CN115400199A

CN115400199A - Traditional Chinese medicine composition for treating liver-stagnation and spleen-deficiency type insomnia and preparation thereof

Info

Publication number: CN115400199A
Application number: CN202211125375.1A
Authority: CN
Inventors: 王景新; 王宇璇
Original assignee: Shijiazhuang Fushengtang Traditional Chinese Medicine Hospital Co ltd
Current assignee: Shijiazhuang Fushengtang Traditional Chinese Medicine Hospital Co ltd
Priority date: 2022-09-15
Filing date: 2022-09-15
Publication date: 2022-11-29

Abstract

The invention relates to a traditional Chinese medicine composition for treating liver depression and spleen deficiency type insomnia, which comprises the following components in parts by weight: 200 to 250 parts of radix bupleuri, 125 to 175 parts of Chinese angelica, 125 to 175 parts of white paeony root, 100 to 150 parts of mint, 125 to 175 parts of radix curcumae, 225 to 275 parts of cortex albiziae, 275 to 325 parts of poria cocos, 200 to 250 parts of bighead atractylodes rhizome, 200 to 250 parts of rhizoma pinellinae praeparata, 125 to 175 parts of ginger, 125 to 175 parts of cape jasmine, 125 to 175 parts of rhizoma anemarrhenae, 125 to 175 parts of fructus forsythiae, 275 to 325 parts of spina date seed, 225 to 275 parts of platycladi seed and 100 to 150 parts of honey-fried licorice root. The invention has the effects of soothing liver, strengthening spleen, clearing heart and nourishing heart, mainly clears stagnated fire of heart and liver, and nourishes yin and blood of heart and liver, and can be used for treating liver stagnation and spleen deficiency type insomnia.

Description

Traditional Chinese medicine composition for treating liver-stagnation and spleen-deficiency type insomnia and preparation thereof

Technical Field

The invention belongs to the field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating liver depression and spleen deficiency type insomnia and a preparation thereof.

Background

Insomnia usually means that the sleep time and depth are insufficient, the patient is not easy to fall asleep, the patient is difficult to fall asleep again after waking, and even the patient does not sleep all night, so that normal work, study, life and health are affected.

The factors causing insomnia are many, are usually complicated by multiple causes and can be generally divided into primary insomnia and secondary insomnia, the secondary insomnia is caused by various mental diseases, single-system or multi-system body diseases and inaccurate medication, the knowledge of students on the primary insomnia causes is not unified, and the pathogenesis is mainly related to the hypothalamus-pituitary-adrenal axis hyperactivity of a stress heatstroke system, the functional hypofunction of the brain central gamma-aminobutyric acid neuron system and the like.

The clinical treatment of insomnia is mainly based on drug therapy, and the clinically common drug types are melatonin, melatonin receptor agonists and the like. According to the traditional Chinese medicine, insomnia belongs to the category of insomnia, doctors of different generations summarize that people have excess of five emotions, incoordination between the spleen and the stomach, overstrain and malaise degree, pathogenic qi infection or consumptive disease after illness and the like according to years of clinical experience, the treatment method is mainly based on an internal treatment method and an external treatment method, and through Chinese herbal medicines, acupuncture, catgut embedding, massage and other methods, the opposition and restriction of five internal organs are balanced, and the abundance and insufficiency of yin and yang of ying and wei are saved.

In modern society, the imbalance of the structure and the law of food and drink often occurs when the pressure of work and study is increased, people worry too much and desire too much or are difficult to meet basic appeal, meanwhile, spleen soil cannot obtain sufficient nutrition and is weak, spleen qi is added in pairs, the spleen qi cannot transport and transform the body fluid, and the body fluid cannot be carried and distributed, so that the yin and yang of the body are disharmony to cause insomnia. For insomnia caused by liver depression and spleen deficiency, the disease is located in the liver and spleen, and how to sooth the liver and strengthen the spleen by planting herbal medicines is an urgent problem to be solved.

Disclosure of Invention

The invention aims to provide a traditional Chinese medicine composition for treating liver depression and spleen deficiency type insomnia and a preparation thereof, wherein the traditional Chinese medicine composition has the functions of soothing liver, strengthening spleen, clearing heart and nourishing heart, mainly clears away stagnated fire of heart and liver and supplements yin and blood of heart and liver.

The invention adopts the following technical scheme:

a traditional Chinese medicine composition for treating liver depression and spleen deficiency type insomnia comprises the following components in parts by weight: 200 to 250 portions of bupleurum, 125 to 175 portions of angelica, 125 to 175 portions of white peony root, 100 to 150 portions of mint, 125 to 175 portions of curcuma, 225 to 275 portions of cortex albiziae, 275 to 325 portions of tuckahoe, 200 to 250 portions of atractylodes, 200 to 250 portions of rhizoma pinellinae praeparata, 125 to 175 portions of ginger, 125 to 175 portions of gardenia, 125 to 175 portions of rhizoma anemarrhenae, 125 to 175 portions of forsythia, 275 to 325 portions of spina date seed, 225 to 275 portions of platycladi seed and 100 to 150 portions of honey-fried licorice root.

Further, the paint comprises the following components in parts by weight: 225 parts of radix bupleuri, 150 parts of angelica, 150 parts of white peony root, 125 parts of mint, 150 parts of radix curcumae, 250 parts of cortex albiziae, 300 parts of poria cocos, 225 parts of bighead atractylodes rhizome, 225 parts of rhizoma pinellinae praeparata, 150 parts of ginger, 150 parts of cape jasmine fruit, 150 parts of rhizoma anemarrhenae, 150 parts of fructus forsythiae, 300 parts of spina date seed, 250 parts of platycladi seed and 125 parts of radix glycyrrhizae preparata.

Further, it is prepared by the following method:

(1) Weighing the medicinal materials according to the weight ratio;

(2) Decocting radix bupleuri, angelica sinensis, radix paeoniae alba, radix curcumae, cortex albiziae, poria cocos, bighead atractylodes rhizome, rhizoma pinellinae praeparata, ginger, gardenia, rhizoma anemarrhenae, fructus forsythiae, spina date seed, platycladi seed and radix glycyrrhizae preparata with 6 times of water, adding mint when extracting for 100-110 minutes, extracting for 10-20 minutes, and filtering;

(3) Adding 6 times of water into the solid filtered in the step (2) for decoction, extracting for 85-95 minutes, and filtering;

(4) Combining the filtrates in the step (2) and the step (3), and concentrating under reduced pressure to obtain clear paste with the relative density of 1.05-1.16;

(5) And spray drying the clear paste to obtain spray dry powder.

In the preparation method, the step (2) is that the bupleurum, the angelica, the white paeony root, the turmeric root-tuber, the albizia bark, the tuckahoe, the largehead atractylodes rhizome, the rhizoma pinellinae praeparata, the ginger, the gardenia, the rhizoma anemarrhenae, the forsythia, the spina date seed, the platycladi seed and the honey-fried licorice root are added with 6 times of water for decoction, the mint is added when the extraction is carried out for 105 minutes, the extraction is carried out for 15 minutes, and the filtration is carried out.

In the preparation method, the step (3) is to take the solid filtered in the step (2) and add 6 times of water for decoction, extract for 90 minutes and filter.

In the preparation method, in the step (4), the vacuum degree of the reduced pressure concentration is 0.06-0.08 MPa.

In the preparation method, in the step (5), the air inlet temperature during spray drying is 170-180 ℃, and the air outlet temperature is 75-85 ℃.

A preparation containing the traditional Chinese medicine composition for treating insomnia caused by liver depression and spleen deficiency is provided.

Wherein the preparation is powder and comprises 498 to 682 parts by weight of spray dry powder and 1000 parts by weight of dextrin.

Wherein the preparation is granules, the spray dry powder and the dextrin are uniformly mixed and then are granulated by a dry method, and the granules with 10-50 meshes are collected.

The composition of the invention is used by the following methods: 10g each time, 3 times daily.

Function and indication: soothe the liver, strengthen the spleen, clear heart and nourish heart. Can be used for treating insomnia with syndrome of liver stagnation and spleen deficiency, manifested by insomnia, vexation, irritability, abnormal stool and urine, red tongue tip, yellow and greasy fetus, and superficial and wiry pulse.

The invention has the beneficial effects that: the invention is suitable for dialectical treatment of liver-stagnation and spleen-deficiency type insomnia, and has remarkable curative effect and no obvious side effect.

Drawings

Fig. 1 is a water absorption curve chart of the decoction pieces.

Fig. 2 is a process flow diagram of the formulation.

Detailed Description

The technical solutions of the present invention will be described clearly and completely below, and it should be apparent that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without making any creative effort based on the embodiments in the present invention, belong to the protection scope of the present invention.

