Application of qi-blood foundation strengthening oral liquid in preparation of medicine with effects of tonifying qi, soothing nerves and improving insomnia

Abstract

The invention provides application of qi and blood strengthening oral liquid to preparation of a medicine with the effects of tonifying qi, soothing the nerves and improving insomnia, and belongs to the technical field of medicine preparations. According to the invention, the mass ratio relationship among the components and the preparation method thereof are researched, and especially in the preparation process, the traditional Chinese medicine components are extracted by adopting the modes of high-pressure steam heating, vacuum concentration and the like under different pressures in batches and stages, so that the obtained oral liquid for consolidating qi and blood not only has the effective component content, but also has the health-care effect. The oral liquid for consolidating qi and blood improves heart-spleen deficiency type insomnia through multiple ways of tonifying heart and spleen, regulating qi and blood, balancing neurotransmitters and the like, the multi-target action characteristic of the oral liquid conforms to the overall view of traditional Chinese medicine, and the oral liquid has potential clinical application value.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to the application of Qi Xue Gu Ben Oral Liquid in the preparation of drugs with the effects of invigorating Qi, calming the mind, and improving insomnia. Background Technology

[0002] Insomnia is a common clinical condition characterized by difficulty falling asleep, sleep maintenance disorders, or early awakening. Traditional Chinese medicine (TCM) theory holds that insomnia is closely related to the imbalance of Yin and Yang and the dysfunction of the internal organs. The *Ling Shu* (Spiritual Pivot) states, "When Wei Qi (defensive Qi) cannot enter Yin, it remains in Yang. When it remains in Yang, Yang Qi is full; when Yang Qi is full, Yang Qiao (the yang meridian) is excessive. When it cannot enter Yin, Yin Qi is deficient, hence the eyes cannot close." This indicates that the core pathogenesis of insomnia is the disharmony of Ying and Wei Qi, the imbalance of Yin and Yang, the inability of Yang to enter Yin, the dysfunction of the five internal organs, and the inability of the organs to store the spirit. The causes of insomnia are often related to irregular diet, emotional disturbances, imbalance between work and rest, and post-illness weakness. The main manifestations are insufficient sleep time and depth, and the inability to eliminate fatigue and restore physical strength and energy. Mild cases present with difficulty falling asleep, restless sleep, frequent awakenings, or inability to fall back asleep after waking; severe cases present with complete sleeplessness throughout the night.

[0003] As research into insomnia deepens, the theory of the interrelationship of the five internal organs has gradually become mainstream. Exploring the pathological mechanisms of insomnia from the perspective of this theory allows for a clearer understanding of the pathological changes that lead to insomnia, providing a more substantial theoretical basis for TCM's diagnosis and treatment of insomnia. The heart governs the mind; a peaceful mind leads to sleep, while an unsettled mind leads to insomnia. The source of Yin and Yang, Qi and Blood, is the essence of food and water, which ascends to the heart, nourishing the mind; is stored in the liver, ensuring its harmony; is governed by the spleen, ensuring continuous transformation; and through proper regulation, transforms into essence, stored internally in the kidneys. Kidney essence ascends to the heart, and heart Qi descends to the kidneys, resulting in a peaceful mind. If liver stagnation transforms into fire, or phlegm-heat disturbs the mind, the restlessness is primarily a case of excess. Deficiency of both the heart and spleen, insufficient Qi and Blood, or disharmony between the heart and kidneys, leading to imbalance of water and fire, and malnourishment of the mind, are mostly deficiency patterns. However, prolonged illness may present as a mixture of deficiency and excess, or may be caused by blood stasis.

[0004] Researching the TCM classification of insomnia is of great significance for improving clinical treatment outcomes. Currently, insomnia has become a major problem affecting people's health and quality of life. TCM treatment of insomnia not only focuses on symptom relief but also emphasizes holistic regulation of bodily functions and restoration of Yin-Yang balance, thereby achieving a comprehensive cure. This holistic treatment approach embodies the TCM philosophy of "people-centeredness" and provides modern medicine with a unique perspective and methodology.

[0005] For example, Chinese patent CN115006492A discloses a traditional Chinese medicine composition for treating insomnia and its application. The composition is made from the following raw materials in parts by weight: 6-15 parts of Ziziphus jujuba seed, 5-12 parts of Eupatorium fortunei, 3-9 parts of Gardenia jasminoides, 3-9 parts of Citrus reticulata peel, 1-5 parts of Oroxylum indicum, 3-9 parts of Dendrobium nobile, 1-5 parts of Mentha haplocalyx, 3-9 parts of Aucklandia lappa, 22-38 parts of Os draconis, 3-9 parts of Glycyrrhiza uralensis, 12-27 parts of Polygonatum sibiricum, 2-8 parts of Chrysanthemum morifolium, and 2-8 parts of Rosa rugosa. This invention has the comprehensive effects of calming the mind and soothing the nerves, regulating qi and relieving depression, and clearing heat and promoting body fluids, thus improving mental symptoms such as insomnia and excessive dreaming.

[0006] For example, Chinese patent CN104147379A discloses a traditional Chinese medicine composition for treating insomnia due to yin deficiency and excessive fire, comprising the following raw materials in parts by weight: 13-17 parts of Polygonatum sibiricum, 10-14 parts of Dendrobium nobile, 13-17 parts of Morus alba, 28-32 parts of Dioscorea opposita, 13-17 parts of Longan aril, 28-32 parts of Ostrea gigas, and 18-22 parts of Tortoise shell. This invention has the effects of nourishing yin and reducing fire, nourishing the heart and calming the mind. It is used to treat insomnia due to yin deficiency and excessive fire, and its efficacy is definite. The dosage form is stable, the quality is controllable, and there are no toxic side effects. It is a modern preparation that is easy to use and widely applicable.

[0007] However, existing Chinese herbal combinations cannot effectively alleviate insomnia caused by insufficient Qi and blood, or deficiency of both the heart and spleen, nor can they effectively promote sleep. Therefore, there is a need to develop an oral liquid for strengthening Qi and blood that can alleviate insomnia caused by insufficient Qi and blood, or deficiency of both the heart and spleen, and promote sleep, as well as its application. Summary of the Invention

[0008] Based on the shortcomings of existing technologies, this invention uses Qi Xue Gu Ben Oral Liquid as a foundation. It studies the mass ratio between components and its preparation method, particularly the preparation method itself. During the preparation process, different solvents are used to extract the Chinese herbal ingredients, resulting in the Qi Xue Gu Ben Oral Liquid described in this invention. This oral liquid improves insomnia caused by deficiency of both heart and spleen through multiple pathways, including tonifying the heart and spleen, regulating Qi and blood, and balancing neurotransmitters. Its multi-target effect aligns with the holistic view of traditional Chinese medicine and has potential clinical application value.

[0009] This invention is implemented as follows: On the one hand, this invention provides the application of Qi Xue Gu Ben Oral Liquid in the preparation of drugs with the effects of invigorating Qi, calming the mind, and improving insomnia.

[0010] Furthermore, the drug is one that can reduce LDH levels; Furthermore, the drug is one that can reduce CK levels; Furthermore, the drug is one that can reduce OXA content; Furthermore, the drug is one that can reduce OXB content; Furthermore, the drug is one that can increase 5-HT levels; Furthermore, the drug is a drug that can reduce DA content; Furthermore, the drug is one that can increase GABA content; Furthermore, the drug is one that can reduce Glu content.

