CN114788845A - Traditional Chinese medicine composition with sleep improving effect and preparation method and application thereof - Google Patents

Traditional Chinese medicine composition with sleep improving effect and preparation method and application thereof Download PDF

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CN114788845A
CN114788845A CN202110114474.9A CN202110114474A CN114788845A CN 114788845 A CN114788845 A CN 114788845A CN 202110114474 A CN202110114474 A CN 202110114474A CN 114788845 A CN114788845 A CN 114788845A
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sleep
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chinese medicine
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不公告发明人
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Sichuan Fushengyuan Technology Co ltd
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Sichuan Fushengyuan Technology Co ltd
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
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    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
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    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/734—Crataegus (hawthorn)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying

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Abstract

The invention provides a traditional Chinese medicine composition with a sleep improving effect and a preparation method thereof, wherein the traditional Chinese medicine composition comprises the following raw material medicines in parts by weight: 3-30 parts of salvia miltiorrhiza, 2-25 parts of pseudo-ginseng, 3-30 parts of bighead atractylodes rhizome and 1-25 parts of hawthorn. The pharmacological experiment result of the traditional Chinese medicine composition provided by the invention shows that the traditional Chinese medicine composition can obviously improve sleep, and has no toxic or side effect after being taken for a long time.

Description

Traditional Chinese medicine composition with sleep improving effect and preparation method and application thereof
Technical Field
The invention relates to a traditional Chinese medicine composition or a health-care product composition, in particular to a traditional Chinese medicine composition with a function of improving sleep and a preparation method and application thereof.
Background
Insomnia is characterized by loss of normal sleep due to emotional, dietary internal injury, after illness and old age, deficient endowment, deficiency of heart and timidity and other causes, and loss of nourishment or uneasiness. The symptoms of insufficient sleeping time and depth, incapability of eliminating fatigue and recovering physical strength and energy, difficulty in sleeping for light people, or sleep soundly, waken when sleeping, or sleep incapability after waking, and insomnia all the night when sleeping. As one of the common clinical symptoms, insomnia is not a critical disease, but often obstructs normal life, work, study and health of people, and aggravates or induces symptoms such as palpitation, thoracic obstruction, vertigo, headache and apoplexy. Intractable insomnia can bring long-term pain to patients, even form dependence on hypnotic drugs, and iatrogenic diseases can be caused by long-term administration of the hypnotic drugs.
According to statistics of 'sleeping white skin book', the insomnia rate of adults in China is up to 38%, and many people suffer from a plurality of related diseases due to long-term insomnia. Sleep disorder has become a killer of human beings, and brings great hidden danger to life, work and study of people. At present, various popular sleep improving products in the market are mainly sedative hypnotics and melatonin traditional Chinese medicine compositions. Currently, hypnotics commonly used in clinic include benzodiazepines, barbiturates and other non-barbiturates, the effect of treating insomnia is obvious, but the hypnotics have great influence on liver and kidney, so that a user is easy to have dependence on the medicine, the effect can be maintained by increasing the medicinal dosage continuously, and great toxic and side effects are generated, and the hypnotic is not a medicine suitable for long-term administration. The sleep improving effect of melatonin is not clear, and long-term or high-dose administration of melatonin may cause harm to human bodies, such as obvious inhibition of the functions of human reproductive systems. If melatonin is left in large amount in the daytime, middle-aged and old people (due to reduced melatonin secretion) have side effects of dizziness, unstable walking and the like, and may bring danger to the elderly and weak people.
The traditional Chinese medicine considers that insomnia has two types of deficiency and excess, which are caused by the dysfunction of qi and blood and viscera in the organism. Therefore, for treating insomnia, the traditional Chinese medicine is popular because the traditional Chinese medicine regulates and treats internal organs to harmonize qi and blood, balance yin and yang and normalize the functions of internal organs, can obviously improve sleep symptoms and does not cause medicine dependence and iatrogenic diseases. Therefore, on the basis of the traditional Chinese medicine theory, the development of the traditional Chinese medicine composition capable of safely and effectively improving sleep has important significance in solving the sleep trouble of insomnia people.
Disclosure of Invention
The invention aims to provide a traditional Chinese medicine composition with the function of improving sleep, which is prepared from natural plants, has no toxic or side effect on a human body and can be taken for a long time.
The invention also aims to provide a preparation method and application of the traditional Chinese medicine composition.
The invention relates to a traditional Chinese medicine composition with sleep improvement effect, which comprises the following components: red sage root, notoginseng, white atractylodes rhizome and haw.
The traditional Chinese medicine composition with the sleep improving effect is prepared from the following traditional Chinese medicine raw materials: red sage root, notoginseng, white atractylodes rhizome and haw.
Insomnia refers to frequent poor sleep, which is difficult to fall asleep after getting to bed, shallow sleep and easy to wake up, and is caused by imbalance of excitation and inhibition processes of the central nervous system. The disease belongs to the categories of insomnia and insomnia in traditional Chinese medicine. The traditional Chinese medicine considers that the heart governs the mind and the mind cannot sleep if the mind does not enter the house, namely if the heart cannot be sufficiently supplied, the heart and blood deficiency can cause palpitation, shortness of breath and drowsiness; the spleen governs transportation and transformation, the transportation and transformation function is abnormal, the function of nutrient delivery and heart nourishing is poor, the heart is lack of nutrient supply, and the sleep is not achieved when the spirit fails to enter the house; "liver stores blood, blood sheds soul", liver stores blood, but soul gives up blood, so it can be considered that soul belongs to liver, if liver blood is insufficient, people will have soul not keep, dreaminess fighting 32429. The invention is based on the theory of traditional Chinese medicine, takes four traditional Chinese medicines of salvia miltiorrhiza, bighead atractylodes rhizome, pseudo-ginseng and hawthorn as raw materials, and the medicines are scientifically compounded and mutually cooperated to play the effects of tonifying heart and spleen, nourishing heart, soothing nerves, soothing liver, nourishing blood, promoting blood circulation, removing blood stasis, harmonizing stomach and resolving stagnation, thereby fundamentally solving the intrinsic cause of insomnia. In the formula, the salvia miltiorrhiza has the effects of entering heart and liver channels, activating blood and dissolving stasis, stimulating the menstrual flow and relieving pain, clearing away heart-fire and relieving restlessness, and has the effects of activating blood and dissolving stasis, calming nerves and calming heart; the pseudo-ginseng enters liver and stomach channels and has the effects of removing blood stasis, stopping bleeding, promoting blood circulation and relieving pain, and the pseudo-ginseng and the stomach channels are monarch drugs and play the effects of nourishing heart, soothing nerves, soothing liver and nourishing blood together. The bighead atractylodes rhizome has the functions of tonifying spleen and stomach, strengthening spleen and replenishing qi, eliminating dampness and promoting diuresis and the like, the hawthorn has the functions of promoting digestion and invigorating stomach, and promoting qi circulation and dissipating blood stasis and the like, and the hawthorn and the spleen and stomach have the functions of tonifying spleen to nourish heart, harmonizing stomach to remove stagnation, and nourishing liver to nourish blood. The raw materials of the product are compatible and supplement each other to achieve the effect of improving sleep.