1. Square solution of the invention

Monarch drug: the bupleurum root, radix bupleuri, bitter in taste and mild in nature, enters liver, gallbladder and lung channels, soothes liver and relieves depression, it is used as monarch drug to regulate liver qi. "Changsha Yao Jie" (Changsha Yao Jie) is a medicine for clearing away the fire in gallbladder meridian and disturbing heat in heart and home.

Ministerial drugs: (1) Chinese angelica root, radix Angelicae sinensis, sweet, pungent, bitter and warm in taste, nourishes blood and harmonizes blood: white peony root, radix Paeoniae alba and bupleuri radix, radix Paeoniae alba and bupleuri radix, all can nourish liver to help liver, make blood and liver harmonize, blood replenishes liver to soften, and enrich blood and check soul to help sleep: (2) The mint is light cooling powder, can sooth liver and relieve depression, the turmeric root-tuber is bitter and cold, and can clear heart and relieve depression: the cortex albiziae is sweet and neutral and enters heart and liver channels, can calm nerves and relieve depression, and the three medicines are used together to help the radix bupleuri to relieve liver depression: (3) The rhizoma pinelliae and the ginger are pungent and warm and disperse, can help the radix bupleuri to dissipate stagnation, can lower qi flowing down the stomach and can warm and resolve phlegm-dampness. The medicines are all monarch medicines.

Adjuvant drugs: gardenia jasminoides ellis relieves fire of triple energizer, rhizoma anemarrhenae clears fire of triple energizer deficiency and excess, forsythia is good at clearing heart fire, and the three medicines are used together to clear heat of heart and liver caused by stagnation of liver qi so as to treat insomnia caused by disquieted spirit; the spina date seed is sour and sweet in nature, can nourish heart and benefit liver, and the semen boitae can nourish yin and blood and communicate heart and kidney, so that the effect of nourishing heart and soothing nerves can be achieved directly by combining the two medicines. Are used as adjuvant drugs.

A messenger drug: prepared licorice root, radix Glycyrrhizae Praeparata, as a guiding drug, has the effects of tonifying qi, strengthening the middle-jiao, relieving the liver-fire, and harmonizing the effects of the other drugs in the recipe.

2. Single medicine

Bupleurum root: zhangyan et al found 23428that saikoside could significantly suppress the activities of rat hippocampal Acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), and reduce the death of hippocampal nerve cells, which indicates that saikoside could regulate cholinergic nervous system to inhibit the activation of hypothalamus-pituitary-adrenal axis, and reduce the level of Cortisol (Cortisol); or reducing cholinergic nervous system activity, and increasing 5-hydroxytryptamine (5-HT) hormone level to achieve antidepressant effect. Related pharmacological researches find that the saikosaponin d can improve the activity of superoxide dismutase (SOD) in liver tissues of liver fibrosis rats, reduce the contents of IV type collagen (IV-C), laminin (LN) and Hyaluronic Acid (HA) in hematochezia, reduce the levels of aspartate Aminotransferase (AST) and glutamate-pyruvate transaminase (ALT) in hematochezia, and reduce the contents of Malondialdehyde (MDA) in liver tissues and blood serum, so that the saikosaponin d (SSd) HAs the effects of resisting hepatic fibrosis, protecting liver cells and the like.

Chinese angelica root: the polysaccharide in the angelica can stimulate bone marrow macrophages and mononuclear cells in hematopoietic induction niche, promote the synthesis and secretion of hematopoietic regulatory factors, thereby promoting the proliferation and differentiation of hematopoietic related cells such as granulo-monosystem hematopoietic progenitor cells, myeloid pleiotropic hematopoietic progenitor cells and the like, and promoting hematopoiesis.

White peony root: liweiqi et al found that paeoniflorin can exert antidepressant effect by regulating the expression of glutamic acid and its receptor in hippocampal tissue. Researches on the Li Yao and the like show that the white paeony root extract can obviously improve the oxidation resistance of liver and serum, thereby inhibiting liver injury and various inflammatory reactions caused by oxidative stress.

Mint: the study shows that a certain amount of herba Menthae or oleum Menthae Dementholatum can stimulate central nervous system, and has effects of inducing perspiration, relieving fever, tranquilizing mind and relieving pain. In addition, the mentha rotundifolia essential oil and the mentha piperita essential oil can obviously prolong the sleep time induced by the pentobarbital sodium, can relieve mental fatigue symptoms, has the function of resisting mental fatigue, and is characterized in that the content of amino acid neurotransmitters in brain regions related to mental fatigue can be regulated and controlled by using olfaction. The menthol can block the internal flow of sodium ions, thereby generating local nerve block and playing the role of analgesia.

Turmeric root-tuber: clinical observation and animal experiments show that the curcuma wenyujin volatile oil can reduce S-GDT activity, has certain repairing effect on liver function, and can correct A/G ratio inversion caused by hepatitis; meanwhile, the liver cell can be protected, and the liver tissue regeneration can be promoted.

Silktree albizzia bark: the inventor finds that the n-butyl alcohol extraction part plays an anxiolytic role by improving the GABA content in the mouse brain and reducing the Glu and 5-HT content in the mouse brain. Liaoying et al found that the cortex Albizziae extract can shorten the accumulated immobility time of mouse tail suspension test and forced swim ice test, and can resist the body temperature drop and eyelid ptosis of mice caused by reserpine, which fully indicates that the cortex Albizziae extract has antidepressant effect.

Tuckahoe, poria cocos: research shows that the diuretic action mechanism of tuckahoe is related to the potential antagonism of aldosterone receptor activity of tuckahoe, and tuckahoe exerts on total ATP enzyme and Na in cells ⁺ -K ⁺ -ATPase has a certain degreeHas activating effect, and can promote water and salt metabolism and improve myocardial motion. The pachymanol can reduce transaminase activity, prevent hepatocyte necrosis, and protect liver injury of carbon tetrachloride-induced liver cirrhosis model rat.

White atractylodes rhizome: plum established an acetaminophen-induced mouse acute liver injury model, and studied the effect and mechanism of bighead atractylodes rhizome volatile oil on mouse acute liver injury. The experimental results show that: the mice with acute liver injury are pretreated by the bighead atractylodes rhizome volatile oil, so that the ALT and AST levels in blood of the mice with liver injury can be reduced, and the GSH level in livers can be increased.

Pinellia ternata: it is discovered by Tangying and the like that pinellia ternate alkaloids have an effect of improving learning and memory disorders of aging model mice caused by D-galactose, can obviously improve SOD activity in brain tissues of the mice, obviously reduce Malondialdehyde (MDA) content, and can obviously reduce acetylcholinesterase (AChE) content at medium and high doses, and are presumed to be related to antioxidation of the pinellia ternate alkaloids and inhibition of acetylcholinesterase activity.

Ginger: experimental research shows that the ginger ethanol extract can obviously improve the blood fat quality of experimental rabbits and reduce the change of atherosclerosis. The ginger alcohol extract can also obviously inhibit platelet aggregation induced by adenosine diphosphate and delay blood coagulation. The ginger extract can prevent lipoprotein from immersing in the arterial wall, improve the vascular structure, regulate the conversion of cholesterol, promote the transport function of high-density lipoprotein and promote the function of gallbladder to excrete cholesterol, and is an atherosclerosis inhibitor with development prospect.

Gardenia: in a mouse model of carbon tetrachloride-induced hepatotoxicity, geniposide can reduce the activities of blood glutamate aminotransferase and aspartate aminotransferase and increase the concentration of Glutathione (GSH) in the liver, thereby playing a role in protecting the liver.

Rhizoma anemarrhenae: saponin of rhizome of Anemarrhena asphodeloides has effects of significantly reducing oxygen consumption rate increase caused by thyroxine and inhibiting activity of Na (+) K (+) -ATP acid, wherein the total saponin has inhibition rate of 59.8% on Na (+) K (+) -ATP enzyme and inhibition rate of 89.8% on hemisuccinate derivative, and is considered to be related to effects of clearing heat and purging fire.

Fructus forsythiae: experiments for studying the liver protection effect of the forsythia suspense aqueous extract on mice through a hyperlipidemia model show that the serum of the hyperlipidemia mice has higher levels of Total Cholesterol (TC), triacylglycerol (TG) and low-density lipoprotein (LDL) compared with the normal mice, and the level of high-density lipoprotein (HDL) compared with the normal mice is lower. The oral fructus forsythiae aqueous extract of the hyperlipidemic mouse can reduce the content of TC, TG and LDL in serum and increase the content of HDL; in addition, fructus forsythiae water extract also reduces liver Malondialdehyde (MDA) content, improves superoxide dismutase (SOD) activity, and regulates serum Total Bilirubin (TBIL) metabolism, thereby achieving liver protecting effect.

