Composition for treating sleep disorder, preparation and preparation method thereof

Abstract

The invention provides a composition for treating sleep disorder, a preparation and a preparation method thereof. The composition comprises spina date seeds, poria with hostwood, cooked pseudo-ginseng, astragalus membranaceus, codonopsis pilosula and fried hawthorn. The traditional Chinese medicine composition is suitable for the technical field of traditional Chinese medicine preparations and can solve the problem of lack of traditional Chinese medicine compositions for improving sleep disorders caused by blood deficiency in the prior art.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine preparations, and in particular to a composition and preparation for treating sleep disorders and a preparation method thereof. Background Art

[0002] Insomnia is a disease characterized by the frequent inability to obtain normal sleep. The main manifestations are difficulty falling asleep, easy waking during sleep, inability to fall asleep again after waking up, frequent sleeping and waking, frequent dreams, fatigue after waking up, and in severe cases, the patient has the subjective physiological experience of difficulty sleeping all night and feeling sleepy and lethargic during the day.

[0005] There are many causes of insomnia, but in general, they fall into five categories: exogenous pathogenic factors, internal emotional disturbance, unhealthy diet, deficiency of vital energy, and pathological products. (1) Exogenous pathogenic factors, if they invade the human body, disrupt the circulation of qi and blood, and easily cause restlessness, thus causing insomnia. For example, the intense heat of summer can easily damage qi and yin, making people irritable and unable to sleep. (2) Internal emotional disturbance, such as excessive worry and anger that damages the liver, can all lead to visceral qi disorder, which in turn affects the mind and causes insomnia. (3) Unhealthy diet, overeating, or overeating of fatty and sweet foods can damage the spleen and stomach, generate phlegm and dampness, or accumulate heat, which disturbs the mind and can also cause insomnia. (4) Vital energy deficiency, old age, or long-term illness can lead to insufficient qi and blood, imbalance of yin and yang, and decline of visceral function, which makes it impossible to nourish the mind, thus causing insomnia. This is especially common in patients with deficiency of both the heart and spleen and deficiency of liver and kidney yin. (5) Pathological products, such as blood stasis and phlegm, block the meridians and affect the circulation of qi and blood, which can also be the cause of insomnia. These pathological products are mostly transformed from the aforementioned causes, intertwined with each other, and aggravate the condition. Among them, deficiency of vital energy, especially the imbalance of yin and yang and the decline of organ function caused by insufficient qi and blood, is one of the important factors causing insomnia.

[0006] Existing Chinese medicine compositions have made certain progress in improving sleep disorders, but most Chinese medicine compositions are not specifically optimized for sleep disorders caused by blood deficiency. For example, some Chinese medicine compositions mainly improve sleep quality by nourishing the heart and calming the mind, clearing away heat and relieving restlessness, etc., but ignore the impact of blood deficiency on sleep. Blood deficiency refers to insufficient blood, which cannot nourish various parts of the body, especially the heart, liver and other internal organs closely related to sleep, resulting in restlessness and decreased sleep quality. The Chinese medicine compositions in the prior art often lack targeted supplementation of qi and blood, making it difficult to effectively improve sleep disorders caused by blood deficiency. Therefore, the prior art lacks a Chinese medicine composition for sleep disorders caused by blood deficiency, which can fundamentally improve sleep quality by supplementing qi and blood and regulating the balance of yin and yang. Summary of the invention

[0007] The main purpose of the present invention is to provide a composition, a preparation and a preparation method thereof for treating sleep disorders, so as to solve the problem in the prior art that there is a lack of a traditional Chinese medicine composition that can improve sleep disorders caused by blood deficiency.

[0008] To achieve the above object, according to a first aspect of the present invention, a composition for treating sleep disorders is provided, comprising spiny jujube seeds, poria, cooked panax notoginseng, astragalus, codonopsis and stir-fried hawthorn.

[0009] Furthermore, the composition comprises, by weight, 9-15 parts of spinach seed, 7-12 parts of poria, 6-10 parts of notoginseng, 9-15 parts of astragalus, 6-15 parts of codonopsis and 5-20 parts of stir-fried hawthorn.

[0010] Furthermore, the composition also includes a solvent and / or an auxiliary material; preferably, the solvent includes water; preferably, the auxiliary material includes a molding agent and / or a wetting agent; preferably, the molding agent includes one or more of dextrin, starch, lactose powder, mannitol or sucrose powder; preferably, the wetting agent includes ethanol and / or water; preferably, the concentration of ethanol is 50-90%; preferably, the composition also includes 0.8-1.5 parts of a molding agent and 0.2-0.4 parts of a wetting agent.

[0011] According to a second aspect of the present invention, there is provided a method for preparing a preparation for treating sleep disorders, the method comprising: S1) extracting active ingredients from a composition to obtain a composition extract; S2) mixing the composition extract with auxiliary materials to obtain a preparation; the composition comprises spiny jujube seeds, poria, cooked panax notoginseng, astragalus, codonopsis and stir-fried hawthorn.

[0012] Furthermore, the composition comprises, by weight, 9-15 parts of spinach seed, 7-12 parts of poria, 6-10 parts of notoginseng, 9-15 parts of astragalus, 6-15 parts of codonopsis and 5-20 parts of stir-fried hawthorn.

[0013] Further, the active ingredients include jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4, ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5 and ginsenoside Rh2;

[0014] Further, S1) comprises: mixing the composition with water, and sequentially performing extraction, filtration, concentration and first drying to obtain a composition extract; preferably, the extraction method comprises one or more of ultrasonic extraction, electromagnetic wave extraction or microwave extraction; preferably, the extraction time is 1 to 3 hours; preferably, the number of extractions is 1 to 5 times; preferably, the volume ratio of the composition to water is 1:10 to 1:20; preferably, the filtration mesh size is 300 to 400 mesh; preferably, the concentration temperature is 30 to 60°C; preferably, the first drying temperature is 40 to 70°C; preferably, concentration comprises one or more of reduced pressure distillation concentration, membrane concentration or centrifugal concentration.

[0015] Further, S2) comprises: drying the composition extract for the first time and sieving it, and then mixing it with an auxiliary material to obtain a soft material; granulating, drying and granulating the soft material in sequence to obtain a preparation; preferably, the mesh size of the sieving is 80-200 meshes; preferably, the auxiliary materials include a molding agent and / or a wetting agent; preferably, the molding agent includes one or more of dextrin, starch, lactose powder, mannitol or sucrose powder; preferably, the wetting agent includes ethanol and / or water; preferably, the mass ratio of the composition extract to the molding agent is 1:0.8-1:1.5; preferably, the mass ratio of the sum of the mass of the composition extract and the molding agent to the mass ratio of the wetting agent is 1:0.3-1:0.35; preferably, the mesh size of the granulation is 5-15 meshes; preferably, the temperature of the second drying is 50-80°C; preferably, the mesh size of the granulation is 10-80 meshes.

[0016] According to a third aspect of the present invention, there is provided a preparation for treating sleep disorders, the preparation comprising the above-mentioned composition and a pharmaceutically acceptable carrier and / or excipient, or prepared by the above-mentioned preparation method.

[0017] Further, the active ingredients in the preparation include jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4, ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5 and ginsenoside Rh2;

[0018] Preferably, the mass ratios of jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4, ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5 and ginsenoside Rh2 in the active ingredients are: (18.18-22.78): (3.65-14.60): (0.78-1.17): (10.44-12.58): (0.96-1.05): (2.88-4.53): (27.28-39.28): (6.56-9.49): (2.45-3.97): (5.16-7.15): (1.14-1.41).

[0019] Furthermore, the dosage form of the preparation includes granules, pills, pastes, tablets, capsules or oral liquids.

[0020] The technical scheme of the present invention is applied, and by utilizing the Chinese medicine composition of this application, which includes Chinese jujube seeds, poria, cooked Panax notoginseng, astragalus, codonopsis, and stir-fried hawthorn, the composition is mainly characterized by flat and warm properties, and the components cooperate with each other, and the effects of multiple parties are combined to improve the sleep disorders caused by blood deficiency. The Chinese medicine composition of this application has the effects of nourishing the heart and calming the mind, replenishing qi and blood, regulating qi and strengthening the spleen, and promoting blood circulation and unblocking collaterals. Poria nourishes the heart and calms the mind, and is compatible with Chinese jujube seeds, and the power of nourishing the heart and calming the mind is stronger; Codonopsis replenishes the middle and replenishes qi, and is combined with astragalus, and the function of replenishing qi and generating blood is more prominent; cooked Panax notoginseng replenishes qi and nourishes blood, and is a ministerial medicine. Stir-fried hawthorn is used to promote blood circulation and unblock collaterals; various qi-invigorating and blood-nourishing drugs are combined, and qi and blood are nourished. Compared with the existing Chinese medicine prescriptions for treating sleep disorders, the Chinese medicine composition of this application is better for improving sleep disorders caused by blood deficiency, and the therapeutic effect is more stable. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The drawings constituting a part of the present application are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0022] Figure 1 The schematic diagram shows the effect of each group treatment on the peripheral blood routine test of blood deficiency mice in Example 5 of the present invention. Figure 1 A to C are schematic diagrams of the number of white blood cells, platelets, and hemoglobin, respectively. Figure 1 D to F in the middle are schematic diagrams of hematocrit, number of red blood cells, and mean corpuscular volume, respectively.

[0023] Figure 2 The figure shows the effect of each group treatment on the hematopoietic factor EPO content and CSF content in blood deficiency mice in Example 5 of the present invention. Figure 2 A and B are schematic diagrams of EPO content and CSF content, respectively.