[0011] Preferably, the drug is one that can reduce the levels of LDH, CK, OXA, OXB, DA and Glu, and increase the levels of 5-HT and Glu.

[0012] Preferably, the Qi and Blood Strengthening Oral Liquid is prepared by the following method: (1) Weigh lotus seeds and pine nuts, crush them, and then soak them to obtain soaking liquid for later use; (2) Weigh the rose hips and extract them to obtain extract A, which is then set aside. (3) Weigh out Acanthopanax senticosus, Schisandra chinensis, Epimedium, Morinda officinalis, Cuscuta chinensis, Ligustrum lucidum, Anemarrhena asphodeloides, Phellodendron chinense, Lycium barbarum, Rehmannia glutinosa, Polygonum multiflorum, Polygonatum sibiricum, Rubus idaeus, Dioscorea opposita, Ziziphus jujuba var. spinosa, pine needles and Platycladus orientalis seeds for extraction to obtain extract B, which is used for later use; (4) Take the soaking solution, extract A and extract B and concentrate them to obtain the extract; mix the extract with honey and purified water to obtain the Qi and Blood Strengthening Oral Liquid.

[0013] The particle size of the pulverized material in step (1) above is 250μm-850μm; the ratio of water added to the mass of the medicinal material during soaking is 4-6:1; preferably 4:1; the soaking time is 3-5 hours; preferably 4 hours.

[0014] In step (1) above, stir for 2-5 minutes every 30 minutes during the soaking process.

[0015] In step (2) above, the ratio of water added to the mass of medicinal materials is 5-8:1, preferably 6:1; the extraction is by decoction, and the number of decoctions is 2-3, preferably 2; the first decoction time is 1.5-2.5 hours, preferably 2 hours, and the second decoction time is 0.5-1.5 hours, preferably 1 hour.

[0016] The extraction process in step (3) above involves a water-to-medicinal-material ratio of 5-8:1, preferably 6:1. The extraction is performed by decoction, which is performed 2-3 times, preferably 2 times. The first decoction takes 3-6 hours, preferably 5 hours, and the second decoction takes 2-4 hours, preferably 3 hours.

[0017] The extraction described in step (3) above needs to be carried out under high-pressure steam heating conditions.

[0018] The steam pressure is 0.05-0.2 MPa from the initial heating to before boiling, 0.01-0.05 MPa within 1 hour after boiling, and 0.1-0.15 MPa from 1 hour after boiling to the end.

[0019] The temperature in step (3) above is 95-100℃.

[0020] The concentration pressure in step (4) above is 0.01-0.15 MPa, the vacuum degree is less than 0.08 MPa, the temperature is 55-75℃, and the concentration is stopped when the relative density is 1.16-1.21 (60-70℃).

[0021] The Qi and Blood Strengthening Oral Liquid, by weight, comprises the following components: 70-90 parts of Rosa rugosa fruit, 70-90 parts of Acanthopanax senticosus, 20-30 parts of Schisandra chinensis, 20-30 parts of Epimedium brevicornu, 5-10 parts of Morinda officinalis, 5-10 parts of Cuscuta chinensis, 5-10 parts of Ligustrum lucidum, 15-30 parts of Anemarrhena asphodeloides, 15-30 parts of Phellodendron chinense, 5-10 parts of Lycium barbarum, 30-50 parts of Nelumbo nucifera, 5-10 parts of Rehmannia glutinosa, 15-30 parts of Polygonum multiflorum, 10-20 parts of Polygonatum sibiricum, 20-30 parts of Rubus idaeus, 5-15 parts of Dioscorea opposita, 30-50 parts of Pine nuts, 10-15 parts of Ziziphus jujuba var. spinosa, 5-15 parts of pine needles, and 5-15 parts of Platycladus orientalis.

[0022] Preferably, the Qi and Blood Strengthening Oral Liquid comprises, by weight, the following components: 75-85 parts of Rosa rugosa fruit, 75-85 parts of Acanthopanax senticosus, 22-28 parts of Schisandra chinensis, 22-28 parts of Epimedium brevicornu, 6-8 parts of Morinda officinalis, 6-8 parts of Cuscuta chinensis, 6-8 parts of Ligustrum lucidum, 20-25 parts of Anemarrhena asphodeloides, 20-25 parts of Phellodendron chinense, 6-8 parts of Lycium barbarum, 35-45 parts of Nelumbo nucifera, 6-8 parts of Rehmannia glutinosa, 20-25 parts of Polygonum multiflorum, 12-18 parts of Polygonatum sibiricum, 22-28 parts of Rubus idaeus, 8-12 parts of Dioscorea opposita, 35-45 parts of Pine nuts, 12-14 parts of Ziziphus jujuba var. spinosa, 8-12 parts of pine needles, and 8-12 parts of Platycladus orientalis.

[0023] Preferably, the Qi and Blood Strengthening Oral Liquid comprises, by weight, the following components: 80 parts of Rosa rugosa fruit, 80 parts of Acanthopanax senticosus, 25 parts of Schisandra chinensis, 25 parts of Epimedium, 8 parts of Morinda officinalis, 8 parts of Cuscuta chinensis, 8 parts of Ligustrum lucidum, 20 parts of Anemarrhena asphodeloides, 20 parts of Phellodendron chinense, 8 parts of Lycium barbarum, 40 parts of Nelumbo nucifera, 8 parts of Rehmannia glutinosa, 25 parts of Polygonum multiflorum, 15 parts of Polygonatum sibiricum, 25 parts of Rubus idaeus, 10 parts of Dioscorea opposita, 40 parts of Pine nut, 12 parts of Ziziphus jujuba var. spinosa, 10 parts of pine needles, and 10 parts of Platycladus orientalis seed.

[0024] Compared with the prior art, the present invention has the following beneficial effects: 1. This invention studies the mass ratio between components and their preparation methods, especially the preparation methods. In the preparation process, the traditional Chinese medicine components are extracted by batch extraction, pressurized extraction, and depressurized concentration to obtain the Qi and Blood Strengthening Oral Liquid of this invention. This Qi and Blood Strengthening Oral Liquid improves insomnia caused by deficiency of both heart and spleen through multiple pathways such as tonifying the heart and spleen, regulating qi and blood, and balancing neurotransmitters. Its multi-target effect is in line with the holistic view of traditional Chinese medicine and has potential clinical application value.

[0025] Especially when extracting seventeen kinds of medicinal materials such as Acanthopanax senticosus and Schisandra chinensis, high-pressure steam heating is used for extraction. The steam pressure is controlled from the initial heating to boiling at 0.05-0.2 MPa, and within 1 hour after boiling at 0.01-0.05 MPa; and from 1 hour after boiling to the end at 0.1-0.15 MPa. This helps to quickly dissolve the active ingredients, increases the content of active ingredients in the extract, and is more conducive to the efficacy of the medicine. Controlling the pressure to 0.01-0.15 MPa, the vacuum degree to less than 0.08 MPa, and the temperature to 55-75℃ during the drug concentration process can better reduce the loss of the active ingredients in the drug and retain the active ingredients in the drug to a greater extent, thereby ensuring the stability of the drug.