Wild jujube seed: the julep and the like prove that the spina date seed total alkaloids have a certain depression resistance effect on mice by adopting a mouse tail suspension experiment, an empty field experiment and an experiment for reducing the body temperature caused by antagonizing reserpine. Sunlizhi et al observed that the spina date seed decoction can obviously improve the behaviouristics of chronic depressed rats, and the mechanism of the spina date seed decoction is possibly related to the expression level of regulatory protein. Zuojun et al have proved the mechanism of antidepressant action of jujuba seeds through the research on the influence of jujuba seeds on monoamine neurotransmitters, inflammatory cytokines and neurotrophic factors. The results of Wang Gekko Swinhonis and the like which adopt an international general anxiety animal model, namely an elevated plus maze model, show that polysaccharide and flavonoid components in the spina date seed aqueous solution extract are probably material bases with the effect of resisting anxiety.

Seed of Chinese arborvitae: the effects of tranquilizing, hypnotizing and resisting anoxia of the total terpene components in the platycladi seeds are researched by maoxin and the like. The total terpene components can inhibit the spontaneous activity of mice, prolong the sleep time of the mice induced by pentobarbital sodium, increase the sleep number of the mice and prolong the survival time of anoxic mice.

Honey-fried licorice root: a large number of documents show that liquorice and honey-fried licorice root exist in most anti-depression traditional Chinese medicine prescriptions, wherein the bupleurum liver-soothing powder (white paeony root, bupleurum, liquorice, dried orange peel, ligusticum wallichii and rhizoma cyperi) can improve hippocampal neurons by regulating and controlling hippocampal dendrite and synapse morphology so as to achieve the anti-depression effect. The spina date seed decoction is used for intervening the development of depression by influencing inflammatory cytokines and monoamine neurotransmitters.

3. Formulation examples

Formulation example 1

A traditional Chinese medicine composition for treating liver depression and spleen deficiency type insomnia comprises 225g of radix bupleuri, 150g of Chinese angelica, 150g of radix paeoniae alba, 125g of mint, 150g of radix curcumae, 250g of cortex albiziae, 300g of poria cocos, 225g of rhizoma atractylodis macrocephalae, 225g of rhizoma pinellinae praeparata, 150g of ginger, 150g of fructus gardeniae, 150g of rhizoma anemarrhenae, 150g of fructus forsythiae, 300g of spina date seed, 250g of semen boitae and 125g of honey-fried licorice root.

Formulation example 2

The difference from the example 1 is that the composition comprises the following components in parts by weight: 200g of radix bupleuri, 125g of angelica, 125g of radix paeoniae alba, 100g of mint, 125g of radix curcumae, 225g of cortex albiziae, 275g of poria cocos, 200g of rhizoma atractylodis macrocephalae, 200g of rhizoma pinellinae praeparata, 125g of ginger, 125g of fructus gardeniae, 125g of rhizoma anemarrhenae, 125g of fructus forsythiae, 275g of spina date seed, 225g of semen boitae and 100g of honey-fried licorice root.

Formulation example 3

The adhesive is the same as the adhesive in example 1, except that the adhesive comprises the following components in parts by weight: 250g of radix bupleuri, 175g of angelica sinensis, 175g of radix paeoniae alba, 150g of mint, 175g of radix curcumae, 275g of cortex albiziae, 325g of poria cocos, 250g of rhizoma atractylodis macrocephalae, 250g of rhizoma pinellinae praeparata, 175g of ginger, 175g of fructus gardeniae, 175g of rhizoma anemarrhenae, 175g of fructus forsythiae, 325g of spina date seed, 275g of semen boitae and 150g of honey-fried licorice root.

4. Extraction process

4.1 immersion time of decoction pieces, water absorption

Weighing 9g of radix bupleuri, 6g of angelica sinensis, 6g of radix paeoniae alba, 5g of mint, 6g of radix curcumae, 10g of cortex albiziae, 12g of poria cocos, 9g of rhizoma atractylodis macrocephalae, 9g of rhizoma pinellinae praeparata, 6g of ginger, 6g of fructus gardeniae, 6g of rhizoma anemarrhenae, 6g of fructus forsythiae, 12g of spina date seeds, 10g of semen boitae and 5g of radix glycyrrhizae preparata according to the formula proportion (formula example 1), putting the weighed materials into a 3L beaker, adding 10 times of water, filtering out unabsorbed water at 0min, 10min, 20min, 30min, 50min and 90min respectively, weighing the medicine residues, calculating the water absorption rate (table 1), and drawing a water absorption dynamic change graph (see fig. 1).

TABLE 1 study of water absorption of decoction pieces

Time t/min	0	10	20	30	50	90
							Water absorption/%)	0	63.39	93.72	110.82	116.76	121.93

As can be seen from table 1 and fig. 1: the water absorption rate is high after 0-30 min, and after 30min, the water absorption rate tends to be gentle, so the soaking time can reach balance after 30min, and as the heating and boiling process of large-scale production is generally more than 30min, the soaking time is selected to be 30min during small-scale examination, and the soaking is not selected during large-scale production.

Weighing 9g of radix bupleuri, 6g of angelica sinensis, 6g of radix paeoniae alba, 5g of mint, 6g of radix curcumae, 10g of cortex albiziae, 12g of poria cocos, 9g of rhizoma atractylodis macrocephalae, 9g of rhizoma pinellinae praeparata, 6g of ginger, 6g of fructus gardeniae, 6g of rhizoma anemarrhenae, 6g of fructus forsythiae, 12g of spina date seeds, 10g of semen boitae and 5g of radix glycyrrhizae preparata according to the formula proportion (formula example 1), weighing 3 parts of 123g of each part, putting the 3L beaker into a beaker, adding 10 times of water, soaking for 30 minutes, stirring once every 10 minutes, filtering out unabsorbed water, weighing dregs of a decoction, and calculating (see table 2).

Water absorption (%) = (wet weight of herb residue-dry weight of herb material)/dry weight of herb material)% 100%

TABLE 2 dynamic Water uptake test mean values

The results show that the water absorption rates of the three decoction pieces after 30 minutes soaking are 113.41%, 114.71% and 111.63%, respectively, and the average water absorption rate is 113.25%.

4.2 investigation of different water addition times

4.2.1 addition of Water

Weighing 45g of radix bupleuri, 30g of Chinese angelica, 30g of white paeony root, 25g of mint, 30g of radix curcumae, 50g of cortex albiziae, 60g of poria cocos, 45g of bighead atractylodes rhizome, 45g of rhizoma pinellinae praeparata, 30g of ginger, 30g of cape jasmine fruit, 30g of rhizoma anemarrhenae, 30g of fructus forsythiae, 60g of spina date seed, 50g of platycladi seed and 25g of honey-fried licorice root according to the formula proportion (formula example 1), weighing 3 parts, respectively placing the 3 parts in a round-bottomed flask, connecting a reflux device, adding water for decocting twice for fifteen medicines (except the mint), adding water with the amount of 6, 8 and 10 times of the prepared slices for the first time, soaking for 30 minutes, adding the mint after extracting for 105 minutes, extracting for 15 minutes, and filtering the decoction for later use by a 200-mesh screen; adding water in an amount which is 6, 8 and 10 times that of the decoction pieces for the second time, extracting for 90 minutes, filtering decoction liquid by a 200-mesh screen, and combining the filtrates.

4.2.2 determination of cream yield

Decocting and extracting according to the conditions, combining the decoctions extracted twice, decompressing and concentrating the decoction, and fixing the volume to 5000mL. Precisely transferring 25mL of the extract into an evaporation dish dried to constant weight, evaporating the extract in a water bath, drying the extract in an oven at 105 ℃ for 3 hours, placing the dried extract in a dryer for cooling for 30 minutes, rapidly and precisely weighing the extract, calculating the paste yield, and parallelly measuring two parts in each group, wherein the results are shown in Table 3.

TABLE 3 cream yield for different water addition times

General water addition times	Multiple of water addition for two-decoction	Percentage of cream discharged (%)
			6	6	19.1
8	8	20.3
			10	10	20.6

The data in table 3 show that when the water addition amount is 6 times, 8 times and 10 times, the paste yield is 19.1%, 20.3% and 20.6% respectively, the difference is small, and according to the actual large-scale production and the water resource saving, the final selection is to add 6 times of water for the first time and 6 times of water for the second time.

