterilize and then sub - package to obtain the decoction. [[ID=ll]]

[0018] The foregoing pills are prepared as follows: Weigh each medicinal material according to the prescription ratio, add 8 times the amount of water, boil under reflux for 2 times, each time for 1 h. Combine the two extraction liquids, mix well, concentrate to 65% of the original medicinal liquid, filter while it is hot, concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70 °C. Dry the extract at 70 - 85 °C to obtain a dry extract, pulverize it into fine powder. Take 1 part of the extract and 2 parts of refined honey, knead evenly, let it stand for 20 - 30 min, then roll it into strips and make pills to obtain the pills.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] The drug for treating insomnia of the syndrome of deficiency of both the heart and spleen according to the present invention is prepared from Schisandra chinensis (Turcz.) Baill. processed with vinegar, Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H.F.Chou processed with stir-frying, Dolichos lablab L. processed with stir-frying, Polygonatum kingianum Coll. et Hemsl. processed with wine, Caulis Polygoni Multiflori, Rosa rugosa Thunb., Gastrodia elata Blume, Chrysanthemum morifolium Ramat., Eupatorium fortunei Turcz. and Chinese date. The properties and effects of each component are as follows: Schisandra chinensis (Turcz.) Baill. processed with vinegar is the processed product of the dried ripe fruit of Schisandra chinensis (Turcz.) Baill., a plant of the Magnoliaceae family; sour and sweet in taste, warm in nature; attributing to the lung, heart and kidney meridians; having the effects of astringing and arresting sweating, replenishing qi and promoting production of body fluid, tonifying the kidney and tranquillizing the heart; being used for chronic cough with dyspnea, spermatorrhea, enuresis, chronic diarrhea, spontaneous sweating and night sweating, thirst due to body fluid deficiency, internal heat and polydipsia, palpitation and insomnia. Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H.F.Chou processed with stir-frying is the processed product of the dried ripe seed of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H.F.Chou, a plant of the Rhamnaceae family; sweet and sour in taste, neutral in nature; attributing to the liver, gallbladder and heart meridians; having the effects of nourishing the heart and liver, tranquillizing the mind, arresting sweating and promoting production of body fluid; commonly being used for vexation and insomnia, palpitation and dreaminess, excessive sweating due to weakness of the body, and thirst due to body fluid deficiency. Dolichos lablab L. processed with stir-frying is the processed product of the dried ripe seed of Dolichos lablab L., a plant of the Leguminosae family; sweet in taste, slightly warm in nature; attributing to the spleen and stomach meridians; having the effects of strengthening the spleen and promoting diuresis, regulating the middle-jiao and dispelling summer heat; being used for weakness of the spleen and stomach, loss of appetite, loose stools, leukorrhea, vomiting and diarrhea due to summer heat and dampness, chest distress and abdominal distension; Dolichos lablab L. processed with stir-frying strengthens the spleen and promotes diuresis; being used for diarrhea due to weakness of the spleen and excessive leukorrhea. Polygonatum kingianum Coll. et Hemsl. is the dried rhizome of Polygonatum kingianum Coll. et Hemsl., Polygonatum sibiricum Red. or Polygonatum cyrtonema Hua of the Liliaceae family; according to different shapes, commonly known as "large Polygonatum kingianum Coll. et Hemsl.", "chicken-head Polygonatum sibiricum Red." and "ginger-shaped Polygonatum cyrtonema Hua"; dug in spring and autumn, removing fibrous roots, washing, scalding in boiling water or steaming until thoroughly cooked, and drying; Polygonatum kingianum Coll. et Hemsl. processed with wine is the processed product of Polygonatum kingianum Coll. et Hemsl., sweet in taste, neutral in nature; attributing to the spleen, lung and kidney meridians; having the effects of replenishing qi and nourishing yin, strengthening the spleen, moistening the lung and tonifying the kidney; being used for qi deficiency of the spleen and stomach, fatigue and weakness, deficiency of stomach yin, dry mouth and poor appetite, dry cough due to lung deficiency, chronic cough with hemoptysis, insufficiency of essence and blood, weakness of the waist and knees, premature whitening of hair, and internal heat and polydipsia. Caulis Polygoni Multiflori is the dried vine stem of Polygonum multiflorum Thunb. of the Polygonaceae family; sweet in taste, neutral in nature; attributing to the heart and liver meridians; having the effects of nourishing blood and tranquilizing the mind, expelling wind and dredging collaterals; being used for insomnia and dreaminess, general pain due to blood deficiency, rheumatic arthralgia, and skin pruritus. Rosa rugosa Thunb. is the flower of Rosa rugosa Thunb. of the Rosaceae family, Rosa genus; sweet and slightly bitter in taste, warm in nature; having the effects of regulating qi and relieving depression, promoting blood circulation and removing stasis; treating liver and stomach qi pain, new and old wind arthralgia, hematemesis and hemoptysis, irregular menstruation, leukorrhea, dysentery, breast abscess, and swelling toxin.The dry tuber of the orchid plant Gastrodia elata Bl.; sweet in taste, neutral in nature; attributive to the liver meridian; having the effects of calming endogenous wind and stopping convulsions, suppressing the hyperactive liver-yang, dispelling wind and dredging collaterals; mainly used for infantile convulsions, epilepsy convulsions, tetanus, headache and dizziness, flaccidity of hands and feet, limb numbness, rheumatic arthralgia. Chrysanthemum is the dry capitulum of the composite plant Chrysanthemum morifolium Ramat.; sweet and bitter in taste, slightly cold in nature; attributive to the lung and liver meridians; having the effects of dispersing wind and clearing heat, soothing the liver and improving eyesight, clearing heat and detoxifying; used for wind-heat cold, headache and dizziness, red and swollen eyes, dim eyesight, sores and boils. Eupatorium fortunei Turcz. is the dry above-ground part of the composite plant Eupatorium fortunei Turcz.; harvested by cutting twice in summer and autumn, removing impurities and drying in the sun; pungent in taste, neutral in nature; attributive to the spleen, stomach and lung meridians; having the effects of aromatic dampness elimination, awakening the spleen and promoting appetite, inducing diaphoresis and relieving summer heat; used for dampness obstruction in the middle energizer, stuffiness and nausea in the epigastrium, sweet taste in the mouth, bad breath, excessive salivation, summer dampness syndrome, initial stage of damp-warm disease, fever and lassitude, chest distress and discomfort. Chinese date is the mature fruit of the plant Ziziphus jujuba Mill. of the Rhamnaceae family; sweet in taste, warm in nature; attributive to the spleen and stomach meridians; having the effects of invigorating the middle energizer and replenishing qi, nourishing blood and tranquilizing the mind, nourishing the spleen and stomach; used for treating disharmony between the spleen and stomach, indigestion, cough due to overstrain, anemia and emaciation.

[0021] Analysis of the formula

[0022] Principal drugs: Schisandra chinensis, Ziziphus jujuba var. spinosa, Polygonatum sibiricum

[0023] Insomnia is one of the common symptoms of modern people. Traditional Chinese medicine believes that insomnia and sleeplessness are often caused by internal injuries, regardless of emotional distress, timidity due to heart deficiency, excessive thinking, improper diet or congenital deficiency, resulting in restlessness of the mind. To relieve it, the mind must be calmed first. "Huangdi Neijing" points out: "Medicines are used to dispel diseases, and food follows." This shows the close relationship between sleep and diet. Traditional Chinese medicine has always had the saying of "medicines and foods having the same origin". By regulating diet, the sleep condition can be effectively improved. This invention takes "invigorating the spleen and replenishing qi, nourishing the heart and tranquilizing the mind" as the principle. Schisandra chinensis and Ziziphus jujuba var. spinosa are used in combination. Schisandra chinensis has the effects of astringing and consolidating, promoting the production of body fluid and qi, tonifying the kidney and calming the heart. Ziziphus jujuba var. spinosa is sweet in taste and neutral in nature, entering the liver and heart meridians, and is often known as the "sedative medicine", having the effects of nourishing the heart and tranquilizing the mind, benefiting the liver and arresting sweating. The combination of the two medicines not only tonifies the liver and kidney, but also benefits the heart and kidney, converges internally and externally, nourishes the heart blood and astringes yin essence, so as to calm the mind. Then, Polygonatum sibiricum is combined. It is sweet in taste and neutral in nature, entering the lung, spleen and kidney meridians. It can not only tonify the kidney, spleen, liver, nourish the lung and promote the production of body fluid, but also nourish yin and blood. The combination of the three medicines together exerts the effects of calming the heart and tranquilizing the mind, promoting the production of body fluid and quenching thirst, tonifying the mind, so they are the principal drugs together.