[0026] 2. In this invention, Acanthopanax senticosus, Rosa rugosa, Schisandra chinensis, and Ziziphus jujuba var. spinosa are the principal herbs, accompanied by Anemarrhena asphodeloides, Phellodendron chinense, Rehmannia glutinosa, and Polygonum multiflorum (processed), as well as Epimedium brevicornu, Morinda officinalis, Cuscuta chinensis, and Rubus idaeus, and further supplemented by Platycladus orientalis seed and pine needles. The overall formula focuses on regulating and tonifying qi and blood, strengthening the spleen and kidneys, and calming the mind and spirit. The principal, assistant, and adjuvant herbs complement each other, and the medicinal properties are coordinated. It can not only improve insomnia and palpitations, but also strengthen the spleen and replenish qi, nourish yin and reduce fire, and tonify the kidneys and replenish essence. The overall formula reflects the principles and methods of traditional Chinese medicine. In the preparation process, the various extract components are comprehensively utilized and rationally combined, which can be efficiently absorbed to exert their effects. At the same time, through specific extracts and extraction methods, the Qi and Blood Strengthening Oral Liquid has a high content of effective ingredients, which can not only replenish qi and calm the mind and promote sleep, but also significantly improve insomnia symptoms. Attached Figure Description

[0027] Figure 1 The activity trajectories of rats in each group are shown in the diagram. Figure 2 The activity calorimetry of rats in each group is shown in the figure. Detailed Implementation

[0028] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0029] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0030] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all chemical reagents used in the embodiments of the present invention are obtained through conventional commercial means.

[0031] In the following examples, “part” and “g” have the same meaning, that is, 1 part = 1g.

[0032] Example 1: A Qi and Blood Strengthening Oral Liquid and its Preparation Method The ingredients are as follows by weight: 80 parts of Rosa rugosa fruit, 80 parts of Acanthopanax senticosus, 25 parts of Schisandra chinensis, 25 parts of Epimedium, 8 parts of Morinda officinalis, 8 parts of Cuscuta chinensis, 8 parts of Ligustrum lucidum, 20 parts of Anemarrhena asphodeloides, 20 parts of Phellodendron chinense, 8 parts of Lycium barbarum, 40 parts of Nelumbo nucifera, 8 parts of Rehmannia glutinosa, 25 parts of Polygonum multiflorum, 15 parts of Polygonatum sibiricum, 25 parts of Rubus idaeus, 10 parts of Dioscorea opposita, 40 parts of Pine nuts, 12 parts of Ziziphus jujuba var. spinosa, 10 parts of pine needles, and 10 parts of Platycladus orientalis seed.

[0033] The preparation method is as follows: (1) Weigh lotus seeds and pine nuts and crush them to 500μm. Then add 4 times the amount of water and soak for 4 hours. Stir for 5 minutes every 30 minutes during the soaking process to obtain the soaking solution for later use. (2) Weigh out the rose hips and add 6 times the amount of water for decoction extraction. The first extraction time is 2 hours and the second decoction time is 1 hour. Combine the decoctions to obtain extract A for later use. (3) Weigh out Acanthopanax senticosus, Schisandra chinensis, Epimedium, Morinda officinalis, Cuscuta chinensis, Ligustrum lucidum, Anemarrhena asphodeloides, Phellodendron chinense, Lycium barbarum, Rehmannia glutinosa, Polygonum multiflorum, Polygonatum sibiricum, Rubus idaeus, Dioscorea opposita, Ziziphus jujuba var. spinosa, pine needles and Platycladus orientalis seeds, add 6 times the amount of water and decoct for extraction twice. The first extraction time is 5 hours and the second decoction time is 3 hours. The extraction must be carried out under high pressure steam heating. During the extraction process, the steam pressure should be controlled as follows: from the initial heating to before boiling, the steam pressure is 0.1 MPa; within 1 hour after boiling, the steam pressure is 0.03 MPa; from 1 hour after boiling to the end, the steam pressure is 0.12 MPa and the temperature is 95℃. Combine the decoction liquids to obtain extract B, which is ready for use. (4) Take the soaking solution, extract A and extract B and concentrate them. The concentration steam pressure is 0.03-0.06 MPa, the vacuum degree is -0.06 to -0.08 MPa, the temperature is 55-60℃, and the concentration is carried out until the relative density is 1.16-1.21 (60-70℃) to obtain the extract. Mix the extract with honey at a mass ratio of 1:1, and then add purified water to mix to obtain the Qi and Blood Strengthening Oral Liquid.

[0034] Example 2: A Qi and Blood Strengthening Oral Liquid and its Preparation Method The ingredients are as follows by weight: 70 parts of Rosa rugosa fruit, 90 parts of Acanthopanax senticosus, 20 parts of Schisandra chinensis, 30 parts of Epimedium, 10 parts of Morinda officinalis, 5 parts of Cuscuta chinensis, 5 parts of Ligustrum lucidum, 30 parts of Anemarrhena asphodeloides, 30 parts of Phellodendron chinense, 10 parts of Lycium barbarum, 30 parts of Nelumbo nucifera, 10 parts of Rehmannia glutinosa, 15 parts of Polygonum multiflorum, 10 parts of Polygonatum sibiricum, 30 parts of Rubus idaeus, 5 parts of Dioscorea opposita, 50 parts of Pine nuts, 10 parts of Ziziphus jujuba var. spinosa, 5 parts of pine needles, and 15 parts of Platycladus orientalis seed.

[0035] The preparation method is as follows: (1) Weigh lotus seeds and pine nuts and crush them to 500μm. Then add 6 times the amount of water and soak for 3 hours. Stir for 5 minutes every 30 minutes during the soaking process to obtain the soaking solution for later use. (2) Weigh out the rose hips and add 5 times the amount of water for decoction extraction. The first extraction time is 2.5 hours and the second decoction time is 1.5 hours. Combine the decoctions to obtain extract A for later use. (3) Weigh out Acanthopanax senticosus, Schisandra chinensis, Epimedium, Morinda officinalis, Cuscuta chinensis, Ligustrum lucidum, Anemarrhena asphodeloides, Phellodendron chinense, Lycium barbarum, Rehmannia glutinosa, Polygonum multiflorum, Polygonatum sibiricum, Rubus idaeus, Dioscorea opposita, Ziziphus jujuba var. spinosa, pine needles and Platycladus orientalis seeds, add 6 times the amount of water and decoct twice for extraction. The first extraction time is 3 hours and the second extraction time is 4 hours. The extraction should be carried out under high pressure steam heating. During the extraction process, the steam pressure should be controlled as follows: from the initial heating to before boiling, the steam pressure should be 0.05 MPa; within 1 hour after boiling, the steam pressure should be 0.05 MPa; from 1 hour after boiling to the end, the steam pressure should be 0.1 MPa and the temperature should be 98℃. Combine the decoctions to obtain extract B, which is ready for use. (4) Take the soaking solution, extract A and extract B and concentrate them. The concentration steam pressure is 0.03-0.06 MPa, the vacuum degree is -0.06 to -0.08 MPa, the temperature is 55-60℃, and the concentration is carried out until the relative density is 1.16-1.21 (60-70℃) to obtain the extract. Mix the extract with honey at a mass ratio of 1:1, and then add purified water to mix to obtain the Qi and Blood Strengthening Oral Liquid.