4.3 different extraction time review

4.3.1 extraction time

Weighing 45g of radix bupleuri, 30g of Chinese angelica, 30g of white paeony root, 25g of mint, 30g of radix curcumae, 50g of cortex albiziae, 60g of poria cocos, 45g of bighead atractylodes rhizome, 45g of rhizoma pinellinae praeparata, 30g of ginger, 30g of cape jasmine, 30g of rhizoma anemarrhenae, 30g of fructus forsythiae, 60g of spina date seed, 50g of platycladi seed and 25g of honey-fried licorice root according to the proportion of a formula (formula embodiment 1), weighing 3 parts, respectively placing the 3 parts in a round-bottom flask, connecting a reflux device, adding water into the fifteen medicines (except the mint), decocting the medicines twice, adding water in an amount which is 6 times that of the prepared medicines into the first time, soaking the medicines for 30 minutes, respectively extracting the medicines for 150 minutes, 120 minutes and 90 minutes, respectively adding the mint 15 minutes before the extraction is finished, and filtering the decoction by a 200-mesh screen for later use; adding water 6 times the amount of the decoction pieces for the second time, extracting for 120, 90, and 60 minutes respectively, filtering the decoction with 200 mesh sieve, and mixing the filtrates.

4.3.2 determination of cream yield

Decocting and extracting according to the conditions, mixing decoctions extracted twice, decompressing and concentrating the decoctions, and fixing the volume to 5000mL. Precisely transferring 25mL of the extract into an evaporation dish dried to constant weight, evaporating the extract in a water bath, drying the extract in an oven at 105 ℃ for 3 hours, placing the dried extract in a dryer for cooling for 30 minutes, rapidly and precisely weighing the extract, calculating the paste yield, and parallelly measuring two parts in each group, wherein the results are shown in Table 4.

TABLE 4 cream yield at different extraction times

One time frying (min)	Two decocting time (min)	Percentage of cream discharged (%)
			150	120	20.0
120	90	19.1
			90	60	18.9

The data in table 4 show that the extraction rates of the paste are 20.0%, 19.1% and 18.9% respectively under 3 different extraction times, the difference is not great, and one decoction for 120 minutes and two decoctions for 90 minutes are selected as the extraction times in combination with the actual situation of mass production.

4.4 investigation of separation Process

4.4.1 separation Process

Weighing 45g of radix bupleuri, 30g of Chinese angelica, 30g of white paeony root, 25g of mint, 30g of radix curcumae, 50g of cortex albiziae, 60g of poria cocos, 45g of bighead atractylodes rhizome, 45g of rhizoma pinellinae praeparata, 30g of ginger, 30g of cape jasmine fruit, 30g of rhizoma anemarrhenae, 30g of fructus forsythiae, 60g of spina date seed, 50g of platycladi seed and 25g of honey-fried licorice root according to the proportion of a formula (formula embodiment 1), weighing 3 parts, respectively placing the 3 parts in a round-bottomed flask, connecting a reflux device, adding water to decoct the fifteen medicines (except the mint), adding water for twice, adding water with the amount 6 times of the amount of the prepared slices for the first time, soaking for 30 minutes, adding the mint after extracting for 105 minutes, and extracting for 15 minutes; adding water 6 times the amount of the decoction pieces for the second time, extracting for 90min, performing solid-liquid separation with 100, 200, and 300 mesh sieves, respectively, and mixing the two decoctions.

4.4.2 determination of cream yield

Decocting and extracting according to the conditions, mixing decoctions extracted twice, decompressing and concentrating the decoctions, and fixing the volume to 5000mL. Precisely transferring 25mL of the extract into an evaporation dish dried to constant weight, evaporating the extract by a water bath, drying the extract in an oven at 105 ℃ for 3h, placing the dried extract in a dryer for cooling for 30min, rapidly and precisely weighing the extract, calculating the paste yield, and parallelly measuring two parts in each group. The results are shown in Table 5.

TABLE 5 cream yield at different extraction times

The data in table 5 show that the extraction rate of the extract is 19.6%, 19.1% and 17.5% respectively by using 100 mesh, 200 mesh and 300 mesh screens, the clarity of the filtrate is not high by using 100 mesh filtration, but 300 mesh filtration is adopted, the filtration time is longer, and the 200 mesh screen is selected for filtration during solid-liquid separation in combination with the actual situation of large-scale production.

4.5 drying Process

4.5.1 selection of drying means

The common drying methods of the traditional Chinese medicine extract mainly comprise vacuum oven drying and spray drying. Vacuum oven drying still has certain drawbacks and limitations. The vacuum oven has long drying time, high energy consumption and easy contamination and moisture absorption in intermittent operation. The spray drying method has the characteristics of high drying speed, short material heating time, simple production process, simple and convenient operation, good controllability, uniform product texture, good dissolubility and the like. Therefore, the product is spray-dried.

4.5.2 spray drying test

Weighing 135g of radix bupleuri, 90g of Chinese angelica, 90g of white paeony root, 75g of mint, 90g of radix curcumae, 150g of cortex albiziae, 180g of poria cocos, 135g of bighead atractylodes rhizome, 135g of rhizoma pinellinae praeparata, 90g of ginger, 90g of cape jasmine fruit, 90g of rhizoma anemarrhenae, 90g of fructus forsythiae, 180g of spina date seed, 150g of platycladi seed and 75g of honey-fried licorice root according to the formula proportion (formula embodiment 1), extracting by using a multifunctional extraction and concentration tank, adding 6 times of water into the fifteen medicines (except the mint), adding the mint after extracting for 105 minutes, extracting for 15 minutes again, and filtering a 200-mesh decoction solution for later use; adding 6 times of water into the decoction pieces for the second time, extracting for 90 minutes, filtering the decoction through a 200-mesh screen, and combining the filtrates. Concentrating the filtrate, fixing the volume to 3000ml, precisely transferring 25ml into an evaporating dish dried to constant weight, evaporating in a water bath, drying in an oven at 105 ℃ for 3h, cooling in a dryer for 30min, rapidly and precisely weighing, and calculating the cream yield to obtain the theoretical cream yield of 17.8%. According to the optimal working conditions and material properties of the spray drying equipment, the air inlet temperature is set to be 180 ℃, the spraying is carried out under the condition that the air outlet temperature is 80 ℃, the spray powder does not have the wall sticking phenomenon, loose spray powder can be collected, the spraying effect is good, and the selected spray drying process is feasible.

4.6 granulation Process Studies

4.6.1 granulation Process

The common granulation modes of the granules comprise wet granulation and dry granulation, the wet granulation process is complex, materials are mixed with proper auxiliary materials and then added with adhesive to prepare soft materials, and the soft materials are granulated by a granulator and then dried, so the production period is long; the dry granulation adopts a granulation method that a screw feeder extrudes dry powdery materials into slices through a pressing wheel, and then the slices are crushed into dry particles with proper sizes.

After dry granulation, collecting granules of 10-50 meshes as a finished product of the final granules.

4.6.2 examination of the amount of auxiliary materials

The spray powder is taken, dextrin with different proportions is added, dry granulation is adopted, the influence of the dextrin dosage on the granulation is inspected, the result shows that the auxiliary materials have no influence on the granule yield, the granule dissolubility also accords with the regulation, and the effect of the dry granulation and the granule dissolubility are not influenced by adding the auxiliary materials. The results are shown in Table 6.

TABLE 6 Effect of adjuvant dosage on granulation

Amount of spray powder (g)	Paste precision (g)	Particle yield (%)	Solubility in water	Situation of granulation
					300	0(％)	91.1	Qualified	Good compressibility and uniform particle size
270	30(10％)	91.3	Qualified	Good compressibility and uniform particle
					225	75(25％)	91.7	Qualified	Good compressibility and uniform particle
150	150(50％)	91.8	Qualified	Good compressibility and uniform particle size

4.7 pilot study

4.7.1 extraction

Weighing 135g of radix bupleuri, 90g of Chinese angelica, 90g of white paeony root, 75g of mint, 90g of radix curcumae, 150g of cortex albiziae, 180g of poria cocos, 135g of bighead atractylodes rhizome, 135g of rhizoma pinellinae praeparata, 90g of ginger, 90g of cape jasmine fruit, 90g of rhizoma anemarrhenae, 90g of fructus forsythiae, 180g of spina date seed, 150g of platycladi seed and 75g of honey-fried licorice root according to the formula proportion (formula embodiment 1), weighing three parts, respectively using a multifunctional extraction and concentration tank to extract the fifteen medicines (except the mint), adding water for decoction twice, adding water with the amount being 6 times of that of the decoction pieces for the first time, soaking for 30 minutes, adding the mint after extracting for 105 minutes, extracting for 15 minutes again, and filtering decoction for later use; adding water with the amount 6 times of the decoction pieces for the second time, extracting for 90 minutes, filtering decoction, and mixing filtrates.

4.7.2 concentration, drying

The decoction is decompressed and concentrated to an extract with the relative density of 1.05-1.15 (60 ℃). And (3) taking the extract, spray-drying, controlling the air inlet temperature to be 170-180 ℃ and the air outlet temperature to be 75-85 ℃, collecting spray powder, weighing, and calculating the cream yield, wherein the cream yield is shown in table 7.