A traditional Chinese medicine composition with sleep improvement effect comprises the following raw materials in parts by weight:
3-30 parts of salvia miltiorrhiza, 2-25 parts of pseudo-ginseng, 3-30 parts of bighead atractylodes rhizome and 1-25 parts of hawthorn.
As a preferred scheme, the weight ratio of each raw material medicine is as follows:
6-25 parts of salvia miltiorrhiza, 5-20 parts of pseudo-ginseng, 6-25 parts of bighead atractylodes rhizome and 3-20 parts of hawthorn.
As a further preferred scheme, the weight ratio of each raw material medicine is as follows:
10-20 parts of salvia miltiorrhiza, 10-18 parts of pseudo-ginseng, 10-20 parts of bighead atractylodes rhizome and 8-15 parts of hawthorn.
The weight ratio of each raw material medicine is also preferably as follows:
12 parts of salvia miltiorrhiza, 20 parts of pseudo-ginseng, 18 parts of bighead atractylodes rhizome and 24 parts of hawthorn.
The weight ratio of each raw material medicine is also preferably as follows:
15 parts of salvia miltiorrhiza, 15 parts of pseudo-ginseng, 15 parts of bighead atractylodes rhizome and 15 parts of hawthorn.
The weight ratio of each raw material medicine is also preferably as follows:
18 parts of salvia miltiorrhiza, 12 parts of pseudo-ginseng, 30 parts of bighead atractylodes rhizome and 2 parts of hawthorn.
The weight ratio of each raw material medicine is also preferably as follows:
30 parts of salvia miltiorrhiza, 18 parts of pseudo-ginseng, 6 parts of bighead atractylodes rhizome and 10 parts of hawthorn.
The weight ratio of each raw material medicine is also preferably as follows:
3 parts of salvia miltiorrhiza, 25 parts of pseudo-ginseng, 21 parts of bighead atractylodes rhizome and 20 parts of hawthorn.
The weight ratio of each raw material medicine is also preferably as follows:
25 parts of salvia miltiorrhiza, 3 parts of pseudo-ginseng, 25 parts of bighead atractylodes rhizome and 6 parts of hawthorn.
The weight ratio of each raw material medicine is also preferably as follows:
6 parts of salvia miltiorrhiza, 6 parts of pseudo-ginseng, 3 parts of bighead atractylodes rhizome and 18 parts of hawthorn.
The traditional Chinese medicine composition with the sleep improving effect can be prepared into decoction, tea, oral liquid, syrup, ointment, powder, granules, capsules, tablets or pills by adding pharmaceutically or health-care product acceptable carriers to each raw medicinal material or extract thereof.
The composition of the raw medicinal materials or the composition of the extract thereof can also be added with any other medicinal or edible components or medicinal materials, and the mixture is processed and then prepared into tea, oral liquid, syrup, paste, powder, granules, capsules, tablets or pills with pharmaceutically acceptable carriers; the processing includes, but is not limited to, slicing, pulverizing into powder, and extracting and obtaining the extract.
The preparation method of the traditional Chinese medicine composition comprises the following process steps:
A. adding ethanol into Saviae Miltiorrhizae radix and Notoginseng radix, heating and reflux extracting to obtain ethanol extractive solution;
B. b, adding water into the dregs of the decoction, the bighead atractylodes rhizome and the hawthorn fruit which are extracted by the ethanol in the step A, and heating and extracting to obtain a water extracting solution;
C. concentrating the ethanol extract in the step A until no ethanol smell exists, concentrating the water extract in the step B, and mixing to obtain an extract concentrate;
D. and C, preparing the extract concentrate obtained in the step C and a pharmaceutically acceptable carrier into a preparation.
Preferably, the preparation method of the traditional Chinese medicine composition with the sleep improvement effect is characterized by comprising the following steps:
A. taking the salvia miltiorrhiza and the pseudo-ginseng, adding 10-90% ethanol (volume concentration) which is 1-10 times of the weight of the medicinal materials, heating, refluxing and extracting for 1-3 times, each time for 1-3 hours, mixing to obtain an ethanol extract, and recovering the ethanol;
B. b, taking the dregs of the decoction extracted by the ethanol in the step A, the bighead atractylodes rhizome and the hawthorn, adding water which is 1-15 times of the total weight of the medicinal materials, heating and extracting for 1-3 times, and mixing to obtain a water extract;
C. concentrating the alcohol extract obtained in the step A until the equivalent of the medicinal materials is 0.6-2: 1, concentrating the water extract obtained in the step B until the equivalent of the medicinal materials is about 0.6-2: 1, mixing, and continuously concentrating until the equivalent of the medicinal materials is about 0.8-2: 1;
D. and D, combining the extract concentrate obtained in the step C with one or more of sucrose powder, starch, microcrystalline cellulose, chitosan, mannitol, sorbitol, xylitol, sucralose, dextrin and the like, and preparing oral liquid, syrup, paste, granules, capsules, tablets or pills.
As a more preferable scheme, the preparation method of the traditional Chinese medicine composition with the sleep improvement effect comprises the following steps:
extracting Saviae Miltiorrhizae radix and Notoginseng radix with 5 times of 50% ethanol under reflux for 2 times (each for 2 hr), and mixing to obtain ethanol extractive solution;
b, taking the ethanol extraction dregs in the step A, the bighead atractylodes rhizome and the hawthorn, adding water which is 10 times of the total weight of the medicinal materials, heating, decocting and extracting for 2 times, 2 hours each time, and mixing to obtain a water extract;
in the step C, the alcohol extract in the step A is concentrated until the equivalent of the medicinal materials is 0.8:1, the water extract in the step B is concentrated until the equivalent of the medicinal materials is about 1:1, and after mixing, the alcohol extract is continuously concentrated until the equivalent of the medicinal materials is about 1.2: 1.
Has the beneficial effects that: compared with the prior art, the traditional Chinese medicine composition with the function of improving sleep and the preparation method thereof provided by the invention have the following advantages:
the invention preferably obtains the traditional Chinese medicine composition with the optimal formula ratio through a large number of experiments according to the theory of treatment based on syndrome differentiation of traditional Chinese medicines, and the traditional Chinese medicine composition is rigorous in medication and scientific and reasonable in ratio.
The formulation composition and dosage screening test results show that: the incomplete composition of each formula is similar to a negative control group (sterile water), the effect of prolonging the sleep time of a pentobarbital sodium induced mouse is avoided, and all components in the composition are necessary components for improving the sleep of the composition; within the scope of the prescription claimed in the claims, the compositions of the invention all have the effect of prolonging the sleep time of the mice induced by pentobarbital sodium, and the effect is gradually enhanced as the prescription dosage increases until the corresponding threshold (the dosage of group 8) is reached, and the effect of continuously increasing the prescription dosage after reaching the threshold has no obvious effect on improving the effect of promoting sleep.
According to the invention, the optimal extraction and separation method is screened out through a large number of experiments according to the physicochemical properties of the medicinal materials, the extraction process is reasonable, the operability is strong, the content of the extracted effective components is high, and the impurities are few.
The pharmacological experiment result of the traditional Chinese medicine composition provided by the invention shows that the traditional Chinese medicine composition can obviously improve sleep, and has no toxic or side effect after being taken for a long time.