[0036] Example 3: A Qi and Blood Strengthening Oral Liquid and its Preparation Method The ingredients are as follows by weight: 85 parts of Rosa rugosa fruit, 75 parts of Acanthopanax senticosus, 28 parts of Schisandra chinensis, 22 parts of Epimedium, 6 parts of Morinda officinalis, 6 parts of Cuscuta chinensis, 6 parts of Ligustrum lucidum, 20 parts of Anemarrhena asphodeloides, 20 parts of Phellodendron chinense, 8 parts of Lycium barbarum, 45 parts of Nelumbo nucifera, 6 parts of Rehmannia glutinosa, 20 parts of Polygonum multiflorum, 18 parts of Polygonatum sibiricum, 22 parts of Rubus idaeus, 12 parts of Dioscorea opposita, 45 parts of Pine nuts, 12 parts of Ziziphus jujuba var. spinosa, 12 parts of pine needles, and 8 parts of Platycladus orientalis seeds.

[0037] The preparation method is as follows: (1) Weigh lotus seeds and pine nuts and crush them to 500μm. Then add 5 times the amount of water and soak for 3 hours. Stir for 5 minutes every 30 minutes during the soaking process to obtain the soaking solution for later use. (2) Weigh out the rose hips and add 8 times the amount of water for decoction extraction. The first extraction time is 1.5 hours and the second decoction time is 0.5 hours. Combine the decoctions to obtain extract A for later use. (3) Weigh out Acanthopanax senticosus, Schisandra chinensis, Epimedium, Morinda officinalis, Cuscuta chinensis, Ligustrum lucidum, Anemarrhena asphodeloides, Phellodendron chinense, Lycium barbarum, Rehmannia glutinosa, Polygonum multiflorum, Polygonatum sibiricum, Rubus idaeus, Dioscorea opposita, Ziziphus jujuba var. spinosa, pine needles and Platycladus orientalis seeds, add 6 times the amount of water and decoct twice for extraction. The first extraction time is 6 hours and the second extraction time is 2 hours. The extraction should be carried out under high pressure steam heating. During the extraction process, the steam pressure should be controlled as follows: from the initial heating to before boiling, the steam pressure should be 0.2 MPa; within 1 hour after boiling, the steam pressure should be 0.01 MPa; from 1 hour after boiling to the end, the steam pressure should be 0.1 MPa and the temperature should be 95℃. Combine the decoctions to obtain extract B, which is ready for use. (4) Take the soaking solution, extract A and extract B and concentrate them. The concentration steam pressure is 0.03-0.06 MPa, the vacuum degree is -0.06 to -0.08 MPa, the temperature is 55-60℃, and the concentration is carried out until the relative density is 1.16-1.21 (60-70℃) to obtain the extract. Mix the extract with honey at a mass ratio of 1:1, and then add purified water to mix to obtain the Qi and Blood Strengthening Oral Liquid.

[0038] Comparative Example 1 The difference from Example 1 lies in the preparation method, as detailed below: Weigh the medicinal materials used in the formula of Example 1, crush the lotus seeds and pine nuts to 500μm, soak them in 4 times the amount of water for 4 hours, stir, filter, and set aside the filtrate; boil the rose hips twice with 6 times the amount of water, the first time for 2 hours and the second time for 1 hour, filter, combine the filtrates, and set aside; boil the remaining medicinal materials twice with 6 times the amount of water, the first time for 3 hours and the second time for 2 hours, filter, combine the filtrates, combine with the above medicinal liquid, heat and concentrate to a thick paste with a relative density of not less than 1.10 (20℃), add honey and mix with the thick paste in a 1:1 ratio, then add purified water and mix, stir well, dispense and sterilize to obtain the final product.

[0039] Comparative Example 2 The difference from Example 1 is that: in step (3), the steam pressure is controlled to be 0.25 MPa from the initial heating to before boiling, and 0.08 MPa within 1 hour after boiling; the steam pressure is 0.18 MPa from 1 hour after boiling to the end, and the temperature is 95°C. The rest is the same as in Example 1.

[0040] Comparative Example 3 The difference from Example 1 is that the specific operation of step (3) is different, specifically: (3) Weigh out Acanthopanax senticosus, Schisandra chinensis, Epimedium, Morinda officinalis, Cuscuta chinensis, Ligustrum lucidum, Anemarrhena asphodeloides, Phellodendron chinense, Lycium barbarum, Rehmannia glutinosa, Polygonum multiflorum, Polygonatum sibiricum, Rubus idaeus, Dioscorea opposita, Ziziphus jujuba var. spinosa, pine needles and Platycladus orientalis seeds, add 6 times the amount of water and decoct once for 8 hours. The extraction should be carried out under high pressure steam heating. During the extraction process, the steam pressure should be controlled as follows: from the initial heating to before boiling, the steam pressure should be 0.2 MPa; within 1 hour after boiling, the steam pressure should be 0.01 MPa; from 1 hour after boiling to the end, the steam pressure should be 0.1 MPa and the temperature should be 95℃. Combine the decoctions to obtain extract B, which is ready for use.

[0041] Comparative Example 4 The difference from Example 1 is that the concentration pressure in step (4) is 0.2 MPa, the vacuum degree is -0.08 MPa, the temperature is 60°C, and the rest is the same as in Example 1.

[0042] Effect test: I. Detection of active ingredient content: (1) Berberine hydrochloride Determined by high performance liquid chromatography (General Chapter 0512, Chinese Pharmacopoeia 2025).

[0043] Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel was used as the stationary phase, and acetonitrile-0.1% phosphoric acid solution (containing 0.1 mL of triethylamine per 100 mL) (30:70) was used as the mobile phase; the detection wavelength was 345 nm. The theoretical plate number, calculated based on the berberine hydrochloride peak, should not be less than 2000.

[0044] Preparation of reference solution: Take an appropriate amount of berberine hydrochloride reference standard, accurately weigh it, and add methanol to prepare a solution containing 6 μg per 1 mL.

[0045] Preparation of the test solution: Accurately measure 5 mL of this product and place it in a 25 mL volumetric flask. Add an appropriate amount of hydrochloric acid-methanol (1:99) mixed solution, shake, and then dilute to the mark with hydrochloric acid-methanol (1:99) mixed solution. Shake well, filter, and take the filtrate to obtain the test solution.

[0046] Assay: Accurately pipette 20 μL each of the reference solution and the test solution into the liquid chromatograph. Measure the solution to obtain the final result.

[0047] (2) Epimedoside Determined by high performance liquid chromatography (General Chapter 0512, Chinese Pharmacopoeia 2015).

[0048] Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel was used as the stationary phase, and acetonitrile-water (25:75) was used as the mobile phase; the detection wavelength was 270 nm. The theoretical plate number, calculated based on the icariin peak, should not be less than 1500.

[0049] Preparation of reference solution: Take an appropriate amount of icariin reference standard, accurately weigh it, and add methanol to prepare a solution containing 15 μg per 1 mL.

[0050] Preparation of the test solution: Accurately measure 10 mL of this product and place it in a 25 mL volumetric flask. Add an appropriate amount of methanol, shake, then dilute with methanol to the mark, shake well, filter, and take the filtrate to obtain the test solution.

[0051] Determination method: Accurately pipette 20 μL of the reference solution and the test solution into the liquid chromatograph and determine the result.

[0052] The test substances for the above-mentioned test samples are extract B and Qi Xue Gu Ben oral liquid obtained in Examples 1-3 and Comparative Examples 1-4, respectively.