TABLE 7 cream yield of three lots of small trials

Batch number	Amount of spray powder (g)	Percentage of cream discharged (%)
			202103011	319.2	17.3
202103012	324.7	17.6
			202103013	328.4	17.8

The data in Table 7 show that the cream yield of the three batches of small tests is 17.3%, 17.6% and 17.8%, respectively, and the differences are not great. Test results show that the spray drying is carried out by adopting the process parameters, the yield of the spray powder is relatively stable, and no wall sticking phenomenon exists in the spraying process, so that the spray drying conditions are determined as follows: 170-180 ℃ and the air outlet temperature is 75-85 ℃.

4.7.3 Dry granulation

According to the optimal working conditions and material properties of dry granulation equipment, setting dry granulation conditions, taking spray powder, adding a proper amount of dextrin, uniformly mixing, performing dry granulation, and collecting 10-50-mesh granules. The results are shown in Table 8.

Table 8 small test granulation results

Batch number	Amount of spray powder (g)	Paste quantity (g)	Gross combined weight (g)	Amount of particles (g)	Particle yield (%)
						202103011	319.2	280.8	600	550.4	91.7
202103012	324.7	275.3	600	549.4	91.6
						202103013	328.4	271.6	600	547.6	61.3

The test results show that the parameters and the particle yield of each link are stable, and the dry granulation process is feasible.

4.8 summary of the technology

According to the production capacity of production equipment, feeding according to the prescription amount, preparing three batches of products according to the determined production process, and verifying the feasibility of the production process.

4.8.1 formulation

1350g of radix bupleuri, 900g of angelica, 900g of radix paeoniae alba, 750g of mint, 900g of radix curcumae, 1500g of cortex albiziae, 1800g of poria cocos, 1350g of rhizoma atractylodis macrocephalae, 1350g of rhizoma pinellinae praeparata, 900g of ginger, 900g of fructus gardeniae, 900g of rhizoma anemarrhenae, 900g of fructus forsythiae, 1800g of spina date seed, 1500g of semen boitae and 750g of honey-fried licorice root.

4.8.2 pretreatment of decoction pieces

Bupleurum root: removing impurities and residual stem, cleaning, moistening, slicing, and drying.

Chinese angelica: removing impurities, cleaning, moistening, slicing, and drying at low temperature.

White peony root: cleaning, moistening, slicing, and drying.

Mint: removing old stems and impurities, slightly spraying clear water, slightly moistening, cutting into short segments, and drying at low temperature in time.

Turmeric root-tuber: cleaning, moistening, slicing, and drying.

Silktree albizzia bark: removing impurities, cleaning, moistening, shredding, and drying.

Poria cocos: soaking Poria, cleaning, moistening, steaming, removing outer skin, cutting into blocks or thick pieces, and sun drying.

White atractylodes rhizome: removing impurities, cleaning, moistening, slicing, and drying.

Rhizoma pinelliae preparata: taking pinellia ternata, separating the pinellia ternata into different sizes, soaking the pinellia ternata in water until no dry core exists in the pinellia ternata, and taking out the pinellia ternata; and decocting a proper amount of liquorice in water twice, mixing decoction, pouring into lime liquor prepared from a proper amount of water, uniformly stirring, adding the soaked pinellia ternata, soaking, stirring for 1-2 times every day, keeping the pH value of the soaking solution above 12 until the section is yellow and uniform, taking out when the mouth tastes slightly numb and tongue, cleaning, and drying in the shade or drying to obtain the rhizoma pinelliae beverage.

Ginger: removing impurities, and cleaning. It is available in the form of thick slices.

Gardenia: removing impurities, and grinding.

Rhizoma anemarrhenae: removing impurities, cleaning, moistening, slicing, drying, and removing hair and dandruff.

Fructus forsythiae: and removing impurities.

Wild jujube seed: the residual core shell was removed. Pounding into pieces for use.

Arborvitae seed: removing impurities and residual seed coats.

Honey-fried licorice root: parching Glycyrrhrizae radix tablet with honey until it is yellow to dark yellow, taking out when it is not sticky, and cooling.

4.8.3 preparation technology (fig. 2)

(1) Weighing the medicinal materials according to the weight ratio;

(2) Decocting bupleuri radix, radix Angelicae sinensis, radix Paeoniae alba, radix Curcumae, cortex Albizziae, poria, atractylodis rhizoma, rhizoma Pinelliae Preparata, rhizoma Zingiberis recens, fructus Gardeniae, rhizoma anemarrhenae, fructus forsythiae, semen Ziziphi Spinosae, semen Platycladi and radix Glycyrrhizae Preparata with 6 times of water, extracting for 105 min, adding herba Menthae, extracting for 15 min, and filtering (200 mesh screen);

(3) Adding 6 times of water into the solid filtered in the step (2) for decocting, extracting for 90 minutes, and filtering (200-mesh screen);

(4) Combining the filtrates in the step (2) and the step (3), and concentrating under reduced pressure at a vacuum degree of 0.06-0.08 MPa to obtain clear paste with a relative density (60 ℃) of 1.05-1.16;

(5) And spray drying the clear paste, wherein the air inlet temperature is 170-180 ℃, the air outlet temperature is 75-85 ℃, and spray dry powder is obtained.

(6) Collecting spray powder, adding a proper amount of dextrin, uniformly mixing, performing dry granulation (the conveying speed is less than or equal to 220rpm, the working pressure is 12-25 MPa), granulating, collecting 10-50-mesh granules, and subpackaging 10g of granules in each bag.

Table 9 Process verification results

Batch number	210601	210602	210603
				Extracting and feeding amount (kg)	6.15	6.15	6.15
Amount of spray powder (kg)	1.21	1.19	1.14
				Extraction yield (%)	19.7	19.3	18.5
Dextrin amount (kg)	0.79	0.81	0.86
				Gross combined weight (kg)	2.0	2.0	2.0
Amount of particles (kg)	1.86	1.88	1.90
				Theoretical quantity of finished product (bag)	200	200	200
Finished product quantity (bag)	183	186	187
				Yield of finished products	91.5	93.0	93.5

The samples of each batch were examined according to the relevant regulations under 0104 granules, 2020 edition of the four ministry of communications in Chinese pharmacopoeia, and the data of the examination are shown in Table 10.

Table 10 process verification test results

The results show that the average cream yield of the three batches of samples is 19.2%, the cream yield is stable, and all detection indexes meet the regulations, which indicates that the production process is stable and feasible.

5. Stability test

According to the guiding principle of stability test of medicines and preparations of four parts 9001 in the 2020 edition of Chinese pharmacopoeia, samples for stability research are divided into 3 batches with the batch numbers of 210601, 210602 and 210603, and the used packages are medicinal aluminum-plastic composite films.

5.1 accelerated test

Taking 3 batches of test articles, placing and observing for 6 months under the conditions of 40 +/-2 ℃ and 75 +/-5% of relative humidity, and sampling and detecting for 0, 1, 2, 3 and 6 months respectively. The results are shown in tables 11 to 13.

TABLE 11 test results of accelerated test on test article lot 210601

Table 12 test sample accelerative test investigation results of lot number 210602

Table 13 test sample Accelerator test investigation results of batch number 210603

5.2 Long term test

Taking 3 batches of test articles, placing and observing for 24 months under the conditions that the temperature is 25 +/-2 ℃ and the relative humidity is 60 +/-5%, and sampling and detecting for 0, 3, 6, 9, 12, 18 and 24 months respectively. The results are shown in tables 14 to 16.

Table 14 test results of Long-term test on test article lot 210601

Table 15 test results of Long term test on test article lot 210602

TABLE 16 Long-term test examination of test article under batch No. 210603

5.3 results of the experiment

The experiment is intended to carry out an accelerated test of 6 months and a long-term test of 24 months, the current accelerated test finishes the detection of 6 months, the long-term test finishes the detection of 12 months, and all the investigation items are within the range specified by the quality standard, which indicates that the quality of the particles prepared by the process of the invention is stable.

6. Treatment cases

The traditional Chinese medicine formula has been used clinically for many years, has a good treatment effect on insomnia with liver depression and spleen deficiency, and only a part of specific cases are listed below for explanation due to a plurality of cases of successful treatment.

Case 1 a certain, male, age 67.