[0024] Ministerial drugs: Dolichos lablab, Caulis Polygoni multiflori, Rosa rugosa, Gastrodia elata

[0025] Caulis Polygoni Multiflori tastes sweet and is neutral in nature. It is good at nourishing blood and calming the mind, and can guide yang into yin to soothe the nerves; Rosa rugosa flower tastes bitter and is warm in nature, promoting circulation. It is especially good at dispersing liver depression, activating blood circulation and regulating menstruation to relieve vexation and calm the nerves. The combination of the two herbs enhances the effects of nourishing blood and relieving depression, and calming the mind and nerves. Gastrodia elata is sweet and neutral in flavor, gentle and not dry, neutral and not biased, mainly entering the liver meridian, with the effects of calming endogenous wind and stopping convulsions, suppressing liver yang, and dispelling wind and dredging collaterals, which can assist the monarch herb Semen Ziziphi Spinosae to enhance the effect of sedation and calming the nerves. Dolicho lablab purpureum has a light flavor and thin qi, tonifying without stagnation, and is good at strengthening the spleen and resolving dampness, and invigorating the spleen and replenishing qi to assist the spleen and stomach in transportation and transformation and reduce the gastrointestinal burden. Therefore, the above herbs are all ministerial herbs.

[0026] Adjuvant herbs: Flos Chrysanthemi, Herba Eupatorii

[0027] The combination of Flos Chrysanthemi and Herba Eupatorii, on the one hand, Flos Chrysanthemi has the effects of clearing heat, dispelling wind, and detoxifying, which helps to dispel dampness and heat in the body, and Herba Eupatorii can resolve dampness and also clear heat and relieve summer heat. The combination of the two can more effectively dispel dampness and heat in the body; on the other hand, Flos Chrysanthemi can also soothe the liver and clear the liver, and Herba Eupatorii can arouse the spleen and promote appetite. The combination of the two enhances the effect of clearing the liver and improving eyesight.

[0028] Guiding herb: Fructus Jujubae

[0029] Fructus Jujubae tastes sweet and is warm in nature, belonging to the spleen and stomach meridians. Its juice is thick, smooth and moist, most capable of nourishing the heart meridian, moistening the muscles, strengthening the spleen and stomach, coordinating all herbs, relieving the strong and fierce nature of powerful herbs so that they do not harm the spleen and stomach, neutralizing the medicinal properties and reducing side effects to protect the healthy qi of the human body. Therefore, it is the guiding herb.

[0030] Overall, the whole formula takes both the root cause and the symptoms into consideration, and together achieves the effects of calming the mind and nerves, soothing the liver and relieving depression, strengthening the spleen and regulating the stomach, nourishing blood and promoting fluid production, and dispelling dampness and heat. It is applicable to the population of insomnia patients with deficiency of both heart and spleen. Moreover, all the herbs in the whole formula are both medicinal and edible herbs, with small toxic and side effects, safe to use, and can be taken for a long time. Description of the Drawings

[0031] Figure 1 : Typical Case 1;

[0032] Figure 2 : Typical Case 2;

[0033] Figure 3 : Typical Case 3;

[0034] Figure 4 : Typical Case 4;

[0035] Figure 5 : Typical Case 5;

[0036] Figure 6 : Target diagrams of diseases and active ingredients (A: Distribution diagram of insomnia targets in major databases; B: Intersection diagram of drug active ingredient targets and insomnia targets)

[0037] Figure 7 : PPI network diagram;

[0038] Figure 8 ; Protein map of the top 5 in Degree ranking;

[0039] Figure 9 : Pathway - target network diagram;

[0040] Figure 10 : Docking binding energy diagram of the core components and core targets;

[0041] Figure 11 : Small molecule - protein docking diagram. Detailed implementation manners

[0042] The present invention will be further described below in conjunction with embodiments, but it shall not be used as a basis for limiting the present invention.

[0043] Embodiment 1.

[0044] Prescription: Schisandra chinensis (Turcz.) Baill. var. chinensis 500 g, Semen Ziziphi Spinosae 500 g, Semen Lablab Album 500 g, Polygonatum sibiricum Delar. ex Redoute var. kingianum (Coll. et Hemsl.) Y. C. Tang et Wang 300 g, Caulis Polygoni Multiflori 300 g, Rosa rugosa Thunb. 300 g, Rhizoma Gastrodiae 300 g, Flos Chrysanthemi 200 g, Herba Eupatorii 300 g, and Fructus Jujubae 300 g.

[0045] Process: Weigh each medicinal material according to the prescription ratio, add 3 times the amount of water, boil and reflux for extraction 2 times, 0.5 h each time. Combine the two extraction solutions, filter while it is hot, concentrate to an extract with a relative density of 1.10 - 1.30 at 70 °C. Dry the extract at 70 - 85 °C to obtain a dry extract, pulverize it into fine powder, pass through a 100 - mesh sieve, sterilize and then package it to obtain the powder.

[0046] Dosage and administration: Take it three times a day, in the morning, noon and evening, 2 - 4 g each time.

[0047] Indications: Insomnia of the syndrome of deficiency of both heart and spleen.

[0048] Embodiment 2.

[0049] 1. Prescription: Schisandra chinensis (Turcz.) Baill. var. chinensis 200 g, Semen Ziziphi Spinosae 200 g, Semen Lablab Album 200 g, Polygonatum sibiricum Delar. ex Redoute var. kingianum (Coll. et Hemsl.) Y. C. Tang et Wang 500 g, Caulis Polygoni Multiflori 500 g, Rosa rugosa Thunb. 500 g, Rhizoma Gastrodiae 100 g, Flos Chrysanthemi 50 g, Herba Eupatorii 500 g, and Fructus Jujubae 500 g.

[0050] Process: Weigh each medicinal material according to the prescription ratio, add 8 times the amount of water, boil and reflux for extraction 3 times, 1 h each time. Combine the three extraction solutions, mix well, concentrate to 65% of the original medicinal liquid, filter while it is hot, concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70 °C. Dry the extract at 70 - 85 °C to obtain a dry extract, pulverize it into fine powder, add 10% of starch and 1% of magnesium stearate based on the prepared amount, mix evenly, granulate with 90% ethanol, dry at 70 °C, size the granules, and fill them into capsules to obtain the hard capsule.

[0051] Dosage and Administration: Take it three times a day, in the morning, at noon and in the evening, 5 - 8 capsules each time (0.5g per capsule).

[0052] Indications: Insomnia due to deficiency of both the heart and spleen.

[0053] Example 3

[0054] Prescription: Schisandra chinensis (Turcz.) Baill. var. chinensis f. exilis (Rehd.) A. C. Smith 800g, Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow 800g, Dolichos lablab L. 800g, Polygonatum sibiricum Delar. ex Redoute 100g, Caulis Polygoni multiflori 100g, Rosa rugosa Thunb. 100g, Gastrodia elata Blume 500g, Chrysanthemum morifolium Ramat. 400g, Eupatorium fortunei Turcz. 100g and Ziziphus jujuba Mill. 100g.

[0055] Process: Weigh each medicinal material according to the prescription ratio, add 10 times the amount of water, boil and reflux for extraction twice, each time for 0.5h. Combine the two extraction solutions, mix well, concentrate to 65% of the original medicinal liquid, filter while it is hot, and concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70℃. Dry the extract at 70 - 85℃ to obtain a dry extract, and pulverize it into fine powder to obtain the dry extract. Take the dry extract, add 1% talc powder and 1% sodium carboxymethylcellulose, granulate with 10% starch paste, dry at 70℃, press into tablets, and film coat to obtain tablets.

[0056] Dosage and Administration: Take it three times a day, in the morning, at noon and in the evening, 4 - 8 tablets each time (0.5g per tablet).

[0057] Indications: Insomnia due to deficiency of both the heart and spleen.

[0058] Example 4

[0059] Prescription: Schisandra chinensis (Turcz.) Baill. var. chinensis f. exilis (Rehd.) A. C. Smith 600g, Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow 300g, Dolichos lablab L. 250g, Polygonatum sibiricum Delar. ex Redoute 500g, Caulis Polygoni multiflori 450g, Rosa rugosa Thunb. 320g, Gastrodia elata Blume 400g, Chrysanthemum morifolium Ramat. 300g, Eupatorium fortunei Turcz. 200g and Ziziphus jujuba Mill. 280g.

[0060] Process: Weigh each medicinal material according to the prescription ratio, add 6 times the amount of water, boil and reflux for extraction three times, each time for 1h. Combine the three extraction solutions, mix well, concentrate to 65% of the original medicinal liquid, filter while it is hot, and concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70℃. Take 40% of the refined honey by weight of the above extract, slowly add it to the above extract, stir well, continue to heat and collect the extract over a slow fire. When a little can be pulled into filaments flatly, or when dropped on paper, no water marks are seen, fill it into a sterile bottle and seal to obtain the extract.

[0061] Dosage and Administration: Take it three times a day, in the morning, at noon and in the evening, 10 - 20g each time.

[0062] Indications: Insomnia due to deficiency of both the heart and spleen.

[0063] Example 5

[0064] Prescription: 700g of Schisandra chinensis (Turcz.) Baill. processed with vinegar, 600g of Semen Ziziphi Spinosae stir-fried, 650g of Dolichos lablab L. stir-fried, 450g of Polygonatum sibiricum Delar. ex Redoute processed with wine, 300g of Caulis Polygoni Multiflori, 330g of Rosa rugosa Thunb., 250g of Gastrodia elata Blume, 100g of Chrysanthemum morifolium Ramat., 250g of Eupatorium fortunei Turcz., and 100g of Ziziphus jujuba Mill.

