Traditional Chinese medicine composition as well as preparation method and application thereof

Abstract

The invention provides a traditional Chinese medicine composition. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 355-400 parts of radix rehmanniae recen; 355-400 parts of Chinese yam stir-fried with bran; 285 to 315 parts of radix ophiopogonis; 285 to 315 parts of poria cocos; 175 to 200 parts of poria with hostwood; 175-200 parts of honey polygala tenuifolia; 175 to 200 parts of fried spina date seed; 70-80 parts of vinegar schisandra chinensis; 70 to 80 parts of tortoise-shell glue; and 70-80 parts of oxhide gelatin. By adopting the specific components and proportions, the traditional Chinese medicine composition has a synergistic effect and has a remarkable curative effect in the aspects of treating insomnia and dreaminess, palpitation and amnesia, anxiety and dysphoria, neurasthenia, climacteric syndrome and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition and a preparation method and application thereof. Background Art

[0002] As people's life pressure increases and the pace of life becomes faster, insomnia, palpitations, forgetfulness, anxiety, neurasthenia, and menopausal syndrome are gradually increasing. The above are symptoms of insufficient heart and kidney, and lack of nourishment for the spirit. Most of them are caused by insufficient heart and kidney yin and blood, internal disturbance of deficiency heat, and restlessness of mind.

[0003] Therefore, it is very necessary to provide a Chinese medicine composition that can treat the above-mentioned diseases. Summary of the invention

[0004] In view of this, the Chinese medicine composition provided by the present invention has the efficacy of treating insomnia, dreaminess, palpitations, forgetfulness, anxiety, irritability, neurasthenia and menopausal syndrome.

[0005] The present invention provides a traditional Chinese medicine composition, comprising the following raw materials in parts by weight:

[0006] 355-400 parts of Radix Rehmanniae; 355-400 parts of Rhizoma Dioscoreae Rhizoma; 285-315 parts of Radix Ophiopogonis; 285-315 parts of Poria;

[0007] 175-200 parts of Poria; 175-200 parts of honey Polygala; 175-200 parts of stir-fried Ziziphus jujuba seeds;

[0008] 70-80 parts of vinegar schisandra chinensis; 70-80 parts of tortoise shell glue; 70-80 parts of yellow gelatin.

[0009] Preferably, the Chinese medicine composition comprises the following raw materials in parts by weight:

[0010] 360-390 parts of Radix Rehmanniae; 360-390 parts of Rhizoma Dioscoreae Rhizoma; 290-310 parts of Radix Ophiopogonis; 290-310 parts of Poria;

[0011] 180-190 parts of Poria; 180-190 parts of honey Polygala; 180-190 parts of stir-fried Ziziphus jujuba seeds;

[0012] 72-78 parts of vinegar schisandra chinensis; 72-78 parts of tortoise shell glue; 72-78 parts of yellow gelatin.

[0013] Preferably, the tortoise shell glue is tortoise shell glue fine powder; and the yellow gelatin is yellow gelatin fine powder.

[0014] The present invention provides a method for preparing a Chinese medicine composition according to any one of the above technical solutions, comprising:

[0015] A) mixing raw rehmannia root, fried yam with bran, ophiopogon japonicus, tuckahoe, poria, honey polygala root, fried spiny jujube seeds and vinegar schisandra chinensis, soaking in water, decocting, filtering to obtain a filtrate, and concentrating to obtain an extract;

[0016] B) mixing the extract and dextrin, and drying to obtain dry extract powder;

[0017] C) Mix the dry extract powder, dextrin, yellow gelatin powder and tortoise shell glue powder to obtain the product.

[0018] Preferably, the number of times of decocting in step A) is 1 to 3 times;

[0019] The mass ratio of the total amount of the raw rehmannia root, bran-fried yam, ophiopogon japonicus, tuckahoe, poria, honey polygala root, fried spiny jujube seeds and vinegar schisandra chinensis mixed with water is 1: (9-11);

[0020] The soaking time is 0.5 to 1.3 hours; the decoction time is 0.5 to 1.3 hours;

[0021] The filtration is carried out using a 100-mesh stainless steel mesh.

[0022] Preferably, the concentration in step A) is specifically: 60-80° C., vacuum degree -0.08 to -0.04 MPa; the relative density of the extract is 1.02 to 1.1.

[0023] Preferably, in step B), the mass ratio of the dextrin to the extract is (8-16):(100-102).

[0024] Preferably, the drying method in step B) is spray drying; the air inlet temperature of the spray drying is 170-180°C; the liquid inlet speed is 27Hz;

[0025] The mixing time in step C) is 30 to 40 minutes.

[0026] The present invention provides the use of any of the above-mentioned compositions or a composition prepared by the preparation method described in any of the above-mentioned technical solutions in the preparation of a drug; the efficacy of the drug includes treating at least one of insomnia, dreaminess, palpitations, forgetfulness, anxiety, irritability, neurasthenia or menopausal syndrome.

[0027] The present invention provides a medicine, comprising the composition described in any one of the above technical solutions or the composition prepared by the preparation method described in any one of the above technical solutions.

[0028] Compared with the prior art, the present invention provides a Chinese medicine composition, comprising the following raw materials in parts by weight: 355-400 parts of raw rehmannia root; 355-400 parts of bran-fried yam; 285-315 parts of ophiopogon; 285-315 parts of tuckahoe; 175-200 parts of poria; 175-200 parts of honey polygala; 175-200 parts of stir-fried spiny jujube seeds; 70-80 parts of vinegar schisandra chinensis; 70-80 parts of tortoise shell glue; 70-80 parts of yellow gelatin. The present invention adopts the above-mentioned specific components and proportions, has a synergistic effect, and has significant therapeutic effects in treating insomnia, palpitations, forgetfulness, anxiety, neurasthenia, menopausal syndrome, etc. DETAILED DESCRIPTION

[0029] The present invention provides a Chinese medicine composition, a preparation method and application thereof, and those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It should be particularly noted that all similar replacements and modifications are obvious to those skilled in the art, and they all fall within the scope of protection of the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the method and application of this article without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0030] The present invention provides a traditional Chinese medicine composition, comprising the following raw materials in parts by weight:

[0031] 355-400 parts of Radix Rehmanniae; 355-400 parts of Rhizoma Dioscoreae Rhizoma; 285-315 parts of Radix Ophiopogonis; 285-315 parts of Poria;

[0032] 175-200 parts of Poria; 175-200 parts of honey Polygala; 175-200 parts of stir-fried Ziziphus jujuba seeds;

[0033] 70-80 parts of vinegar schisandra chinensis; 70-80 parts of tortoise shell glue; 70-80 parts of yellow gelatin.

[0034] In some preferred embodiments of the present invention, the Chinese medicine composition comprises the following raw materials in parts by weight:

[0035] 360-390 parts of Radix Rehmanniae; 360-390 parts of Rhizoma Dioscoreae Rhizoma; 290-310 parts of Radix Ophiopogonis; 290-310 parts of Poria;

[0036] 180-190 parts of Poria; 180-190 parts of honey Polygala; 180-190 parts of stir-fried Ziziphus jujuba seeds;

[0037] 72-78 parts of vinegar schisandra chinensis; 72-78 parts of tortoise shell glue; 72-78 parts of yellow gelatin.

[0038] In some preferred embodiments of the present invention, the Chinese medicine composition comprises the following raw materials in parts by weight:

[0039] 362-388 parts of Radix Rehmanniae; 363-388 parts of Rhizoma Dioscoreae Rhizoma; 292-308 parts of Radix Ophiopogonis; 290-308 parts of Poria;

[0040] 182-188 parts of Poria; 182-188 parts of Polygala root with honey; 182-188 parts of stir-fried Ziziphus jujuba seeds;

[0041] 73-77 parts of vinegar schisandra chinensis; 73-77 parts of tortoise shell glue; 73-77 parts of yellow gelatin.

[0042] In some preferred embodiments of the present invention, the Chinese medicine composition comprises the following raw materials in parts by weight:

[0043] 365-385 parts of Radix Rehmanniae; 365-385 parts of Rhizoma Dioscoreae Rhizoma; 295-305 parts of Radix Ophiopogonis; 295-305 parts of Poria;

[0044] 183-187 parts of Poria; 183-187 parts of honey Polygala; 183-187 parts of stir-fried Ziziphus jujuba seeds;

[0045] 74-76 parts of vinegar schisandra chinensis; 74-76 parts of tortoise shell glue; 74-76 parts of yellow gelatin.