The patient had difficulty falling asleep for 2 years. In the last 2 years, patients have difficulty in falling asleep, are easy to wake up after sleeping, are irritative, dreamful, have palpitation and forgetfulness, have poor spirit and fatigue and poor appetite, and are accompanied by light headedness, lusterless complexion, lassitude of limbs, abdominal distension and loose stool; a pale tongue with thin coating and a thready and weak pulse. Has no history of hypertension, diabetes, coronary heart disease, etc. Once the diazepam tablets are orally taken at 2.5mg and 1 night, the diazepam tablets are gradually added until the diazepam tablets are orally taken at 5mg and 1 night, so that drug dependence gradually appears, and a patient asks for traditional Chinese medicine conditioning treatment. Initial diagnosis in 8 months and 16 days in 2017. Traditional Chinese medicine diagnosis: insomnia, liver stagnation and spleen deficiency.

After the patient takes the medicine (formula example 1) for 1 week, the symptoms are improved, dreaminess does not exist, fatigue and weakness are improved, excrement is normal, abdominal distension does not exist, and sleep is improved. After the medicine is continuously taken by the original formula, the symptoms are obviously improved after 7 times of taking the medicine, and the disease is recuperated with the symptoms and does not relapse.

Case 2 somebody, female, age 56.

Insomnia was observed for 3 years. The patients have insomnia in the last 3 years, are easy to wake up after sleeping, are sleepless after waking up, are dreaminess, are tired and lack of strength, have poor appetite, are tired in limbs, are dizziness, palpitation, short breath, sigh, loose stool and frequent night urination; dark tongue with thin coating and wiry, thready and weak pulse; first diagnosis in 2021 year 3, month 25. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency.

After the medicine is taken (formula example 1), the symptoms are improved after 7 doses, the original formula is continued to be taken, and the symptoms are obviously improved after 7 doses, and then the symptoms are conditioned along with the symptoms.

Case 3 Zhao somebody, female, 60 years old.

Insomnia was observed for 3 years. The patients have insomnia in the last 3 years, are easy to wake up after sleeping, are sleepless after waking up, are dreaminess, are tired and lack of strength, have poor appetite, are tired in limbs, are dizziness, palpitation, short breath, sigh, loose stool and frequent night urination; dark tongue with thin coating and wiry, thready and weak pulse; initial diagnosis in 12 months and 20 days in 2020. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency.

Case 4 jingzheng, female, 71 years old.

The patients complain about the difficulty of falling asleep for 3 years, and have the symptoms of insomnia after waking up, headache, amnesia, listlessness, irritability, dry and bitter mouth and unformed stool. Pale and swollen with teeth marks, dark tongue with yellow and greasy coating, and wiry and slippery pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency.

After 7 doses (one dose per day) of the medicine (formula example 1), the patient can better sleep before sleeping, the sleep time is improved, and the patient does not have headache, hypodynamia, dry mouth, bitter taste and improved stool. After the original prescription is continuously taken for 7 days, the tongue is pale, the tongue coating is yellow, the pulse is wiry and smooth, the sleep is obviously improved, the headache is not caused, the fatigue is caused, the mouth is dry, the mouth is bitter, and the stool is improved to some extent. The composition is administered continuously to consolidate the treatment.

Case 5, a vigorous male, age 67.

The patient mainly complains about the difficulty in falling asleep for 2 years, easily arouses the patient after sleeping, is irritable, dreamful, has palpitation and amnesia, has mental fatigue and poor appetite, and is accompanied with dizziness, lusterless complexion, lassitude of limbs, abdominal distension and loose stool. Once orally administered diazepam tablets 2.5mg late 1, were gradually added to 5mg late 1 for oral administration. A pale tongue with thin coating and a thready and weak pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency.

After 7 doses (one dose per day) of the medicine (formula example 1) are taken, the sleep is improved obviously, dreams do not exist, the mental fatigue and the fatigue are improved, the excrement is normal, and abdominal distension does not exist. After the original formula is continuously taken for 7 days, the symptoms are improved, dreaminess is avoided, the spirit fatigue and the fatigue are improved, the excrement is normal, abdominal distension is avoided, and the sleep is improved. The composition is administered continuously to consolidate the treatment.

Case 6, tanacetum parthenium, female, age 53.

Complaining about difficulty in falling asleep for 3 years, dreaminess, insomnia all night, irritability, dizziness, fullness of head, conjunctival congestion, tinnitus, dry and bitter mouth, poor appetite, constipation, and dark urine. Once orally administered diazepam tablets 2.5mg late 1, were gradually added to 5mg late 1 for oral administration. A red tongue with yellow coating and a wiry and rapid pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency, and liver fire disturbing the heart.

After 7 doses (one dose per day) of the medicine (formula example 1), all symptoms are relieved, the sleep can reach 4 to 6 hours, the mouth is still dry, and the stool is normal. After the original formula is continuously taken for 7 days, the sleep is obviously improved before the original formula is taken, and the stool is normal. The composition is administered continuously to consolidate the treatment.

Case 7 defends a bridge, female, age 54.

Complaining of difficulty in falling asleep for 5 years, easy to wake up, insomnia after waking up, dreaminess, insomnia throughout the night, irritability, dizziness, fullness in the head, conjunctival congestion, tinnitus, dry and bitter mouth, poor appetite, constipation, and dark urine. Right lung middle lower lobe resection. A red tongue with yellow coating and a wiry and rapid pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency, and liver fire disturbing the heart.

After 7 doses (one dose per day) of the medicine (formula example 1), the symptoms are relieved, the sleep can reach 4 to 6 hours, the mouth is still dry, and the stool is normal. After the original formula is continuously taken for 7 days, the sleep is obviously improved before the original formula is taken, and the stool is normal. The composition is administered continuously to consolidate the treatment.

Case 8, lithe, female, age 49.

The chief complaints are half a year of difficulty in falling asleep, easy to wake up after sleeping, dreaminess, irritability, vexation, dry mouth and bitter taste, dysphoria with feverish sensation in the chest, dry throat and less body fluid, normal menstrual cycle, small dosage and dark blood. The history of hypertension is 6 years, the blood pressure is up to 180/120mmHg, and the levamlodipine besylate tablet is orally taken. The tongue is red with little coating and the pulse is thready and rapid. And (3) diagnosis: insomnia, liver stagnation, spleen deficiency, disharmony between heart and kidney.

After 7 doses (one dose per day) of the medicine (formula example 1), all symptoms are improved, and the medicine is small in dosage, dark in blood and lumpy in menstrual period; the tongue is red with little coating and the pulse is thready and rapid. After the original formula is continuously taken for 7 days, the sleep is obviously improved and the symptoms are improved. The composition is administered continuously to consolidate the treatment.

Case 9, swallow certain way, male, 60 years old.

Complaining of insomnia after waking up for 2 years. Poor sleep quality, easy waking after sleeping, insomnia after waking up, dreaminess, vexation, chest distress, epigastric fullness, nausea, belch, heavy head and blurred vision; the stool is normal. A reddish tongue with yellow and greasy coating and a slippery and rapid pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency, and phlegm-heat disturbing the heart.

After 7 doses (one dose per day) of the medicine (formula example 1), all symptoms are improved, and the sleep is improved better. The stool is normal. The medicine is continuously taken in the front to consolidate the treatment.

Case 10 Liu somebody organ, female, 63 years old.

Complaining about the difficulty in falling asleep for 1 year. It often falls asleep after 1 o 'clock, and awakens about 4 o' clock, dreaminess, restlessness, irritability, palpitation, amnesia, mental fatigue, poor appetite, dizziness, lusterless complexion, lassitude of limbs, abdominal distension and loose stool. Left lung lobe carcinoma 3 years after surgery; the history of hypertension is 1 year. A pale tongue with thin coating and a thready and weak pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency.

After 7 doses (one dose per day) of the medicine (formula example 1) are taken, all symptoms are improved, dreaminess, mental fatigue, fatigue and fatigue are improved, excrement is normal, abdominal distension is avoided, and sleep is improved. The composition is administered continuously to consolidate the treatment.

Case 11 cotton Wang, female, 63 years old.

Master complaints and easy waking for 2 years. Easy to wake up after sleeping, difficult to fall asleep after waking up, dreaminess, vexation, timidity, palpitation, easy to fright when touching, shortness of breath, spontaneous perspiration, lassitude and hypodynamia. Pale tongue and wiry and thready pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency.

After 7 doses (one dose per day) of the medicine (formula example 1), all symptoms are improved, but the symptoms are listlessness, hypoappetite and limb lassitude. After the original formula is continuously taken for 7 days, all symptoms are obviously improved, and the sleep is obviously improved. The composition is administered continuously to consolidate the treatment.

Case 12, liaohua, female, 60 years old.