[0024] Figure 3 A schematic diagram showing the effects of the treatments of each group in Example 5 of the present invention on pathological damage of spleen tissue in blood deficiency mice. Figure 3 A to D are 10× microscopic results of H&E staining of spleen tissue of mice in blank control group, blood deficiency model group, positive control group and high-dose group of the combination, respectively; E to H are 40× microscopic results of H&E staining of spleen tissue of mice in blank control group, blood deficiency model group, positive control group and high-dose group of the combination, respectively.

[0025] Figure 4 The results of the open field test of insomniac mice treated in each group in Example 6 of the present invention are shown. Figure 4 Middle A is the average heat map of the open field test. Figure 4 Middle B is the activity trajectory of mice.

[0026] Figure 5 The results of the open field test of insomniac mice treated in each group in Example 6 of the present invention are shown. Figure 5 A in the middle is a statistical diagram of the total distance of mouse activities. Figure 5 B in the middle is a statistical chart of the average moving speed of mice. Figure 5 Middle C is a statistical chart of the immobility time of mice. Figure 5 D in the middle is a statistical graph of the total peripheral movement distance of mice.

[0027] Figure 6 The results of the sodium pentobarbital-induced sleep test on insomniac mice treated in each group in Example 6 of the present invention are shown. Figure 6 A in the middle is a schematic diagram of the mouse morphology in a sleeping state assisted by sodium pentobarbital; Figure 6 Middle B is a statistical chart of the sleeping rate of mice in each group of cooperative sleeping; Figure 6 Middle C is a time statistics chart of coordinated sleep in mice; Figure 6 Middle D is a statistical chart of the sleep latency time of mice.

[0028] Figure 7 The schematic diagram shows the effect of the Chinese medicine composition of Example 6 of the present invention on the content of sleep-related neurotransmitters in insomnia mice. Figure 7 A in the middle is a statistical graph of 5-HT content in plasma; Figure 7 Middle B is a statistical graph of 5-HT content in hypothalamic homogenate; Figure 7 Middle C is a statistical graph of GABA content in plasma; Figure 7 D in the middle is a statistical graph of GABA content in hypothalamic homogenate.

[0029] Figure 8A schematic diagram showing the effect of the Chinese medicine composition of Example 6 of the present invention on the content of sleep-related neurotransmitters in insomnia mice. Figure 8 A in the middle is a statistical graph of MT content in plasma; Figure 8 Middle B is a statistical graph of MT content in hypothalamic homogenate; Figure 8 Middle C is a statistical graph of DA content in plasma; Figure 8 D in the middle is a statistical graph of DA content in hypothalamic homogenate.

[0030] Fig. 9 A schematic diagram showing the H&E staining results of the effect of the Chinese medicine composition of Example 6 of the present invention on pathological damage in the hippocampus of brain tissue of insomnia mice.

[0031] Fig.10 A schematic diagram showing the Nissl staining results of the effect of the Chinese medicine composition of Example 6 of the present invention on the nerve damage in the hippocampus of the brain tissue of insomnia mice.

[0032] Fig.11 A schematic diagram showing the effect of the Chinese medicine composition of Example 6 of the present invention on cell damage in the hippocampus CA1 region of the brain tissue of insomnia mice. DETAILED DESCRIPTION

[0033] It should be noted that, in the absence of conflict, the embodiments in this application and the features in the embodiments can be combined with each other. The present invention will be described in detail below in conjunction with the embodiments. As mentioned in the background technology, the use of Western medicine to treat sleep disorders in clinical practice may cause side effects such as drug resistance, dependence, and addiction. However, Chinese medicine believes that the causes of sleep disorders are complex and diverse, and there is currently a lack of Chinese medicine compositions that can effectively treat sleep disorders caused by blood deficiency. Therefore, the present invention has formulated a new Chinese medicine composition that can be used to treat sleep disorders caused by blood deficiency, aiming to reconcile yin and yang, balance the Ying and Wei, restore the functions of the five internal organs, and synergistically improve the symptoms of sleep disorders in patients caused by blood deficiency. The efficacy is stable and the side effects are small. Based on this, a series of protection schemes of this application are proposed.

[0034] In a first typical embodiment of the present application, a composition for treating sleep disorders is provided, the composition comprising spiny jujube seeds, poria, cooked panax notoginseng, astragalus, codonopsis and stir-fried hawthorn.

[0035] The composition for treating sleep disorders in the present application combines the effects of calming the mind, replenishing qi and blood, relieving stagnation and relieving arthralgia, regulating qi and strengthening the spleen, etc., and treats sleep disorders from the perspective of "mind", that is, while emphasizing replenishing qi and blood and balancing yin and yang, it also focuses on harmonizing the spleen and stomach, relieving stagnation and relieving arthralgia, regulating qi and strengthening the spleen, and jointly promoting the body's qi and blood transportation and nourishment to ensure the transportation of water and grain, reconciling the balance of yin and yang, and reversing the imbalance of yin and yang dominated by yang excess and yin deficiency, and yang not entering yin, to achieve the effect of tranquilizing the mind, so as to improve sleep disorders caused by blood deficiency. Among them, the formula of the composition of the present application is mainly flat and warm in nature, and the components cooperate with each other, and the comprehensive effects of multiple parties are used to jointly improve sleep disorders, and compared with the existing Chinese medicine prescriptions for treating insomnia, it is quick to take effect and has a more stable therapeutic effect.

[0036] Treatment from the perspective of the heart and kidney: The heart governs the mind, and the kidney stores essence. When the heart and kidney interact, water and fire are in harmony, and sleep is peaceful. If the heart fire is hyperactive and the kidney water is insufficient, the heart and kidney will not interact, leading to insomnia. The Complete Book of Jingyue says: "The true yin essence and blood are insufficient, the yin and yang do not interact, and the spirit is restless in its room." Ziziphus jujuba seeds and Poria cocos, as the "main medicine" in the composition of this application, jointly bear the effects of nourishing the heart and kidney, calming the mind and settling the mind. The two are used together to nourish the yin of the heart and kidney, so that people can feel at ease and sleep peacefully at night.

[0037] Treatment from the perspective of liver and gallbladder: The liver and gallbladder are the exterior and interior of each other. The liver is responsible for regulating the flow of qi. If the liver qi is stagnant or the liver fire is strong, it is easy to disturb the mind and cause insomnia. "Suwen·Six-section Zang-Xiang Theory" points out: "The liver is the root of the body and the residence of the soul." As the "minister drug", cooked Panax notoginseng in this combination has the functions of harmonizing the liver and gallbladder, promoting blood circulation and removing blood stasis, nourishing blood and calming the mind, and nourishing blood and promoting blood circulation. It has a significant improvement effect on insomnia caused by liver and gallbladder disharmony, blood stasis blocking the collaterals, and blood deficiency.

[0038] Treatment from the perspective of the spleen and stomach: The spleen and stomach are the foundation of the acquired constitution and the source of qi and blood production. If the spleen and stomach are healthy, the qi and blood are sufficient and the mind is nourished. If the spleen and stomach are weak, the qi and blood production is insufficient, the mind is not nourished, and insomnia occurs. The Yellow Emperor's Classic of Internal Medicine says: "If the stomach is not harmonious, you will not be able to sleep well", which is a brilliant summary of this theory. Therefore, during treatment, attention should be paid to strengthening the spleen and stomach and restoring the spleen and stomach functions. Codonopsis and Astragalus are used as "minister drugs" to strengthen the spleen and replenish qi to provide the source. The two drugs are matched to nourish the soil of the spleen and stomach, so that the qi and blood production is active and the mind is nourished.

[0039] Treatment from the perspective of phlegm and fire: Phlegm and fire intertwine and disturb the mind, which can also lead to insomnia. "Danxi's Heart Method" says: "If you have phlegm, you will not be able to sleep well." Stir-fried hawthorn is an "adjuvant" that can nourish yin, moisten dryness, strengthen the spleen and harmonize the stomach.

[0040] The nature and flavor of Chinese jujube seeds: sweet and sour, neutral in nature, and enter the liver, gallbladder, and heart meridians. It is mild in nature and can nourish the heart and calm the mind, as well as stop sweating. Functions and indications: Mainly used to treat symptoms such as insomnia, palpitations and dreams, excessive sweating due to physical weakness, and thirst due to loss of body fluids. "Shennong's Herbal Classic" records: "Chinese jujube seeds can nourish the middle and benefit the liver, strengthen the tendons and bones, and help the yin qi, all of which are the functions of Chinese jujube seeds."

[0041] Poria nature and flavor: sweet, light, neutral, heart and spleen meridians. As the part of the sclerotium of Poria cocos with pine roots, Poria cocos focuses more on calming the mind and relieving restlessness. Functions and indications: Mainly used to treat palpitations, insomnia, forgetfulness, epilepsy and other restless symptoms. "Famous Doctors' Records" says: "Poria cocos is used to treat epilepsy, calm the mind and stabilize the spirit, treat wind vertigo, wind deficiency, chest and rib fullness, and phlegm and water between the diaphragm."

[0042] Nature and flavor of cooked Panax notoginseng: Cooked Panax notoginseng tastes sweet and slightly bitter, is warm in nature, and enters the liver and stomach meridians. The effect of cooking Panax notoginseng on promoting blood circulation and removing blood stasis is weaker than that of raw Panax notoginseng, but its ability to nourish and nourish blood is enhanced. Functions and indications: Cooked Panax notoginseng is mainly used to treat symptoms such as anemia, weakness due to blood loss, irregular menstruation, and postpartum blood stasis. "Supplement to Compendium of Materia Medica" says: "Ginseng is the best for replenishing qi, and Panax notoginseng is the best for replenishing blood. They have the same taste and the same effect, so it is called ginseng Panax notoginseng, which is the most precious among traditional Chinese medicines." The processing method of cooked Panax notoginseng in this application includes but is not limited to being obtained by frying, steaming or frying raw Panax notoginseng. Cooked Panax notoginseng obtained by processing methods known to those skilled in the art can achieve the effects of this application, and the processing method can be flexibly selected according to the actual production needs.