[0046] In one preferred embodiment of the present invention, the Chinese medicine composition comprises the following raw materials in parts by weight:

[0047] 375 parts of Radix Rehmanniae; 375 parts of Rhizoma Dioscoreae Rhizoma; 300 parts of Radix Ophiopogonis; 300 parts of Poria;

[0048] 187.5 parts of Poria; 187.5 parts of Polygala tenuifolia root; 187.5 parts of stir-fried Semen Ziziphi Spinosae;

[0049] 75 parts of vinegar schisandra chinensis; 75 parts of tortoise shell glue; 75 parts of yellow gelatin.

[0050] The Chinese medicine compositions within the above range of the present invention can achieve similar technical effects, with an effective rate of more than 80%; especially for the preferred range of the present invention, the effective rate is more than 86%.

[0051] According to the present invention, the tortoise shell glue is tortoise shell glue fine powder; the yellow gelatin is yellow gelatin fine powder.

[0052] Rehmannia glutinosa is the fresh or dried root of Rehmannia glutinosa Libosch. It is dug in autumn, and the root, fibrous roots and mud are removed. The Rehmannia is slowly baked until it is about 80% dry, commonly known as "raw Rehmannia". Raw Rehmannia slices are obtained by removing impurities from raw Rehmannia, washing, steaming, cutting into thick slices, and drying.

[0053] Fried yam with bran is the dried rhizome of Dioscorea opposita Thunb., a plant of the Dioscoreaceae family. It is dug up after the stems and leaves wither in winter, the root head is cut off, washed, the outer skin and fibrous roots are removed, and dried. It is commonly known as "hairy yam". The yam slices are hairy yam slices, which are made by removing impurities, separating large and small pieces, soaking them until thoroughly moistened, cutting them into thick slices, and drying them. The yam slices are hairy yam slices, which are made by removing impurities. Fried yam with bran is hairy yam slices, which are made by frying them according to the bran frying method (General Rule 0213) until they turn yellow.

[0054] Ophiopogon japonicus is the dried root of Ophiopogon japonicus (Lf) Ker-Gawl. It is dug up in summer, washed, repeatedly exposed to the sun and piled until it is 70% to 80% dry, the fibrous roots are removed and dried. Ophiopogon japonicus slices are obtained by removing impurities from Ophiopogon japonicus, washing, moistening, flattening and drying.

[0055] Poria cocos is the dried sclerotium of the Polyporaceae fungus Poria cocos (Schw.) Wolf. It is usually dug from July to September, and after being dug out, the sand is removed, piled up to "sweate", spread out to dry on the surface, and then "sweated" again, repeated several times until wrinkles appear and most of the internal moisture is lost, and then dried in the shade, which is called "Poria cocos piece". Poria cocos decoction pieces are Poria cocos pieces, which are soaked, washed, slightly steamed after moistening, peeled in time, cut into blocks or thick slices, and dried in the sun.

[0056] Fushen is the sclerotium of the Polyporaceae fungus Poria cocos (Schw.) Wolf. with pine roots. Fushen decoction pieces are made from the original Poria cocos, which is cleaned of impurities, rinsed, soaked in water, cut into thick slices or blocks, dried, and sieved to remove ash.

[0057] Honey Polygala is the dried root of Polygala tenuifolia Willd., a plant of the Polygalaceae family. It is dug in spring and autumn, the fibrous roots and mud are removed, and the wood core is extracted and dried. Polygala decoction pieces are obtained by removing impurities from Polygala, washing it slightly, moistening it thoroughly, cutting it into sections, and drying it. Processed Polygala is obtained by taking licorice, adding an appropriate amount of water to boil it, removing the residue, adding clean Polygala, simmering it over low heat until the soup is absorbed, taking it out, and drying it. Honey Polygala is obtained by taking refined honey, adding an appropriate amount of boiling water to dilute it, mixing it with processed Polygala, steaming it thoroughly, and frying it over low heat until it has a slight burnt spot and is not sticky, then taking it out.

[0058] Fried sour jujube kernels are the dried mature seeds of the rhamnaceae plant Ziziphus jujuba Mill.var.spinosa (Bunge) Hu exH.F.Chou. The mature fruits are harvested in late autumn and early winter, the pulp and shell are removed, the seeds are collected and dried. The sour jujube kernel slices are obtained by removing the residual shell from the original sour jujube kernel. Fried sour jujube kernels are pure sour jujube kernels, which are fried according to the stir-fry method (General Rule 0213) until they swell and the color becomes slightly darker.

[0059] Vinegar Schisandra is the dried mature fruit of Schisandra chinensis (Turcz.) Baill., a plant of the Magnoliaceae family. It is commonly known as "Northern Schisandra". The fruit is picked when it is ripe in autumn, dried in the sun or steamed and then dried in the sun, and the fruit stalks and impurities are removed. Schisandra slices are obtained by removing impurities from Schisandra. Vinegar Schisandra is pure Schisandra, which is steamed according to the vinegar steaming method (General Rule 0213) until it turns black.

[0060] Turtle shell glue is a solid glue made by boiling and concentrating tortoise shells.

[0061] Yellow gelatin is made from the hide of Bos taurus domesticus Gmelin, a bovine animal. Take dried yellow cattle hide, cut it into pieces, soak it until soft, wash it, boil it with water, and add rice wine, crystal sugar and other auxiliary materials to collect the gelatin.

[0062] The syndrome treated by this prescription is caused by insufficient yin and blood in the heart and kidney, internal disturbance of deficiency heat, and restlessness. It should be formulated to nourish the kidney and nourish the heart, nourish yin and blood, clear away heat and relieve restlessness, and calm the mind and stabilize the spirit. The raw Rehmannia root in the prescription is sweet, bitter and cold, and it belongs to the heart, liver and kidney meridians. It is an important medicine for nourishing the kidney and nourishing the heart, nourishing yin and blood, and clearing heat and relieving restlessness. Stir-fried sour jujube seeds are sweet, sour and flat in nature, and belong to the heart, liver and gallbladder meridians. They are good at nourishing the heart and calming the mind, nourishing the liver and nourishing blood, and "treating restlessness and insomnia". The combination of the two medicines has good effects of nourishing the kidney and nourishing the heart, nourishing yin and blood, clearing heat and relieving restlessness, and calming the mind and stabilizing the spirit. It treats both the symptoms and the root cause, and is the main medicine.

[0063] Ophiopogon japonicus is sweet and slightly cold, and it belongs to the heart, lung and stomach meridians. It can "replenish the deficiency of heart qi", "remove heart heat, stop irritability and fever", "treat the five kinds of labor and seven kinds of injuries, and calm the soul and spirit". It is the first choice for nourishing heart yin, clearing heart heat, and replenishing heart qi. When combined with Rehmannia root, it nourishes the heart and kidney, clears heat and eliminates irritability. Poria is sweet, mild and flat, and mainly enters the heart meridian, specializing in nourishing the heart and calming the mind; Polygala tenuifolia is bitter, pungent and slightly warm, and it belongs to the heart, kidney and lung meridians, and can "calm the heart qi and stop palpitations", and is good at "treating palpitations and insomnia". The two medicines combined with Ziziphus jujuba seeds can nourish the heart and calm the mind, and the effect of helping sleep and calming palpitations is particularly prominent. They are both ministerial drugs.

[0064] Chinese yam is sweet and mild, and belongs to the spleen, lung and kidney meridians. It is good at "strengthening the spleen and replenishing deficiency, nourishing essence and strengthening the kidney, treating all kinds of deficiency and damage, and curing five kinds of labor and seven kinds of injuries" ("Compendium of Materia Medica"), "benefiting kidney qi, strengthening spleen and stomach, and moisturizing skin and fur" ("Compendium of Materia Medica"), and is a commonly used medicine for nourishing qi and nourishing yin, and nourishing spleen and strengthening kidney. Poria cocos is sweet, mild and mild, and belongs to the heart, spleen and kidney meridians. It is good at nourishing spleen and calming the heart, "taking it for a long time can calm the soul and nourish the spirit" ("Shennong's Materia Medica"), and the predecessors praised it as "benefiting the heart and spleen is indispensable" ("Compendium of Materia Medica"). Chinese yam with Poria cocos can nourish the spleen and move the spleen, which can not only enrich the source of qi and blood biochemical transformation, but also make it nourishing without being too greasy. Turtle shell glue is sweet, salty and cold, and belongs to the liver, kidney and heart meridians, which can nourish yin and suppress yang, nourish the kidney and nourish the liver; Huangming glue is sweet and mild in nature, and belongs to the liver, spleen and lung meridians, which is good at nourishing yin and moistening dryness, nourishing the lungs and clearing gold. Both of them are flesh and blood, which makes the nourishing effect of this prescription particularly good, and it is conducive to collecting ointment and is commonly used as an ointment. Schisandra chinensis is sour, sweet and warm, and enters the heart, lung and kidney meridians. It nourishes the kidneys and astringes the essence, nourishes the heart and calms the mind. It can replenish the deficiency of vital energy, collect the dissipated qi, and restrain the floating spirit, which helps this prescription to replenish the deficiency and calm the mind. Both are adjuvant drugs.