The test for improving the sleep function comprises the following steps: the traditional Chinese medicine composition oral liquid is taken for a month in three dosage groups of 2.5ml/kg/d, 5ml/kg/d and 10ml/kg/d, and a direct sleep experiment, a pentobarbital sodium sleep time prolonging experiment, a pentobarbital sodium subthreshold dosage sleep experiment and a barbital sodium sleep latency experiment are carried out. The results show that the oral liquid of the traditional Chinese medicine composition has no direct sleep effect on mice in groups of 2.5ml/kg/d, 5ml/kg/d and 10 ml/kg/d. The sleep time of mice in each group is obviously longer than that of the group of 0ml/kg/d, and the difference has statistical significance (P is less than 0.05); the animal sleep incidence rates of the groups of 2.5ml/kg/d, 5ml/kg/d and 10ml/kg/d are obviously increased compared with the group of 0ml/kg/d, wherein the increase of the animal sleep incidence rate of the group of 10ml/kg/d and the group of 0ml/kg/d has statistical significance. The sleep latency of mice in each administration group was significantly shorter than that in the 0ml/kg/d group, and the differences between the 5ml/kg/d and 10ml/kg/d groups were statistically significant (P < 0.05). According to the test result of the sleep improvement function of the health food inspection and evaluation technical specification, the traditional Chinese medicine composition has the function of improving sleep.
Acute oral toxicity test and 30-day feeding test: the traditional Chinese medicine composition provided by the invention is used for female and male mice to have acute oral MTD of more than 22400mg/kg, and belongs to a non-toxic grade according to the grading standard of acute toxicity dosage.
The traditional Chinese medicine composition is administered to rats for 30 days at the doses of 6.0mg/kg/d, 12mg/kg/d and 20.0mg/kg/d (which are 15 times, 30 times and 50 times of the recommended dose of a human body), the tested animals have good general conditions, and the results of body weight, hematology indexes and biochemical indexes show that all indexes are in a normal range. According to the 30-day feeding test of health food inspection and evaluation technical Specification (2003 edition) of Ministry of health, no harmful effect is observed when the traditional Chinese medicine composition of the invention is administered to animals and human bodies with the recommended dosage of 50 times.
The invention also performs a human body feeding trial experiment for improving sleep by the traditional Chinese medicine composition, and the result of the sleep improvement experiment shows that the clinical symptom integral is obviously reduced (P is less than 0.01) by comparing the traditional Chinese medicine composition before and after the feeding trial of a feeding trial group and between a control group, the sleep condition of the crowd of the feeding trial group is obviously improved, other side effects are not reported, and the function of improving sleep by the traditional Chinese medicine composition is shown.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the invention thereto. Various insubstantial modifications of the invention, as viewed by a person skilled in the art after reading the present disclosure, fall within the scope of the claims as set forth herein.
The equivalent weight of the traditional Chinese medicine in the invention refers to the weight ratio of the unit weight of the traditional Chinese medicine to the extracted concentrated solution or extract, and if the equivalent weight of the traditional Chinese medicine is 2:1, the traditional Chinese medicine indicates that 1 part by weight of concentrated solution or extract is obtained after 2 parts by weight of the traditional Chinese medicine is extracted. "parts" as used herein refers to parts by weight, which can be understood as an integral multiple of a unit mass such as grams, kilograms, for example: 1 part to 1 g; 1 part-25 g; 1 part-300 g; 1 part is 1 kg; 12kg in 1 portion; 50kg, etc.
Example 1
The invention relates to a Chinese medicinal composition tea preparation
1. Parts by weight of raw materials
3g of salvia miltiorrhiza, 2g of pseudo-ginseng, 3g of bighead atractylodes rhizome and 1g of hawthorn.
2. Preparation steps
(1) Taking the salvia miltiorrhiza, the pseudo-ginseng, the bighead atractylodes rhizome and the hawthorn in parts by weight, cutting into slices of 2mm or crushing into particles which are sieved by a 10-mesh sieve;
(2) and (2) taking the slices or the crushed particles of the medicinal materials cut in the step (1), adding 100ml of boiled water, and soaking for 20 minutes to obtain the tea (the tea can be repeatedly brewed for 3-5 times).
Example 2
The Chinese medicinal composition powder of the invention
1. Raw materials in parts by weight
6g of salvia miltiorrhiza, 6g of pseudo-ginseng, 3g of bighead atractylodes rhizome and 18g of hawthorn.
2. Preparation procedure
Pulverizing Saviae Miltiorrhizae radix, Notoginseng radix, Atractylodis rhizoma and fructus crataegi in the above weight parts into 100 mesh fine powder; subpackaging to obtain the powder of the composition.
Example 3
The Chinese medicinal composition oral liquid of the invention
1. Parts by weight of raw materials
12kg of salvia miltiorrhiza, 20kg of pseudo-ginseng, 18kg of bighead atractylodes rhizome and 24kg of hawthorn.
2. Preparation steps
(1) Extracting Saviae Miltiorrhizae radix and Notoginseng radix with 160kg 50% ethanol (volume concentration) under reflux for 2 times (each for 2 hr), and mixing to obtain ethanol extractive solution;
(2) mixing the ethanol extraction residue of step (1), Atractylodis rhizoma and fructus crataegi with 740kg water, heating, decocting and extracting for 2 times, each for 2 hr, and mixing to obtain water extractive solution;
(3) concentrating the ethanol extractive solution until no ethanol smell exists, further concentrating to 53kg (about 0.6:1 equivalent of medicinal material), concentrating the water extractive solution to 123kg (about 0.6:1 equivalent of medicinal material), mixing with the ethanol extractive solution, and further concentrating to 92.5kg (about 0.8:1 equivalent of medicinal material).
(4) Dissolving 0.5kg of xylitol and 0.05kg of sucralose in purified water, adding the solution into the concentrated solution, adjusting the volume of the purified water to 150L, adjusting the pH value to 6.0-7.0, refrigerating and standing the solution at the temperature of 4 ℃ for 24 hours, filtering the solution by a 0.45-micron microporous membrane, and filling the solution to obtain the oral liquid.
Example 4
The Chinese medicinal composition granules
1. Parts by weight of raw materials
1.8kg of salvia miltiorrhiza, 1.2kg of pseudo-ginseng, 3kg of bighead atractylodes rhizome and 0.2kg of hawthorn.
2. Preparation procedure
(1) Extracting Saviae Miltiorrhizae radix and Notoginseng radix with 24kg 60% ethanol under reflux for 2 times (each for 1 hr), and mixing to obtain ethanol extractive solution; recovering the ethanol;
(2) adding 49.6kg of water into the ethanol extraction dregs, the bighead atractylodes rhizome and the hawthorn in the step (1), boiling, decocting and extracting for 2 times, wherein each time lasts for 1 hour, and mixing to obtain a water extract;
(3) concentrating the ethanol extractive solution to 2.5kg (equivalent of medicinal material (relative to ethanol extractive part) about 1.2:1), concentrating the water extractive solution to 5.2kg (equivalent of medicinal material about 1.2:1), mixing with the ethanol extractive solution, and concentrating to 3.1kg (equivalent of medicinal material about 2: 1).