[0043] Astragalus nature and flavor: sweet, slightly warm, spleen and lung meridians. It is good at raising yang, can replenish the spleen and lung qi, and is an important medicine for replenishing qi. Functions and indications: It has the effects of replenishing qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, promoting fluid and nourishing blood, relieving stagnation and relieving numbness, expelling toxins and draining pus, and healing sores and promoting tissue regeneration. It is widely used for symptoms such as qi deficiency and fatigue, poor appetite and loose stools, sinking of qi in the middle, chronic diarrhea and prolapse of the anus, and bloody stool and metrorrhagia. "Compendium of Materia Medica" praises it as "a medicine that replenishes the lungs and spleen, strengthens the defense and stops sweating, and drives away wind and transports toxins."

[0044] Codonopsis nature and flavor: Codonopsis is sweet and neutral in nature. It is in the spleen and lung meridians. It is mild in nature, not dry or greasy. It can not only replenish spleen and lung qi, but also replenish blood and produce body fluid. Functions and indications: Codonopsis is mainly used to treat symptoms such as spleen and stomach weakness, deficiency of qi and blood, fatigue and weakness, poor appetite and thirst. "Compendium of Materia Medica" states: "It can replenish the middle qi, harmonize the spleen and stomach, and eliminate thirst. It is very appropriate to use it to regulate and replenish the weak middle qi."

[0045] The nature and flavor of fried hawthorn: sour, sweet, slightly warm, and enters the spleen, stomach, and liver meridians. The digestion effect of fried hawthorn is enhanced, and the sour taste is astringent and can stop diarrhea. Functions and indications: Fried hawthorn is mainly used to treat symptoms such as meat stagnation, stomach distension, diarrhea, and abdominal pain. "Compendium of Materia Medica" says that it: "digests food, eliminates meat accumulation, lumps, phlegm, fullness, acid regurgitation, and blood stasis and pain." The preparation method of fried hawthorn in this application includes but is not limited to frying hawthorn. The fried hawthorn obtained by the preparation means known to those skilled in the art can achieve the effect of this application, and the preparation method can be flexibly selected according to the actual production needs.

[0046] In summary, the Chinese medicine composition composed of the above 6 Chinese medicines in this application is compatible with each other so that each medicinal material can fully exert its efficacy and work together on the internal organs and meridians of the human body to achieve the purpose of harmonizing yin and yang, calming the mind and improving blood deficiency, and can synergistically improve sleep disorders caused by blood deficiency.

[0047] In a preferred embodiment, the composition comprises, by mass, 9-15 parts of Semen Ziziphi Spinosae (including but not limited to 9, 10, 11, 12, 13, 14 or 15 parts), 7-12 parts of Poria (including but not limited to 7, 8, 9, 10, 11 or 12 parts), 6-10 parts of Notoginseng (including but not limited to 6, 7, 8, 9 or 10 parts), 9-15 parts of Astragalus (including but not limited to 9, 10, 11, 12, 13, 14 or 15 parts), 6-15 parts of Codonopsis Pilosula (including but not limited to 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 parts) and 5-20 parts of stir-fried Hawthorn (including but not limited to 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 parts);

[0048] Preferably, the active ingredients in the composition include jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4, ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5 and ginsenoside Rh2; preferably, the active ingredients include jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4 The mass ratios of ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5 and ginsenoside Rh2 are: 18.18-22.78: 3.65-14.60: 0.78-1.17: 10.44-12.58: 0.96-1.05: 2.88-4.53: 27.28-39.28: 6.56-9.49: 2.45-3.97: 5.16-7.15: 1.14-1.41.

[0049] In the specific embodiment of the present application, the Chinese medicine composition of the present application was used to carry out a subtoxicity test on normal adult mice, and the results showed that the Chinese medicine composition had no significant toxic and side effects. The Chinese medicine composition of the present application was used to treat mice with insomnia induced by para-chlorophenylalanine (PCPA), and the results showed that the composition of the present application could significantly improve the symptoms of sleep-disordered mice, and the time of autonomous activity of insomnia mice after treatment was reduced, and the sleep latency of insomnia mice synergized by sodium pentobarbital was shortened, and the sleep time synergized by sodium pentobarbital was prolonged, and the content of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (γ-GABA), and melatonin (MT) in plasma and hypothalamus of insomnia mice was increased, the content of dopamine (DA) in hypothalamus was reduced, the consumption of DA in mouse plasma was reduced, and the cell damage in hippocampus of mouse brain tissue was repaired.

[0050] It can be seen that the Chinese medicine composition of the present application significantly reduces the leukocyte content of blood deficiency mice, and red blood cells, hemoglobin, platelet content, hematocrit and mean corpuscular volume are significantly improved; and improve the pathological damage of blood deficiency mice spleen, reverse the red pulp dispersion, white pulp atrophy, unclear red and white pulp boundaries and loose membrane of blood deficiency mice spleen pathological damage performance; and the composition of the present application directly promotes erythropoietin (EPO, Erythropoietin) generation and inhibits colony stimulating factor (M-CSF, Marcrophage Colony-Stimulating Factor) compensation increase, improves the symptoms of blood deficiency in mice, and further improves the sleep disorder of blood deficiency mice. According to the above results, it is proved that the Chinese medicine composition of the present application can effectively improve the sleep disorder caused by deficiency of both qi and blood, and has small toxic and side effects, quick effect and stable efficacy.

[0051] In a preferred embodiment, the composition further comprises a solvent and / or an auxiliary material; preferably, the solvent comprises water; preferably, the auxiliary material comprises a molding agent and / or a wetting agent; preferably, the molding agent comprises one or more of dextrin, starch, lactose powder, mannitol or sucrose powder; preferably, the wetting agent comprises one or more of ethanol, water, glycerol or polyoxyethylene fatty alcohol ether; preferably, the composition further comprises 0.8 to 1.5 parts of a molding agent and 0.2 to 0.4 parts of a wetting agent.

[0052] In a second typical embodiment of the present application, a method for preparing a preparation for treating sleep disorders is provided, the preparation method comprising: S1) extracting the active ingredients in the composition to obtain a composition extract; S2) mixing the composition extract with auxiliary materials to obtain a preparation; the composition comprises Chinese jujube seeds, poria, cooked Panax notoginseng, astragalus, Codonopsis pilosula and stir-fried hawthorn.

[0053] In a preferred embodiment, the composition comprises, by weight, 9-15 parts of spinach seed, 7-12 parts of poria, 6-10 parts of notoginseng, 9-15 parts of astragalus, 6-15 parts of codonopsis and 5-20 parts of stir-fried hawthorn.

[0054] In a preferred embodiment, the active ingredients include jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4, ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5 and ginsenoside Rh2;

[0055] Preferably, the mass ratios of jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4, ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5 and ginsenoside Rh2 among the active ingredients in the preparation are: (18.18-22.78): (3.65-14.60): (0.78-1.17): (10.44-12.58): (0.96-1.05): (2.88-4.53): (27.28-39.28): (6.56-9.49): (2.45-3.97): (5.16-7.15): (1.14-1.41).

[0056] In a preferred embodiment, S1) comprises: mixing the composition with water, and sequentially performing extraction, filtration, concentration and first drying to obtain a composition extract; preferably, the extraction method comprises one or more of ultrasonic extraction, electromagnetic wave extraction or microwave extraction; preferably, the extraction time is 1 to 3 hours (including but not limited to 1, 1.5, 2, 2.5 or 3 hours); preferably, the number of extractions is 1 to 5 times (including but not limited to 1, 2, 3, 4 or 5 times); preferably, the volume ratio of the composition to water is 1:6 to 1:20 (including but not limited to 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19 or 1:20); preferably, the filtration mesh is 200-600 mesh (including but not limited to 200, 250, 300, 350, 400, 450, 500, 550 or 600 mesh); preferably, the concentration temperature is 30-60°C (including but not limited to 30°C, 35°C, 40°C, 45°C, 50°C, 55°C or 60°C); preferably, the first drying temperature is 50-80°C (including but not limited to 50°C, 55°C, 60°C, 65°C, 70°C, 75°C or 80°C); preferably, concentration comprises one or more of vacuum distillation concentration, membrane concentration or centrifugal concentration.

[0057] The present application controls the solid-liquid ratio, extraction time and number of extractions of the above-mentioned composition in the above-mentioned S1) to fully extract the effective ingredients of the composition, so that the effective ingredients of each component in the composition are completely released, which is beneficial to the preparation of subsequent preparations and ensures the efficacy of the composition, and is beneficial to the preparation of preparations for improving sleep disorders.

[0058] In a preferred embodiment, S2) comprises: drying the composition extract for the first time and sieving it, and then mixing it with the auxiliary materials to obtain a soft material; granulating the soft material, drying it for the second time and granulating it in sequence to obtain a preparation; preferably, the mesh number of the sieving is 80-200 meshes (including but not limited to 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190 or 200 meshes); preferably, the auxiliary materials include a molding agent and / or a wetting agent; preferably, the molding agent includes one or more of dextrin, starch, lactose powder, mannitol or sucrose powder; more preferably, the molding agent includes lactose powder; preferably, the wetting agent includes one or more of ethanol, water, glycerol or polyoxyethylene fatty alcohol ether; more preferably, the wetting agent includes ethanol; more preferably, it is 90% ethanol aqueous solution; preferably, the mass ratio of the composition extract to the molding agent is 1:0.8 to 1:1. 5 (including but not limited to 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4 or 1:1.5); preferably, the mass ratio of the sum of the mass of the composition extract and the shaping agent to the mass ratio of the wetting agent is 1:0.3 to 1:0.35 (including but not limited to 1:0.3, 1:0.31, 1:0.32, 1:0.33, 1:0.34 or 1:0.35); preferably, the preparation The mesh number of the granules is 5-15 mesh (including but not limited to 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 mesh); preferably, the temperature of the second drying is 50-80°C (including but not limited to 50°C, 55°C, 60°C, 65°C, 70°C, 75°C or 80°C); preferably, the mesh number of the whole granules is 10-80 mesh (including but not limited to 10, 20, 30, 40, 50, 60, 70 or 80 mesh).