[0065] The combination of various medicines in the prescription nourishes yin, blood, kidney and spleen to replenish the deficiency, nourishes the heart, softens the liver, clears heat and eliminates restlessness to calm the mind, so that the yin and blood are abundant, the five internal organs are harmonious and the mind is clear. The prescription is sweet, cool, soft and moist, nourishing without stagnation, clearing without cold, so it can be taken for a long time without disturbing the stomach.

[0066] The present invention provides a method for preparing a Chinese medicine composition according to any one of the above technical solutions, comprising:

[0067] A) mixing raw rehmannia root, fried yam with bran, ophiopogon japonicus, tuckahoe, poria, honey polygala root, fried spiny jujube seeds and vinegar schisandra chinensis, soaking in water, decocting, filtering to obtain a filtrate, and concentrating to obtain an extract;

[0068] B) mixing the extract and dextrin, and drying to obtain dry extract powder;

[0069] C) Mix the dry extract powder, dextrin, yellow gelatin powder and tortoise shell glue powder to obtain the product.

[0070] The preparation method of the traditional Chinese medicine composition provided by the invention comprises the following steps: firstly crushing yellow gelatin powder and tortoise shell glue into fine powder, sieving the powder and setting aside; the tortoise shell glue described in the invention is tortoise shell glue fine powder; and the yellow gelatin is yellow gelatin fine powder.

[0071] Mix raw Rehmannia root, fried yam with bran, Ophiopogon japonicus, Poria cocos, Poria cocos, Polygala tenuifolia with honey, fried Ziziphus jujuba seeds and Schisandra chinensis with vinegar, soak in water and boil.

[0072] The number of decoctions of the present invention is 1 to 3 times; more preferably 1 to 2 times; most preferably 2 times.

[0073] According to the present invention, the mass ratio of the total amount of the raw rehmannia root, fried yam with bran, ophiopogon japonicus, tuckahoe, poria, honey polygala root, fried spiny jujube seeds and vinegar schisandra chinensis mixed with water is 1: (9-11); more preferably 1:10.

[0074] In the present invention, the soaking time for each soaking is preferably 0.5 to 0.8 hours, preferably 0.5 to 0.6 hours, and most preferably 0.5 hours. The total soaking time is preferably 0.5 to 1.3 hours, more preferably 0.8 to 1.2 hours, and most preferably 1 hour.

[0075] In the present invention, the preferred boiling time for each time is 0.5 to 0.8 hours, preferably 0.5 to 0.6 hours, and most preferably 0.5 hours. The total soaking time is preferably 0.5 to 1.3 hours, more preferably 0.8 to 1.2 hours, and most preferably 1 hour.

[0076] The extraction process selected by the present invention is: extracting twice, each time for 30 minutes.

[0077] After decoction, filter to obtain a filtrate.

[0078] The filtration described in the present invention is filtering using a 100-mesh stainless steel net.

[0079] The purpose of the filtration of the present invention is only to remove a small amount of solid residues, and static sedimentation may cause the loss of some effective ingredients whose solubility is greatly affected by temperature; the volume of the liquid medicine is large during large-scale production, and the centrifugal technology takes a long time. When decoction is used for release, it is directly filtered with a 100-mesh stainless steel mesh, which can not only filter and remove the solid residues well, but also will not cause the loss of effective ingredients.

[0080] The filtrate is concentrated to obtain an extract; the concentration of the present invention is specifically: 60-80°C, vacuum degree -0.08--0.04Mpa; the relative density of the extract is 1.02-1.1.

[0081] When the extract was concentrated under the above parameters, the spinosin transfer rate did not change much.

[0082] The extract and dextrin are mixed and dried to obtain dry extract powder.

[0083] According to the present invention, the drying method is spray drying; the air inlet temperature of the spray drying is 170-180°C; the liquid inlet speed is 27Hz;

[0084] Spray drying is instant drying and is suitable for heat-sensitive materials; the product has good quality, can maintain the original color, aroma and taste, is easy to dissolve, and has a low bacterial content.

[0085] Under the above spray drying parameters, the yield is high, the powder does not stick to the wall, the dry powder can be collected, the yield is high and it is not easy to absorb moisture.

[0086] According to the present invention, the mass ratio of dextrin to extract is (8-16): (100-102), and the mass ratio of dextrin to dry extract is (1-3): 3. When the ratio of dextrin to dry extract is approximately 1:3, the above effect is good. The dry extract powder, dextrin, yellow gelatin powder and tortoise shell glue powder are mixed to obtain the mixture. The mixing time is 30-40 minutes.

[0087] The present invention also provides a method for preparing Chinese medicine granules, which comprises placing the prepared Chinese medicine composition in a dry granulator to make granules, and then packaging the granules.

[0088] The present invention selects dextrin as the excipient. The process parameters are selected as follows: adding dextrin, the feeding speed is 25rpm, the pressing wheel speed is 1rpm, and the pressing wheel spacing is 0.1mm. The mixing time is 30 to 40 minutes, preferably 30 minutes. The moisture content of the mixed powder should be controlled at 4.8% to 6.2%.

[0089] In one embodiment of the present invention, the parameters of the dry granulation are:

[0090] The stirring speed is 16rpm; the feeding speed is 36rpm, the pressure wheel speed is 6rpm; the pressure wheel spacing is 1.2mm, the crushing speed is 100rpm; the sorting speed is 100rpm.

[0091] The granules are packaged using PET / AL / PE composite film and the temperature is controlled at 150°C for hot pressing and sealing.

[0092] The present invention provides the use of any of the above-mentioned compositions or a composition prepared by the preparation method described in any of the above-mentioned technical solutions in the preparation of a drug; the efficacy of the drug includes treating at least one of insomnia, dreaminess, palpitations, forgetfulness, anxiety, irritability, neurasthenia or menopausal syndrome.

[0093] The present invention provides a medicine, comprising the composition described in any one of the above technical solutions or the composition prepared by the preparation method described in any one of the above technical solutions.

[0094] The dosage form of the drug is an oral preparation; the oral preparation is selected from one of tablets, mixtures, decoctions, capsules, pills, granules, suspensions, extracts, decoctions, pills, and oral liquid preparations.

[0095] The clinical use form of Yiyin Anshen Fang is decoction or decoction paste. After the patient takes back the slices, he can decoct and take them according to the doctor's instructions, or he can entrust the processing into paste. Due to the problems of inconvenience in carrying and storage, inaccurate dosage, etc., it is necessary to improve the dosage form. The oral preparations based on decoctions can have a variety of oral dosage forms such as mixtures, granules, extracts, decoctions, etc. The mixture maintains the medication characteristics of the decoction, but its disadvantages in carrying and storage are the same as those of the decoction; the extract has strong hygroscopicity, and the process control and storage conditions require higher requirements; the decoction paste needs a long time and high temperature to collect the paste, and the mass production takes longer, and the degree of damage to the effective ingredients is higher. In addition, the decoction paste usually needs to be refrigerated, which is inconvenient to carry and store; the granules not only have the characteristics of large dosage and rapid onset relative to the decoction, but also have the advantages of easy to carry and store, good stability, and accurate dosage. Therefore, granules are selected as the dosage form of Yiyin Anshen Fang.

[0096] The medicine also includes pharmaceutically acceptable excipients, which are not limited in the present invention.

[0097] In some embodiments provided by the present invention, the pharmaceutically acceptable excipient is one or a mixture of two or more of fruit powder, edible flavor, sweetener, acidulant, filler, lubricant, preservative, suspending agent, edible coloring, diluent, emulsifier, disintegrant or plasticizer.

[0098] Preferably, the present invention selects dextrin as the excipient.