[0065] Process: Weigh each medicinal material according to the prescription ratio, add 12 times the amount of water, boil under reflux for extraction twice, each time for 1.5 hours. Combine the two extraction liquids, mix well, concentrate to 65% of the original medicinal liquid, filter while it is hot, and concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70°C. Dry the extract at 70 - 85°C and pulverize it into fine powder to obtain the dry extract. Take 1 part of the dry extract, 0.5 part of sucrose, and 0.5 part of dextrin, and prepare granules by wet method with 60% ethanol. After making the granules, dry them at 80 - 90°C, pass through a 14-mesh sieve once, and sieve out the fine powder with a 60-mesh sieve to obtain the granule agent.

[0066] Dosage and administration: Take it three times a day, in the morning, noon, and evening, 10 - 20g each time.

[0067] Indications: Insomnia due to deficiency of both the heart and spleen.

[0068] Example 6.

[0069] Prescription: 200g of Schisandra chinensis (Turcz.) Baill. processed with vinegar, 300g of Semen Ziziphi Spinosae stir-fried, 350g of Dolichos lablab L. stir-fried, 450g of Polygonatum sibiricum Delar. ex Redoute processed with wine, 400g of Caulis Polygoni Multiflori, 500g of Rosa rugosa Thunb., 100g of Gastrodia elata Blume, 150g of Chrysanthemum morifolium Ramat., 400g of Eupatorium fortunei Turcz., and 260g of Ziziphus jujuba Mill.

[0070] Process: Weigh each medicinal material according to the prescription ratio, add 8 times the amount of water, boil under reflux for extraction twice, each time for 1 hour. Combine the two extraction liquids, mix well, concentrate to 65% of the original medicinal liquid, filter while it is hot, and concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70°C. Dry the extract at 70 - 85°C to obtain the dry extract, pulverize it into fine powder. Take 1 part of the extract and 2 parts of refined honey, knead them evenly, let it stand for 20 - 30 minutes, then roll into strips and make pills to obtain the pill agent.

[0071] Dosage and administration: Take it three times a day, in the morning, noon, and evening, 10 - 20 pills (0.3g per pill) each time.

[0072] Indications: Insomnia due to deficiency of both the heart and spleen.

[0073] Example 7.

[0074] Prescription: 500g of Schisandra chinensis (Turcz.) Baill. processed with vinegar, 500g of Semen Ziziphi Spinosae stir-fried, 500g of Dolichos lablab L. stir-fried, 300g of Polygonatum sibiricum Delar. ex Redoute processed with wine, 300g of Caulis Polygoni Multiflori, 300g of Rosa rugosa Thunb., 300g of Gastrodia elata Blume, 200g of Chrysanthemum morifolium Ramat., 300g of Eupatorium fortunei Turcz., and 300g of Ziziphus jujuba Mill.

[0075] Process: Weigh each medicinal material according to the prescription ratio, add 6 times the amount of water, boil and reflux for extraction twice, each time for 0.5 h. Combine the extraction solutions of the two times, filter while it is hot, sterilize and then dispense into containers to obtain the decoction.

[0076] Dosage and administration: Take it orally as a tea substitute, 300 - 600 mL per day.

[0077] Indications: Insomnia due to deficiency of both heart and spleen.

[0078] In this invention, clinical experimental research was carried out, and the mechanism of action of Wuwei Anshen Yin in treating insomnia was explored based on network pharmacology and molecular docking:

[0079] 1. Typical outpatient cases

[0080] Typical case 1

[0081] Patient Yu XX, male, 25 years old, student, unmarried.

[0082] Chief complaint: Difficulty in falling asleep for more than 2 months.

[0083] Initial diagnosis on May 24, 2024: Difficulty in falling asleep for more than 2 months. Present illness history: Difficulty in falling asleep, having many dreams and easy to wake up, accompanied by palpitations, forgetfulness, fatigue, occasional headache and chest tightness. The spirit is okay, the appetite is normal, defecation and urination are normal. The tongue is light red, the tongue coating is white and greasy, and the pulse is stringy and slippery. Past history: Denied past medical history. Epidemiological history: Denied epidemiological history and allergy history.

[0084] Physical examination: Stable vital signs, negative for heart, lungs and abdomen.

[0085] Evaluate sleep quality: Pittsburgh Sleep Quality Index (PSQI) score: Used to evaluate the sleep quality of the subjects in the recent 1 month, including sleep disorder, sleep efficiency, sleep duration, sleep quality, sleep onset latency, daytime dysfunction, and hypnotic drug use. Each item has a full score of 3 points. The higher the total score, the worse the sleep quality (the results are shown in Table 1).

[0086] Table 1 PSQI score of each evaluation index

[0087]

[0088]

[0089] Sleep quality evaluation:

[0090] According to the total PSQI score, the sleep quality of the subjects can be evaluated:

[0091] 0-?5 points: Excellent sleep quality.

[0092] 6-10 points: Good sleep quality.

[0093] 11-15 points: General sleep quality. It should be noted that there seems to be an error in the original text where "0-?5 points" is written. It should probably be "0-5 points". This translation is based on the corrected understanding.

[0094] 16 - 21 minutes: Poor sleep quality.

[0095] According to the score, it shows that the patient has poor sleep quality.

[0096] Course of diagnosis and treatment: The medical history was carefully inquired, including specific sleep conditions, history of using sedative and psychiatric drugs, and possible substance dependence. The patient denied all of them. The patient denied a history of smoking and drinking, and usually had a preference for fatty, sweet, and greasy foods. After insomnia, the patient did not take antidepressants, central stimulants, analgesics, theophylline drugs, and steroid psychiatric drugs, and had no obvious snoring history. After insomnia, the patient felt fatigued during the day and had a psychological fear of sleep at night, which seriously affected sleep quality. The patient's weight did not decrease in the past 3 months.

[0097] Based on the above condition, after excluding other underlying diseases, attending physician Ye Tao conducted a sleep quality assessment on the patient. Through the measurement of Pittsburgh Sleep Quality Index (PSQI), it was found that the patient had sleep disorders, and psychological counseling was actively provided to the patient. Attending physician Ye Tao believes that this disease belongs to the category of "insomnia" in traditional Chinese medicine. Zhang Jingyue in the Ming Dynasty pointed out in "Complete Works of Jingyue - Insomnia": "Although there are various causes of insomnia, only understanding the two aspects of pathogenic factors and healthy qi can summarize it... When the mind is at peace, one can sleep; when the mind is restless, one cannot sleep. The reasons for restlessness are either due to the disturbance of pathogenic factors or the deficiency of nutrient qi. Those with pathogenic factors are mostly excess syndromes, and those without pathogenic factors are all deficiency syndromes." This patient is a young male with irregular daily routines and usually has great learning pressure, resulting in disharmony between yin and yang, disharmony of qi and blood, and disharmony of zang - fu functions such as over - fatigue and internal injury. It is easy to cause qi deficiency, fire transformation, phlegm production, and blood stasis, leading to abnormal qi movement, yang not entering yin or yin not containing yang, abnormal yin - yang interaction, and restlessness of the mind, resulting in insomnia. Combining the four diagnostic methods of traditional Chinese medicine for this patient, the diagnosis is insomnia (syndrome of deficiency of both heart and spleen).

[0098] Diagnosis:

[0099] Traditional Chinese medicine diagnosis: Insomnia (syndrome of deficiency of both heart and spleen); Western medicine diagnosis: Insomnia disorder.

[0100] Prescription:

[0101] Schisandra chinensis (Turcz.) Baill. var. chinensis (processed with vinegar) 5g, Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow (stir - fried) 5g, Polygonatum sibiricum Delar. ex Redoute (processed with wine) 3g, Dolichos lablab L. (stir - fried) 3g, Caulis Polygoni multiflori 3g, Rosa rugosa Thunb. 3g, Gastrodia elata Bl. 3g, Chrysanthemi Flos 2g, Eupatorium fortunei Turcz. 3g, Ziziphus jujuba Mill. 3g

[0102] Method of use: Decoct in water for oral administration, a total of 7 doses, one dose per day (for drinking as tea).

[0103] Follow - up visit on June 1, 2024: The patient's sleep quality improved compared with before. It was easier to fall asleep, with fewer dreams, less likely to wake up, and no obvious palpitations. However, the patient still occasionally felt headache, chest tightness, and fatigue. The spirit was okay, appetite was normal, bowel movements and urination were normal. The tongue was pale red, the tongue coating was white, and the pulse was string - slippery. After taking the medicine, the patient felt that the sleep was better than before. The prescription was not changed for the time being, and the above - mentioned prescription was continued for 7 doses.

[0104] Follow-up visit on June 8, 2024: The patient reported that his sleep quality had improved significantly, he fell asleep quickly and was not easy to wake up, he could sleep up to 7-8 hours a day, he had no symptoms such as chest tightness and headache, he was in good spirits, had a good appetite, normal bowel movements, pale red tongue, white fur, and a stringy pulse.

[0105] Reassess your sleep quality:

[0106] Table 2 PSQI evaluation index scores

[0107] Evaluation Index Score before Treatment Score after Treatment Sleep Quality 3 1 Sleep Onset Time 3 1 Sleep Duration 3 1 Sleep Efficiency 2 1 Sleep Disorder 3 1 Daytime Function 3 1 Hypnotic Medication Use 0 0 Total Score 17 6

[0108] According to the scores, the patients' sleep quality improved significantly after taking the medicine, with the score dropping to 6 (see Table 2). This result proves that the prescription has a significant effect in improving patients' sleep disorders, improving sleep efficiency, and extending sleep duration.