[0059] The present application controls the parameters of the granulation method in S2), the type of excipients, and the mass ratio of the excipients to the composition extract within the above range to obtain a granule with loose soft material, moderate hardness, and easy sieving, thereby improving the efficiency of preparing the composition of the present application into medicine and making it easier to take.

[0060] By utilizing the preparation method of the preparation for treating sleep disorders of the present application, the prepared preparation can fully extract the active ingredients in the composition, improve the efficiency of drug production, and the preparation method is simple, which is conducive to promotion.

[0061] In a second typical embodiment of the present application, a preparation for treating sleep disorders is provided, wherein the preparation comprises any one of the above-mentioned compositions and a pharmaceutically acceptable carrier and / or excipient, or is prepared by the above-mentioned preparation method.

[0062] In a preferred embodiment, the active ingredients in the preparation include jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4, ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5 and ginsenoside Rh2;

[0063] Preferably, the mass ratios of jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4, ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5 and ginsenoside Rh2 in the active ingredients are: (18.18-22.78): (3.65-14.60): (0.78-1.17): (10.44-12.58): (0.96-1.05): (2.88-4.53): (27.28-39.28): (6.56-9.49): (2.45-3.97): (5.16-7.15): (1.14-1.41).

[0064] In a preferred embodiment, the dosage form of the preparation includes granules, pills, pastes, tablets, capsules or oral solutions.

[0065] The beneficial effects of the present application will be further explained in detail below in conjunction with specific embodiments.

[0066] Example 1

[0067] 1. By mass, take 10 parts of Ziziphus jujuba seeds, 10 parts of Poria, 6 parts of Panax notoginseng, 9 parts of Astragalus, 10 parts of Codonopsis pilosula, and 5 parts of stir-fried Hawthorn.

[0068] The preparation method of the cooked Panax notoginseng in the embodiment of the present application is as follows: wash the raw Panax notoginseng, put it into a high-pressure steam cooker, and steam it at 120° C. for 3 hours until the inside is cooked thoroughly, and dry the steamed Panax notoginseng to obtain the cooked Panax notoginseng.

[0069] The preparation method of stir-fried hawthorn in the embodiment of the present application is as follows: wash the raw hawthorn, drain the water and slice it, then put the raw hawthorn slices in a stir-frying container, heat and stir-fry over medium heat until the color becomes darker, take out and let cool to obtain cooked hawthorn.

[0070] The weighed components were added to 10 times the mass of water and soaked for 30 minutes, refluxed and extracted at 93°C for 1 hour, extracted 3 times in total, filtered while hot with a 300-mesh gauze, filtered again after standing overnight, and the filtrate was rotary evaporated in a 60°C water bath (Shanghai Ailang Instrument Co., Ltd., model: 0SB-2200) to obtain an extract of the traditional Chinese medicine composition with a density of 1.2-1.5. The extract was dried at 60°C (Bielefeld, Germany, model: ED series) to obtain a dry extract powder of the traditional Chinese medicine composition.

[0071] Weigh a certain amount of dry extract powder, add methanol and ultrasonicate for 20 minutes, centrifuge at 10000 rpm for 10 minutes, take the supernatant, and filter it with a 0.22 μm organic phase filter membrane for HPLC analysis.

[0072] 2. Preparation of mixed standard 1: Accurately weigh 0.8, 1, 0.7, 0.4, 0.7, 0.9, 1, 0.9, 1, 1.3, and 0.6 mg of jujuboside A, astragaloside I, ginsenoside Rh1, Rh2, Rh4, Rk3, 20(S)-Rg3, 20(R)-Rg3, Rd, F4, and Rg5 to obtain mixed standard solution 1, which is used to calculate the proportion and content of the main components in the dry powder of the extract (the calculation adopts the external standard method, i.e., Cx=Cr×Ax÷Ar).

[0073] 3. Preparation of test solution: Accurately weigh 200 mg of the dry powder of the composition extract, add 1 mL of methanol, ultrasonicate for 20 min, centrifuge at 10000 rpm for 10 min, take the supernatant, filter with a 0.22 μm organic phase filter membrane, and use for HPLC analysis.

[0074] The results showed that the 11 active ingredients in the dry powder of the extract included jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4, ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5, and ginsenoside Rh2;

[0075] The ratios of the above ingredients in each 1 mg of dry extract powder are: (18.18-22.78): (3.65-14.60): (0.78-1.17): (10.44-12.58): (0.96-1.05): (2.88-4.53): (27.28-39.28): (6.56-9.49): (2.45-3.97): (5.16-7. 15): (1.14-1.41), the contents of each are: 1.56-2.08, 0.25-1.67, 0.0801-0.0887, 0.715-1.44, 0.066-0.12, 0.31-0.33, 2.69-3.12, 0.65-0.75, 0.26-0.28, 0.49-0.59, 0.097-0.13 μg / mg respectively.

[0076] Example 2

[0077] The above-mentioned Chinese medicine composition was extracted by changing different material-liquid ratios (composition and water), extraction time and extraction times. The extraction method was the same as that in Example 1. The dry paste yield and the quantitative evaluation of seven components, namely, jujuboside A, astragaloside I, ginsenoside Rh1, Rh4, Rk3, 20(S)-Rg3, and 20(R)-Rg3, were used as evaluation criteria for a single factor experiment. Based on the single factor experimental results, a response surface experiment was designed using design expert DX10, and variance analysis of a binary multiple regression model was performed to obtain the optimal extraction process.

[0078] Preparation of mixed standard solution 2: Accurately weigh jujuboside A, astragaloside I, ginsenoside Rh1, Rh4, Rk3, 20(S)-Rg3, and 20(R)-Rg3, and prepare mixed standard solutions with concentrations of 0.3, 0.3, 1.2, 0.2, 0.7, 0.2, and 0.2 mg / mL, respectively, for quantitative analysis of the main component content in compound extraction process optimization. The final content is based on the main component content (mg) of each 1 / 5 dose of the composition in the prescription as the evaluation indicator.

[0079] The main medicinal ingredients of soothing nerves, replenishing qi and nourishing blood were selected as the main medicinal ingredients of Ziziphus jujuba seed (Ziziphus jujuba saponin A), Astragalus (Astragaloside I), and Panax notoginseng (Ginsenosides Rh1, Rh4, Rk3, 20(S)-Rg3, 20(R)-Rg3) as preparation evaluation indicators.

[0080] Reason: The ingredients of one herb each for calming the nerves, replenishing qi and nourishing blood, namely, Chinese jujube seed, astragalus, and Panax notoginseng, were selected as evaluation indicators respectively. Therefore, Chinese jujube seed saponin and astragaloside I were retained. Because the main components of Panax notoginseng are ginsenosides Rh1, Rh4, Rk3, 20(S)-Rg3, and 20(R)-Rg3, and the contents of other components are relatively low, the above 7 components were finally selected as preparation evaluation indicators.

[0081] The specific experimental arrangements and the variance analysis results of the binary multiple regression model of the composition extraction response surface design are shown in Tables 1 and 2 .

[0082] Table 1

[0083] Group Material-liquid ratio Extraction time (h) Number of extractions (times) Yield (%) Content (mg) Overall Rating 1 16 1.5 4 31.05 170.19 114.54 2 14 1.5 3 37.36 170.68 117.35 3 16 1.5 2 27.48 147.6 99.55 4. 14 1 2 24.44 130.99 88.37 5 12 1 3 23.57 118.52 80.54 6 12 2 3 25.45 148.57 99.33 7 14 1.5 3 33.81 178.7 120.75 8 14 2 2 27.24 151.4 101.74 9 14 1.5 3 33.08 175.72 118.66 10 12 1.5 4 26.33 157.57 105.08 11 14 1 4 26.98 163.64 108.97 12 16 1 3 26.6 160.2 106.76 13 16 2 3 28.03 169.5 112.91 14 14 1.5 3 31.74 174.08 117.14 15 12 1.5 2 25.05 136.38 91.85 16 14 1.5 3 31.61 175.95 118.21 17 14 2 4 29.57 170.58 114.18

[0084] Note: Comprehensive score = dry paste yield × 40% + main component content × 60%.

[0085] Table 2

[0086]

[0087]

[0088] In Table 2, “R 2 adj" refers to R 2 The corrected coefficient of determination is “R 2 "pre" refers to the error reduction ratio; "CV%" is the coefficient of variation, which refers to the ratio of the mean to the average; "AP" refers to the average precision.

[0089] The results show that the quadratic polynomial equation of the relationship between the dry extract yield and the comprehensive score of the HPLC main component content and the three extraction conditions was obtained by fitting the indicators in Table 2 in design expert DX10: Y = 118.42 + 7.12A + 5.44B + 7.66C-3.16AB + 0.44AC-2.04BC-9.55A2-8.99B2-6.12C2 (Y is the comprehensive score of the dry extract yield and the main component content of the extract, A is the solid-liquid ratio, B is the extraction time, and C is the number of extractions). The response surface results show that the relationship between the factors affecting the extraction efficiency of the compound is: number of extractions > solid-liquid ratio > extraction time. The optimal extraction method is solid-liquid ratio of 1:14.56, extraction time of 1.61h, and extraction times of 2.76 times. Therefore, combined with production cost and actual situation, the best extraction scheme is determined as: solid-liquid ratio of 1:14, extraction time of 1.5h, and extraction times of 3 times.