[0099] The present invention provides a Chinese medicine composition, comprising the following raw materials in parts by weight: 355-400 parts of raw rehmannia root; 355-400 parts of fried yam with bran; 285-315 parts of ophiopogon; 285-315 parts of tuckahoe; 175-200 parts of poria; 175-200 parts of honey polygala; 175-200 parts of stir-fried spiny jujube seeds; 70-80 parts of vinegar schisandra chinensis; 70-80 parts of tortoise shell glue; and 70-80 parts of yellow gelatin. The present invention adopts the above-mentioned specific components and proportions, has a synergistic effect, and has significant therapeutic effects in treating insomnia, palpitations, forgetfulness, anxiety, neurasthenia, menopausal syndrome, etc.

[0100] The numerical ranges and parameters involved in the present invention have presented the relevant numerical values ​​in the specific embodiments as accurately as possible. However, any numerical value essentially inevitably contains standard deviations due to individual testing methods. Therefore, unless otherwise explicitly stated, it should be understood that all numerical ranges or specific data used in this disclosure may have certain reasonable deviations within a certain range, for example: within 1% or 0.5%.

[0101] It should be understood that in the various embodiments of the present application, the size of the serial numbers of the above-mentioned processes does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0102] In order to further illustrate the present invention, a Chinese medicine composition, a preparation method and application thereof provided by the present invention are described in detail below in conjunction with examples.

[0103] Table 1-1 Manufacturer, name and batch number of the medicinal pieces used in the study

[0104]

[0105] Table 1-2 Instruments and manufacturers

[0106]

[0107]

[0108] Table 1-3 Batch number and source of reference substances

[0109]

[0110] Acetonitrile (chromatographic grade, TEDIA); water is ultrapure water.

[0111] Example 1 Preparation process

[0112] 1.1 Prescription

[0113] 375g of raw Rehmannia root, 375g of fried yam with bran, 300g of Ophiopogon japonicus, 300g of Poria cocos

[0114] Poria 187.5g Honey Polygala 187.5g Stir-fried Ziziphus jujuba seeds 187.5g Vinegar Schisandra 75g Tortoise shell glue 75g Yellow gelatin 75g

[0115] The above medicinal flavors, tortoise shell glue and yellow gelatin are crushed into fine powder for later use. The remaining pieces are extracted and concentrated, and then spray-dried with dextrin to obtain dry extract powder; appropriate amounts of dextrin, yellow gelatin and tortoise shell glue powder are added to make granules, making a total of 1000g. Each 1g is equivalent to 2.14g of the pieces. Take 1 to 2 bags at a time, twice a day, and a maximum of 85.5g of the pieces can be taken a day, which is consistent with the daily dose.

[0116] 1.2 Preparation method

[0117] The above ten pieces of medicinal materials, tortoise shell glue and yellow gelatin are crushed into fine powder, sieved and set aside. The remaining eight pieces of medicinal materials are decocted twice with water. The first time, 10 times the amount of water is added to the medicinal materials, soaked for 0.5h, decocted for 0.5h, and filtered; the second time, 10 times the amount of water is added to the medicinal materials, decocted for 0.5h, and filtered. Combine the above filtrates, reduce pressure and concentrate to a relative density of 1.02-1.10 (about 60℃). Add 200g of dextrin and spray dry to obtain dry extract powder. Add appropriate amount of dextrin, yellow gelatin and tortoise shell glue fine powder, mix well, put in a dry granulator, make granules, and package them to make a total of 1000g.

[0118] Dextrin addition amount (g) = 1000-1987.5*solid content yield - 150-200

[0119] Finished product yield (%) = actual finished product quantity produced in this batch / theoretical finished product quantity in this batch * 100%.

[0120] 1.3 Investigation of water absorption

[0121] According to the prescription ratio, weigh the remaining pieces except for tortoise shell glue and yellow gelatin, a total of 79.5g, operate according to the conventional decoction method, add appropriate amount of water to immerse the pieces, soak for 30 minutes, first boil with high heat, then adjust to low heat to keep slightly boiling, decoct twice, each time for 45 minutes, filter, weigh the decoction pieces after decoction, and calculate the water absorption rate of the prescription pieces. The results are shown in Table 1-4.

[0122] Table 1-4 Water absorption rate of decoction pieces

[0123]

[0124]

[0125] 1.4 Determination of the paste yield

[0126] Accurately pipette an appropriate amount of water extract sample, place it in a dry constant-weight evaporating dish, evaporate it to dryness in a water bath, place it in a 105°C oven and dry it for 3 hours. Take it out and cool it in a desiccator for 30 minutes, accurately weigh it and calculate it according to the following formula.

[0127]

[0128] 1.5 Conventional decoction study

[0129] Weigh the remaining pieces of medicine except yellow gelatin and tortoise shell glue according to the prescription ratio, a total of 80.0g, and operate according to the conventional decoction method. Add appropriate amount of water to immerse the pieces of medicine, soak for 30 minutes, boil over high heat first, then boil over low heat, decoct twice, each time for 45 minutes, and combine the two decoctions. Process 6 samples, and measure the spinosum transfer rate and extract yield of the conventional decoction recipe according to the internal control quality standard method. The results are shown in Tables 1-5.

[0130] Table 1-5 Results of conventional decoction investigation

[0131]

[0132] 1.6 Orthogonal test

[0133] 1.6.1 Orthogonal Experimental Design

[0134] Combined with the actual situation of conventional decoction and production, the number of extractions, extraction time and water addition were selected as the investigation factors. Under the parallel operation conditions, the spinosum transfer rate and the paste yield were used as evaluation indicators. According to L9(3 4 )Orthogonal array design experiment.

[0135] 1.6.2 Selection of water decoction process factor levels

[0136] (1) Orthogonal experimental design

[0137] The extraction time, extraction times and water addition were selected as the investigation factors. Under the parallel operation conditions, the transfer rate of spinosad and the yield of paste were used as evaluation indicators. According to L9(3 4 )Orthogonal array design experiment.

[0138] (2) Selection of process factor levels

[0139] Select orthogonal test table L9(3 4 ), see Table 1-6.

[0140] Table 1-6 Factor level table

[0141]

[0142] (3) Results of orthogonal test of water decoction

[0143] Assuming the weight of spinoside transfer rate is 0.8 and the weight of cream yield rate is 0.2, the comprehensive score is spinoside transfer rate × 0.8 + cream yield rate × 0.2. The results are shown in Tables 1-7 and 1-8.

[0144] Table 1-7 Intuitive analysis table

[0145]

[0146] Table 1-8 Variance analysis results

[0147]

[0148] As can be seen from the table, factor A has a significant effect on the test results, while factors B and C have no significant effect on the test results. The influence of the three selected factors on the test results is in the order of A>B>C, and the best extraction process is A3B3C3. The extraction time and the amount of water added have no significant effect on the test results. Referring to conventional decoction and taking into account production factors, the extraction time is 30min and the amount of water added is 10 times the amount of slices; the number of extractions has a significant effect on the test results, but considering the consistency with the results of conventional decoction tests, and taking into account production energy saving and convenient operation, extraction is selected twice. The final extraction process is: extraction twice, 30min each time, and the amount of water added each time is 10 times the amount of slices.

[0149] 1.6.3 Water decoction process verification

[0150] According to the prescription, the same batch of decoction pieces as in the orthogonal test were weighed, a total of 6 portions. The decoction was performed according to the preferred extraction process parameters, and the results are shown in Table 1-9.

[0151] Table 1-9 Verification test results

[0152]

[0153] The obtained results are basically close to the orthogonal results and better than the conventional decoction. It can be judged that the optimal process is feasible and stable.

[0154] 1.7 Filtration

[0155] For the large solid particles in the decoction of traditional Chinese medicine, there are sieve filtration separation and centrifugation technology, both of which can be well separated and convenient for the later process. There is also static sedimentation separation. However, we believe that the purpose of filtration is only to remove a small amount of solid residue, and static sedimentation may cause the loss of some effective ingredients whose solubility is greatly affected by temperature; the volume of the liquid is large during large-scale production, and the use of centrifugation technology takes a long time. When decoction is used, it is directly filtered with a 100-mesh stainless steel mesh, which can not only filter and remove the solid residue well, but also will not cause the loss of effective ingredients.

[0156] 1.8 Concentration

[0157] In actual production, the concentration of Chinese medicine water extracts is mostly done by vacuum concentration (the equipment can be vacuum concentration tanks, single-effect, double-effect and multi-effect, but the basic point is vacuum decompression conditions). Compared with normal pressure concentration, vacuum concentration has high thermal efficiency and less damage to heat-sensitive components. In combination with actual production, the inventor studied and compared the temperature of vacuum concentration based on the main index components of stir-fried spiny jujube seeds.