[0053] The extraction rate is calculated as follows: W% = [(C × V) / m] × 100% in: W represents the extraction rate; C represents the concentration of berberine hydrochloride or icariin; V represents the volume of extract B or Qi and Blood Strengthening Oral Solution; m represents the mass of Phellodendron bark or Epimedium.

[0054] The test results are shown in Table 1 below.

[0055] Table 1

[0056] According to the detection results in Table 1 above, it can be seen that the extraction efficiency of the active ingredients berberine hydrochloride or icariin in the Qi and Blood Strengthening Oral Liquid provided in Examples 1 - 3 of the present invention, that is, the content of the active ingredients is relatively high, and a relatively high extraction rate can still be maintained after concentration, indicating that the content of the active ingredients in the Qi and Blood Strengthening Oral Liquid of Examples 1 - 3 is high and stable.

[0057] In Comparative Example 1, a conventional extraction method was used, and the extraction efficiency of berberine hydrochloride or icariin obtained was significantly reduced, and the stability was also significantly reduced.

[0058] In Comparative Example 2, the pressure before and after boiling was changed during extraction, and the content of berberine hydrochloride or icariin in the product was significantly reduced, and the content of the active ingredient decreased.

[0059] In Comparative Example 3, the extraction time and the pressure before and after boiling were changed during extraction, and the content of berberine hydrochloride or icariin in the product was significantly reduced. The content of the active ingredient in the product obtained by extending the extraction time decreased instead, which may be due to the loss of the active ingredient caused by long - time extraction.

[0060] In Comparative Example 4, changing the pressure parameter of concentration will, to a certain extent, cause loss of the active ingredient, reduce the content of the active ingredient, and the change rate of the active ingredient is significantly higher than that in Examples 1 - 3.

[0061] II. Pharmacodynamic Detection 1. Influence on promoting sleep: 1.1 Experimental animals: SPF - level healthy male KM mice (Speywood (Beijing) Biotechnology Co., Ltd., license number: SCXK (Beijing) 2024 - 0001), body weight 20 - 22 g. They were housed in the animal house of Beijing University of Chinese Medicine. The temperature of the housing room was 20℃ - 22℃, and the relative humidity was 60% - 70%. During the experiment, the mice drank water freely, and the light and darkness were alternated for 12 h to simulate day and night. Ethical review number: BUCM - 2024062401 - 2201.

[0062] 1.2 Experimental drugs: The extract prepared in Example 1 was dried, crushed, and sieved to obtain dried extract powder.

[0063] 1.3 Experimental reagents Table 2 Main reagents

[0064] Table 3 Main experimental instruments

[0065] 1.4. Experimental methods 1.4.1 Grouping and drug administration Mice were divided into three batches: A, B, and C, with 50 mice in each batch. Batch A underwent direct sleep experiments and sodium pentobarbital-induced hypnosis experiments; batch B underwent experiments to prolong sodium pentobarbital-induced sleep time; and batch C underwent experiments to prolong the sleep latency of barbiturates. After 7 days of acclimatization feeding, the mice were weighed as their initial weight and randomly divided into 5 groups according to their weight: a blank control group, a positive drug control group, and low, medium, and high dose groups of Qi Xue Gu Ben oral liquid, with 10 mice in each group. Every morning from 8:00 to 10:00, mice in each dose group were administered the corresponding test drug by gavage, while mice in the blank control group were administered an equal volume of distilled water by gavage. The gavage volume was 0.1 mL / 10 g, and the administration was continued for 30 consecutive days.

[0066] The daily dosage of Qi Xue Gu Ben Oral Liquid for humans is 30 mL. 95.25 g of dry extract powder is equivalent to the standard prescription dosage (1000 mL). Based on 5, 10, and 20 times the daily dosage, and assuming a body weight of 60 kg, the daily dosages for the low, medium, and high dose groups of Qi Xue Gu Ben are 238 mg / kg, 476 mg / kg, and 953 mg / kg, respectively. The daily dosage of Zao Ren An Shen Granules for humans is 5 g. Based on a 10-fold equivalent dose for humans and mice, and assuming a body weight of 60 kg, the daily dosage for mice is 833 mg / kg.

[0067] 1.4.2 Direct Sleep Experiment Observe the mice for sleep within 30 minutes after daily gavage, and record the number of animals that fall asleep and the duration of sleep.

[0068] 1.4.3 Subthreshold dose hypnotic experiment with sodium pentobarbital In the experiment, mice were placed in a dorsal position (back down). If a mouse failed to right itself within 30 to 60 seconds, the righting reflex was considered to have disappeared, indicating that the mouse had entered a sleep state. Recovery of the righting reflex was defined as the time it took for the mouse to return to its normal position from the dorsal position. Based on preliminary experiments, the subthreshold hypnotic dose of sodium pentobarbital (45 mg / kg) was determined, which is the maximum subthreshold dose of sodium pentobarbital that would prevent the righting reflex from disappearing in 80-90% of mice. Thirty minutes after the last administration, sodium pentobarbital was injected intraperitoneally at a dose of 0.1 mL / 10 g. The number of animals falling asleep within 30 minutes (those whose righting reflex had disappeared for more than one minute) was observed and recorded, using the disappearance of the righting reflex as an indicator.

[0069] 1.4.4 Experiment on prolonging sodium pentobarbital sleep time Based on preliminary experiments, the sodium pentobarbital dose (55 mg / kg) that would induce 100% sleep in mice without causing excessively long sleep duration was determined. Thirty minutes after the last administration, sodium pentobarbital was injected intraperitoneally at a dose of 0.1 mL / 10 g. The duration of sleep was observed and recorded using the disappearance of the righting reflex as an indicator (the period from the disappearance to the recovery of the righting reflex was defined as the sleep duration).

[0070] 1.4.5 Sodium barbital sleep latency test Based on preliminary experiments, the optimal dose of sodium barbital (300 mg / kg) was determined to induce 100% sleep in mice without causing excessively long sleep duration. Thirty minutes after the last administration, sodium barbital was injected at a dose of 0.1 mL / 10 g. The time it took for mice to fall asleep was observed and recorded, and the sleep latency (from the injection of sodium barbital to the disappearance of the righting reflex) was calculated.

[0071] 1.4.6 Indicator Testing Mice were fasted for 12 hours, then euthanized by enucleation of the eyeballs to collect blood, followed by cervical dislocation. Brain tissue was quickly removed on ice and cryopreserved. Blood was allowed to stand at room temperature for 2 hours, then centrifuged at 4°C and 3000 r / min for 15 min. The BDNF content in mouse serum was measured according to the ELISA kit instructions. Mouse brain tissue was ground with physiological saline, centrifuged, and the supernatant was collected. The levels of 5-HT, GABA, DA, NE, and Glu in the brain tissue were measured according to the corresponding kit instructions.

[0072] Test results: Table 4. Mouse body weight before and after drug administration ( (n=10, g)

[0073] According to the test results in Table 4, based on the body weight records of mice in each group on days 0, 5, 10, 15, 20, 25, and 30 after drug administration, the body weight of mice in each group increased with the duration of feeding. Furthermore, the mice maintained normal activity and had shiny fur during the feeding period. Statistical results showed no significant difference in body weight among the groups. P >0.05).

[0074] Table 5. Effects on direct sleep and subthreshold dose pentobarbital sodium hypnotic experiments

[0075] Note: The same letter 'a' indicates that there is no significant difference in the number of babies falling asleep among the subthreshold dose groups.