(4) Adding dextrin 3kg, starch 3.2kg and appropriate amount of purified water into the concentrated solution, mixing to obtain soft material, wet extruding and granulating, drying, grading to obtain granule about 8 kg.
Example 5
The Chinese medicinal composition capsule of the invention
1. Raw materials in parts by weight
1.5kg of salvia miltiorrhiza, 1.5kg of pseudo-ginseng, 1.5kg of bighead atractylodes rhizome and 1.5kg of hawthorn.
2. The preparation step (1) takes the salvia miltiorrhiza, the bighead atractylodes rhizome, the pseudo-ginseng and the hawthorn in parts by weight, and the salvia miltiorrhiza, the bighead atractylodes rhizome, the pseudo-ginseng and the hawthorn are crushed into fine powder which is sieved by a 100-mesh sieve; adding magnesium stearate, mixing, and making into capsule with weight of 0.3 g/capsule.
Example 6
The Chinese medicinal composition capsule of the invention
1. Raw materials in parts by weight
2100g of salvia miltiorrhiza, 1500g of pseudo-ginseng, 900g of bighead atractylodes rhizome and 1800g of hawthorn.
2. Preparation steps
(1) Extracting Saviae Miltiorrhizae radix and Notoginseng radix with 36kg of 80% ethanol under reflux for 2 times (each for 2 hr), and mixing to obtain ethanol extractive solution;
(2) adding 32kg of water into the ethanol extraction residues in the step (1), the bighead atractylodes rhizome and the hawthorn, heating and extracting for 2 times, each time for 2 hours, and mixing to obtain a water extract;
(3) concentrating the ethanol extractive solution to 2400g (equivalent of medicinal material is about 1.5:1), concentrating the water extractive solution to 5200g (equivalent of medicinal material is about 1.2:1), mixing with the ethanol extractive solution, and concentrating to 3500g (equivalent of medicinal material is about 1.8: 1).
(4) Spray drying the above concentrated solution to obtain 1600g granules, adding appropriate amount of magnesium stearate, mixing well, and filling into capsule with content of 0.1 g/granule.
Example 7
The Chinese medicinal composition tablet of the invention
1. Parts by weight of raw materials
3.0kg of salvia miltiorrhiza, 1.8kg of pseudo-ginseng, 0.6kg of bighead atractylodes rhizome and 1.0kg of hawthorn.
2. Preparation steps
(1) Extracting Saviae Miltiorrhizae radix and Notoginseng radix with 14.4kg 70% ethanol under reflux for 3 times (each for 1 hr), and mixing to obtain ethanol extractive solution;
(2) adding 38.4kg of water into the ethanol extraction dregs, the bighead atractylodes rhizome and the hawthorn in the step (1), heating and extracting for 3 times, wherein each time lasts for 1 hour, and mixing to obtain a water extract;
(3) concentrating the ethanol extractive solution to 2.4kg (equivalent of medicinal material (about 2:1) and water extractive solution to 5.3kg (equivalent of medicinal material about 1.2:1), mixing with the ethanol extractive solution, and concentrating to 3.5kg (equivalent of medicinal material about 1.8: 1).
(4) Adding microcrystalline cellulose 3.5kg and starch 1.5kg into the concentrated solution, mixing to obtain soft material, wet-extruding and granulating, drying, adding magnesium stearate, mixing, and making into tablet of 0.5 g/tablet.
Example 8
The Chinese medicinal composition pill of the invention
1. Raw materials in parts by weight
1.5kg of salvia miltiorrhiza, 2.5kg of pseudo-ginseng, 1.2kg of bighead atractylodes rhizome and 2kg of hawthorn.
2. Preparation procedure
(1) Pulverizing Saviae Miltiorrhizae radix and Notoginseng radix into 100 mesh fine powder;
(2) adding 19kg of water into Atractylodis rhizoma and fructus crataegi, decocting for 3 times (each time for 1 hr), mixing to obtain water extractive solution, and concentrating to 1.6kg (equivalent of medicinal materials is about 2: 1);
(3) adding the concentrated solution into the fine powder prepared in the step (1), uniformly mixing to obtain a soft material, extruding by a pill making machine, rolling pills, and drying to obtain 4.5kg of Chinese medicinal concentrated pills with the weight of 5g per 100 pills.
Example 9
The Chinese medicinal composition pill of the invention
1. Raw materials in parts by weight
1.5kg of salvia miltiorrhiza, 1.5kg of pseudo-ginseng, 1.2kg of bighead atractylodes rhizome and 1.0kg of hawthorn.
2. Preparation steps
(1) Pulverizing Saviae Miltiorrhizae radix, Atractylodis rhizoma, Notoginseng radix and fructus crataegi into 80 mesh fine powder;
(2) and (2) adding a proper amount of the fine powder obtained in the step (1) into a coating pot, adding purified water, making a mother pill, continuously adding the purified water and the medicinal powder, repeatedly rolling and enlarging the diameter of the mother pill to prepare a small pill with the diameter of about 4mm, polishing and drying the small pill to obtain the traditional Chinese medicine watered pill.
Example 10
The syrup of the Chinese medicinal composition of the invention
1. Raw materials in parts by weight
3kg of salvia miltiorrhiza, 25kg of pseudo-ginseng, 21kg of bighead atractylodes rhizome and 20kg of hawthorn.
2. Preparation steps
(1) Extracting Saviae Miltiorrhizae radix and Notoginseng radix with 156kg 50% ethanol (volume concentration) under reflux for 2 times (each for 1.5 hr), and mixing to obtain ethanol extractive solution;
(2) adding 828kg of water into the ethanol extraction residues in the step (1), the bighead atractylodes rhizome and the hawthorn, heating, decocting and extracting for 2 times, wherein each time lasts for 1.5 hours, and mixing to obtain a water extract;
(3) concentrating the ethanol extractive solution to 18.5kg (equivalent of medicinal material is about 1.5:1), concentrating the water extractive solution to 34.5kg (equivalent of medicinal material is about 2:1), mixing with the ethanol extractive solution, concentrating to 34.5kg (equivalent of medicinal material is about 2:1), adding simple syrup solution 45.5kg, stirring, and mixing to obtain syrup.
Example 11
The Chinese medicinal composition paste
1. Raw materials in parts by weight
2.5kg of salvia miltiorrhiza, 2.5kg of bighead atractylodes rhizome, 0.3kg of pseudo-ginseng and 0.6kg of hawthorn.
2. Preparation steps
(1) Extracting Saviae Miltiorrhizae radix and Notoginseng radix with 30kg 60% ethanol under reflux for 2 times (each for 2 hr), and mixing to obtain ethanol extractive solution;
(2) adding 75kg of water into the ethanol extraction dregs, the bighead atractylodes rhizome and the hawthorn in the step (1), heating, decocting and extracting for 2 times, wherein each time lasts for 1 hour, and mixing to obtain a water extract;
(3) concentrating the ethanol extractive solution to 5kg (equivalent of medicinal material is about 1:1), concentrating the water extractive solution to 5.9kg (equivalent of medicinal material is about 1:1), mixing with the ethanol extractive solution, and concentrating to 2.5kg (equivalent of medicinal material is about 2.5: 1).