[0158] 1.8.1 Instruments and reagents

[0159] SHZ-D (III) circulating water vacuum pump (Shanghai Qiuzuo Scientific Instrument Co., Ltd.); induction cooker (Taigroo); RE52CS-2 rotary evaporator (Shanghai Yarong Biochemical Instrument Factory); the test drugs are the same as those in item “4.3.1” of this chapter.

[0160] 1.8.2 Chromatographic conditions

[0161] Octadecylsilane bonded silica gel was used as filler; acetonitrile was used as mobile phase A, water was used as mobile phase B, and gradient elution was performed according to the table below, with a flow rate of 1.0 ml / min; the detection wavelength was 335 nm; and the injection volume was 10 μl.

[0162]

[0163]

[0164] 1.8.3 Methods and Results

[0165] Usually, the extract is concentrated to a relative density of 1.02-1.10 (60°C) as needed. However, the study on the effect of concentration on the composition is still conducted at a concentration higher than the endpoint index of 1.10 (60°C), that is, it is concentrated to about 1.20 (60°C) at one time.

[0166] Take an appropriate amount of the water extract of the Chinese medicine composition, set different concentration temperatures (60°C, 70°C, 80°C), and concentrate under reduced pressure (vacuum degree -0.08 to -0.04MPa) to a relative density of about 1.20 (60°C). Determine the transfer rate of the main index components of the stir-fried spiny jujube kernels. The test results are shown in Tables 1-10.

[0167] Table 1-10 Effect of vacuum concentration temperature on spinosad transfer rate (n=3)

[0168]

[0169] From the above test results, it can be seen that when the extract is concentrated at 60℃, 70℃ and 80℃, the transfer rate of spinosum does not change much. The concentration process is determined as follows: the extract is concentrated under reduced pressure (T: 60~80℃, vacuum degree -0.08~-0.04MPa) to a clear paste with a relative density of 1.02~1.10 (60℃) for use.

[0170] 1.9 Spray Drying

[0171] Spray drying is a method of concentrating liquid materials to a suitable density, materializing them into fine droplets, exchanging heat with hot air at a certain flow rate, evaporating the water quickly, and drying the materials into powder or granules. The spray drying conditions, dry powder properties, water content, and yield were used as the evaluation indicators for the test.

[0172] 1.9.1 Investigation of relative density of extract

[0173] Spray drying requires the extract to be concentrated to a suitable density. According to the instrument parameters and actual operation experience, the relative density of the extract selected for the Chinese medicine composition granules is in the range of 1.02 to 1.10 (60°C).

[0174] 1.9.2 Investigation of inlet air temperature

[0175] Take the clear paste that has been concentrated under reduced pressure to a relative density of 1.02-1.10 (60°C) and divide it into three equal parts. Set the air inlet temperatures to 160°C, 170°C and 180°C respectively, and the liquid inlet speed to 45rpm. Observe the spray drying situation and calculate the yield. The test results are shown in Table 1-11.

[0176] Table 1-11 Results of investigation on inlet air temperature

[0177]

[0178] The experimental results show that the yield is higher when the inlet air temperature is 180℃, so the inlet air temperature is selected to be 180℃.

[0179] 1.9.3 Investigation of the amount of auxiliary materials

[0180] Take the clear paste concentrated under reduced pressure to a relative density of 1.02-1.10 (60°C), divide it into five equal parts, add different proportions of dextrin to each part, set the liquid inlet speed to 27Hz, the air inlet temperature to 180°C, spray dry, and record the process parameters. The test results are shown in Table 1-12.

[0181] Table 1-12 Results of investigation on auxiliary material dosage

[0182]

[0183] The test results in the table above show that in terms of formability, the greater the amount of dextrin, the better, but in terms of dosage and economy, the less the better; when the ratio of dextrin to dry clear paste is approximately 1:3, the spray-dried powder does not stick to the wall, the dry powder can be collected, the yield is high and it is not easy to absorb moisture. Taking all factors into consideration, the ratio of dextrin to dry clear paste is 1:3.

[0184] 1.9.4 Spray Drying Process Validation

[0185] Take three portions of the clear paste concentrated under reduced pressure to a relative density of 1.02-1.10 (60°C), add dextrin at a ratio of dextrin: dry clear paste = 1:3, set the liquid inlet speed to 27Hz, the air inlet temperature to 180°C, and perform spray drying. The test results are shown in Table 1-13.

[0186] Table 1-13 Spray drying process verification results

[0187]

[0188] In summary, the above spray drying process is stable and feasible, and the above process will be used for spray drying in pilot and large-scale production.

[0189] 1.10 Crushing

[0190] Melting is a special decoction method for gelatinous Chinese medicines such as donkey-hide gelatin, yellow gelatin, and tortoise shell glue. [9] After adding the glue to the decoction to melt, the texture is sticky and difficult to dry. Therefore, the deer antler glue and tortoise shell glue in the prescription are directly crushed into fine powder, and then mixed with other drug powders and auxiliary materials and granulated.

[0191] Since the target powder is fine powder, all of it must pass through the No. 5 sieve and contain no less than 95% of the powder that can pass through the No. 6 sieve. The results of the small-scale crushing tests of three batches of yellow gelatin and tortoise shell glue are shown in Table 1-14.

[0192] Table 1-14 Results of three batches of small-scale crushing tests

[0193]

[0194] The above-mentioned crushed powder was subjected to a particle size inspection. The inspection results are shown in Table 1-15.

[0195] Table 1-15: Particle size inspection results of three batches of small-scale crushing process.

[0196]

[0197] It can be seen from the above results that the purpose of crushing has been well achieved after the above crushing.

[0198] 1.11 Sieving

[0199] Although the above crushing process has basically achieved the requirements of fine powder, it still needs to go through the screening process to ensure that the products of each different production period and batch are qualified. There are many screening methods. We use a rotary screen according to the equipment conditions of large-scale production. Since the target powder is fine powder, all of its powder must pass through the No. 5 sieve, and the powder that can pass through the No. 6 sieve is not less than 95%, so the No. 6 sieve is selected for screening to ensure the screening effect.

[0200] The screening effect is related to the crushing process, as well as the selection of the screening mesh and equipment, but after this process, the preparation particles (mainly referring to the particle size) that meet the production quality can be basically obtained. If the crushed powder is moderate, the highest yield can be achieved. The screening results of three batches are shown in Table 1-16.

[0201] Table 1-16 Results of three batches of small-scale screening tests

[0202]

[0203] It can be seen from the above table that after the sieving process, the amount of powder obtained is basically the same as that after pulverization, which further illustrates that the pulverization process is relatively ideal and of course ensures that the particle size of the product meets the requirements (since the particle size inspection has been carried out in the above pulverization process, and the texture of the drug powder has basically not changed after sieving, there is no need to conduct a particle size inspection to judge the effect of sieving).

[0204] 1.12 Molding process

[0205] The present invention selects dry granulation.

[0206] 1.13 Investigation of dry powder compressibility

[0207] Take 10kg of the clear paste concentrated under reduced pressure to a relative density of 1.02-1.10 (60°C), add dextrin at a ratio of dextrin: dry clear paste = 1:3, spray dry, and make 3.125kg of test dry paste powder. In order to determine whether auxiliary materials need to be added during the dry granulation process, the dry granulation molding condition and one-time molding rate are used as the inspection indicators to study the compressibility of the dry powder.

[0208] Take 3 portions of 200g of dry paste powder, add the medicinal material powder (yellow gelatin and tortoise shell glue powder) in the prescribed proportion, and perform dry granulation. The test results are shown in Table 1-17.

[0209] Table 1-17 Compressibility test results

[0210]

[0211] Note: Forming rate = forming particle weight / mixed powder weight × 100%

[0212] The test results show that the dry powder has good compressibility, does not stick to the roller, does not fall off and is not easy to absorb moisture, so dry granulation can be carried out without adding auxiliary materials or with a small amount of auxiliary materials.

[0213] 1.14 Selection of auxiliary materials

[0214] The properties of Chinese medicine extracts are complex and highly hygroscopic. Different excipients used in granulation will affect their properties, color, fluidity, shelf life, etc. The excipients of Chinese medicine granules usually include starch, dextrin, lactose, etc. In order to investigate the effect of the type of excipients on the preparation molding, 3 portions of dry extract powder obtained by spray drying were taken, and medicinal material powder (yellow gelatin and tortoise shell glue powder) in the prescribed proportion were added. Then, appropriate amounts of different excipients were added to adjust the preparation dosage (the preparation prescription dosage is 2137.5g of decoction pieces to make 1000g of granular finished products), and dry granulation was performed, and the process parameters were recorded. The test results are shown in Table 1-18.