[0109] Typical Case 2

[0110] The patient, Mr. He, is a 58-year-old male, retired and unmarried.

[0111] Chief complaint: Insomnia for 8+ years.

[0112] First visit, May 24, 2024: Insomnia for 8+ years. Current medical history: Difficulty falling asleep, frequent dreams and frequent awakenings. For the past 8 years, the patient has only been able to sleep 3-4 hours per night, accompanied by an irritable and uncontrollable temperament, dizziness, forgetfulness, fatigue, poor spirits, normal appetite, regular urination, unformed stools, pale red tongue with a greasy white coating, and a slippery pulse. Past medical history: Denies any past medical history. Epidemiological history: Denies any history of epidemiological or allergic reactions.

[0113] Physical examination: vital signs are stable, heart, lungs and abdomen are negative.

[0114] Assess sleep quality:

[0115] Pittsburgh Sleep Quality Index (PSQI) is used to assess the sleep quality of the subjects in the past month, including sleep disorders, sleep efficiency, sleep duration, sleep quality, sleep onset time, daytime dysfunction, and hypnotic medication use. Each item has a maximum score of 3 points. The higher the total score, the worse the sleep quality (see Table 3):

[0116] Table 3 PSQI evaluation index scores

[0117]

[0118]

[0119] Sleep quality evaluation:

[0120] Assessment of sleep quality: Pittsburgh Sleep Quality Index (PSQI) score (see Table 3):

[0121] Sleep quality evaluation:

[0122] Based on the total PSQI score, the sleep quality of the subject can be evaluated as follows:

[0123] 0 - 5 points: Excellent sleep quality.

[0124] 6 - 10 points: Good sleep quality.

[0125] 11 - 15 points: Average sleep quality.

[0126] 16 - 21 points: Poor sleep quality.

[0127] According to the score, it shows that the patient has poor sleep quality.

[0128] Course of diagnosis and treatment: The medical history was carefully inquired, including specific sleep conditions, history of taking sedative and psychiatric drugs, and possible substance dependence. The patient reported taking sedative and hypnotic drugs for a long time. He had a "hypertensive history" of more than 10 years and usually took "Nifedipine 20mg qd", stating that his blood pressure was usually well controlled. He had a smoking history of more than 30 years, with an average of 6 cigarettes per day, denied a history of alcohol consumption, and usually had a preference for fatty and sweet foods. After insomnia, he had been taking "Eszopiclone Tablets 1mg qd" for a long time. Initially, his sleep improved, but the improvement weakened in the later stage of taking the drug. He had a history of snoring. After insomnia, he felt fatigued and weak during the day, had difficulty concentrating, had a psychological fear of sleep at night, which seriously affected his sleep quality, and his weight had not decreased in the past 3 months.

[0129] Based on the above condition, after excluding other underlying diseases, attending physician Ye Tao conducted a sleep quality assessment on the patient. Through the measurement of Pittsburgh Sleep Quality Index (PSQI), it was found that the patient had sleep disorders, and psychological counseling was actively provided to the patient. Attending physician Ye Tao believed that this disease belongs to the category of "insomnia" in traditional Chinese medicine. Zhang Jingyue in the Ming Dynasty pointed out in "Complete Works of Jingyue - Insomnia": "Although there are various causes of insomnia, only understanding the two aspects of pathogenic factors and healthy qi can cover all aspects... When the mind is at peace, one can sleep; when the mind is restless, one cannot sleep. The reasons for restlessness are either due to the disturbance of pathogenic factors or the deficiency of nutrient qi. Those with pathogenic factors are mostly excessive syndromes, and those without pathogenic factors are all deficiency syndromes." This patient is an elderly male. Affected by the seven emotions, improper diet, overwork, etc., it leads to hyperactivity of yang and decline of yin, disharmony between yin and yang, yang not entering yin or yin not containing yang, abnormal combination of yin and yang, and restlessness of the mind, resulting in insomnia. Combining the four diagnostic methods of traditional Chinese medicine for this patient, the diagnosis is insomnia (syndrome of deficiency of both the heart and spleen).

[0130] Diagnosis:

[0131] Traditional Chinese medicine diagnosis: Insomnia (syndrome of deficiency of both the heart and spleen); Western medicine diagnosis: Insomnia disorder.

[0132] Prescription (for internal administration as a tea):

[0133] Vinegar Schisandra 5g, stir-fried Ziziphus jujuba seeds 5g, wine-soaked Polygonatum 3g, stir-fried white hyacinth bean 3g, Polygonum multiflorum 3g, rose 3g, Gastrodia elata 3g, chrysanthemum 2g, Cymbidium orientale 3g, and jujube 3g.

[0134] Directions for use: Decoction in water for oral administration, 7 doses in total, one dose per day (drink instead of tea).

[0135] Follow-up visit on May 30, 2024: The patient's sleep quality has improved compared to before. He can fall asleep easily, has fewer dreams, and is in better spirits than before. He experiences fewer dizziness and drowsiness and is less tired after daytime activities. However, he still sleeps only 3-4 hours per night and still has forgetfulness. His spirits are good, his appetite is normal, his bowel movements are regular, his tongue is light red, his tongue coating is greasy, and his pulse is smooth. After taking the medicine, the patient feels that his sleep has improved compared to before. He is advised to reduce the dose of "Zopiclone Tablet" to half a tablet and continue to take 7 doses of the above medicine without changing the prescription for the time being.

[0136] Follow-up visit on June 8, 2024: The patient reported that his sleep quality had improved significantly, he could fall asleep quickly with fewer dreams and was not easy to wake up, he could sleep 5-6 hours a day, his attention was more focused during the day, he was not easily tired or irritable, he had no symptoms such as palpitations and chest tightness, but he still felt dizzy occasionally, his spirits were good, his appetite was good, his bowel movements were normal, his tongue was pale red, his tongue coating was white, and his pulse was stringy.

[0137] Reassess your sleep quality:

[0138] Table 4 PSQI evaluation index scores

[0139] Evaluation Index Score before Treatment Score after Treatment Sleep Quality 3 2 Sleep Onset Time 3 2 Sleep Duration 3 3 Sleep Efficiency 3 3 Sleep Disorder 3 2 Daytime Function 3 2 Hypnotic Medication Use 2 1 Total Score 20 15

[0140] According to the scores, the patients' sleep quality improved significantly after taking the medicine, with the score dropping to 15 points (see Table 4). This result proves that the prescription has a significant effect in improving patients' sleep disorders, improving sleep efficiency, and extending sleep duration.

[0141] Typical Case 3

[0142] The patient, Yue Moumou, is a 25-year-old female student who is unmarried.

[0143] Chief complaint: Insomnia for 3+ months.

[0144] First visit on May 24, 2024: Insomnia for 3+ months. Current medical history: Complaints of difficulty falling asleep for 3+ months, frequent awakening after sleep, frequent dreams, daytime fatigue, depression, a general feeling of heaviness and discomfort, loss of appetite, palpitations, dizziness, poor spirits, frequent urination, unformed stools, red tongue with a thin white coating, and a stringy pulse. Past medical history: Denies any previous medical history. Epidemiological history: Denies any history of epidemiological or allergic reactions.

[0145] Physical examination: vital signs are stable, heart, lungs and abdomen are negative.

[0146] Evaluating sleep quality: The Pittsburgh Sleep Quality Index (PSQI) score is used to assess the sleep quality of the subjects in the recent one month, including sleep disorders, sleep efficiency, sleep duration, sleep quality, sleep onset latency, daytime dysfunction, and the use of hypnotic drugs. Each item has a full score of 3 points. The higher the total score, the worse the sleep quality (see Table 5):

[0147] Table 5 Scoring of each PSQI evaluation index

[0148]

[0149]

[0150] Sleep quality evaluation:

[0151] According to the total PSQI score, the sleep quality of the subjects can be evaluated as follows:

[0152] 0 - 5 points: Excellent sleep quality.

[0153] 6 - 10 points: Good sleep quality.

[0154] 11 - 15 points: Moderate sleep quality.

[0155] 16 - 21 points: Poor sleep quality.

[0156] According to the score, it shows that the patient has poor sleep quality.

[0157] Course of diagnosis and treatment: The medical history was carefully inquired, including specific sleep conditions, the history of using sedative and psychiatric drugs, and possible substance dependence. The patient denied all of them. The patient denied a history of smoking and drinking, and usually had a preference for fatty and sweet foods. After insomnia, the patient did not take antidepressants, central stimulants, analgesics, theophylline drugs, and steroids and other psychiatric drugs, and had no obvious snoring history. After insomnia, the patient was easily fatigued during the day, occasionally felt pain and discomfort in multiple parts of the body, had a psychological fear of sleep at night, which seriously affected sleep quality, and did not lose weight in the past 3 months.