Complaining about difficulty falling asleep for 10 years. Easy waking after sleeping, difficult falling asleep after waking, dreaminess, gradual aggravation, even insomnia all night, irritability, dizziness and fullness, tinnitus, dry mouth and bitter taste, poor appetite, dry stool and frequent night urination; once orally taken, various sedatives have unsatisfactory effect, and can fall asleep when being taken and repeatedly after being stopped. A red tongue with yellow coating and a wiry and rapid pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency, and liver fire disturbing the heart.

After 7 doses (one dose per day) of the medicine (formula example 1) are taken, all symptoms are relieved, the patient can better turn before falling asleep, the mouth is still dry, the stool is normal, the frequent micturition is caused at night, and the lower limbs are afraid of cold. After the original formula is continuously taken for 7 days, all symptoms are obviously improved, and the sleep is obviously improved. The composition is administered continuously to consolidate the treatment.

Case 13 Liu Yi Yu, male, age 54.

Complaining about insomnia for 2 years. Difficulty in falling asleep, easy to wake up after sleep, insomnia after waking up, vexation, belch, chest distress, abdominal fullness, hiccup, heavy head, blurred vision, and restlessness in lying. A reddish tongue with yellow and greasy coating and a slippery and rapid pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency, and phlegm-heat disturbing the heart.

After 7 doses (one dose per day) of the medicine (formula example 1), all symptoms are improved, and the sleep is improved better. The medicine is continuously taken in the front to consolidate the treatment.

Case 14 Liu someping, male, age 59.

The patients have the symptoms of insomnia of 1 year, difficulty in falling asleep, easy waking up after sleeping, irritability, dreaminess, palpitation, amnesia, mental fatigue, anorexia, dizziness, lusterless complexion, lassitude of limbs, abdominal distension and loose stool. The history of hypertension is 10 years, diabetes is 10 years, and hyperlipidemia is 3 years. A pale tongue with thin coating and a thready and weak pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency.

After 7 doses (one dose per day) of the medicine (formula example 1), the symptoms are improved, no dreams occur, the spirit and the fatigue are improved, the excrement is normal, the abdominal distension does not occur, and the sleep is improved. The original prescription is continued to take for consolidation treatment.

Case 15 li-bi, female, 79 years old.

Complaining about insomnia for 5 years. Poor sleep quality, easy to fall asleep, but easy to wake up after sleeping, difficult to fall asleep after waking up, shallow sleep, dysphoria with smothery sensation in chest, dreaminess, dizziness, tinnitus, soreness and weakness of waist and knees, night sweat, dry throat and dry mouth. The history of coronary heart disease is 8 years. The tongue is red with little coating and the pulse is thready and rapid. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency, disharmony between heart and kidney.

After 7 doses (one dose per day) of the medicine (formula example 1), all symptoms are improved, and the sleep is improved better.

Case 16 week old, female, age 52.

Complaining about insomnia for 2 years. Insomnia and dreaminess, easy waking after sleeping, insomnia after waking, insomnia all the night, irritability, vexation, dizziness, tinnitus, dry mouth, bitter taste, anorexia, constipation, and frequent micturition at night. A red tongue with yellow coating and a wiry and rapid pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency, and liver fire disturbing the heart.

After 7 doses (one dose per day) of the medicine (formula example 1) are taken, all symptoms are relieved, the patient can better turn to sleep, the mouth is still dry, the stool is normal, and the frequent micturition at night is still realized. After the original formula is taken for 7 days, all symptoms are improved obviously, and the symptoms are improved before the patient falls asleep.

Case 17 wangzheng show, female, 56 years old.

Complaining about insomnia for 3 years. Difficulty in falling asleep, easy awakening after sleep, dreaminess, vexation, dizziness, tinnitus, dysphoria with feverish sensation in chest, palms and soles, night sweat, dry mouth and throat, gingival loosening, soreness and weakness of waist and knees, cold lower limbs, frequent micturition at night, dry stool. The tongue is red with little coating and the pulse is thready and rapid. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency, disharmony between heart and kidney.

After 7 doses (one dose per day) of the medicine (formula example 1), all the symptoms are improved, but the lower limbs are still cool, frequent urination at night and dry stools. After the original formula is continuously taken for 7 days, all symptoms are obviously improved, but the lower limbs are still cool, the urine is frequent at night, and the sleep is obviously improved. The original prescription is continued to take for consolidation treatment.

Case 18 adult, female, age 74.

Complaining about insomnia for 2 years. Difficulty in falling asleep, dreaminess and easy wakefulness, difficulty in falling asleep after waking up, irritability, dry eyes, dizziness and eye distension, mental fatigue and hypodynamia, poor appetite, lassitude of limbs, loose stool and frequent urination. The history of hypertension is 20 years, the number of heart stents is 2, and the history of diabetes is 11 years. Dark tongue with thin coating and wiry, thready and weak pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency.

After 7 doses (one dose per day) of the medicine (formula example 1) are taken, the symptoms are improved, and the sleep is better than before.

Case 19 Zhang some river, male, age 76.

Complain about difficulty falling asleep for 3 years. Difficulty in falling asleep, easy to wake up after sleep, dreaminess, irritability, vexation, dry mouth, bitter taste, dysphoria with feverish sensation in the chest, dry throat, scanty body fluid, soreness of waist, frequent nocturia, dry stool and urine. The history of hypertension is 3 years. The tongue is red with little coating and the pulse is thready and rapid. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency.

After 7 doses (one dose per day) of the medicine (formula example 1), all symptoms are improved, and the symptoms still include dry throat, dysphoria with feverish sensation in chest, palms and soles, frequent urination at night and dry stool. After the original formula is continuously taken for 7 days, all symptoms are obviously improved, and the frequent urination and the dry stool are still remained. The original prescription is continued to take for consolidation treatment.

Case 20 king of a army, male, age 62.

Complaining about insomnia for 1 year. Frequent insomnia, difficulty in falling asleep or easy waking after sleeping, dreaminess, irritability, tinnitus, dry throat, soreness and weakness of waist and knees, dysphoria with feverish sensation in the chest, dry skin, frequent urination at night, dry stool. The history of hypertension is 10 years. The tongue is red with little coating and the pulse is thready and rapid. And (3) diagnosis: insomnia, liver stagnation, spleen deficiency, and kidney yin deficiency.

After 7 doses (one dose per day) of the medicine (formula example 1), all symptoms are improved, and the symptoms still include dry throat, dysphoria with feverish sensation in chest, palms and soles, frequent urination at night and dry stool. The original prescription is continued to take for consolidation treatment.

Case 21 wangzhi, male, age 55.

Complaining about insomnia for 2 years. Easy to wake up after sleeping, difficult to fall asleep after waking up, dreaminess, vexation, timidity, palpitation, easy to fright when touching, shortness of breath, spontaneous perspiration, lassitude and hypodynamia. Pale tongue and wiry and thready pulse. And (3) diagnosis: insomnia, liver stagnation, spleen deficiency, heart deficiency, timidity.

After 7 doses (one dose per day) of the medicine (formula example 1), all symptoms are improved, but the symptoms are listlessness, hypoappetite and limb lassitude. After the original formula is continuously taken for 7 days, the symptoms are obviously improved, the spirit is tired, the fatigue is reduced, the appetite is poor, the limbs are tired, the sleep is improved. The original prescription is continued to take for consolidation treatment.

Case 22, korea, male, age 48.

Complaining about insomnia for 3 months. Easy to wake up after sleeping, difficult to fall asleep after waking up, dreaminess, vexation, timidity, palpitation, easy to fright when touching, shortness of breath, spontaneous perspiration, lassitude and hypodynamia. Pale tongue and wiry and thready pulse. And (3) diagnosis: insomnia, liver stagnation, spleen deficiency, and qi deficiency of heart and gallbladder.

After 7 doses (one dose per day) of the medicine (formula example 1) are taken, the symptoms are relieved, the patient can better turn to sleep before going to sleep, the mouth is still dry, the stool is normal, the night is frequent, and the lower limbs are afraid of cold. After the original formula is continuously taken for 7 days, the symptoms are relieved, the patients are improved obviously before falling asleep, nocturia is frequent, and lower limbs are afraid of cold. The original prescription is continued to take for consolidation treatment.

Case 23, a bell, female, 56 years old.

Complaining about insomnia for 3 years. Easy waking up after sleeping, insomnia after waking up, dreaminess, listlessness, hypodynamia, anorexia, lassitude of limbs, dizziness, palpitation, short breath, sigh, loose stool and frequent urination at night. Dark tongue with thin coating and wiry, thready and weak pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency.

After 7 doses of the medicine (formula example 1) are taken (one dose per day), the symptoms are improved, and the sleep is obviously improved. The original prescription is continued to take orally, and the treatment is consolidated.

Case 24 guo, female, 72 years old.