[0215] Table 1-18 Granulation parameter screening results

[0216]

[0217] The test results in the table above show that when the auxiliary material is dextrin, the dry powder has good compressibility, does not stick to the roller, has no powder loss and is not easy to absorb moisture. Starch and lactose have large hygroscopicity, and lactose is expensive, so the production cost is too high. Considering the factors of formability, hygroscopicity, and economy, dextrin is selected as the excipient. The process parameters are: adding dextrin, feeding speed is 25rpm, pressing wheel speed is 1rpm, and pressing wheel spacing is 0.1mm.

[0218] 1.15 Choice of flavoring agents

[0219] A certain amount of flavor correctors can be added to the granules to improve the taste and increase the compliance of patients taking the product. The extract, extract concentrate and small test samples of the preparation were tasted by many people. Generally speaking, the taste was good and sweet, and a few people thought it was slightly bitter. Since the granules of the Chinese medicine composition are actually only slightly bitter and have acceptable palatability, there is no need for flavor correction, which can also avoid patients from misunderstanding and affecting medication. However, according to clinical recommendations, no flavor correctors are added to correct the taste.

[0220] 1.16 Mixing time investigation

[0221] Mixing is another important process in the preparation of particles. It can ensure the uniformity of batch production, make the sample color uniform, without spots and spots, and ensure the safety and effectiveness of the preparation. Take the dry paste powder obtained by spray drying, add the medicinal material powder (yellow gelatin and tortoise shell glue powder) in the prescribed proportion, and then add an appropriate amount of dextrin. Use a three-dimensional mixer to mix, observe the mixed powder every 10 minutes, and determine the mixing time.

[0222] The mixing results of three batches of small tests are shown in Table 1-19.

[0223] Table 1-19 Mixing time investigation results

[0224]

[0225] From the test results, we can see that the mixing time is 30 minutes, which can fully mix the dry paste powder and auxiliary materials, so the mixing time is determined to be 30 minutes.

[0226] 1.17 Investigation of moisture content of mixed powder

[0227] Take 0.5 kg of the mixed powder obtained in the "mixing time test" and divide it into five equal parts. Use vacuum drying or spraying 95% ethanol to obtain mixed powders with different moisture contents. Use the dry granulation conditions as an indicator to determine the moisture requirement of the mixed powder.

[0228] The test results are shown in Table 1-20.

[0229] Table 1-20 Investigation of moisture content of mixed powder

[0230]

[0231] The above test results show that in order to ensure the compressibility of the material and the controllability of the moisture content of the finished particles, the moisture content of the mixed powder should be controlled at 4.8% to 6.2%.

[0232] 1.18 Dry granulation process parameters

[0233] Take 1.2 kg of the mixed powder obtained in the "mixing time study" for dry granulation, record the process parameters, and granulate three times. Observe the dry granulation and granule properties respectively, weigh the granules and calculate the molding rate. The test results are shown in Table 1-21.

[0234] Table 1-21 Dry granulation process parameter investigation results

[0235]

[0236]

[0237] The experimental results show that the dry granulation is good, the particle shape is good, and the three-time forming rate is 97.6%.

[0238] 1.19 Selection of packaging materials

[0239] The Yiyin Anshen Fang Chinese medicine composition is a Chinese medicine granule, which is easy to absorb moisture and deteriorate, thus affecting the efficacy. Therefore, it is extremely important to select suitable packaging materials to ensure its quality. The granules are intended to use PET / AL / PE composite film as the packaging material, and the temperature is controlled at 150°C for hot pressing and sealing.

[0240] Example 2 Clinical trial results

[0241] The research team selected patients who visited the outpatient department of neurology at the First Affiliated Hospital of Soochow University from July 2021 to June 2022, and included a total of 100 cases of insomnia (yin deficiency and hyperactivity of fire syndrome) who met the criteria. The patients were randomly divided into two groups, 50 cases in each group. The two groups were given the same basic treatment, on this basis, the treatment group took oral Chinese medicine composition, and the control group took oral Shumian capsules. A four-week treatment and a three-month follow-up were carried out. After the study, the PSQI scores and TCM syndrome scores of the patients were statistically analyzed to draw conclusions.

[0242] 1 Clinical Data

[0243] 1.1 Source of cases

[0244] The subjects of this research project were all from the outpatient department of Neurology of the First Affiliated Hospital of Soochow University from July 2021 to June 2022. A total of 100 patients with insomnia (Yin deficiency and hyperactivity of fire syndrome) who met the inclusion criteria were observed and divided into two groups, treatment and control, with 50 cases in each group.

[0245] 1.2 Diagnostic criteria

[0246] 1.2.1 Western medicine diagnostic criteria

[0247] The Western medicine diagnostic criteria for this study are based on the International Classification of Sleep Disorders, Third Edition (ICSD-3). Chronic insomnia must meet all of the following AF criteria:

[0248] A. Patient reports, or parents or caregivers observe, 1 or more of the following: 1) difficulty falling asleep; 2) difficulty staying asleep; 3) waking up earlier than the desired time; 4) refusing to go to bed at an appropriate time; 5) difficulty falling asleep without a parent or caregiver;

[0249] B. Patients report, or parents or caregivers observe, one or more of the following associated with nighttime sleep difficulties: 1) fatigue or listlessness; 2) decreased attention, concentration, and memory; 3) impairment of social, family, occupational, and academic functions; 4) emotional instability or irritability; 5) daytime sleepiness; 6) behavioral problems (e.g., hyperactivity, impulsivity, or aggression); 7) decreased motivation, energy, or work initiative; 8) prone to making mistakes or accidents; 9) very concerned about or dissatisfied with the quality of their sleep;

[0250] C. These sleep / wake complaints cannot be fully explained by inadequate sleep opportunity (e.g., insufficient sleep time) or environment (e.g., dark, quiet, safe, comfortable environment);

[0251] D. These sleep conditions and related daytime symptoms occur at least 3 times per week;

[0252] E. These sleep difficulties and related daytime symptoms persist for at least 3 months;

[0253] F. These sleep difficulties and related daytime symptoms are not better explained by another sleep disorder. Short-term insomnia differs in that the duration is less than 3 months and there is no frequency requirement, but is otherwise similar.

[0254] 1.2.2 TCM diagnostic criteria

[0255] The TCM diagnostic criteria for this research project are based on the TCM Clinical Practice Guidelines for Insomnia (WHO / WPO)

[0256] Combined with the functions and indications of the experimental drug, Yin deficiency and hyperactivity of fire syndrome is the indication. Any one of the main symptoms is sufficient, and at least two of the secondary symptoms must be present, and combined with the patient's tongue coating and pulse condition, it can be identified as the main syndrome.

[0257] Main symptoms: insomnia due to weakness and restlessness, difficulty falling asleep, restless sleep, or even difficulty sleeping all night.

[0258] Secondary symptoms: hot palms and soles, night sweats, dry mouth, forgetfulness, tinnitus, backache, nocturnal emission, palpitations and restlessness. Tongue and pulse: red tongue with little coating and fine pulse.

[0259] 1.2.3 Criteria for inclusion of cases

[0260] ① Meet the Chinese and Western medicine diagnosis in 1.2.1 above;

[0261] ② Meet the TCM diagnosis in 1.2.2 above;

[0262] ③Pittsburgh Sleep Quality Index (PSQI) total score ≥ 7 points;

[0263] ④ Hamilton Depression Rating Scale 24 (HAMD) score < 8 points;

[0264] ⑤ Hamilton Anxiety Scale 14-item (HAMA) score <14 points;

[0265] ⑥ Aged between 18 and 70 years old;

[0266] ⑦ The subjects volunteered to participate and signed the informed consent.