[0076] The direct sleep status of mice in each group was observed within 30 minutes of daily administration. The results showed that the number of mice falling asleep was 0 in each dosage group, indicating that neither Qi Xue Gu Ben oral liquid nor Zao Ren An Shen granules had a direct sleep effect. Through previous experiments, the subthreshold hypnotic dose of sodium pentobarbital was determined to be 45 mg / kg. The results of the subthreshold dose hypnotic experiment with sodium pentobarbital showed that the sleep rates of mice in the blank control group, positive control group, and the low, medium, and high dose groups of Qi Xue Gu Ben were 10%, 50%, 30%, 20%, and 30%, respectively. Compared with the blank control group, the sleep rates of all dosage groups of Qi Xue Gu Ben and the positive control group were increased (χ²).P ,

[0082] , , * ,

[0081] , ,

[0084] ,

[0083] , ** , P ,

[0085] , , P , , The test results showed that there was no significant difference in the number of mice falling asleep among groups.

[0077] Table 6 Effects on the experiment of prolonging the sleeping time of pentobarbital sodium and the sleep latency of barbital sodium

[0078] Note: Compared with the blank group * P <0.05, ** P <0.01.

[0079] Through the previous experiments, the dose of pentobarbital sodium that could make 100% of the mice fall asleep without prolonging the sleeping time too long was 55 mg / kg. The results of the experiment on prolonging the sleeping time of pentobarbital sodium showed that, compared with the blank control group, the low, medium, and high dose groups of Qixue Guben and the positive control group could all significantly prolong the sleeping time (<0.01). Through the previous experiments, the dose of barbital sodium that could make 100% of the mice fall asleep without prolonging the sleeping time too long was 300 mg / kg. The results of the barbital sodium sleep latency experiment showed that, compared with the blank control group, the low, medium, and high dose groups of Qixue Guben and the positive control group could all significantly shorten the sleep latency time (<0.01). P <00002; Through the previous experiments, the dose of barbital sodium that could make 100% of the mice fall asleep without prolonging the sleeping time too long was 300 mg / kg. The results of the barbital sodium sleep latency experiment showed that, compared with the blank control group, the low, medium, and high dose groups of Qixue Guben and the positive control group could all significantly shorten the sleep latency time (<0.01). P <0.01).

[0080] Table 7 Effects on the contents of monoamine neurotransmitters 5-HT, DA, and NE in the mouse brain

[0081] Note: Compared with the blank group * P <0.05, ** P <0.01.

[0082] Compared with the blank control group, the low, medium, and high dose groups of Qixue Guben and the positive control group could all significantly increase the 5-HT content in the mouse brain (<0.05, <0.01); there was no significant difference in the contents of DA and NE among groups. P <0.05, P <0.01); there was no significant difference in the contents of DA and NE among groups.

[0083] Table 8 Effects on the contents of neurotransmitter amino acids GABA, Glu in the mouse brain and the BDNF content in the serum

[0084] Note: Compared with the blank group * P <0.05, ** P <0.01.

[0085] Compared with the blank control group, both the high-dose group of Qixue Guben and the positive control group could significantly increase the GABA content in the brains of mice ( P <0.01); both the medium- and high-dose groups of Qixue Guben and the positive control group could significantly reduce the Glu content in the brains of mice ( P <0.01). Compared with the blank control group, both the medium- and high-dose groups of Qixue Guben could significantly increase the BDNF content in the sera of mice ( P <0.01).

[0086] 2. Improvement effect on insomnia 2.1 Experimental animals Sixty SPF-grade male SD rats, weighing 160 - 180 g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. [License number: SCXK (Beijing) 2024-0001]; the SPF-grade maintenance feed for rats was purchased from Beijing Keao Xieli Feed Co., Ltd. The experimental animals were housed in the animal house of Beijing University of Chinese Medicine. During the experiment, the rats had free access to water. The room temperature in the animal house was 20 - 22°C, the relative humidity was 60 - 70%, and the light and darkness were simulated for 12 hours each to mimic day and night alternation. The experiment complied with relevant ethical requirements, with the serial number: BUCM-2024120102-4194.

[0087] 2.2 Experimental drugs The extract prepared in Example 1 was dried, pulverized, and sieved to obtain the dry powder of the extract.

[0088] Low-, medium-, and high-dose Qixue Guben oral liquid; the daily dosage of Qixue Guben oral liquid for humans is 30 mL, and 95.25 g of dry extract powder is equivalent to the standard prescription amount (1000 mL). Calculated based on 3.15 times, 6.3 times, and 12.6 times the daily dosage for humans and a body weight of 6 kg, the daily dosages of the low-, medium-, and high-dose groups of Qixue Guben are 150 mg / kg, 300 mg / kg, and 600 mg / kg, respectively.

[0089] Positive control drug: Estazolam tablets (National Medicine Approval Number H42021522), purchased from Huazhong Pharmaceutical Co., Ltd., with a daily dosage of 0.105 mg / kg.

[0090] 2.3 Preparation of the modeling drug p-Chlorophenylalanine (PCPA, batch number C6506) was purchased from Sigma, USA. Preparation of the PCPA suspension: 5 g of sodium bicarbonate powder was dissolved in injection physiological saline and made up to 100 mL to prepare a 5% sodium bicarbonate weak alkaline solution. Then, 4 g of PCPA was dissolved in the above solution to prepare a PCPA suspension with a concentration of 0.04 g / mL.

[0091] 2.4 Experimental reagents and instruments Table 9 Main reagents

[0092] Table 10 Main Experimental Instruments

[0093] 2.5 Experimental Methods 2.5.1 Animal Grouping Sixty SPF-grade male SD rats were randomly divided into six groups: a control group, a model group, a diazepam group, and low-, medium-, and high-dose groups of Qi Xue Gu Ben oral liquid. Except for the control group, the other groups were injected intraperitoneally with chlorophenylalanine (PCPA) and diet deprivation to induce a sleep deprivation model of heart and spleen deficiency.

[0094] 2.5.2 Modeling method and drug administration Modeling method: After 7 days of adaptive feeding, except for the control group, the other groups were fasted on odd-numbered days and fed sufficient feed on even-numbered days with free access to water to create an abnormal state of hunger and satiety for 21 consecutive days. On the 13th-14th day of the abnormal state of hunger and satiety, PCPA suspension was injected intraperitoneally. After two days of continuous injection, the rats were observed to have lost their diurnal rhythm, ruffled and hair loss, lethargy, easily cracked claws, and strong stress response, which indicated that the model was successful.

[0095] Administration: The low, medium, and high dose groups of Qi Xue Gu Ben oral liquid were administered at concentrations of 150 mg / kg, 300 mg / kg, and 600 mg / kg, respectively. The estazolam group was administered at a concentration of 0.105 mg / kg. After the start of the experiment, rats in each dose group were administered the corresponding test drug by gavage from 8:00 AM to 10:00 AM daily. Rats in the model group and blank group were administered an equal volume of distilled water by gavage. The gavage volume was 0.1 mL / 10 g, and the administration was continued for 21 consecutive days.

[0096] During the experiment, the general condition of rats in each group was observed, and the body weight of rats was measured on days 1, 7, 14, and 21 after drug administration. The rats' grip strength was measured on day 18, the pentobarbital sleep test was performed on day 19, and the open field test was performed on day 20.