(4) And (3) refining 0.5kg of honey into refined honey, adding the extracting solution obtained in the step (3), continuously decocting until flag is pulled or water drops form beads, taking out, cooling to obtain about 2.5kg of ointment, and subpackaging into 100 g/can to obtain the traditional Chinese medicine composition.
Effect example 1
The formula composition and dosage screening test of the traditional Chinese medicine composition
In order to examine the sleep-promoting effect of the composition of the invention with different prescription compositions and dosages and to determine the effective prescription composition and dosage range of the composition, the compositions were prepared respectively according to the prescription in table 1 for testing, and animal tests were carried out with the positive drug diazepam as a control.
1 materials and methods
1.1 sample: test samples were prepared for each group according to the following recipe and preparation method:
TABLE 1 prescription composition of each group of samples
Group of Salvia miltiorrhiza (in parts) Notoginseng radix (share) Atractylodes rhizome (share) Haw (in parts)
Group 1 20 8 15 /
Group 2 10 18 / 24
Group 3 12 / 24 9
Group 4 / 25 12 18
Group 5 3 2 3 1
Group 6 12 6 25 20
Group 7 24 15 9 12
Packet 8 30 25 30 25
Packet 9 36 30 36 30
In the table, "1 part" ═ 10g, as: the dosage of Saviae Miltiorrhizae radix in group 1 is 10 parts, so the actual dosage of the medicinal materials is 100 g.
Weighing Saviae Miltiorrhizae radix and Notoginseng radix, adding 2000g 60% ethanol, heating and reflux-extracting for 2 times, each for 2 hr, and mixing to obtain ethanol extractive solution; mixing the ethanol extraction residue with Atractylodis rhizoma and fructus crataegi, adding 5000g purified water, heating and decocting for 2 times, each for 1 hr, and mixing to obtain water extractive solution; and (3) decompressing and concentrating the alcohol extract to remove ethanol, continuously concentrating to about 500ml, concentrating the water extract to about 1000ml, combining the concentrated water extract and the alcohol extract, and continuously concentrating to 500ml to be used as a drug administration sample of each group.
1.2 Experimental animals: 132 SPF-level healthy female mice bred by the Kyoho animal Co., Ltd are selected, the weight is 18.0-22.0g, the production license number of the experimental animal is SCXK (Chuan) 2020-: 20200508-03.
The mice were acclimated (temperature 20-25 ℃, relative humidity 40-70%), and after 4 days of quarantine were randomly divided into 11 groups (9 test drug groups, 1 negative control group and 1 positive control group) of 12 mice each by body weight.
1.3 dose selection and subject administration: the test drug groups are respectively administered with 0.15ml/10g of the body weight of the diluent of the prepared sample solution (diluted with sterile water according to a ratio of 1:9 and shaken up), and the negative control group is administered with 0.15ml/10g of the body weight of the sterile water; the positive control group was gavaged with 4mg/kg of diazepam in water (0.15 ml/10g body weight).
1.4 Main instruments and reagents
1.4.1 Main instruments: a T1000 type electronic balance, a JA2003 type electronic balance, an electronic stopwatch.
1.4.2 Primary reagents: pentobarbital sodium, diazepam water solution and sterile water.
1.5 test methods and results
An experiment for prolonging the sleep time of the pentobarbital sodium is carried out by referring to a sleep improvement function test method of health food test and evaluation technical specification (2003 edition), animals of each test drug group, a negative control group and a positive control group are respectively and continuously administrated by intragastric administration for one month, after 15min of the last administration, the animals of each group are intraperitoneally injected with the pentobarbital sodium according to the dose of 50mg/kg, the injection volume is 0.1ml/10g, and the test sample can be observed whether the sleep time of the pentobarbital sodium can be prolonged or not by taking 1min of the righting disappearance of the mice as a sleep index. The differences in the prolongation of sleep time between groups were compared and the results are shown in table 2:
TABLE 2 Effect of different prescribed amounts of the composition on prolonging sleep time in pentobarbital sodium-induced mice
Group of Animal number (only) Sleep time(s) P value 1 P value 2
Negative control group 12 448.11±43.31 / ＜0.01％
Positive control group 12 571.96±41.65 ＜0.01％ /
Group 1 12 476.11±51.02 0.61 ＜0.01％
Group 2 12 483.25±36.28 0.75 ＜0.01％
Group 3 12 464.92±25.93 0.44 ＜0.01％
Group 4 12 456.34±47.24 0.52 ＜0.01％
Group 5 12 529.16±33.29 ＜0.05％ ＜0.01％
Group 6 12 566.71±41.48 ＜0.01％ 0.36
Group 7 12 589.32±31.11 ＜0.01％ 0.17
Packet 8 12 629.13±51.01 ＜0.01％ ＜0.05％
Packet 9 12 633.70±32.84 ＜0.01％ ＜0.05％
Carrying out the homogeneity of variance test on each test original data, carrying out pairwise comparison and statistical treatment on the mean between a plurality of test groups and a negative control group (P value 1) or a positive control group (P value 2) by using a single-factor variance analysis method, wherein the mean is subjected to two-to-two comparison and statistical treatment (carrying out appropriate variable conversion on data with non-normal distribution or uneven variance, and carrying out statistical treatment on data obtained by conversion after the data meets the requirement of normal or uniform variance). The results show that: the group 1, the group 2, the group 3 and the group 4 with incomplete compositions are similar to a negative control group, and the effect of prolonging the sleep time of the pentobarbital sodium induced mice is avoided; compared with a negative control group and a positive control group, the group 5 has the effect of prolonging the sleep time of the pentobarbital sodium induced mice, and the difference has statistical significance (P is less than 0.05), but the prolonging time is shorter than that of the positive control group; compared with a negative control group and a positive control group, the group 6 and the group 7 have the effect of remarkably prolonging the sleep time of the pentobarbital sodium induced mice, and the prolonging effect is equivalent to that of the positive control group; compared with a negative control group and a positive control group, the group 8 and the group 9 both have the effect of remarkably prolonging the sleep time of the pentobarbital sodium induced mice, and the prolonging effect is better than that of the positive control group. The results show that all the components in the composition are necessary components for the composition to improve the sleep; within the scope of the prescription claimed in the claims, the compositions of the invention all have the effect of prolonging the sleep time of the mice induced by pentobarbital sodium, and as the dosage of the prescription increases, the effect is gradually enhanced until a corresponding threshold value (the dosage of group 8) is reached, after which the effect of continuing to increase the dosage of the prescription on the improvement of the sleep-promoting effect is insignificant.
Effect example 2
The Chinese medicinal composition of the invention improves the functional test of sleep
1 materials and methods
1.1 sample: the oral liquid prepared in the embodiment 3 of the invention has the following batch numbers: 20200518 the sample is in the form of a brown yellow liquid and is stored in a cool, dry and ventilated place.
1.2 Experimental animals: 144 SPF-level healthy female mice bred by the Kyoho animal Co., Ltd are selected, the weight is 18.0-22.0g, the production license number of the experimental animal is SCXK (Chuan) 2020-: 20200812-01.