[0267] 1.2.4 Exclusion criteria

[0268] ① Any secondary insomnia caused by physical illness, surgery, mental illness, etc.;

[0269] ② Patients with serious primary diseases such as cardiovascular, cerebrovascular, lung, liver, kidney, endocrine and hematopoietic system;

[0270] ③ Those suffering from mental disorders or having a family history of mental illness;

[0271] ④ Those with sleep apnea syndrome;

[0272] ⑤ Insomnia caused by interference from external environmental factors such as work and life;

[0273] ⑥Breastfeeding women, pregnant women and women who are planning to become pregnant;

[0274] ⑦ Drug abusers and addicts, as well as those who are allergic to or have adverse reactions to the drugs in this study;

[0275] ⑧ The patient is an alcoholic and / or psychoactive drug user;

[0276] 1.2.5 Elimination criteria

[0277] ① Those who are not suitable to continue the trial: special physiological changes or serious adverse events occur during the observation study;

[0278] ② Poor compliance: Failure to take study drugs as required, use of drugs not included in the study, etc.;

[0279] ③Those who requested to withdraw or were lost to follow-up due to various reasons;

[0280] ④ Mistaken inclusion: not meeting the inclusion criteria or meeting the exclusion criteria;

[0281] ⑤ Natural dropouts: no usable data can be collected during the observation process or the data have logical inconsistencies;

[0282] 2 Research Methods

[0283] 2.1 Clinical Grouping

[0284] The 100 patients were randomly divided into a control group and a treatment group, with 50 patients in each group. All subjects were trained and understood the form filling method.

[0285] 2.2 Experimental plan

[0286] 2.2.1 Group treatment

[0287] Treatment group: basic treatment + oral Chinese medicine combination.

[0288] Control group: basic treatment + oral Shumian capsules.

[0289] 2.2.2 Basic treatment

[0290] Sleep health education: popularize sleep-related knowledge to the patients, mainly including forming a good work and rest routine, creating a suitable sleeping environment, maintaining a normal sleeping mentality, reducing the anxiety caused by insomnia in patients, and enhancing their confidence in treating insomnia.

[0291] 2.2.3 Study treatment

[0292] 1) Control group drug: Shumian Capsules, approval number: National Medicine Standard Z20000105, manufacturer: Guizhou Dalong Pharmaceutical Co., Ltd., dosage form: capsules, specification: 0.4 grams per capsule. Usage and dosage: Oral, 3 capsules at a time, twice a day; take once after dinner and before going to bed, the course of treatment is 4 weeks.

[0293] 2) Treatment group drugs: Chinese medicine composition, the formula is as follows: 15g of Rehmannia root, 12g of Ophiopogon japonicus, 7.5g of stir-fried Ziziphus jujuba seeds, 12g of Poria cocos, 7.5g of Poria cocos, 7.5g of Polygala tenuifolia, 15g of stir-fried Chinese yam with bran, 3g of Schisandra chinensis with vinegar, 3g of Tortoise shell glue, 3g of yellow gelatin. Dosage: Take with warm water, 20g / time; take once after dinner and before going to bed, the course of treatment is 4 weeks.

[0294] 2.2.4 Research time

[0295] Treatment: Treatment lasts for 4 weeks.

[0296] Follow-up: Follow-up was conducted 3 months after the treatment.

[0297] 2.3 Observation Record Content

[0298] 2.3.1 Basic Information

[0299] (1) Collect and record the name, first visit date, gender, age, outpatient card number, and contact information (mainly mobile phone number and WeChat ID) of the patients participating in this study;

[0300] (2) Observe and record the changes in the subjects' conditions during the study, including medical history, symptoms and signs;

[0301] 2.3.2 Safety observation:

[0302] (1) Blood pressure, respiration, heart rate, pulse, etc. are used as data to observe drug safety and are measured once before and after treatment;

[0303] (2) Liver and kidney function, blood, urine and stool routine tests, electrocardiogram, etc. should be checked once before and after treatment if necessary.

[0304] (3) During the study, attention should be paid to possible adverse reactions and discomfort reactions of the subjects, and they should be tested using relevant scales. If any abnormality is found, the study should be terminated immediately and relevant treatment should be given in a timely manner. If necessary, the subjects should be referred to a specialist hospital for diagnosis and treatment, and detailed records should be kept of the above situations.

[0305] 2.3.3 Observation of efficacy

[0306] (1) TCM syndrome scores before treatment, 4 weeks after treatment, and 3 months after follow-up.

[0307] (2) PSQI scores before treatment, 4 weeks after treatment, and 3 months after follow-up.

[0308] 2.4 Efficacy determination

[0309] 2.4.1 Main standards

[0310] Western medicine completes clinical efficacy evaluation based on the PSQI scale scores.

[0311] Recovery: The original insomnia symptoms are significantly improved, the sleep time is extended to normal, the sleep is deep, the energy is good after waking up, and the main symptoms disappear; the PSQI score index rate is ≥75%.

[0312] Markedly effective: Insomnia symptoms were significantly improved, with most of the main clinical symptoms disappearing, and the PSQI score index rate was 50%≤<75%.

[0313] Effective: Insomnia symptoms improved, sleep time prolonged, but not reaching normal sleep time, PSQI score index rate 25%≤<50%.

[0314] Ineffective: There is no significant improvement in insomnia symptoms, and the PSQI score index rate is <25%.

[0315] PSQI score index rate = (PSQI score before treatment - PSQI score after treatment) / PSQI score before treatment × 100%.

[0316] 2.4.2 Secondary standards

[0317] Syndrome efficacy is a secondary criterion in this research, referring to the "Guidelines for Clinical Research of New Chinese Medicines (Trial)"

[10] Evaluate the corresponding content in the score sheet and calculate according to the score sheet:

[0318] Recovery: TCM symptom score reduction rate ≥ 95%).

[0319] Markedly effective: reduction rate of TCM syndrome scores ≥70%).

[0320] Effective: TCM syndrome score reduction rate ≥30%).

[0321] Ineffective: TCM syndrome score reduction rate <30%).

[0322] 2.5 Statistical analysis

[0323] SPSS22.0 statistical software was used, and the count data were tested with the X2 test. If p < 0.05, the difference was significant;

[0324] The measurement data were described by mean and standard deviation (x±s), and the t test or rank sum test was used; the rank sum test was used for the ordinal data, and p<0.05 indicated statistical significance.

[0325] 3 Basic data comparison

[0326] All 100 patients in this study completed treatment and follow-up, and there was no dropout. There were 14 males and 36 females in the treatment group, with the oldest age of 68 and the youngest age of 25, and the average age of 49.06±11.39; there were 19 males and 31 females in the control group, with the oldest age of 66 and the youngest age of 26, and the average age of 45.44±12.07; after statistical analysis, there was no difference in the baseline data of gender, age, and pre-treatment scale scores between the two groups (P>0.05), so they are equally comparable, as shown in the table below.

[0327] 3.1 Gender

[0328] Table 2-1 Comparison of gender distribution of patients in the two groups

[0329]

[0330] Note: The X2 test showed that P = 0.316 (P > 0.05), indicating no statistically significant difference. In terms of gender, there was no difference in the distribution of patients between the two groups, and they can be compared, as shown in Table 2-1.

[0331] 3.2 Age

[0332] Table 2-2 Comparison of age distribution of patients in the two groups

[0333]

[0334] Note: According to the rank sum test, P=0.290 (P>0.05), there is no statistical difference. There is no difference in age composition and distribution between the two groups, so they can be compared, as shown in Table 2-2.

[0335] 3.3 PSQI score before treatment

[0336] Table 2-3 Comparison of PSQI scores between the two groups before treatment

[0337]

[0338] Note: Normality test: W = 0.957, P = 0.168 (P > 0.05), t test, t = -0.193, P = 0.848 (P > 0.05), there is no statistical difference, which can be compared, as shown in Table 2-3.

[0339] 3.4 TCM syndrome score before treatment

[0340] Table 2-4 Comparison of TCM syndrome scores between the two groups of patients before treatment

[0341]

[0342] Note: Normality test: W = 0.952, P = 0.121 (P > 0.05), showing normal distribution. After t-test, t = -0.188, P = 0.852 (P > 0.05), there is no statistical difference, which can be compared, as shown in Table 2-4.

[0343] 4 Comparison of clinical efficacy

[0344] 4.1 Comparison of PSQI scores before and after treatment

[0345] Table 2-5 Comparison of PSQI scores before and after treatment

[0346]

[0347] Note: 1) Intra-group comparison in the treatment group: W = 0.868, P = 0.001 (P < 0.05), non-normal, rank sum test, Z = -5.253, P = 0.00 (P < 0.05), there is a statistical difference, and the drugs in the treatment group can improve sleep quality, as shown in Table 2-5.

[0348] 2) Comparison within the control group: W = 0.921, P = 0.013 (P < 0.05), non-normal, rank sum test, z = -5.242, P = 0.00 (P < 0.05), there is a statistical difference, the control group drug can improve sleep quality, as shown in Table 2-5.