[0090] Example 3

[0091] Granulation method:

[0092] The extract powder of the Chinese medicine composition obtained by extraction in Example 1-1 was passed through a 100-mesh sieve, the extract powder and auxiliary materials (forming agent, 90% ethanol as a wetting agent) were mixed to prepare a soft material, granulated through a 10-mesh sieve, dried at 60°C, and sized through 10-mesh and 80-mesh sieves to obtain granules (preparation).

[0093] The comprehensive score was calculated based on the molding rate, dissolution rate, moisture absorption rate, bulk density and angle of repose as evaluation indicators. The best molding agent excipients were selected from dextrin, soluble starch, lactose powder, mannitol and sucrose powder, and the amount of excipients and wetting agent was further determined. The experimental design arrangement for optimizing the ratio of molding agent and wetting agent in the preparation of compound granules is shown in Table 3, and the molding rate, dissolution rate, moisture absorption rate, bulk density, angle of repose and comprehensive score results of different adjustment groups are shown in Table 4.

[0094] Among them, the methods of each evaluation index are as follows:

[0095] Forming rate (%): The dried granules were passed through a 10-mesh sieve and an 80-mesh sieve, and the mass was recorded. This was repeated three times. Forming rate (%) = mass of granules that can pass through a 10-mesh sieve but cannot pass through an 80-mesh sieve / total mass of dried granules × 100%.

[0096] Dissolution rate (%): Weigh 0.3g of particles with qualified forming rate accurately, add 5mL of boiling water, stir and shake for 5min, centrifuge at 3000rmp for 15min, remove the supernatant, dry the precipitate at 60℃ for 6h, record the mass of the dry precipitate and calculate the dissolution rate, repeat three times. Dissolution rate (%) = (mass of particles - mass of dry precipitate) / mass of particles × 100%.

[0097] Moisture absorption rate (%): 0.3g of particles with qualified forming rate were accurately weighed and placed in a glass desiccator balanced with supersaturated sodium chloride solution for 24 hours. After 24 hours, the particles were taken out immediately and the mass was recorded to calculate the moisture absorption rate. This was repeated three times. Moisture absorption rate (%) = (mass after moisture absorption - mass before moisture absorption) / mass before moisture absorption × 100%.

[0098] Angle of repose (°): Set the distance h between the funnel and the plane to 1.5 cm, slowly pour the particles with qualified forming rate along the wall of the funnel, stop when the particles just pile up to the funnel mouth, measure the radius r of the cone, calculate the angle of repose, and repeat three times. Angle of repose (°) = arctan height h / radius r.

[0099] Bulk density (g / mL): slowly pour the particles with qualified forming rate into a 10mL measuring cylinder that has been dried to constant weight, record the volume of particles in the measuring cylinder, calculate the bulk density, and repeat three times. Bulk density (g / mL) = particle mass / particle volume.

[0100] Comprehensive score = forming rate × 30% + melting rate × 20% + moisture absorption rate × 20% + angle of repose × 15% + bulk density × 15%.

[0101] Table 3

[0102] Group Excipients Chinese medicine composition: excipients Chinese medicine composition + excipients: wetting agent 1 dextrin 1：1 1：0.2 2 Soluble starch 1：1 1：0.2 3 Sucrose powder 1：1 1：0.2 4 Lactose powder 1：1 1：0.2 5 Mannitol 1：1 1：0.2 6 Lactose powder 1：0.6 1：0.2 7 Lactose powder 1：0.8 1：0.2 8 Lactose powder 1：1 1：0.2 9 Lactose powder 1：1.2 1：0.2 10 Lactose powder 1：1.4 1：0.2 11 Lactose powder 1：1 1：0.25 12 Lactose powder 1：1 1：0.275 13 Lactose powder 1：1 1：0.3 14 Lactose powder 1：1 1：0.325 15 Lactose powder 1：1 1：0.35 16 Lactose powder 1：1 1：0.375 17 Lactose powder 1：1 1：0.4

[0103] Table 4

[0104]

[0105]

[0106] The results show that when lactose powder is selected as the auxiliary material for the preparation of the granules, when the lactose powder mass ratio is ≥1, the dry powder is mixed evenly, the soft material is loose, the hardness is moderate, and the comprehensive score is high, so the dry powder and lactose ratio of 1:1 is selected as the best ratio. When the wetting agent (ethanol 90%) is added to the ratio of 1:0.3-1:0.35, the comprehensive score of the granules is high, the soft material is loose, the hardness is moderate, and it is easy to sieve, so the ratio of the wetting agent is determined to be between 1:0.3-1:0.35.

[0107] Example 4

[0108] Subtoxicity test in mice:

[0109] The 7-day administration + 7-day observation method was adopted, and 3 dose gradients (3.6, 7.2, 10.8 g / kg, 20, 40 and 60 times the human dose, respectively) of the extract powder of the Chinese medicine composition of Example 1 were set for continuous gavage for 7 days, and 7 days were observed after the end of the 7th day of administration. The human dose was converted based on 3 g of Panax notoginseng per day, and the mouse dose was converted using the human body surface area conversion formula (mouse dose = 9.1 × human dose / 60 kg).

[0110] Animals and breeding environment: 32 healthy adult Kunming mice of SPF grade, half female and half male, weighing 18-22 g were selected from Sibeifu (Beijing) Biotechnology Co., Ltd. The experimental animal production license number is SYXK (Yunnan) 2019-0010, the experimental animal quality certificate number is 110324230104370916, and the experimental animal use license number is SCXK (Beijing) 2022-0001. The temperature of the experimental animal room is 22-25℃, and the relative humidity is 55%-70%.

[0111] 1.8, 3.6, and 5.4 g of the extract powder of the Chinese medicine composition were weighed, and 7.5 mL of normal saline was added to prepare 0.24, 0.48, and 0.72 mg / μL fluid extracts, respectively. The mice were gavaged at a dosage volume of 15 μL / g for 7 days, and the state of the mice, including hair, body weight, and food intake, was observed. The results of the observation of the body shape of mice in the subtoxicity experiment are shown in Table 5.

[0112] On the 14th day, after fasting for 12 hours, the eyeballs were removed and blood was collected and placed in a centrifuge tube with anticoagulant added. After shaking, the blood was immediately placed in a blood analyzer (Jinan Hanfang Medical Instrument Co., Ltd., model: HF-3800) to detect the number of peripheral blood cells. The results of the routine peripheral blood examination of mice in the subtoxicity experiment are shown in Table 6.

[0113] Then centrifuge for 15 min at 3000 rpm in a differential low-temperature centrifuge (Hunan Xiangyi Laboratory Instrument Development Co., Ltd., H1650R desktop high-speed centrifuge) to separate the upper plasma for liver and kidney function testing. The results of liver and kidney function tests in subtoxicity experiments in mice are shown in Table 7.

[0114] After removing the eyeballs and drawing blood, the mice were immediately killed, and the thymus, liver, spleen, kidney and lung tissues were removed and weighed using an analytical balance to calculate the organ index. Organ index = tissue mass / body mass × 100%. The results of the organ index examination of the mouse subtoxicity experiment are shown in Table 8.

[0115] Table 5

[0116]

[0117]

[0118] Table 6

[0119]

[0120] Note: “*” in Table 6 indicates that the P value is less than 0.05.

[0121] Table 7

[0122]

[0123] Note: In Table 7, "*" indicates that the P value is less than 0.05, and "**" indicates that the P value is less than 0.01, all of which are significantly different.

[0124] Table 8

[0125]

[0126]

[0127] Note: In Table 8, “*” indicates that the P value is less than 0.05, and “**” indicates that the P value is less than 0.01, all of which are significantly different.

[0128] The results showed that compared with the blank group mice, after 7 days of intragastric administration of 20, 40 and 60 times the human dose of Chinese medicine composition extract and 7 days of drug withdrawal, the body weight of mice increased normally, and there was no poisoning or death (Table 5). The peripheral blood of mice was normal, with only differences in platelet items and 60 times the white blood cell items, and no significant effect on the peripheral blood of mice overall (Table 6). All indicators of liver and kidney function were not significantly different from the blank group at 20 times the dose (Table 7). After intragastric administration of different doses of Chinese medicine composition extract, the organ index of mice was not significantly different from the blank group (Table 8). It can be seen that the Chinese medicine composition of the present application has no obvious toxic and side effects.

[0129] Example 5

[0130] A blood deficiency mouse model was established using acetylphenylhydrazine (APH) and cyclophosphamide (CTX). After different doses of the extract dry powder of the traditional Chinese medicine composition of Example 1 were gavaged into the mice for treatment, blood routine and organ indexes were observed and the content of hematopoietic factors was determined to investigate the improving effect of the composition on blood deficiency.

[0131] Animals and breeding environment: 60 healthy adult Kunming male mice of SPF grade were selected from Sibeifu (Beijing) Biotechnology Co., Ltd., weighing 18-22g, experimental animal production license number: SYXK (Yunnan) 2019-0010, experimental animal quality certificate number: 110324241101535123, experimental animal use license number: SCXK (Beijing) 2023-0013. The temperature of the experimental animal room is 22-25℃, and the relative humidity is 55%-70%.

[0132] Model establishment method: On the 1st and 5th day after the end of adaptive feeding, 20 mg / kg APH (Chengdu Huaxia Chemical Reagent Co., Ltd., CAS No.: 114-83-0) was subcutaneously injected. On the 4th to 7th day, 40 mg / kg CTX (Shanghai McLean Biochemical Technology Co., Ltd., CAS No.: 6055-19-2) was intraperitoneally injected. The method for preparing APH and CTX solutions was to weigh 22.5 mg APH and 48 mg CTX respectively, add 5.625 and 6 mL of 0.9% saline respectively to prepare solutions with a final concentration of 4 mg / mL and 8 mg / mL, and the injection volume was 5 μL / g.