The mice adapt to the environment (the temperature is 20-25 ℃, the relative humidity is 40-70%), after quarantine for 4 days, the mice are randomly divided into three large groups according to the weight, wherein 1 group of mice is 48, the mice are randomly divided into 4 dose groups, each group is 12, a direct sleep experiment is firstly carried out, and an experiment for prolonging the sleep time of the pentobarbital sodium is carried out the next day; 48 mice in 2 groups are randomly divided into 4 dose groups, and each group comprises 12 mice, and a pentobarbital sodium subliminal dose hypnosis experiment is carried out; 48 mice in 3 groups were randomly divided into 4 dose groups of 12 mice each, and subjected to barbital sodium sleep latency experiments.
1.3 dose selection and subject administration: three dose groups of 2.5ml/kg/d, 5ml/kg/d and 10ml/kg/d (corresponding to about 5-fold, 10-fold and 20-fold of the recommended human intake of the test sample, respectively) were set, and sterile water was used in place of the test sample in the 0ml/kg/d group. The tested sample is prepared by sterile water, the preparation concentration of low, medium and high dosage is respectively 25%, 50% and 100%, the tested sample with corresponding dosage is orally administered to the mouse once a day, and the intragastric administration dosage of the mouse is 0.1ml/10 g.
1.4 Main instruments and reagents
1.4.1 Main instruments: a T1000 type electronic balance, a JA2003 type electronic balance, an electronic stopwatch.
1.4.2 Primary reagents: sodium pentobarbital, and sodium barbital.
1.5 test methods
The method is carried out according to the method for testing sleep improvement of the technical Specification for testing and evaluating health food (2003 edition).
1.5.1 mouse direct sleep experiment
And continuously intragastrically feeding animals of each dose group for one month, taking the disappearance of mouse righting reflex for 1min as sleep entrance after the last administration, taking the restoration of righting reflex as a mouse awakening judgment standard, and recording the number of the animals falling asleep and the sleep time of each group.
1.5.2 experiment for prolonging sleep time of sodium pentobarbital
And continuously intragastrically injecting the animals of each dose group for one month, and after 15min of final administration, intraperitoneally injecting the pentobarbital sodium into the animals of each dose group according to the dose of 50mg/kg, wherein the injection volume is 0.1ml/10g, and observing whether the tested sample can prolong the sleep time of the pentobarbital sodium by taking 1min of the mice which are rightly turned and disappear as a sleep index. And comparing the difference between the control group and the experimental group in the sleep time extension, wherein the sleep time extension is significant, and the experimental result is positive.
1.5.3 sub-threshold dose hypnotic test of sodium pentobarbital
And continuously intragastrically injecting animals of each dose group for one month, and after 15min of the last administration, performing intraperitoneal injection on pentobarbital sodium of each group according to the dose of 35mg/kg, wherein the injection volume is 0.1ml/10g, taking 1min of mice after turning over and disappearing as a sleep index, and recording the number of animals falling asleep in each group within 30min after the administration of the pentobarbital sodium. And comparing the difference between the numbers of the animals falling asleep in the control group and the experimental group, wherein the incidence rate of the animals falling asleep is obviously increased, and the experimental result is positive.
1.5.4 test for sleep latency period of barbiturate sodium
And continuously intragastrically injecting the animals of each dose group for one month, and after 15min of the last administration, carrying out intraperitoneal injection on the barbital sodium of each dose of 250mg/kg on the animals of each group, wherein the injection volume is 0.1ml/10g, and observing the influence of the tested sample on the sleep latency of the barbital sodium by taking 1min of the mouse which is just over as normal as a sleep index. Comparing the difference between the sleep latency of the control group and the sleep latency of the experimental group, if the sleep latency is obviously shortened, the experimental result is positive.
1.6 statistics of test data: carrying out the homogeneity of variance test on each test original data, carrying out statistical treatment on data meeting the homogeneity of variance requirement by using a pairwise comparison method of mean between a plurality of test groups and a comparison group in a single-factor variance analysis method; and carrying out proper variable conversion on data with non-normal distribution or uneven variance, and carrying out statistical processing on data obtained by conversion after meeting the requirements of normal distribution or uniform variance.
2 results
In the experimental process, the animals have normal drinking water and normal ingestion and no abnormal appearance.
2.1 the influence of the oral liquid of the Chinese medicinal composition of the invention on the weight of mice
Before the oral administration of the oral liquid of the traditional Chinese medicine composition of the invention to the mice at different doses and after the administration for one month, the mice are respectively weighed, the initial weight and the weight gain value are calculated, and statistical analysis is carried out, the results show that: the initial body weight of the mice is 2.5ml/kg/d, 5ml/kg/d, 10ml/kg/d and the difference is not significant when compared with the 0ml/kg/d group (P is more than 0.05); after administration, the weight gain of each dose group is subjected to variance and homogeneity test to meet the requirement of variance and homogeneity, and statistical treatment is carried out by using a pairwise comparison method of mean between a plurality of experimental groups and a control group in a single-factor variance analysis method. In each test group, the 2.5ml/kg/d, 5ml/kg/d, 10ml/kg/d groups had no statistical significance (P > 0.05) compared to 0ml/kg/d, as shown in Table 3.
TABLE 3 influence of the oral liquid of the Chinese medicinal composition of the present invention on the body weight of mice
Figure BDA0002916147410000161
Figure BDA0002916147410000171
2.2 the influence of the oral liquid of the traditional Chinese medicine composition on the direct sleep of mice
The oral liquid of the traditional Chinese medicine composition is orally administered to mice with different dosages for one month, and after the last administration, the mice of all groups do not sleep directly. As shown in Table 4, the traditional Chinese medicine composition oral liquid of the invention has no effect of directly sleeping mice in groups of 2.5ml/kg/d, 5ml/kg/d and 10 ml/kg/d.
Table 4 influence of the oral liquid of the present invention on the direct sleep of mice
Dosage (ml/kg/d) Animal number (only) Sleep number of occurrence
0 12 0
2.5 12 0
5 12 0
10 12 0
2.3 the effect of the oral liquid of the Chinese medicinal composition on prolonging the sleep time of the mice induced by the sodium pentobarbital
Different doses of the traditional Chinese medicine composition oral liquid are orally administered to mice for one month, pentobarbital sodium is injected into abdominal cavities, and the sleep time of the mice is observed. As can be seen from the results in Table 5, the sleep time of the mice administered to each group was significantly longer than that of the 0ml/kg/d group, and the difference was statistically significant (P < 0.05).
TABLE 5 influence of the oral liquid of the Chinese medicinal composition on prolonging the sleep time of pentobarbital sodium induced mice
Dosage (ml/kg/d) Animal number (only) Sleep time(s) P value
0 12 534.92±24.1
2.5 12 629.67±17.24 ＜0.05％
5 12 720.08±38.97 ＜0.05％
10 12 867.75±42.48 ＜0.05％
2.4 Effect of the oral liquid of the Chinese medicinal composition of the invention on the subthreshold dose hypnosis of the sodium pentobarbital
The oral liquid of the traditional Chinese medicine composition is orally administered to mice with different dosages for one month, pentobarbital sodium is injected into the abdominal cavity, and the sleep incidence rate of each group of mice within 30min is observed. As can be seen from the results in Table 6, the sleep occurrence rates of animals in groups of 2.5ml/kg/d, 5ml/kg/d and 10ml/kg/d are significantly higher than those in the group of 0ml/kg/d, wherein the higher sleep occurrence rate of animals in the group of 10ml/kg/d is statistically significant compared with that in the group of 0 ml/kg/d.