[0349] 3) Comparison between the two groups, z = -2.664, P = 0.008 (P < 0.05), there was a statistically significant difference. In terms of improving sleep quality, the treatment group was better than the control group, as shown in Table 2-5.

[0350] 4.2 Comparison of TCM Syndromes

[0351] Table 2-6 Comparison of TCM syndrome scores before and after treatment

[0352]

[0353] Note: 1) Intra-group comparison in the treatment group: P = 0.000 (P < 0.05), non-normal, rank sum test, z = -5.249, P = 0.00 (P < 0.05), statistically significant, the drugs in the treatment group can improve the TCM symptoms, as shown in Table 2-6.

[0354] 2) Comparison within the control group: P = 0.009 (P < 0.05), non-normal, rank sum test, z = -5.241, P = 0.000 (P < 0.05), there is a statistical difference, the drugs in the control group can improve the TCM symptoms, as shown in Table 6.

[0355] 3) Comparison between the groups, z = -2.562, P = 0.010 (P < 0.05). The treatment group was superior to the control group in improving TCM symptoms, as shown in Table 2-6.

[0356] 4.3 Comparison of effective rate

[0357] According to the previous 2.4.1, the sleep quality effectiveness rate of the treatment group was 91.67%, and that of the control group was 83.33%.

[0358] Table 2-7 Comparison of sleep quality between the two groups of patients after treatment

[0359]

[0360] Note: According to the rank sum test: z = -2.276, P = 0.023 (P < 0.05), there is a statistical difference, and the sleep quality effect of the treatment group is better than that of the control group. See Table 2-7.

[0361] Table 2-8 Comparison of the efficacy of TCM symptoms after treatment in the two groups of patients

[0362]

[0363] Note: According to the rank sum test: z = -2.082, P = 0.037 (P < 0.05), there is a statistical difference, and the symptom efficacy of the treatment group is better than that of the control group. See Table 2-8.

[0364] 5 Follow-up comparison

[0365] 5.1 Comparison of PSQI scores after 3-month follow-up

[0366] Table 2-9 Comparison of PSQI scores between the two groups before treatment and after 3 months of follow-up

[0367]

[0368] Note: 1) Intra-group comparison in the treatment group: W = 0.893, P = 0.002 (P < 0.05), non-normal, rank sum test, Z = -1.825, P = 0.068 (P > 0.05), no statistical difference; Intra-group comparison in the control group: W = 0.903, P = 0.004 (P < 0.05), non-normal, rank sum test, Z = -4.162, P = 0.000 (P < 0.05), there is a statistical difference, indicating that in terms of improving sleep quality, the long-term efficacy of the treatment group drugs is stable. As shown in Table 2-9.

[0369] 2) Intergroup comparison: W = 0.977, P = 0.653 (P > 0.05), normal, t test, t = -3.082, P = 0.015 (P < 0.05), there is a statistical difference, indicating that in terms of improving the sleep quality of patients, the long-term effect of the treatment group drugs is more stable than that of the control group drugs. See Table 2-9.

[0370] 5.2 TCM syndrome score after 3-month follow-up

[0371] Table 2-10 Comparison of TCM syndrome scores between the two groups of patients after treatment and 3 months of follow-up

[0372]

[0373] Note: 1) Intra-group comparison in the treatment group: W = 0.902, P = 0.004 (P < 0.05), non-normal, rank sum test, Z = -1.896, P = 0.058 (P > 0.05), no statistical difference; intra-group comparison in the control group: rank sum test, Z = -4.146, P = 0.000 (P < 0.05), statistical difference. This shows that in terms of improving TCM syndromes, the long-term efficacy of the drugs in the treatment group is more stable than that of the drugs in the control group. As shown in Table 2-10.

[0374] 2) Intergroup comparison: W = 0.959, P = 0.019 (P < 0.05), non-normal, t test, t = -2.998, P = 0.003 (P < 0.05), there is a statistical difference, indicating that in terms of improving TCM symptoms, the long-term effect of the treatment group is more stable. See Table 2-10.

[0375] 5.3 Comparison of follow-up efficacy between groups

[0376] Table 2-11 Comparison of sleep quality effectiveness between the two groups of patients after 3-month follow-up

[0377]

[0378] Note: Rank sum test: z = -2.964, P = 0.003 (P < 0.05) has statistical significance, indicating that after three months of follow-up, the long-term efficacy of the treatment group in improving sleep quality is better than that of the control group. See Table 2-11.

[0379] Table 2-12 Comparison of the effectiveness of TCM syndromes in the two groups of patients after 3-month follow-up

[0380]

[0381] Note: Rank sum test: z = -2.417, P = 0.016 (P < 0.05) has statistical significance, indicating that after three months of follow-up, the long-term efficacy of the treatment group in improving TCM syndromes is better than that of the control group. See Table 2-12.

[0382] 6. Trial safety and adverse reaction monitoring

[0383] (1) No adverse reactions occurred in either group during medication or during follow-up.

[0384] (2) Three months after stopping the medication, statistical analysis was performed on the patients' TCM syndrome scores and PSQI scores. The vast majority of patients had no dependence after stopping the medication and no adverse reactions after stopping the medication.

[0385] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A Chinese medicine composition, characterized in that: The invention comprises the following raw materials in parts by weight: 355-400 parts of Radix Rehmanniae; 355-400 parts of Rhizoma Dioscoreae Rhizoma; 285-315 parts of Radix Ophiopogonis; 285-315 parts of Poria; 175-200 parts of Poria; 175-200 parts of honey Polygala; 175-200 parts of stir-fried Ziziphus jujuba seeds; 70-80 parts of vinegar schisandra chinensis; 70-80 parts of tortoise shell glue; 70-80 parts of yellow gelatin.

2. The composition according to claim 1, characterized in that The Chinese medicine composition comprises the following raw materials in parts by weight: 360-390 parts of Radix Rehmanniae; 360-390 parts of Rhizoma Dioscoreae Rhizoma; 290-310 parts of Radix Ophiopogonis; 290-310 parts of Poria; 180-190 parts of Poria; 180-190 parts of honey Polygala; 180-190 parts of stir-fried Ziziphus jujuba seeds; 72-78 parts of vinegar schisandra chinensis; 72-78 parts of tortoise shell glue; 72-78 parts of yellow gelatin.

3. The composition according to claim 2, characterized in that The tortoise shell glue is tortoise shell glue fine powder; the yellow gelatin is yellow gelatin fine powder.

4. A method for preparing a Chinese medicine composition according to any one of claims 1 to 3, characterized in that: include: A) mixing raw rehmannia root, fried yam with bran, ophiopogon japonicus, tuckahoe, poria, honey polygala root, fried spiny jujube seeds and vinegar schisandra chinensis, soaking in water, decocting, filtering to obtain a filtrate, and concentrating to obtain an extract; B) mixing the extract and dextrin, and drying to obtain dry extract powder; C) Mix the dry extract powder, dextrin, yellow gelatin powder and tortoise shell glue powder to obtain the product.

5. The preparation method according to claim 4, characterized in that: Step A) The number of times of decoction is 1 to 3 times; The mass ratio of the total amount of the raw rehmannia root, fried yam with bran, ophiopogon japonicus, tuckahoe, poria, honey polygala root, fried spiny jujube seeds and vinegar schisandra chinensis mixed with water is 1: (9-11); The soaking time is 0.5 to 1.3 hours; the decoction time is 0.5 to 1.3 hours; The filtration is carried out using a 100-mesh stainless steel mesh.

6. The preparation method according to claim 4, characterized in that: The concentration in step A) is specifically: 60-80° C., vacuum degree -0.08-0.04 Mpa; the relative density of the extract is 1.02-1.

1.

7. The preparation method according to claim 4, characterized in that: In step B), the mass ratio of dextrin to extract is (8-16):(100-102), and the mass ratio of dextrin to dry extract is (1-3):

3.

8. The preparation method according to claim 4, characterized in that: The drying method in step B) is spray drying; the air inlet temperature of the spray drying is 170-180°C; the liquid inlet speed is 27Hz; The mixing time in step C) is 30 to 40 minutes.

9. Use of the composition according to any one of claims 1 to 3 or the composition prepared by the preparation method according to any one of claims 4 to 8 in the preparation of a drug; the efficacy of the drug includes treating at least one of insomnia, palpitations, forgetfulness, anxiety, irritability, neurasthenia or menopausal syndrome.

10. A drug, characterized in that The invention comprises the composition according to any one of claims 1 to 3 or the composition prepared by the preparation method according to any one of claims 4 to 8.

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