[0133] Dose selection and sample processing: Using the mouse and human surface area conversion formula (mouse dose = 9.1 × human dose / 60kg), the mouse dose was converted according to the adult daily dosage of 3g Panax notoginseng of the Chinese medicine composition. Three test groups with doses of 0.9, 1.8, and 3.6g / kg of the extract powder of the Chinese medicine composition (equivalent to 5, 10, and 20 times the recommended human dose, respectively) were set up. At the same time, a blank control group, a blood deficiency model group and a positive control group were set up, with 10 animals in each group.

[0134] Experimental animal grouping: 10 mice per group, 6 groups in total, namely blank control group, blood deficiency model group, positive control group, low-dose group, medium-dose group and high-dose group.

[0135] Low-dose group, medium-dose group and high-dose group: The preparation method of the extract powder solution of the Chinese medicine composition is as follows: weigh 562.5, 1125, and 1875 mg of the sample, add 5, 5, and 6 mL of 0.9% saline, respectively, mix well, and prepare suspensions with concentrations of 0.1125, 0.225, and 0.45 mg / μL;

[0136] Positive control group: The positive control group was given 8 mL / kg of compound donkey-hide gelatin (compound donkey-hide gelatin, Shandong Dong'e Donkey-hide Gelatin Co., Ltd.). Blank control group and blood deficiency model group: Both groups were given an equal volume of 0.9% normal saline.

[0137] Each group of animals was gavaged with a gavage volume of 8 μL / g, starting from the first day after the end of adaptive feeding, once a day for 15 consecutive days.

[0138] Blood routine test method: fasting for 12 hours after the last administration, blood was collected by removing the eyeball after anesthesia and placed in a centrifuge tube containing 1.5 mL of sodium heparin anticoagulant, shaken and immediately placed in a blood analyzer (Jinan Hanfang Medical Instrument Co., Ltd., model: HF-3800) to detect the number of peripheral blood cells. The white blood cell count, platelet count, hemoglobin count, hematocrit, red blood cell count and mean corpuscular volume are shown in the figure below. Figure 1 As shown, Figure 1 A to C are schematic diagrams of the number of white blood cells, platelets, and hemoglobin, respectively. Figure 1 D to F in the middle are schematic diagrams of hematocrit, red blood cell count, and mean corpuscular volume.

[0139] Figure 1 Middle A~F, Figure 2 In the horizontal axis of A~B, "CON" refers to the blank control group, "MOD" refers to the blood deficiency model group, "FFEJ" refers to the positive control group, "L-SQFF" refers to the low-dose group, "M-SQFF" refers to the middle-dose group, and "H-SQFF" refers to the high-dose group.

[0140] Among them, "*" indicates significant differences between each treatment group and the model group, wherein "*" indicates that the P value is less than 0.05, "**" indicates that the P value is less than 0.01, and "***" indicates that the P value is less than 0.001, all of which indicate that there are significant differences, and "ns" means no significant difference; "#" indicates significant differences between the model group and the blank group, wherein "#" indicates that the P value is less than 0.05, "##" indicates that the P value is less than 0.01, and "###" indicates that the P value is less than 0.001", all of which indicate that there are significant differences. The meanings of the symbols of statistical significance in the drawings of other embodiments in the present application are the same as here.

[0141] Hematopoietic factor index content determination method: fasting but not water for 12 hours after the last administration, remove the eyeball after anesthesia and take blood into a 1.5mL centrifuge tube containing sodium heparin anticoagulant, then centrifuge for 15 minutes at 3000rmp in a differential low-temperature centrifuge (Hunan Xiangyi Laboratory Instrument Development Co., Ltd., H1650R desktop high-speed centrifuge), separate the upper plasma for determination of EPO, CSF, etc. The detection method uses ELISA kits according to the instructions (EPO-ELISA research kits and CSF-ELISA research kits are purchased from Enzyme Immunity Biotechnology Co., Ltd., with catalog numbers 20230925NX and 20231011NX, respectively). Figure 2 A in the middle is a statistical chart of EPO content in kidney homogenate. Figure 2 B is a statistical chart of CSF content in serum. Figure 2 Figure C is a statistical chart of TNF-α content in serum. Figure 2 D in the figure is a statistical chart of IL-3 content in serum.

[0142] Spleen H&E staining method: After removing the eyeballs and drawing blood, the mice were immediately killed, the abdominal cavity was opened, the spleen was taken out, washed with saline, and immediately fixed in 4% neutral tissue fixative. After paraffin embedding, sectioning, staining and decolorization, the pathological damage of spleen tissue was observed.

[0143] Schematic diagram of pathological damage to spleen tissue in blood deficiency mice Figure 3 As shown, Figure 3 A, B, C, and D are the 10× microscopic results of H&E staining of mouse spleen tissue in the blank control group, blood deficiency model group, positive control group, and high-dose group (3.6 g / kg) of the combination, respectively; E, F, G, and H are the 40× microscopic results of H&E staining of mouse spleen tissue in the blank control group, blood deficiency model group, positive control group, and high-dose group of the combination, respectively (the spleen capsule is highlighted). The white arrow points to the white pulp, the red arrow points to the red pulp, the black triangle is the intercellular matrix where the lymphocytes and macrophages are located, and the red circle is the capsule of the spleen tissue in each group.

[0144] The results showed that the Chinese medicine composition of the present application significantly reversed the increase in the number of white blood cells in blood deficiency mice, and significantly reduced the number of red blood cells, hemoglobin, platelets, hematocrit, and mean corpuscular volume ( Figure 1 ) and improve the pathological damage of spleen in blood-deficient mice, and reverse the pathological damage of spleen in blood-deficient mice, such as red pulp dispersion, white pulp atrophy, unclear red and white pulp boundary and loose capsule ( Figure 3 ); The composition directly promotes EPO production and inhibits the increase of CSF compensatory, thereby improving the blood deficiency symptoms of mice ( Figure 2 ).

[0145] Example 6

[0146] An insomnia mouse model was established using p-chlorophenylalanine (PCPA, Shanghai Entech Development Co., Ltd., CAS No.: 7424-00-2). After oral administration of different doses of the composition, the mice's spontaneous activities and sleep time assisted by sodium pentobarbital were observed, the levels of sleep transmitters were determined, and the cell damage in the hippocampus of the mouse brain tissue was compared.

[0147] Animals and breeding environment: 120 healthy adult Kunming male mice of SPF grade were selected from Sibeifu (Beijing) Biotechnology Co., Ltd., weighing 18-22g, experimental animal production license number: SYXK (Yunnan) 2024-0001, experimental animal quality certificate number: 110324241102183353, animal use license number: SCXK (Beijing) 2023-0013. The temperature of the experimental animal room is 22-25℃, and the relative humidity is 55%-70%.

[0148] Model establishment method: On the 1st to 5th day after the end of adaptive feeding, PCPA 350mg / kg was injected intraperitoneally. PCPA solution preparation method: Weigh 796.25mg PCPA, add 182μL (1%) of 2M sodium hydroxide and 1.82mL (10%) of Tween 80, and then use 0.9% saline to make up the volume to 18.2mL, and prepare a suspension with a concentration of 43.75μg / μL. According to the injection volume of 8μL / g, intraperitoneal injection was performed for 5 days. After the end, the circadian rhythm of the mice was observed. Compared with the blank group, the mice had circadian rhythm disorders, were more active during the day, and had less rest time, which means that the insomnia mouse model was successfully established.

[0149] Dose selection and sample processing of the extract powder of the Chinese medicine composition (Example 1): Using the mouse and human body surface area conversion formula (mouse dosage = 9.1 × human dosage / 60kg), the mouse dosage was converted according to the adult daily dosage of 3g of Panax notoginseng of the Chinese medicine composition, and three test groups of 0.9, 1.8, and 3.6g / kg of the extract powder of the Chinese medicine composition (equivalent to 5, 10, and 20 times the recommended human dosage, respectively) were set. At the same time, a blank control group, an insomnia model group and a positive control group were set, with 10 animals in each group.

[0150] Experimental animal grouping: 10 mice per group, a total of 12 groups. Among them, 6 groups were the first batch (blank control group, insomnia model group, positive control group, low-dose group, medium-dose group and high-dose group) for open field test and sodium pentobarbital-induced sleep experiment; the remaining 6 groups were the second batch, used for index detection after sacrifice.

[0151] Low-dose group, medium-dose group and high-dose group: weigh 562.5, 1125, and 1875 mg of compound extract powder, add 5, 5, and 6 mL of 0.9% saline, mix well, and prepare 0.1125, 0.225, and 0.45 mg / μL solutions.

[0152] Positive control group: The dosage was 3 mg / kg, 49.5 mg of diazepam tablets (containing 1.875 mg of active ingredient, Shanghai SPH Xinyi Pharmaceutical Co., Ltd., H31021151) were weighed and added with 0.9% saline to make a solution with a concentration of 0.375 μg / μL. Blank control group and insomnia model group: Both were given an equal volume of 0.9% saline.

[0153] Each group of animals was gavaged with a volume of 8 μL / g, once a day starting from the 6th day for 10 consecutive days.

[0154] The attached Figures 4 to 11 In the horizontal axis, “CON” refers to the blank control group, “MOD” refers to the insomnia model group, “DZP” refers to the positive control group, “L-SQFF” refers to the low-dose group, “M-SQFF” refers to the medium-dose group, and “H-SQFF” refers to the high-dose group.

[0155] Open field test: One hour after the first batch of mice were administered on the 12th day, the mice were placed one by one in a black open field box (length × width × height = 50 cm × 50 cm × 30 cm). Before the experiment, they were placed in an open environment to adapt for 1 min. The video acquisition system (Nanjing Calvin Company, model: KEMaze) was used to observe and record the mice's activity distance, activity time, movement speed and static time within 5 min in real time. Before each mouse enters the open field, the inner wall and bottom of the box must be sprayed with 75% alcohol to remove foreign matter and odor to avoid interference with the experiment.