Table 6 influence of the oral liquid of the present invention on the sleep incidence of mice induced by subthreshold dose of sodium pentobarbital
Figure BDA0002916147410000172
Figure BDA0002916147410000181
2.5 the Effect of the oral liquid of the Chinese medicinal composition of the invention on the sleep latency of barbital sodium
Different doses of the Chinese medicinal composition oral liquid are orally administered to mice for one month, barbiturate sodium is injected into the abdominal cavity, and the sleep latency of the mice is observed. As can be seen from Table 7, the sleep latency of mice in each administration group was significantly shorter than that in the 0ml/kg/d group, and the difference between the 5ml/kg/d group and the 10ml/kg/d group was statistically significant (P < 0.05) compared with that in the 0ml/kg/d group.
TABLE 7 influence of the oral liquid of the Chinese medicinal composition on sleep latency of barbital sodium
Dosage (ml/kg/d) Animal number (only) Sleep latency(s) P value
0 12 1394.92±98.58
2.5 12 1261.33±210.08 0.06
5 12 1143.5±156.19 ＜0.05
10 12 1030.5±140.6 ＜0.05
According to the test result of the sleep improvement function of the health food inspection and evaluation technical specification, the traditional Chinese medicine composition has the function of improving sleep.
Effect example 3
Safety test of the Chinese medicinal composition
1 materials and methods
1.1 sample: the paste obtained in the embodiment 11 of the invention has the following specification: 100 g/bottle, batch number: 20200827. the sample is brown thick paste, and is stored in a cool, dry and ventilated place, and is diluted by adding a proper amount of distilled water for use.
1.2 Experimental animals: clean-grade healthy adult ICR mice, half male and female, with an animal weight of 18.0-22.0g, were provided by Woods great laboratory animals Co., Ltd, production license number SCXK (Chuan) 2020-: 20200904-01. The clean SD adult rat is half male and female, has a weight of 160-200 g, is provided by Chengdu Shuicho laboratory animals Co., Ltd, and has a production license number of SCXK (Chuan) 2020-: 20200908-02. The experimental animal breeding temperature is 20-25 deg.C, and relative humidity is 40-70%
1.3 Main instruments: t-1000 type electronic balance, JJ-100 type electronic balance, JA-2003 electronic balance, AL104 type electronic balance, centrifuge, OLYMPUS microscope, Hitachi 7100 type full-automatic biochemical analyzer, BAKERSG-603 biosafety cabinet, electrothermal constant temperature incubator, SX-700 autoclave, KYC-100C type constant temperature cradle, and SIEMENSADVIA2120i hematology analyzer.
1.4 Experimental methods
1.4.1 mouse acute toxicity test: the medicinal materials used in the preparation are all Chinese medicinal materials with good safety verified clinically, and the preparation is expected to fail to measure LD 50 To perform the maximum dose test of ICR mice by intragastric administration, the maximum dose of each time is 0.6ml/20g, and the administration is carried out 2 times a day for 14 days.
1.4.2 rat 30 day feeding test: 48 SD rats are respectively taken and divided into a blank group, a low dose group, a medium dose group and a high dose group, wherein the low dose animal group, the medium dose animal group and the high dose animal group are respectively intragastrically administered with the ointment of example 11 with 6.0ml/kg/d, 12ml/kg/d and 20.0ml/kg/d (which are equivalent to about 15 times, 30 times and 50 times of the recommended dose for a human body), the blank group is administered with distilled water with the same volume, after continuous administration for 30 days, the patients are fasted overnight, weighed one by one, and blood is taken from an orbit to detect the hematology index and the blood biochemistry index. Observing general behavior and death condition; ② the weight; (iii) hematological indicators; fourthly, biochemical indexes of blood.
2 results of
2.1 acute toxicity test in mice
During the experimental observation period, the animals in each group have normal diet and activity, good growth, no toxic manifestation and no death. The influence of the Chinese medicinal composition paste on the weight and death number of mice is shown in a table 8, and the result shows that the oral MTD of the Chinese medicinal composition paste for the female and male mice is more than 22400mg/kg, and the sample belongs to a non-toxic grade according to the grading standard of acute toxicity dose.
Table 8 effect of the Chinese medicinal composition paste of the present invention on acute oral toxicity in mice
Figure BDA0002916147410000191
2.2 Long-term toxicity test in rats for 30 days
2.2.1 general behavioral manifestations and mortality: the traditional Chinese medicine composition is administrated to rats for 30 days at the dose of 6.0ml/kg/d, 12ml/kg/d and 20.0ml/kg/d (which is 15 times, 30 times and 50 times of the recommended dose of a human body), and the general performance and behavior of each group of animals have no obvious abnormality, toxic performance and death.
2.2.2 Effect of the Chinese medicinal composition of the invention on rat body weight: the traditional Chinese medicine composition is administrated to rats for 30 days at the dose of 6.0ml/kg/d, 12ml/kg/d and 20.0ml/kg/d (which is equal to 15 times, 30 times and 50 times of the recommended dose of a human body), the weight of the rats in each dose group and the weight gain of the rats after 30 days are compared with those in 0mg/kg/d group, no significant difference exists (P is more than 0.05), and the results are shown in a table 9.
TABLE 9 Effect of the Chinese medicinal composition of the present invention on rat body weight
Figure BDA0002916147410000201
2.2.3 the influence of the Chinese medicinal composition on the hematological indexes of rats: the Chinese medicinal composition is orally administered to rats for 30 days, and the blood white cell count, the red cell count, the hemoglobin level, the classification indexes and the like of the rats in each dose group are measured. As can be seen from tables 10 to 11, the difference between the dose groups and the 0mg/kg/d group has no statistical significance (P > 0.05).
TABLE 10 Effect of the oral liquid of the present invention on the hematological indices of rats
Figure BDA0002916147410000202
Figure BDA0002916147410000211
TABLE 11 influence of the oral liquid of the Chinese medicinal composition of the present invention on the hematological indices of rats
Figure BDA0002916147410000212
2.2.4 the influence of the traditional Chinese medicine composition on the biochemical indexes of the blood of rats: the Chinese medicinal composition of the invention is orally administered to rats with different dosages for 30 days, and the levels of serum glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, total protein, albumin, urea nitrogen, creatinine, blood sugar and total cholesterol of the rats in each dosage group are determined. As can be seen from tables 12 and 13, the difference between each index dose group and 0mg/kg/d group is not statistically significant (P > 0.05).