[0158] Based on the above condition, after ruling out other underlying diseases, the attending physician Ye Tao conducted a sleep quality assessment on the patient. Through the measurement of Pittsburgh Sleep Quality Index (PSQI), it was found that the patient had sleep disorders, and the attending physician actively provided psychological counseling to the patient. The attending physician Ye Tao believes that this disease belongs to the category of "insomnia" in traditional Chinese medicine. Zhang Jingyue in the Ming Dynasty pointed out in "Complete Works of Jingyue - Insomnia": "Although there are various causes of insomnia, only understanding the two aspects of pathogenic factors and healthy qi can cover all aspects... When the mind is at peace, one can fall asleep; when the mind is restless, one cannot fall asleep. The reasons for restlessness are either due to the disturbance of pathogenic factors or the deficiency of nutrient qi. Those with pathogenic factors are mostly excess syndromes, and those without pathogenic factors are all deficiency syndromes." This patient is a young female. Difficulty in falling asleep, frequent dreaming and easy waking up are caused by deficiency of both the heart and spleen, insufficient nutrient blood, failure to nourish the mind, and restlessness of the mind. Insufficient blood to nourish the heart leads to palpitations; deficiency of qi and blood, inability to nourish the brain, and failure of clear yang to rise result in dizziness; deficiency of the spleen qi leads to poor appetite, insufficient source of qi and blood production, and deficiency of qi and blood manifested as fatigue. Combining the four diagnostic methods for this patient, the diagnosis is insomnia (syndrome of deficiency of both the heart and spleen).

[0159] Diagnosis:

[0160] Traditional Chinese medicine diagnosis: Insomnia (syndrome of deficiency of both the heart and spleen); Western medicine diagnosis: Insomnia.

[0161] Prescription (for oral administration as a medicinal tea):

[0162] Schisandra chinensis (Turcz.) Baill. var. chinensis 5g, Semen Ziziphi Spinosae 5g, Polygonatum sibiricum Delar. ex Redoute 3g, Dolichos lablab L. 3g, Caulis Polygoni Multiflori 3g, Rosa rugosa Thunb. 3g, Gastrodia elata Blume 3g, Chrysanthemi Flos 2g, Eupatorium fortunei Turcz. 3g, Fructus Jujubae 3g.

[0163] Usage: Decoct in water for oral administration, a total of 7 doses, one dose per day (as a medicinal tea).

[0164] Follow - up visit on May 30, 2024: The patient reported having a sleepy feeling after taking the medicine and could fall asleep for 5 - 6 hours, but the sleep was still light. There were still occasional dizziness, a feeling of heaviness all over the body, fatigue, and low mood, which were improved compared to before. The appetite increased significantly, there was occasional abdominal distension, the frequency of urination decreased compared to before, and the stool was loose. The tongue was red, the coating was thin and white, and the pulse was string - like and thready. The prescription was not changed temporarily, and the above - mentioned prescription was continued for 7 doses.

[0165] Follow - up visit on June 8, 2024: The patient reported that the sleep quality had improved significantly. The patient could fall asleep quickly, had fewer dreams and was not easy to wake up, and could sleep for 7 - 8 hours every day. The attention during the day was more concentrated than before, and it was not easy to feel tired. There were no symptoms such as dizziness, palpitations, chest tightness, abdominal pain, abdominal distension, or vomiting. The spirit was good, the appetite was normal, the urine and stool were normal. The tongue was light red, the coating was white, and the pulse was thready.

[0166] Re - evaluate the sleep quality:

[0167] Table 6 Scores of PSQI assessment indicators

[0168] Evaluation Index Score before Treatment Score after Treatment Sleep Quality 3 1 Sleep Onset Time 3 2 Sleep Duration 2 3 Sleep Efficiency 2 1 Sleep Disorder 3 1 Daytime Function 3 1 Hypnotic Medication Use 0 0 Total Score 16 9

[0169] According to the score, after the patient took the medicine, the sleep quality was significantly improved, specifically manifested as the score dropped to 9 points (the results are shown in Table 6). This result proves that the prescription has significant effects in improving the patient's sleep disorder, enhancing sleep efficiency, and prolonging sleep duration, etc.

[0170] Typical Case 4

[0171] Patient Yan XX, female, 35 years old, an employee, married.

[0172] Chief complaint: Difficulty falling asleep accompanied by early awakening for more than 1 year, aggravated for more than 1 month.

[0173] Initial diagnosis on May 24, 2024: The patient reported that she began to have difficulty falling asleep due to work pressure more than 1 year ago. The falling asleep time was about 1 hour, the sleep duration was about 3 hours, or sometimes she slept and sometimes woke up, accompanied by dizziness, fatigue, palpitations, sometimes feeling anxious and irritable, thirsty and wanting to drink, having no appetite, being prone to catching colds usually, normal urination, dry and hard stools, red tongue with little coating, and thready and taut pulse. Past history: Denied past medical history. Epidemiological history: Denied epidemiological history and allergy history.

[0174] Physical examination: Stable vital signs, negative for heart, lungs and abdomen.

[0175] Evaluate sleep quality:

[0176] Pittsburgh Sleep Quality Index (PSQI) score: Used to evaluate the sleep quality of the subjects in the recent 1 month, including sleep disorder, sleep efficiency, sleep duration, sleep quality, falling asleep time, daytime dysfunction, and hypnotic drug use. Each item has a full score of 3 points. The higher the total score, the worse the sleep quality (the results are shown in Table 7).

[0177] Table 7 PSQI scores for each evaluation index

[0178]

[0179]

[0180] Sleep quality evaluation:

[0181] According to the total PSQI score, the sleep quality of the subjects can be evaluated:

[0182] 0 - 5 points: Excellent sleep quality.

[0183] 6 - 10 points: Good sleep quality.

[0184] 11 - 15 points: Average sleep quality.

[0185] 16 - 21 points: Poor sleep quality.

[0186] According to the score, it shows that the patient has poor sleep quality.

[0187] Diagnosis and Treatment: A thorough medical history was taken, including details of sleep patterns, use of sedatives and psychotropic medications, and any substance dependence, all of which the patient denied. He also denied smoking and drinking and generally preferred rich, fatty foods. He had not taken antidepressants, stimulants, analgesics, theophylline, or steroids for insomnia, and had no history of significant snoring. However, his insomnia had caused him difficulty concentrating during the day, fatigue, and irritability. He also had a psychological fear of sleeping at night, which severely impacted his sleep quality. He had not lost weight in the past three months.

[0188] Based on the above condition, after excluding other underlying diseases, Dr. Ye Tao, the attending physician, conducted a sleep quality assessment on the patient. Through the measurement of the Pittsburgh Sleep Quality Index (PSQI), it was found that the patient had sleep disorders, and the patient was actively provided psychological counseling. Dr. Ye Tao believed that the disease belongs to the category of "insomnia" in traditional Chinese medicine. Yang is strong outside, Yin is deficient inside, and Yang cannot enter Yin, so there is insomnia; the heart blood is deficient and cannot sleep, and the heart is restless and waking from sleep. This is a symptom of insufficient heart blood and excessive heart fire. The patient usually has high work pressure and stays up late, which consumes Qi and blood. Qi and blood are deficient, Yin is deficient and fire is excessive, which disturbs the mind, so there is insomnia, dreaminess, and dry mouth; the spleen is not functioning properly, so the appetite is poor; the tongue is red with little coating, and the pulse is stringy and thin. Combining the four examinations of the patient, the diagnosis is insomnia (heart and spleen deficiency syndrome).

[0189] diagnosis:

[0190] Traditional Chinese medicine diagnosis: insomnia (heart and spleen deficiency syndrome); Western medicine diagnosis: insomnia.

[0191] Prescription (for internal use instead of tea):

[0192] Vinegar Schisandra 5g, stir-fried Ziziphus jujuba seeds 5g, wine-soaked Polygonatum 3g, stir-fried white hyacinth bean 3g, Polygonum multiflorum 3g, rose 3g, Gastrodia elata 3g, chrysanthemum 2g, Cymbidium orientale 3g, and jujube 3g.

[0193] Directions for use: Decoction in water for oral administration, 7 doses in total, one dose per day (drink instead of tea).

[0194] Follow-up on June 1, 2024: The patient's sleep quality has improved compared to before. She falls asleep easily and wakes up easily. She has no obvious palpitations or irritability, but she still feels dizzy and tired occasionally. Her appetite is poor, but her spirits are good, her appetite is good, and her bowel movements are normal. Her tongue is red with a white coating, and her pulse is stringy and fine. After taking the medicine, the patient feels that her sleep has improved compared to before. No change in the prescription is given for the time being. She continues to take the above medicine for 7 doses.

[0195] Follow-up visit on June 8, 2024: The patient reported that his sleep quality had improved significantly, he fell asleep quickly and was not easy to wake up, he could sleep up to 7-8 hours a day, he occasionally felt dizzy when he woke up in the morning, he was not tired easily, he was in good spirits, had a good appetite, normal bowel movements, a red tongue with a thin white coating, and a stringy pulse.