Complaining about insomnia for 3 years. Difficulty in falling asleep, easy waking after sleep, dreaminess, vexation, accompanied by dizziness, tinnitus, dysphoria with feverish sensation in the chest, night sweat, dry mouth and throat, soreness and weakness of waist and knees, upper half sweating, cold lower limbs, frequent micturition at night, dry stool. The tongue is red with little coating and the pulse is thready and rapid. And (3) diagnosis: insomnia, liver stagnation, spleen deficiency, disharmony between heart and kidney.

After 7 doses (one dose per day) of the medicine (formula example 1), all the symptoms are improved, but the lower limbs are still cool, frequent urination at night and dry stools. After the original formula is continuously taken for 7 days, various symptoms are obviously improved, and the sleep is good.

Case 25 Ning certain Ju, female, 53 years old.

Complaining about difficulty falling asleep for 5 months. The patient is easy to wake up after sleeping, is difficult to fall asleep after waking up, is dreamful, gets worse day by day, and is even sleepless all night, impatient and irritability, accompanied by dizziness and eye swelling, dry mouth and bitter taste, poor appetite, aphthous stomatitis and tongue, and dry stool. A red tongue with yellow coating and a wiry and rapid pulse. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency, and liver fire disturbing the heart.

After 7 doses (one dose per day) of the medicine (formula example 1) are taken, all symptoms are relieved, the patient can be better before falling asleep, and the diet is not good enough. The original prescription is continued to take orally, and the treatment is consolidated.

Case 26 hanzhixiang, female, 73 years old.

After 7 doses (one dose per day) of the medicine (formula example 1) are taken, all the symptoms are improved, but the lower limbs are still cold, frequent urination at night and dry stool. After the original formula is continuously taken for 7 days, all symptoms are obviously improved, the sleep is good, and the stool is normal.

Case 27 jiaozao, male, age 30.

Complaining of insomnia for 2 months. Easy to wake up after sleeping, difficult to fall asleep after waking up, dreaminess, vexation, timidity, palpitation, easy to fright when touching an event, accompanied by shortness of breath, spontaneous perspiration, lassitude and hypodynamia. Pale tongue and wiry and thready pulse. And (3) diagnosis: insomnia, liver stagnation, spleen deficiency, and qi deficiency of heart and gallbladder.

After 7 doses (one dose per day) of the medicine (formula example 1), all symptoms are improved, but the symptoms are listlessness, hypoappetite and limb lassitude. After the original formula is continuously taken for 7 days, various symptoms are obviously improved, and the sleep is obviously improved. The original prescription is continued to be taken orally, and the treatment is consolidated.

Case 28 Rong certain treasure, female, 73 years old.

After 7 doses (one dose per day) of the medicine (formula example 1), all the symptoms are improved, but the lower limbs are still cool, frequent urination at night and dry stools. After the original formula is continuously taken for 7 days, all symptoms are obviously improved, but the lower limbs are still cool and the patient can sleep. The original prescription is continued to take orally, and the treatment is consolidated.

Case 29 continues for a deluxe, female, age 34.

Complaining of insomnia for 2 months. Poor sleep quality, easy to wake up after sleeping, insomnia after waking up, dreaminess, vexation, chest distress, epigastric fullness, nausea, belching, heavy head and blurred vision. The tongue is reddish, the coating is yellow and greasy, and the pulse is slippery and rapid. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency, and phlegm-heat disturbing the heart.

After 7 doses of the medicine (formula example 1) (one dose per day), various symptoms are obviously improved.

Case 30 one kind of a diet, female, 56 years old.

Complaining about the difficulty in falling asleep for 4 years. Difficulty in falling asleep, easy to wake up after sleeping, difficulty in falling asleep after waking up, dreaminess, gradual aggravation, insomnia all night, irritability, dizziness, fullness of the eyes, dry mouth, bitter taste, poor appetite, aphtha of the mouth and tongue, and dry stool. The tongue is red with yellow coating and the pulse is wiry and rapid. And (3) diagnosis: insomnia, liver stagnation and spleen deficiency, and phlegm-heat disturbing the heart.

After 7 doses (one dose per day) of the medicine (formula example 1) are taken, all symptoms are relieved, the sleep is improved, and the mouth and the stool are still dry. The original prescription is continued to take orally, and the treatment is consolidated.

Claims

1. A traditional Chinese medicine composition for treating liver-stagnation and spleen-deficiency type insomnia is characterized by comprising the following components in parts by weight: 200 to 250 parts of bupleurum, 125 to 175 parts of angelica, 125 to 175 parts of white peony root, 100 to 150 parts of mint, 125 to 175 parts of curcuma aromatica, 225 to 275 parts of cortex albiziae, 275 to 325 parts of poria cocos, 200 to 250 parts of bighead atractylodes rhizome, 200 to 250 parts of rhizoma pinellinae praeparata, 125 to 175 parts of ginger, 125 to 175 parts of gardenia, 125 to 175 parts of rhizoma anemarrhenae, 125 to 175 parts of fructus forsythiae, 275 to 325 parts of spina date seed, 225 to 275 parts of platycladi seed and 100 to 150 parts of honey-fried licorice root.

2. The traditional Chinese medicine composition for treating insomnia caused by liver depression and spleen deficiency as set forth in claim 1, which is characterized by comprising the following components in parts by weight: 225 parts of radix bupleuri, 150 parts of angelica, 150 parts of radix paeoniae alba, 125 parts of mint, 150 parts of radix curcumae, 250 parts of cortex albiziae, 300 parts of poria cocos, 225 parts of rhizoma atractylodis macrocephalae, 225 parts of rhizoma pinellinae praeparata, 150 parts of ginger, 150 parts of cape jasmine, 150 parts of rhizoma anemarrhenae, 150 parts of fructus forsythiae, 300 parts of spina date seed, 250 parts of platycladi seed and 125 parts of radix glycyrrhizae preparata.

3. The traditional Chinese medicine composition for treating insomnia caused by liver depression and spleen deficiency as claimed in claim 1 or 2, which is prepared by the following method:

(1) Weighing the medicinal materials according to the weight ratio;

(2) Decocting bupleuri radix, radix Angelicae sinensis, radix Paeoniae alba, radix Curcumae, cortex Albizziae, poria, atractylodis rhizoma, rhizoma Pinelliae Preparata, rhizoma Zingiberis recens, fructus Gardeniae, rhizoma anemarrhenae, fructus forsythiae, semen Ziziphi Spinosae, semen Platycladi and radix Glycyrrhizae Preparata with 6 times of water, extracting for 100 to 110 minutes, adding herba Menthae, extracting for 10 to 20 minutes, and filtering;

(3) Adding 6 times of water into the solid filtered in the step (2), decocting, extracting for 85 to 95 minutes, and filtering;

(4) Mixing the filtrates in the step (2) and the step (3), and concentrating under reduced pressure to obtain a clear paste with the relative density of 1.05-1.16;

(5) And spray drying the clear paste to obtain spray dry powder.

4. The traditional Chinese medicine composition for treating insomnia caused by liver depression and spleen deficiency as claimed in claim 3, wherein in step (2), radix bupleuri, angelica sinensis, radix paeoniae alba, radix curcumae, cortex albiziae, poria cocos, rhizoma atractylodis macrocephalae, rhizoma pinellinae praeparata, ginger, fructus gardeniae, rhizoma anemarrhenae, fructus forsythiae, semen ziziphi spinosae, semen boitae and radix glycyrrhizae preparata are decocted by adding 6 times of water, mint is added when extraction is carried out for 105 minutes, extraction is carried out for 15 minutes, and filtration is carried out.

5. The traditional Chinese medicine composition for treating insomnia caused by liver depression and spleen deficiency as claimed in claim 3, wherein in step (3), the filtered solid obtained in step (2) is added with 6 times of water for decoction, extraction is carried out for 90 minutes, and filtration is carried out.

6. The traditional Chinese medicine composition for treating insomnia caused by liver depression and spleen deficiency as claimed in claim 3, wherein in the step (4), the vacuum degree of the reduced pressure concentration is 0.06 to 0.08MPa.

7. The traditional Chinese medicine composition for treating insomnia caused by liver depression and spleen deficiency as claimed in claim 3, wherein in the step (5), the air inlet temperature during spray drying is 170 to 180 ℃, and the air outlet temperature is 75 to 85 ℃.

8. A preparation comprising the traditional Chinese medicine composition for treating insomnia caused by liver depression and spleen deficiency as set forth in any one of claims 1 to 7.

9. The formulation according to claim 8, characterized in that it is a powder comprising 498 to 682 parts by weight of spray dry powder and the complement 1000 parts by weight of dextrin.

10. The preparation according to claim 9, which is a granule, wherein the spray dry powder and the dextrin are mixed uniformly and then dry granulated, and the 10 to 50-mesh granules are collected.