[0097] 2.5.3 Grip Test Before the formal experiment, rats were given acclimatization training to allow them to adapt to the experimental setup. The gripping force testing platform was placed parallel to the tabletop. The rats were placed on the platform, and their tails were gently pulled parallel to the tabletop to allow them to grip the platform with their forelimbs. The sensor gripping force values ​​were recorded, and this process was repeated three times, with the average value taken.

[0098] 2.5.4 Sodium pentobarbital-assisted sleep experiment The disappearance of the righting reflex for 60 seconds was used as the sleep onset marker, and the completion of three turning movements within 30 seconds was used as the awakening criterion. Sleep latency (i.e., the time interval from drug administration to sleep onset) and sleep duration were observed and recorded to evaluate the drug's sleep-inducing effect on rats and the effectiveness of establishing a sleep model.

[28] . 2.5.5 Open Field Experiment The rat open field apparatus is a cube measuring 100cm long, 100cm wide, and 40cm high. The inner walls are coated with black, and the bottom surface is divided into 25 equal squares of 20cm x 20cm each. The central area consists of 9 squares, with the remaining squares near the edges forming the perimeter. A high-definition camera is installed 2 meters directly above the apparatus to ensure its field of view covers the entire experimental area. Rats are first placed in the central area to acclimatize, then removed and returned to the central area. Simultaneously, the camera recording system is activated, continuously collecting behavioral data for 5 minutes. After each experiment, feces are cleaned, and the interior of the apparatus is thoroughly disinfected with 75% ethanol to eliminate odor interference.

[0099] 2.5.6 Sample Collection Rats were anesthetized after fasting for 12 hours, and euthanized after blood was drawn from the abdominal aorta. The thymus and spleen were then harvested. Brains were harvested on ice. The left brain of the first six rats in each group was fixed in paraformaldehyde, and the hippocampus and hypothalamus of the right brain were isolated and cryopreserved in liquid nitrogen. The hippocampus and hypothalamus of the other six rats were isolated from the whole brain and cryopreserved in liquid nitrogen. Blood samples were allowed to stand at room temperature for 2 hours, then centrifuged at 4 °C and 3000 r / min for 15 min to collect serum. Samples were stored at -80 °C for subsequent testing.

[0100] 2.5.7 HE staining of the hippocampus Samples were fixed with 4% paraformaldehyde. After good fixation, they were trimmed, dehydrated, embedded, sectioned, stained, and mounted according to the standard operating procedure (SOP) for pathological testing. Digital slides were reviewed, and the tissue sections were observed at different magnifications. Basic pathological changes such as congestion, ecchymosis, hemorrhage, edema, degeneration, necrosis, hyperplasia, fibrosis, organization, granulation tissue, and inflammation were observed in each section.

[0101] 2.5.8 Detection Indicators The levels of LDH, CK, OXA, and OXB in rat serum were detected using enzyme-linked immunosorbent assay (ELISA) according to the kit instructions. Hippocampal tissue was ground with pre-cooled PBS buffer, centrifuged, and the supernatant was collected. The levels of 5-HT, DA, NE, GABA, and Glu in the hippocampus were detected according to the corresponding kit instructions.

[0102] Test results: Table 11 Effects on rat body weight ( ± s, n = 10, g)

[0103] Note: Compared with the blank group, a P <0.05, aa P <0.01; compared with the model group, b P <0.05, bb P <0.01.

[0104] According to the results in Table 11, the body weight of rats in each group was recorded on days 1, 7, 14, and 21 after administration. The results showed that there was no significant difference in body weight among the groups on the first day of the experiment (P > 0.05). After one week of the experiment, the body weight of rats in the model group was significantly lower than that in the control group (P < 0.01). Compared with the model group, the body weight of rats in the estazolam group and the low, medium, and high dose groups of Qi Xue Gu Ben was significantly higher (P < 0.05, P < 0.01).

[0105] The general condition of rats in each group was observed. Rats in the model group showed poor appetite and water intake, were emaciated, easily alert, lethargic, arched backs, ruffled fur, high-pitched cries, cloudy and foul-smelling urine, and unformed stools. Rats in the normal group had shiny fur, good growth, normal diurnal rhythms, and were nocturnal. The estazolam group and the low, medium, and high dose groups of the Qi and Blood Strengthening Pill showed improvements in both growth and sleep.

[0106] Table 12 Effects on thymus and spleen indices

[0107] Note: Compared with the blank group, a P <0.05, aa P <0.01; compared with the model group, b P <0.05, bb P <0.01.

[0108] Compared with the control group, the thymus index and spleen index of rats in the model group were both decreased, but the differences were not statistically significant. Compared with the model group, the thymus index of the low-dose and high-dose Qi and Blood Strengthening groups was significantly increased. P <0.05); compared with the model group, the spleen index of the low-dose Qi and Blood Strengthening Group was significantly increased ( P <0.05).

[0109] Table 13 Effects of LDH and CK levels in rat serum

[0110] Note: Compared with the blank group, a P <0.05, aa P <0.01; compared with the model group, b P <0.05, bb P <0.01.

[0111] Compared with the blank group, the serum levels of LDH and CK in the model group rats were significantly increased ( P <0.01); Compared with the model group, the levels of LDH and CK in the estazolam group and the low, medium and high dose groups of Qi Xue Gu Ben were significantly decreased ( P <0.01).

[0112] Table 14 Effects on serum OXA and OXB levels in rats

[0113] Note: Compared with the blank group, a P <0.05, aa P <0.01; compared with the model group, b P <0.05, bb P <0.01.

[0114] Compared with the control group, the serum levels of OXA and OXB in the model group rats were significantly increased ( P <0.01); Compared with the model group, the OXA levels in the estazolam group and the low, medium, and high dose groups of Qi Xue Gu Ben were significantly decreased ( P <0.05, P <0.01), the OXB levels in the estazolam group and the medium and high dose groups of Qi Xue Gu Ben were significantly decreased ( P <0.01).

[0115] Table 15 Effects on the levels of monoamine neurotransmitters 5-HT, DA, and NE in the hippocampus

[0116] Note: Compared with the blank group, a P <0.05, aa P <0.01; compared with the model group, b P <0.05, bb P <0.01.

[0117] Compared with the control group, the 5-HT content in the hippocampus of the model group was significantly reduced. P <0.01); the contents of DA and NE were both significantly increased ( P <0.01). Compared with the model group, the 5-HT content in the estazolam group and the low, medium, and high dose groups of Qi Xue Gu Ben was significantly increased ( P <0.01); the DA content was significantly reduced in both the estazolam group and the medium and high dose groups of Qi Xue Gu Ben (a traditional Chinese medicine formula). P <0.01); the NE content was significantly reduced in all three dose groups of estazolam and Qi Xue Gu Ben (a traditional Chinese medicine formula). P <0.05, P <0.01). See Table 16.

[0118] Table 16 Effects on the content of neuraminic acid neurotransmitters GABA and Glu in the hippocampus

[0119] Note: Compared with the blank group, a P <0.05, aa P <0.01; compared with the model group, b P <0.05, bb P <0.01.

[0120] Compared with the control group, the GABA content in the hippocampus of the model group was significantly reduced. P <0.01); Glu content increased significantly ( P <0.01). Compared with the model group, the GABA content in the estazolam group and the low, medium, and high dose groups of Qi Xue Gu Ben was significantly increased ( P <0.01); the Glu content was significantly reduced in the estazolam group and in the low, medium, and high dose groups of Qi Xue Gu Ben (a traditional Chinese medicine formula). P <0.01). See Table 17.