[0156] The open field test results of this embodiment are as follows Figure 4 and Figure 5 As shown, Figure 4 Middle A is the average heat map of the open field test, and “0S~10S” refers to the time the mouse stays in each area in the open field; Figure 4 Middle B is the mouse trajectory map. Figure 5 This is a schematic diagram of the effects of each treatment group on the autonomic activity of insomnia mice in this example, wherein: Figure 5 A in the middle is a statistical diagram of the total distance of mouse activities. Figure 5 B in the middle is a statistical chart of the average moving speed of mice. Figure 5 Middle C is a statistical chart of the mouse's static time. Figure 5 D in the middle is a statistical graph of the total peripheral movement distance of mice.

[0157] Pentobarbital sodium induced sleep experiment: One hour after the first group of mice were given the drug on the 13th day, each group of mice was intraperitoneally injected with 38 mg / kg of sodium pentobarbital solution, and the sodium pentobarbital powder was prepared into a 1% sodium pentobarbital injection, which was intraperitoneally injected at a dosage volume of 3.8 μL / g, and the sleeping rate of the mice was recorded. One hour after the drug was given on the 14th day, each group of mice was intraperitoneally injected with 58 mg / kg of sodium pentobarbital solution, and the sodium pentobarbital powder was prepared into a 1% sodium pentobarbital injection, which was intraperitoneally injected at a dosage volume of 5.8 μL / g, and the sleeping time and sleep latency of the mice were recorded. The time from the end of the intraperitoneal injection to the disappearance of the righting reflex of the mouse was recorded as the sleep latency, and the time from the disappearance of the righting reflex to the reappearance of the righting reflex was recorded as the sleep time. The righting reflex refers to the ability of the mouse to recover to the crawling position with its four legs down and its back up within 30 seconds when it is in a position with its four legs up and its back down.

[0158] The schematic diagram of the effect of each group of treatments in this example on the sodium pentobarbital-induced sleep in insomnia mice is shown in Figure 6 As shown, Figure 6 A in the middle is a schematic diagram of the mouse morphology in a sleeping state assisted by sodium pentobarbital; Figure 6 Middle B is a statistical chart of the number of mice co-sleeping in each group; Figure 6 Middle C is a time statistics chart of coordinated sleep in mice; Figure 6 Middle D is a statistical chart of the sleep latency time of mice.

[0159] Detection of sleep-related neurotransmitter content: The second batch of mice were fasted but not watered at 22:00 on the 13th day after administration. One hour after administration on the 14th day, the mice were anesthetized by intraperitoneal injection of sodium pentobarbital, and the eyeballs were removed to collect blood, and the mice were killed. The whole blood was placed in a 1.5mL EDTA anticoagulant tube, centrifuged at 3000rmp, 4℃ for 15min, and the supernatant was collected. After the eyeballs were collected, the mice were immediately killed, the brain tissue was taken to separate the hypothalamus, 1mL of physiological saline was added for homogenization, and the blood was centrifuged at 3000rmp, 4℃ for 15min, and the supernatant was collected. ELISA kits were used to detect the contents of sleep-related factors 5-HT, GABA, DA, and MT in plasma and hypothalamic homogenate (MT-ELISA research kit and DA-ELISA research kit were purchased from Shanghai ELISA Technology Co., Ltd., with catalog numbers: 20240517XT and 20240517TE, respectively; 5-HT-ELISA research kit and γ-GABA-ELISA research kit were purchased from ELISA Biotechnology Co., Ltd., with catalog numbers: E20140412-24791J and E20140412-20138J, respectively).

[0160] The results of the effects of the treatments of each group on the content of sleep-related neurotransmitters in insomnia mice are shown in the figure below. Figure 7 and Figure 8 As shown. Among them, Figure 7 A in the middle is a statistical graph of 5-HT content in plasma; Figure 7 Middle B is a statistical graph of 5-HT content in hypothalamic homogenate; Figure 7 Middle C is a statistical graph of GABA content in plasma; Figure 7 D in the middle is a statistical graph of GABA content in hypothalamic homogenate. Figure 8 A in the middle is a statistical graph of MT content in plasma; Figure 8 Middle B is a statistical graph of MT content in hypothalamic homogenate; Figure 8 Middle C is a statistical graph of DA content in plasma; Figure 8 D in the middle is a statistical graph of DA content in hypothalamic homogenate.

[0161] H&E staining and Nissl staining of brain tissue: After the mouse's eyeballs were removed and blood was collected, it was immediately killed, the brain was dissected open and the intact brain tissue was taken out. After washing with physiological saline, it was immediately immersed in 4% neutral tissue fixative, rinsed with running water, dehydrated with different concentrations of ethanol, embedded in paraffin after being transparent with xylene, and sliced ​​using a paraffin slicer with a thickness of 4μm. The slices were then washed in xylene, anhydrous ethanol and different concentrations of ethanol to water, then stained with hematoxylin-eosin / toluidine blue, and rapidly differentiated with ethanol, followed by gradient dehydration, and finally transparent with xylene, sealed with neutral gum, and scanned into slices.

[0162] The results of H&E staining of the effects of each group of treatments on pathological damage in the hippocampus of the brain tissue of insomnia mice in this example are shown in the figure. Fig. 9 As shown. Among them, Fig. 9 a~c are the cell morphology images of the hippocampus (“HC” stands for “Hippocampus”), CA1 region, and CA3 region of the hippocampus under a 20× H&E-stained microscope. Fig. 9 Middle d is the cell morphology of the dentate gyrus region of the hippocampus of each group ("DG" stands for "Dentate Gyrus" meaning dentate gyrus) stained with H&E under a 10× and 20× microscope. Fig. 9 Middle e is a picture of the cell morphology of the hypothalamus (“Hy.” stands for “Hypothalamus”, meaning hypothalamus) stained with H&E under a 30× microscope.

[0163] The schematic diagram of Nissl staining results of the effects of each group of treatments on the neurological damage in the hippocampus of the brain tissue of insomnia mice in this example is shown in Fig.10 As shown. Among them, Fig.10 a~c are Nissl-stained cell morphology images under a 20× microscope of the hippocampus, CA1 region, and CA3 region of the hippocampus, respectively. Fig.10 Middle d is the cell morphology of Nissl staining in the dentate gyrus region of the hippocampus of each group under 10× and 20× microscopes. Fig.10 Middle e is a picture of the cell morphology of the hypothalamus stained with Nissl under a 30× microscope.

[0164] The results of the effects of the treatments of each group in this example on the damage of cells in the CA1 region of the hippocampus of the brain tissue of insomnia mice are shown in the figure below. Fig.11 shown. Fig.11 A in the middle is a statistical chart of the number of cells in the CA1 area. Fig.11 Middle B is a statistical diagram of the number of neurons in the CA1 region, where “280×570μm in 40×” means that the area observed under a 40× microscope is 280×570μm.

[0165] The results showed that after treatment with the composition, the moving distance and speed of mice were significantly reduced by 14%-18% compared with the insomnia anxiety group, and the static time was significantly prolonged by 3.58%-18.83%, proving that the composition has a significant improvement effect on the anxiety and restlessness symptoms of insomnia mice ( Figure 4 ); After treatment with the composition, the sleep time of insomniac mice was significantly extended by 72.5%-98.7%, and the sleep latency was significantly shortened by 15.88%-18.6% ( Figure 5); After treatment with the composition, the contents of sleep factors 5-HT, GABA and MT were significantly increased by 16.81%-25.63%, 9.74%-21.81% and 10.26%-26.16% compared with insomnia mice, DA in the hypothalamus decreased by 4.93%, and DA in plasma increased significantly by 2.6%-25.52% ( Figure 6 ). It is proved that the composition can improve the sleep quality of insomnia mice by promoting the increase of sleep factors 5-HT, GABA, MT content and reducing the DA content in the brain.

[0166] In addition, the Chinese medicine composition of the present application significantly improved the damage in the hippocampus of insomnia mice, reversed the unclear cell boundaries, enlarged gaps, loose arrangement, and overall atrophy, and improved the obvious interstitial edema in the DG area ( Figure 7 The composition significantly increases the number of cells, especially neurons, in the CA1 region of the hippocampus ( Figure 8 ), after treatment with the combination, the number of cells in the CA1 region of the hippocampus of insomnia mice increased by 55.57-78.57% ( Fig.11 -A), and nerve cells repaired 17.47-38.46% ( Fig.11 -B). It is proved that the composition can improve sleep by repairing brain tissue damage and nerve cell reduction caused by insomnia.

[0167] Example 7

[0168] The only difference from Example 1 is that the Chinese medicine composition of this example includes: 8 parts of Ziziphus jujuba seeds, 6 parts of Poria cocos, 6 parts of Panax notoginseng, 9 parts of Astragalus, 10 parts of Codonopsis pilosula and 5 parts of stir-fried Crataegus pinnatifida.

[0169] Example 8

[0170] The only difference from Example 1 is that the Chinese medicine composition of this example includes: 20 parts of Ziziphus jujuba seeds, 18 parts of Poria cocos, 6 parts of Panax notoginseng, 9 parts of Astragalus, 10 parts of Codonopsis pilosula and 5 parts of stir-fried Hawthorn.

[0171] Example 9

[0172] The only difference from Example 1 is that the Chinese medicine composition of this example includes: 10 parts of Ziziphus jujuba seeds, 10 parts of Poria cocos, 12 parts of Panax notoginseng, 18 parts of Astragalus, 18 parts of Codonopsis pilosula and 20 parts of stir-fried Hawthorn.