TABLE 12 Biochemical effects of the oral liquid of the Chinese medicinal composition of the present invention on blood of rats
Figure BDA0002916147410000213
TABLE 13 Effect of the oral liquid of the Chinese medicinal composition of the present invention on the biochemistry of rat blood
Figure BDA0002916147410000214
Figure BDA0002916147410000221
Effect example 4
Human body eating test 1 for improving sleep of traditional Chinese medicine composition
Test method 1: the two control designs of the patient and the group are adopted, 160 pure patients suffering from insomnia for a long time (clinically, the patients are in age of 22-70 years and are randomly divided into a trial group and a control group according to the severity of symptoms, and 80 patients are selected, wherein the sleep time and depth are insufficient and fatigue cannot be eliminated due to difficulty in falling asleep, or sleeping without soundness, waking up when sleeping, or failing to sleep after waking up). The test group comprises 36 men and 44 women, and the average age is 54.55 +/-9.48 years; the average age of the control group was 53.75 + -10.22 in 38 men and 42 women. The test group took the capsule (0.3 g/capsule, lot: 20200720) of the Chinese medicinal composition prepared in inventive example 5, and the control group took placebo, which was identical in appearance, color, weight, and taking method to the sample of inventive example 5. The subject takes 2 capsules (about 1.2g of the raw medicinal material) per time every day (1 time in the morning and evening) with warm boiled water. During the test period, the patients were observed after 21 days, and the original eating habits were not changed, and other drugs and health foods for treating insomnia were not used.
Symptom score observation: the cumulative score (severe 3, moderate 2, mild 1, symptom elimination 0) is based on the severity of insomnia. The score for both groups of symptoms was not significantly different before treatment (P > 0.05). The routine examination of blood, urine and feces, liver and kidney function, chest X-ray, electrocardiogram and B-ultrasonic examination in the two groups before eating the trial are all in normal range.
2 results
After the test eating of the test eating group, compared with the self and the control group, the clinical symptom score is obviously reduced (P is less than 0.01), the sleep condition of the crowd of the test eating group is obviously improved, and other side effects are not reported, which shows that the traditional Chinese medicine composition has the function of improving the sleep, and the result is shown in a table 14.
TABLE 14 clinical symptom score before and after test feeding
Figure BDA0002916147410000222
Figure BDA0002916147410000231
P < 0.01 compared to pre-test; the # group was compared, P < 0.01.
Effect example 5
Human body eating test 2 for improving sleep of traditional Chinese medicine composition
Test method 1: by adopting two control designs of self and groups, 120 pure patients suffering from insomnia for a long time (clinically, the patients are in the age of 25-74 years and are randomly divided into a trial group and a control group according to the severity of symptoms, wherein the patients are in the age of 60 cases. The test group 1 comprises 27 men and 33 women, and the average age is 50.14 +/-7.61 years; the average age of 26 men and 34 women in the control group was 49.42. + -. 6.64. The test group took the capsule of the Chinese medicinal composition (0.1 g/capsule, lot number: 20200716) prepared in example 6 of the present invention, and the control group took placebo whose appearance, color, weight and taking method were the same as those of the sample of example 6 of the present invention. The subject takes 2 capsules (about 1.6g of the raw medicinal materials) per time every day (1 time in the morning and evening) with warm boiled water. During the test period, the patients were observed after 21 days, and the original eating habits were not changed, and other drugs and health foods for treating insomnia were not used.
Observation of symptom score: the cumulative score (severe 3, moderate 2, mild 1, symptom elimination 0) is based on the severity of insomnia. The score for both groups of symptoms was not significantly different before treatment (P > 0.05). The routine examination of blood, urine and feces, liver and kidney function, chest X-ray, electrocardiogram and B-ultrasonic examination in the two groups before eating the trial are all in normal range.
2 results
After the test eating of the test eating group, compared with the self and the control group, the clinical symptom score is obviously reduced (P is less than 0.01), the sleep condition of the crowd of the test eating group is obviously improved, and other side effects are not reported, which shows that the traditional Chinese medicine composition has the function of improving the sleep, and the result is shown in a table 14.
TABLE 14 clinical symptom score before and after test feeding
Figure BDA0002916147410000232
Figure BDA0002916147410000241
P < 0.01 compared to before tasting; # group comparison, P < 0.01.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and amendments can be made without departing from the principle of the present invention, and these modifications and amendments should also be considered as the protection scope of the present invention.

Claims (12)

1. A traditional Chinese medicine composition with a sleep improving effect is characterized by comprising the following raw material medicines in parts by weight: 3-30 parts of salvia miltiorrhiza, 2-25 parts of pseudo-ginseng, 3-30 parts of bighead atractylodes rhizome and 1-25 parts of hawthorn.
2. The traditional Chinese medicine composition with the sleep improving effect according to claim 1 is characterized by comprising the following raw material medicines in parts by weight: 6-25 parts of salvia miltiorrhiza, 5-20 parts of pseudo-ginseng, 6-25 parts of bighead atractylodes rhizome and 3-20 parts of hawthorn; preferably 10-20 parts of salvia miltiorrhiza, 10-18 parts of pseudo-ginseng, 10-20 parts of bighead atractylodes rhizome and 8-15 parts of hawthorn.
3. A pharmaceutical preparation with sleep improvement effect, which is characterized by being prepared from the traditional Chinese medicine composition of any one of claims 1-2 and a pharmaceutically acceptable carrier.
4. The pharmaceutical preparation according to claim 3, characterized by comprising a decoction, a tea, an oral liquid, a syrup, a paste, a powder, a granule, a capsule, a tablet, a pill or the like.
5. Pharmaceutical formulation according to claim 3 or 4, characterized in that the pharmaceutically acceptable carrier comprises water, ethanol, sucrose powder, starch, microcrystalline cellulose, chitosan, mannitol, sorbitol, xylitol, sucralose, dextrin and the like.
6. A health food with sleep improving effect, which is characterized in that the health food is prepared from the traditional Chinese medicine composition as claimed in any one of claims 1 to 3 and other medicinal or edible ingredients or medicinal materials.
7. The health food according to claim 6, characterized by comprising a tea, an oral liquid, a syrup, a paste, a powder, a granule, a capsule, a tablet or a pill and the like.
8. The method for preparing a Chinese medicinal composition for improving sleep as claimed in any one of claims 1 to 2, wherein the method comprises mixing radix Salviae Miltiorrhizae, radix Notoginseng, rhizoma Atractylodis Macrocephalae, and fructus crataegi, pulverizing or pulverizing and mixing.
9. The preparation method of the traditional Chinese medicine composition with sleep improvement effect according to any one of claims 1-2, characterized by comprising the following steps:
A. adding Saviae Miltiorrhizae radix and Notoginseng radix into ethanol solution, heating and reflux extracting to obtain ethanol extractive solution;
B. b, adding water into the dregs of the decoction extracted in the step A, the bighead atractylodes rhizome and the hawthorn, and heating and extracting to obtain a water extract;
C. and D, concentrating the ethanol extract in the step A until no ethanol smell exists, adding the water extract in the step B, concentrating, and combining to obtain an extract concentrate.
10. The method for producing a pharmaceutical preparation having an effect of improving sleep according to any one of claims 3 or 4, characterized in that: preparing the Chinese medicinal composition prepared in claim 8 or the extract concentrate prepared in claim 9 and a pharmaceutically acceptable carrier into a Chinese medicinal preparation.
11. The method for preparing a health product with sleep-improving effect according to claim 6 or 7, wherein: preparing the Chinese medicinal composition prepared in claim 8 or the extract concentrate prepared in claim 9 and other medicinal or edible components or medicinal materials.
12. The use of the Chinese medicinal composition of any one of claims 1-2 in the preparation of a medicament or/and health product for improving sleep.
CN202110114474.9A 2021-01-26 2021-01-26 Traditional Chinese medicine composition with sleep improving effect and preparation method and application thereof Pending CN114788845A (en)

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