[0121] Table 17 Effects of suprathreshold doses of sodium pentobarbital on sleep synergistic experiments ( ±s, n = 10)

[0122] Note: Compared with the blank group, a P <0.05, aa P <0.01; compared with the model group, b P <0.05, bb P <0.01.

[0123] Compared with the control group, the sleep latency of rats in the model group was significantly prolonged. P <0.01); compared with the model group, the sleep latency time in the estazolam group was significantly shortened ( P <0.01), while the sleep latency time was shortened in all three groups of Qi and Blood Strengthening, including the low, medium, and high dose groups, with a significant difference in the high dose group ( P <0.05); compared with the blank group, the sleep duration of rats in the model group was significantly shortened ( P <0.01); Compared with the model group, the duration of sleep was significantly prolonged in the estazolam group and the low, medium and high dose groups of Qi Xue Gu Ben (a traditional Chinese medicine formula). P <0.01).

[0124] Table 18 shows the impact on total activity distance, average speed, central zone dwell time, and grip strength. ±s, n=10)

[0125] Note: Compared with the blank group, a P <0.05, aa P <0.01; compared with the model group, b P <0.05, bb P <0.01.

[0126] According to Table 18 above and Figure 1 , Figure 2 Open field experiment analysis showed that, compared with the control group, the total activity distance and average speed of rats in the model group were significantly reduced ( P <0.01); compared with the model group, the total activity distance and average speed of the estazolam group were significantly increased ( P <0.01), while the total activity distance and average speed of the low, medium and high dose groups of Qi and Blood Strengthening were significantly increased ( P <0.05, P <0.01). Compared with the control group, the central region dwell time of rats in the model group was significantly reduced ( P <0.05); Compared with the model group, the central zone residence time increased in the estazolam group, but the difference was not statistically significant, while the central zone residence time was significantly increased in the low, medium, and high dose groups of Qi Xue Gu Ben. P <0.01); the gripping force test results showed that, compared with the blank group, the gripping force of the rats in the model group was significantly reduced ( P <0.05); Compared with the model group, the gripping force value of the estazolam group was not significantly different, while the gripping force values ​​of the low, medium, and high dose groups of Qi Xue Gu Ben were all significantly increased ( P<0.05, P <0.01).

[0127] The above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art can still make modifications or equivalent substitutions to the specific implementation schemes of the present invention, and these modifications or equivalent substitutions do not depart from the spirit and scope of the present invention, and are all within the protection scope of the claims of the present invention.

Claims

1. Application of Qi Xue Gu Ben Oral Liquid in the preparation of drugs with the effects of invigorating qi, calming the mind, and improving insomnia.

2. The application according to claim 1, characterized in that: The drug mentioned is one that can reduce LDH content, CK content, OXA content, OXB content, DA content, or Glu content.

3. The application according to claim 1, characterized in that: The drug mentioned is one that can increase 5-HT content or increase GABA content.

4. The application according to claim 1, characterized in that: The drug described is capable of reducing the levels of LDH, CK, OXA, OXB, DA, and Glu, while increasing the levels of 5-HT and GABA.

5. The application according to any one of claims 1-4, characterized in that: The Qi and Blood Strengthening Oral Liquid is prepared by the following method: (1) Weigh lotus seeds and pine nuts, crush them, and then soak them to obtain soaking liquid for later use; (2) Weigh the rose hips and extract them to obtain extract A, which is then set aside. (3) Weigh out Acanthopanax senticosus, Schisandra chinensis, Epimedium, Morinda officinalis, Cuscuta chinensis, Ligustrum lucidum, Anemarrhena asphodeloides, Phellodendron chinense, Lycium barbarum, Rehmannia glutinosa, Polygonum multiflorum, Polygonatum sibiricum, Rubus idaeus, Dioscorea opposita, Ziziphus jujuba var. spinosa, pine needles and Platycladus orientalis seeds for extraction to obtain extract B, which is used for later use; (4) Take the soaking solution, extract A and extract B and concentrate them to obtain the extract; mix the extract with honey and purified water to obtain the Qi and Blood Strengthening Oral Liquid. The extraction described in step (3) needs to be carried out under high-pressure steam heating conditions; the steam pressure from the initial heating to boiling is 0.05-0.2MPa, the steam pressure is 0.01-0.05MPa within 1 hour after boiling, and the steam pressure is 0.1-0.15MPa from 1 hour after boiling to the end, and the temperature is 95-100℃.

6. The application according to claim 5, characterized in that: The particle size of the pulverized material in step (1) is 250μm-850μm; the ratio of water added to the mass of the medicinal material during soaking is 4-6:1; the soaking time is 3-5 hours; and the material is stirred for 2-5 minutes every 30 minutes during the soaking process.

7. The application according to claim 5, characterized in that: In step (2), the ratio of water added to the mass of medicinal materials is 5-8:

1. The extraction is carried out by decoction, which is carried out twice. The first decoction takes 1.5-2.5 hours, and the second decoction takes 0.5-1.5 hours.

8. The application according to claim 5, characterized in that: The extraction process in step (3) involves a water-to-medicinal-material ratio of 5-8:

1. The extraction is performed by decoction, which is repeated twice. The first decoction takes 3-6 hours, and the second decoction takes 2-4 hours.

9. The application according to claim 5, characterized in that: The Qi and Blood Strengthening Oral Liquid, by weight, comprises the following components: 70-90 parts of Rosa rugosa fruit, 70-90 parts of Acanthopanax senticosus, 20-30 parts of Schisandra chinensis, 20-30 parts of Epimedium brevicornu, 5-10 parts of Morinda officinalis, 5-10 parts of Cuscuta chinensis, 5-10 parts of Ligustrum lucidum, 15-30 parts of Anemarrhena asphodeloides, 15-30 parts of Phellodendron chinense, 5-10 parts of Lycium barbarum, 30-50 parts of Nelumbo nucifera, 5-10 parts of Rehmannia glutinosa, 15-30 parts of Polygonum multiflorum, 10-20 parts of Polygonatum sibiricum, 20-30 parts of Rubus idaeus, 5-15 parts of Dioscorea opposita, 30-50 parts of Pine nuts, 10-15 parts of Ziziphus jujuba var. spinosa, 5-15 parts of pine needles, and 5-15 parts of Platycladus orientalis.

10. The application according to claim 9, characterized in that: The Qi and Blood Strengthening Oral Liquid, by weight, comprises the following components: 80 parts of Rosa rugosa fruit, 80 parts of Acanthopanax senticosus, 25 parts of Schisandra chinensis, 25 parts of Epimedium, 8 parts of Morinda officinalis, 8 parts of Cuscuta chinensis, 8 parts of Ligustrum lucidum, 20 parts of Anemarrhena asphodeloides, 20 parts of Phellodendron chinense, 8 parts of Lycium barbarum, 40 parts of Nelumbo nucifera, 8 parts of Rehmannia glutinosa, 25 parts of Polygonum multiflorum, 15 parts of Polygonatum sibiricum, 25 parts of Rubus idaeus, 10 parts of Dioscorea opposita, 40 parts of Pine nut, 12 parts of Ziziphus jujuba var. spinosa, 10 parts of pine needles, and 10 parts of Platycladus orientalis seed.

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