[0173] Example 10

[0174] The only difference from Example 1 is that the Chinese medicine composition of this example includes: 10 parts of Ziziphus jujuba seeds, 10 parts of Poria cocos, 4 parts of Panax notoginseng, 8 parts of Astragalus, 5 parts of Codonopsis pilosula and 4 parts of stir-fried Crataegus pinnatifida.

[0175] Embodiment 11

[0176] The only difference from Example 1 is that the Chinese medicine composition of this example includes: 9 parts of Ziziphus jujuba seeds, 7 parts of Poria cocos, 10 parts of Panax notoginseng, 15 parts of Astragalus, 15 parts of Codonopsis pilosula and 15 parts of stir-fried Hawthorn.

[0177] Comparative Example 1

[0178] The only difference from Example 1 is that the Chinese medicine composition of this comparative example includes: 10 parts of Polygala tenuifolia, 10 parts of Poria cocos, 6 parts of Panax notoginseng, 9 parts of Astragalus membranaceus, 10 parts of Codonopsis pilosula and 5 parts of stir-fried Crataegus pinnatifida.

[0179] Comparative Example 2

[0180] The only difference from Example 1 is that the Chinese medicine composition of this comparative example includes: 10 parts of Ziziphus jujuba seeds, 10 parts of Poria cocos, 9 parts of Astragalus, 10 parts of Codonopsis pilosula and 5 parts of stir-fried Crataegus pinnatifida.

[0181] Comparative Example 3

[0182] The only difference from Example 1 is that the Chinese medicine composition of this comparative example includes: 10 parts of Ziziphus jujuba seeds, 10 parts of Poria cocos, 6 parts of raw Panax notoginseng, 9 parts of Astragalus, 10 parts of Codonopsis pilosula and 5 parts of stir-fried Hawthorn.

[0183] Test Example 1

[0184] The extraction methods of the extracts in Examples 7-11 and Comparative Examples 1-3 are the same as that in Example 1. The peripheral blood routine and sleep effect comparison experiments in Examples 7-11 and Comparative Examples 1-3 are the same as the test methods and detection methods in Examples 5 and 6.

[0185] The effects of the above-mentioned Example 1, Examples 7-11 and Comparative Examples 1-3 on the peripheral blood routine of blood deficiency mice are shown in Table 9.

[0186] Table 9

[0187]

[0188]

[0189] Note: In Table 9, “*” indicates that the P value is less than 0.05, and the difference is significant; “**” indicates that the P value is less than 0.01, and the difference is extremely significant.

[0190] According to the analysis of the effects of each embodiment and comparative example on the peripheral blood of blood deficiency mice, the number of white blood cells and platelets in embodiment 1 is the least, the number of hemoglobin and red blood cells is the most, and the best blood-tonifying effect is shown. Compared with embodiment 1, there are significant differences in the number of peripheral blood white blood cells, hemoglobin, red blood cells and platelets in embodiments 7, 8 and 10 and comparative examples 1, 2 and 3.

[0191] The effects of the above examples and comparative examples on the sleep of insomnia mice are shown in Table 10.

[0192] Table 10

[0193] Grouping Total number / piece Number of sleeping Sleep rate / % Sleep time / s Sleep latency / s Example 1 10 7 70 4801.22±78.85 188.33±20.56 Example 7 10 4 <![CDATA[40 * ]]> <![CDATA[3628.47±72.14 ** ]]> <![CDATA[280.21±44.01 ** ]]> Example 8 10 6 60 4406.12±96.62 205.3±42.45 Example 9 10 6 60 4368.05±50.77 202.52±9.77 Example 10 10 5 <![CDATA[50 * ]]> <![CDATA[4020.22±68.08 * ]]> <![CDATA[247.75±12.16 * ]]> Embodiment 11 10 6 60 4429.07±73.19 204.33±4.05 Comparative Example 1 10 5 <![CDATA[50 * ]]> <![CDATA[4092.83±45.60 ** ]]> <![CDATA[211.57±38.39 * ]]> Comparative Example 2 10 4 <![CDATA[40 * ]]> <![CDATA[4004±65.04 ** ]]> <![CDATA[224.18±9.53 * ]]> Comparative Example 3 10 5 <![CDATA[50 * ]]> <![CDATA[4176±71.16 * ]]> <![CDATA[219.38±21.04 * ]]>

[0194] Note: In Table 10, “*” indicates that the P value is less than 0.05, and the difference is significant; “**” indicates that the P value is less than 0.01, and the difference is extremely significant.

[0195] According to the data analysis of sodium pentobarbital-induced sleep in insomnia mice in each embodiment and comparative example, the sleep onset rate, sleep time and sleep latency of embodiment 1 were the highest, the sleep onset rate, sleep time and sleep latency of embodiments 7 and 10, and comparative examples 1, 2 and 3 were significantly different compared with embodiment 1.

[0196] From the above description, it can be seen that the above embodiments of the present invention achieve the following technical effects: the preparation for treating sleep disorders using the composition of the present application can improve and treat sleep disorders caused by blood deficiency. The prescription drugs in the present application are mostly flat and warm in nature, and they cooperate with each other, and the comprehensive multi-party joint efforts improve the sleep disorders caused by blood deficiency, and the efficacy is more stable than the prior art.

[0197] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A composition for treating sleep disorders, characterized in that: The composition comprises spiny jujube seeds, poria, cooked panax notoginseng, astragalus, codonopsis and stir-fried hawthorn.

2. The composition according to claim 1, characterized in that Calculated by weight, the composition comprises 9-15 parts of spiny jujube seeds, 7-12 parts of poria, 6-10 parts of cooked panax notoginseng, 9-15 parts of astragalus, 6-15 parts of codonopsis and 5-20 parts of stir-fried hawthorn.

3. The composition according to claim 1, characterized in that The composition further comprises a solvent and / or an auxiliary material; Preferably, the solvent comprises water; Preferably, the auxiliary material comprises a shaping agent and / or a wetting agent; Preferably, the molding agent comprises one or more of dextrin, starch, lactose powder, mannitol or sucrose powder; Preferably, the wetting agent comprises ethanol and / or water; Preferably, the composition comprises 0.8 to 1.5 parts of a forming agent and 0.2 to 0.4 parts of a wetting agent.

4. A method for preparing a preparation for treating sleep disorders, characterized in that: The preparation method comprises S1) extracting the active ingredients in the composition to obtain a composition extract; S2) mixing the composition extract with excipients to obtain the preparation; The composition comprises spiny jujube seeds, poria, cooked panax notoginseng, astragalus, codonopsis and stir-fried hawthorn.

5. The preparation method according to claim 4, characterized in that: The composition comprises, by weight, 9-15 parts of Ziziphus jujuba seeds, 7-12 parts of Poria cocos, 6-10 parts of Radix Notoginseng, 9-15 parts of Radix Astragali, 6-15 parts of Codonopsis pilosula and 5-20 parts of stir-fried Hawthorn; Preferably, the effective ingredients include jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4, ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5 and ginsenoside Rh2.

6. The preparation method according to claim 4, characterized in that: The step S1) comprises: mixing the composition with water, and sequentially performing extraction, filtration, concentration and first drying to obtain an extract of the composition; Preferably, the extraction method comprises one or more of ultrasonic extraction, electromagnetic wave extraction or microwave extraction; Preferably, the extraction time is 1 to 3 hours; Preferably, the extraction is performed 1 to 5 times; Preferably, the volume ratio of the composition to water is 1:10 to 1:20; Preferably, the mesh size of the filtration is 300 to 400 meshes; Preferably, the concentration temperature is 30-60°C; Preferably, the first drying temperature is 40-70°C; Preferably, the concentration comprises one or more of reduced pressure distillation concentration, membrane concentration or centrifugal concentration.

7. The preparation method according to claim 4, characterized in that: The S2) comprises: drying the extract of the composition for the first time, sieving it, and then mixing it with auxiliary materials to obtain a soft material; granulating, drying and granulating the soft material in sequence to obtain the preparation; Preferably, the mesh size of the sieving is 80 to 200 meshes; Preferably, the auxiliary material comprises a shaping agent and / or a wetting agent; Preferably, the molding agent comprises one or more of dextrin, starch, lactose powder, mannitol or sucrose powder; Preferably, the wetting agent comprises ethanol and / or water; Preferably, the mass ratio of the composition extract to the molding agent is 1:0.8 to 1:1.5; Preferably, the mass ratio of the sum of the mass of the composition extract and the molding agent to the mass ratio of the wetting agent is 1:0.3 to 1:0.35; Preferably, the mesh size of the granulation is 5 to 15 meshes; Preferably, the temperature of the second drying is 50-80°C; Preferably, the mesh size of the granules is 10 to 80 meshes.

8. A preparation for treating sleep disorders, characterized in that: The preparation comprises the composition according to any one of claims 1 to 3 and a pharmaceutically acceptable carrier and / or excipient, or is prepared by the preparation method according to any one of claims 4 to 8.

9. The preparation according to claim 8, characterized in that The active ingredients in the preparation include jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4, ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5 and ginsenoside Rh2; Preferably, the mass ratios of jujuboside A, ginsenoside Rh1, astragaloside IV, ginsenoside Rd, ginsenoside F4, ginsenoside Rk3, ginsenoside Rh4, ginsenoside 20(S)-Rg3, ginsenoside 20(R)-Rg3, ginsenoside Rg5 and ginsenoside Rh2 in the active ingredients are: (18.18-22.78): (3.65-14.60): (0.78-1.17): (10.44-12.58)：(0.96-1.05)：(2.88-4.53)：(27.28-39.28)：(6.56-9.49)：(2.45-3.97)：(5.16-7.15)： (1.14-1.41)。 10. The preparation according to claim 8, characterized in that The dosage form of the preparation includes granules, pills, pastes, tablets, capsules or oral liquids.

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