[0196] Reassess your sleep quality:

[0197] Table 8 Scoring of Each PSQI Evaluation Index

[0198] Evaluation Index Score before Treatment Score after Treatment Sleep Quality 3 1 Sleep Onset Time 3 1 Sleep Duration 3 0 Sleep Efficiency 2 1 Sleep Disorder 3 1 Daytime Function 2 0 Hypnotic Medication Use 0 0 Total Score 16 4

[0199] According to the scoring, after the patient took the medicine, the sleep quality was significantly improved, specifically manifested as the score dropped to 4 points (see Table 8 for details). This result proves that the prescription has significant effects in improving the patient's sleep disorder, enhancing sleep efficiency, and prolonging sleep duration, etc.

[0200] Typical Case 5

[0201] Patient Lu XX, male, 63 years old, retired, married.

[0202] Chief complaint: Insomnia for more than 5 years.

[0203] Initial diagnosis on May 24, 2024: The patient complained of insomnia for more than 10 years and had received repeated traditional Chinese and Western medical treatments in many hospitals without obvious effects. Currently, it is difficult to fall asleep at night, or there are many dreams during sleep, easy to wake up, and difficult to fall asleep again after waking up. He has been taking estazolam tablets to fall asleep, and cannot fall asleep after stopping the medicine. Sometimes he feels dizzy and headache, accompanied by palpitation, flustered, limb fatigue, bitter taste in the mouth, and dry stool. The tongue is pale, the coating is thin and white, and the pulse is deep and thready. Past history: Denied past medical history. Epidemiological history: Denied epidemiological history and allergy history.

[0204] Physical examination: The vital signs are stable, and the heart, lungs, and abdomen are negative.

[0205] Evaluate sleep quality: Pittsburgh Sleep Quality Index (PSQI) score: Used to evaluate the sleep quality of the subjects in the recent 1 month, including sleep disorder, sleep efficiency, sleep duration, sleep quality, sleep onset latency, daytime dysfunction, and hypnotic drug use. Each item has a full score of 3 points. The higher the total score, the worse the sleep quality (the results are shown in Table 9).

[0206] Table 9 Scoring of Each PSQI Evaluation Index

[0207] Evaluation Index Score before Treatment Sleep Quality 3 Sleep Onset Time 3 Sleep Duration 3 Sleep Efficiency 2 Sleep Disorder 3 Daytime Function 2 Hypnotic Medication Use 2 Total Score 18

[0208] Sleep quality evaluation:

[0209] According to the total PSQI score, the sleep quality of the subjects can be evaluated as follows:

[0210] 0 - 5 points: The sleep quality is very good.

[0211] 6 - 10 points: The sleep quality is relatively good.

[0212] 11 - 15 points: The sleep quality is average.

[0213] 16 - 21 points: The sleep quality is poor.

[0214] According to the score, the patient's sleep quality was poor.

[0215] Diagnosis and Treatment: A thorough medical history was taken, including details of sleep patterns, history of sedative and psychotropic medication use, and any substance use. The patient reported chronically taking 1 mg of estazolam tablets daily before bed to fall asleep. He denied any history of smoking or alcohol consumption and generally preferred fatty and rich foods. He had not taken any central nervous system stimulants, analgesics, theophylline, or steroids since his insomnia, and had no history of significant snoring. Since his insomnia, he had difficulty concentrating during the day and was easily fatigued. He also had a psychological fear of sleeping at night, which severely impacted his sleep quality. He had not lost any weight in the past three months.

[0216] Based on the above condition, after excluding other underlying diseases, Dr. Ye Tao conducted a sleep quality assessment on the patient. Through the measurement of the Pittsburgh Sleep Quality Index (PSQI), it was found that the patient had sleep disorders and the patient was actively provided psychological counseling. Dr. Ye Tao believed that the disease fell into the category of "insomnia" in Traditional Chinese Medicine. The deficiency of both the heart and spleen, insufficient blood and nutrients, could not nourish the mind, resulting in restlessness, insomnia, frequent dreams, and difficulty falling asleep after waking; insufficient Qi and blood, the lack of nourishment to the clear orifices, resulting in dizziness and headaches; insufficient Qi and blood, unable to nourish the tendons and veins, resulting in palpitations and anxiety. Combining the patient's four examinations, Dr. Ye Tao diagnosed insomnia (heart and spleen deficiency syndrome).

[0217] diagnosis:

[0218] Traditional Chinese medicine diagnosis: insomnia (heart and spleen deficiency syndrome); Western medicine diagnosis: insomnia.

[0219] Prescription (for internal use instead of tea):

[0220] Vinegar Schisandra 5g, stir-fried Ziziphus jujuba seeds 5g, wine-soaked Polygonatum 3g, stir-fried white hyacinth bean 3g, Polygonum multiflorum 3g, rose 3g, Gastrodia elata 3g, chrysanthemum 2g, Cymbidium orientale 3g, and jujube 3g.

[0221] Directions for use: Decoction in water for oral administration, 7 doses in total, one dose per day (drink instead of tea).

[0222] Follow-up visit on June 1, 2024: The patient reported feeling sleepy after taking the medication, and sleep quality improved significantly, with sleep lasting 5-6 hours. However, sleep was still shallow and waking easily. Dizziness, headache, and limb fatigue were improved compared to before. There was no obvious palpitations or heart palpitations. The patient was in good spirits, had a good appetite, and had normal bowel movements. The tongue was red with a white coating, and the pulse was stringy. The patient felt that his sleep had improved after taking the medication. The patient was advised to reduce the dose of estazolam to half a tablet and continue to take 7 doses of the above prescription without changing the prescription for the time being.

[0223] Follow-up visit on June 8, 2024: The patient reported that his sleep quality had improved significantly, he fell asleep quickly and was not easy to wake up, he could sleep for 6-7 hours a day, he occasionally felt dizzy when he woke up in the morning, he did not have a headache during the medication period, he was not easily tired, he was in good spirits, had a good appetite, normal bowel movements, pale red tongue, thin white fur, and a stringy pulse.

[0224] Re-evaluate sleep quality:

[0225] Scores of each evaluation index of PSQI in Table 10

[0226]

[0227]

[0228] According to the scores, after the patients took the medicine, their sleep quality was significantly improved, specifically manifested as the score dropped to 6 points (see Table 10 for details). This result proves that the prescription has significant effects in improving the sleep disorders of patients, enhancing sleep efficiency, and prolonging sleep duration. 2. Explore the mechanism of action of Wuwei Anshen Decoction in treating insomnia based on network pharmacology and molecular docking

[0229] 2.1 Methods

[0230] 2.1.1 Screening of active ingredients and targets

[0231] The chemical components of Wuwei Anshen Decoction were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Components with drug likeness (DL) ≥ 0.18 and OB ≥ 30% were collected as the bioactive components of Wuwei Anshen Decoction. At the same time, the targets of each active ingredient were obtained, and the obtained targets were converted into standard gene names using the UniProt database. For traditional Chinese medicines not included in TCMSP, the Herb data was used to query the components, and the obtained chemical components were retrieved in TCMSP. Similarly, components were screened using drug likeness (DL) ≥ 0.18 and OB ≥ 30%, and then the screened components were queried for their targets in the TCMSP database. Finally, the components of Wuwei Anshen Decoction and the targets of Wuwei Anshen Decoction were sorted out and summarized

[0232] 2.1.2 Screening of insomnia targets

[0233] Using "Insomnia" as the keyword, the GeneCards, PharmGKB, OMIM, and NCBI databases were used to obtain the targets of insomnia. Finally, the targets of insomnia in the four databases were merged and duplicates were removed to obtain the final targets of insomnia. In addition, the intersection of the targets of the components and the targets of insomnia was taken to finally obtain the potential targets of Wuwei Anshen Decoction against Insomnia

[0234] 2.1.3 Construction of PPI

[0235] To obtain potential targets for insomnia, the intersection targets were imported into the STRING (https: / / string-db.org) database to construct a protein-protein interaction network diagram (PPI). Meanwhile, the species was set to Homo sapiens, the required minimum interaction score was set to 0.9, and the disconnected nodes were removed. Then, we imported the complex protein interaction relationship data into Cytoscape 3.7.0 software. And the plugin CytoNCA was used to calculate the node degree value (DC). Finally, the core targets were screened according to the degree value.

[0236] 2.1.4. Enrichment analysis.

[0237] The relevant data packages in R software (enrichplot, clusterProfiler, ggplot2, Enrichplod, pathview) were used to perform GO and KEGG functional enrichment analysis on the intersection targets. The corresponding P-values were calculated, and false discovery rate (FDR) correction was applied. For GO and KEGG pathway enrichment analysis, a significance level with P-value ≤ 0.05 and Q-value ≤ 0.05 was considered statistically significant. The most influential entries in the GO and KEGG analyses were selected to draw the relationship diagram.

[0238] 2.1.5. Molecular docking.

[0239] The main active compounds in Wuwei Anshen Decoction were subjected to molecular docking with the core targets of insomnia. Molecular docking software was used to determine ligand-protein interactions. Ligand preparation: The 2D structure files of the main active compounds in Wuwei Anshen Decoction were obtained from the PubChem (https: / / pubchem.ncbi.nlm.nih.gov / ) database and then imported into Maestro software. Using the LigPrep module, with the default configuration of the OPLS4 force field in Schrödinger, potential ionization at physiological pH, and optical isomers of the ligand, the optimized ligand was obtained. Receptor preparation: In the RCSB Protein Data Bank (PDB, https: / / www.rcsb.org / ), we selected protein files with a resolution < 2.5 Å and a complete pocket structure. After that, they were imported into Maestro software, and the receptor was de-optimized using the Protein Preparation Wizard with default settings. Finally, molecular docking studies were performed using the Glide module of Schrödinger.

[0240] 2.2 Results:

[0241] 2.2.1. Screening of active ingredients and targets of Wuwei Anshen Decoction.

[0242] After meeting the screening criteria (DL≥0.18, OB≥30%), through searching the TCMSP and Herb databases, the bioactive components and targets of 10 Chinese herbs in Wuwei Anshen Decoction were finally obtained. Among them, we retrieved 1 active component of Dolichos lablab, 19 active components of Ziziphus jujuba, 9 active components of Polygonatum sibiricum, 18 active components of Chrysanthemum morifolium, 7 active components of Rosa rugosa, 13 active components of Schisandra chinensis, 4 active components of Gastrodia elata, 1 active component of Caulis Polygoni Multiflori, 7 active components of Ziziphus spinosa, and 7 active components of Eupatorium fortunei.

[0243] 2.2.2. Screening of insomnia targets.

[0244] Using "Insomnia" as the keyword, the GeneCards, PharmGKB, OMIM, and NCBI databases were used to obtain the targets of insomnia. A total of 1 target was retrieved in PharmGKB, 56 + 1 targets were retrieved in NCBI, 6978 + 56 + 1 targets were retrieved in Genecards, and 1 target was retrieved in OMIM. The distribution numbers of insomnia targets in each database are shown in Figure 6 A. The intersection of the predicted targets of the active components in Wuwei Anshen Decoction and the targets of insomnia was obtained, and a total of 145 potential core targets were obtained ( Figure 6 B). These results indicate that Wuwei Anshen Decoction may treat insomnia through 145 different target genes.

[0245] 2.2.3. "Traditional Chinese medicine-active ingredient-target-insomnia" network and screening of active components of Wuwei Anshen Decoction.

[0246] To deeply understand the interaction mechanism of the active compounds in Wuwei Anshen Decoction during the intervention and treatment of insomnia, according to the mapping of intersection targets, the complex corresponding relationship between "traditional Chinese medicine-active ingredient-target-insomnia" was found and imported into the Cytoscape 3.7.0 software to draw the "traditional Chinese medicine-active ingredient-target-insomnia" map. The CytoNCA plugin of Cytoscape 3.7.0 was used to calculate the degree value (Degree) of the component nodes, and the importance of the components was judged according to the Degree of the compounds. The results showed that the top 8 compounds with the Degree of the compounds were: MOL000098 (Degree: 89), MOL000422 (Degree: 35), MOL000006 (Degree: 33), MOL000358 (Degree: 27), MOL000449 (Degree: 21), MOL007213 (Degree: 21), MOL012921 (Degree: 20), MOL000627 (Degree: 19). The top 8 active components with the Degree of the compounds are very likely to represent most of the pharmacodynamic effects of Wuwei Anshen Decoction.

[0247] 2.2.4. PPI Analysis

[0248] To obtain potential targets for insomnia, the intersecting targets were imported into the STRING (https: / / string-db.org) database to establish a protein-protein interaction relationship file. Then, we imported the complex protein interaction relationship file into Cytoscape 3.7.0 software to construct a PPI network diagram ( Figure 7 ). The plug-in CytoNCA was used to calculate the topological parameters of the nodes, and the top 5 proteins ranked by Degree were selected ( Figure 8 ). It was found that TP53 had the highest Degree, which was 25. In addition, the DEGREE of AKT1 was 23. The Degrees of these 5 targets were much higher than those of other proteins. Therefore, these 5 targets may play an important role in insomnia.

[0249] 2.2.5. Enrichment Analysis

[0250] A total of 2727 GO terms (P < 0.05) were obtained from the GO ontology analysis results, including 2431 biological process GO terms (BP), 107 cellular component GO terms (CC), and 189 molecular function GO terms (MF). The results showed that the potential targets of Wuwei Anshen Decoction in the treatment of insomnia were mainly concentrated in other biological processes such as response to xenobiotic stimulus (GO:0009410), etc. CC analysis found that it was mainly involved in membrane raft (GO:0045121). MF analysis was mainly enriched in aspects such as neurotransmitter receptor activity.

[0251] In the KEGG analysis, with P < 0.05 as the threshold, a total of 170 signaling pathways were obtained. The top 15 signaling pathways with the highest gene enrichment were selected for analysis. It was found that the core genes were mainly enriched in pathways such as Lipid and atherosclerosis, Chemical carcinogenesis-receptor activation, AGE-RAGE signaling pathway in diabetic complications, etc. The top 15 pathways with the highest enrichment degree were selected, and the "pathway - target" network diagram was constructed using Cytoscape 3.7.0 software. The results are shown in Figure 9 as shown, and it can be found that the treatment of insomnia with Wuwei Anshen Decoction is multi-target and multi-pathway.

[0252] 2.2.6. Molecular Docking

[0253] Generally, the lower the binding energy between a ligand and a receptor, the more stable the structure. Figure 10 Figure 10 shows the docking binding energy of the core components docked with the core targets. It can be found that the docking binding energy of Nuciferine with the HSP90AA1 protein is the lowest, at -10.62 Kcal / mol. We selected the complexes with the lowest binding energy between each protein and the small molecule for detailed analysis. The specific docking diagrams of each small molecule with each protein are shown in Figure 11 As shown. Taking the complex formed by Nuciferine and HSP90AA1 as an example for analysis: It can be found that the Nuciferine small molecule can be embedded in the HSP90AA1 protein and interact with multiple amino acid residues. Among them, the Nuciferine small molecule can have Pi-Pi stacking with the Phe138 residue of the HSP90AA1 protein and Pi-cation with the Trp162 residue. In addition, it also has hydrophobic interactions with the Ala111 residue, Tyr139 residue, Phe138 residue, Leu107 residue, Trp162 residue, Leu103 residue, Val150 residue, Met98 residue, Leu48 residue, Val186 residue, and polar interactions with the Asn51 residue. To sum up, the molecular docking results can prove that most of the active ingredients in Wuwei Anshen Decoction can bind more tightly and firmly to the 5 core proteins, thus forming relatively stable complexes.

[0254] 2.3 Discussion

[0255] Insomnia is a common sleep disorder, which is considered to be mainly caused by factors such as HPA axis dysfunction, central neurotransmitter disorders, inflammatory response factors, and changes in vagal tone. This study used network pharmacology and molecular docking methods to explore the potential of Wuwei Anshen Decoction in the treatment of insomnia.

[0256] In this study, through PPI and network topology analysis, it was found that tumor protein P53 (TP53), protein kinase B1 (AKT1), heat shock protein (HSP90AA1), tumor necrosis factor (TNF), and interleukin 6 (IL-6) were the core targets of Wuwei Anshen Decoction in the treatment of insomnia. IL-6 and TNF-α are common inflammatory factors. It has been reported that the levels of IL-6 and TNF-α in insomnia patients are significantly higher than those in healthy individuals, and reducing their levels has a sedative effect. IL-6 is an important cytokine in the inflammatory response. Based on the close relationship between inflammation and sleep, IL-6 also plays an important role in sleep regulation. Studies have shown that sleep deprivation or sleep disorders can lead to upregulation of IL-6 expression. IL-6 can also affect sleep by regulating the transcription of circadian rhythm genes. TNF is a typical inflammatory mediator. Domestic and foreign literature has pointed out that inflammatory mediators can induce insomnia by regulating the sleep-wake cycle and affecting slow-wave sleep. AKT1, as a class of serine / threonine protein kinases, plays a key role in many biological processes. The processes it participates in cover multiple aspects such as cell proliferation, growth, and metabolism. Li Hong et al. conducted a study on non-organic insomnia during the perimenopausal period. The research results showed that the expression level of AKT mRNA in such insomnia patients showed a significant upward trend, which in turn increased the content of AKT and p-AKT proteins. After a series of cascade reactions, it ultimately led to an increase in the content of TNF-α in the serum. TNF-α, as a key inflammatory factor, has a wide range of biological activities and can participate in the activation of the HPA axis to affect insomnia; in addition, it is also an important immune regulatory factor that affects the sleep process by influencing central nervous regulation. TP53 is an oncogene and is regulated by the biological clock. The circadian rhythm disorder caused by abnormal biological clocks may lead to abnormal cell division and significantly affect the fluctuation of the sleep / wake cycle.

[0257] By performing GO functional analysis and KEGG pathway enrichment analysis on the targets of Wuwei Anshen Decoction acting on insomnia, it was found that the treatment of insomnia with Wuwei Anshen Decoction might be mainly related to the following pathways: lipid and atherosclerosis pathway, AGE-RAGE signaling pathway in diabetic complications, chemical carcinogenesis-receptor activation signaling pathway, and fluid shear stress and atherosclerosis pathway, etc. Through comparison, it was found that most of the core targets were concentrated in the lipid and atherosclerosis pathway. Subsequently, the lipid and atherosclerosis pathway (hsa05417) can be retrieved on the KEGG website, and the pathway branch participated by the core targets is the PI3K / AKT signaling pathway. Therefore, the treatment of insomnia with Wuwei Anshen Decoction may involve the PI3K / AKT signaling pathway, and the PI3K / AKT signaling pathway plays a regulatory role in the normal activity of neuronal cells. Among them, the increase in the levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) can regulate the activity of genes related to the transduction of the pathogenesis of insomnia driven by inflammatory cytokines. The PI3K / AKT signaling pathway can regulate the processes of differentiation, proliferation and apoptosis of neuronal cells in the brain, thereby inhibiting the excessive activity of cells and participating in the repair of neurons and the recovery of cognitive function after sleep deprivation, which is achieved by regulating apoptosis and inflammation. Studies have shown that if the expression of PI3K and AKT proteins is inhibited, it will cause severe sleep deprivation in rats, disrupt their circadian rhythm, and then damage neuronal cells and affect learning and memory abilities. On the contrary, when the expression of PI3K and AKT proteins is activated, it can inhibit the excessive autophagy and apoptosis of neurons, reduce the number of neurons induced by sleep deprivation, and thus improve the sleep state. Some studies have pointed out that the diabetic complication signaling pathway can promote the increase in the phosphorylation level of MAPK, and then increase the expression levels of factors such as IL-1, IL-6, TNF-α, etc., and these factors are closely related to the occurrence and development of insomnia.

[0258] The molecular docking results showed that both the key disease targets and the main active components in Wuwei Anshen Decoction had good docking activities, confirming that the active components of Wuwei Anshen Decoction could achieve the therapeutic effect on insomnia by regulating core target genes such as AKT1, TP53, IL-6, HSP90AA1, TNF, etc., through the above various signaling pathways. This phenomenon indicates that the treatment of insomnia with Wuwei Anshen Decoction works synergistically through multiple signaling pathways and multiple targets, reflecting the complexity of its treatment mechanism.

[0259] In summary, this study explained the potential mechanism of action of Wuwei Anshen Decoction in the treatment of insomnia to a certain extent, demonstrating the advantages of traditional Chinese medicine compound preparations in the treatment of diseases by acting synergistically with multiple active components, multiple pathways and multiple targets. This study provided a theoretical and basic basis for the clinical research of Wuwei Anshen Decoction in the treatment of insomnia.

Claims

1. A drug for treating insomnia of the syndrome of deficiency of both the heart and spleen, characterized in that: The medicinal active ingredients are calculated according to weight components: prepared from 200 - 800 parts of Schisandra chinensis (Turcz.) Baill. var. chinensis f. acida (Rehd.) Law, 200 - 800 parts of Semen Ziziphi Spinosae stir-fried, 200 - 800 parts of Dolicho lablab L. stir-fried, 100 - 500 parts of Polygonatum sibiricum Delar. ex Redoute var. kingianum (Coll. et Hemsl.) Y. C. Tang et Wang steamed with wine, 100 - 500 parts of Caulis Polygoni Multiflori, 100 - 500 parts of Rosa rugosa Thunb., 100 - 500 parts of Gastrodia elata Blume, 50 - 400 parts of Chrysanthemum morifolium Ramat., 100 - 500 parts of Eupatorium fortunei Turcz. and 100 - 500 parts of Ziziphus jujuba Mill..

2. The drug for treating insomnia of the syndrome of deficiency of both the heart and spleen as claimed in claim 1, wherein: The medicinal active ingredients are calculated according to weight components: prepared from 400 - 600 parts of Schisandra chinensis (Turcz.) Baill. var. chinensis f. acida (Rehd.) Law, 400 - 600 parts of Semen Ziziphi Spinosae stir-fried, 400 - 600 parts of Dolicho lablab L. stir-fried, 200 - 400 parts of Polygonatum sibiricum Delar. ex Redoute var. kingianum (Coll. et Hemsl.) Y. C. Tang et Wang steamed with wine, 200 - 400 parts of Caulis Polygoni Multiflori, 200 - 400 parts of Rosa rugosa Thunb., 200 - 400 parts of Gastrodia elata Blume, 100 - 300 parts of Chrysanthemum morifolium Ramat., 200 - 400 parts of Eupatorium fortunei Turcz. and 200 - 400 parts of Ziziphus jujuba Mill..

3. The drug for treating insomnia of the syndrome of deficiency of both the heart and spleen according to claim 1 or 2, characterized in that: The medicinal active ingredients are calculated according to weight components: prepared from 500 parts of Schisandra chinensis (Turcz.) Baill. var. chinensis f. acida (Rehd.) Law, 500 parts of Semen Ziziphi Spinosae stir-fried, 500 parts of Dolicho lablab L. stir-fried, 300 parts of Polygonatum sibiricum Delar. ex Redoute var. kingianum (Coll. et Hemsl.) Y. C. Tang et Wang steamed with wine, 300 parts of Caulis Polygoni Multiflori, 300 parts of Rosa rugosa Thunb., 300 parts of Gastrodia elata Blume, 200 parts of Chrysanthemum morifolium Ramat., 300 parts of Eupatorium fortunei Turcz. and 300 parts of Ziziphus jujuba Mill..

4. The preparation method of the drug for treating insomnia of the syndrome of deficiency of both the heart and spleen as described in any one of claims 1-3, characterized in that: Weigh all the medicinal materials in the prescription according to the proportion and process them according to the conventional preparation method to make the corresponding pharmaceutical preparations.

5. The preparation method of the drug for treating insomnia of the syndrome of deficiency of both the heart and spleen as claimed in claim 4, wherein: The pharmaceutical preparations include powder, hard capsule, tablet, extractum, granule, decoction or pill.

6. The preparation method of the drug for treating insomnia of the syndrome of deficiency of both the heart and spleen as claimed in claim 5, wherein: The powder is prepared as follows: Weigh each medicinal material according to the prescription proportion, add 3 times the amount of water, boil and reflux for extraction twice, each time for 0.5 h. Combine the two extraction solutions, filter while it is hot, concentrate to an extract with a relative density of 1.10 - 1.30 at 70 °C. Dry the extract at 70 - 85 °C to obtain a dry extract, crush it into fine powder, pass through a 100-mesh sieve, sterilize and then package, and that's it.

7. The preparation method of the drug for treating insomnia with deficiency of both the heart and spleen as described in claim 5, characterized in that: The hard capsule is prepared as follows: Weigh each medicinal material according to the prescription proportion, add 8 times the amount of water, boil and reflux for extraction three times, each time for 1 h. Combine the three extraction solutions, mix well, concentrate to 65% of the original medicinal liquid, filter while it is hot. Concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70 °C. Dry the extract at 70 - 85 °C to obtain a dry extract, crush it into fine powder, add 10% of starch and 1% of magnesium stearate according to the prepared amount, mix evenly, granulate with 90% ethanol, dry at 70 °C, size the granules, and fill them into capsules, then you get it.

8. The preparation method of the drug for treating insomnia of the syndrome of deficiency of both the heart and spleen as claimed in claim 5, wherein: The tablet is prepared as follows: Weigh each medicinal material according to the prescription proportion, add 10 times the amount of water, boil and reflux for extraction twice, each time for 0.5 h. Combine the two extraction solutions, mix well, concentrate to 65% of the original medicinal liquid, filter while it is hot. Concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70 °C. Dry the extract at 70 - 85 °C to obtain a dry extract, and crush it into fine powder to get the dry extract. Take the dry extract, add 1% of talc powder and 1% of sodium carboxymethylcellulose, granulate with 10% starch paste, dry at 70 °C, press tablets, and perform film coating, then you get it.

9. The preparation method of the drug for treating insomnia of the syndrome of deficiency of both the heart and spleen as described in claim 5, wherein: The medicated extract is prepared as follows: Weigh each medicinal material according to the prescription ratio, add 6 times the amount of water, boil under reflux for 3 times, each time for 1 hour. Combine the extraction solutions of the three times, mix well, and concentrate to 65% of the original medicinal liquid. Filter while it is hot, and concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70°C. Separately take refined honey accounting for 40% of the weight of the above extract, slowly add it to the above extract, stir evenly, continue to heat and collect the extract with a gentle fire. When a little can be pulled into filaments horizontally, or when dropped on paper, no water marks are seen, fill it into a sterile bottle and seal it to obtain the product.

10. The preparation method of the drug for treating insomnia of the syndrome of deficiency of both the heart and spleen as claimed in claim 5, characterized in that: The granule is prepared as follows: Weigh each medicinal material according to the prescription ratio, add 12 times the amount of water, boil under reflux for 2 times, each time for 1.5 hours. Combine the extraction solutions of the two times, mix well, and concentrate to 65% of the original medicinal liquid. Filter while it is hot, and concentrate the filtrate to an extract with a relative density of 1.10 - 1.30 at 70°C. Dry the extract at 70 - 85°C and pulverize it into fine powder to obtain the dry extract. Take 1 part of the dry extract, 0.5 part of sucrose and 0.5 part of dextrin, prepare granules by wet method with 60% ethanol. After making the granules, dry them at 80 - 90°C, sieve them through a 14-mesh sieve once, and separate the fine powder with a 60-mesh sieve to obtain the product.

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