CN113952408B - Pharmaceutical composition for improving sleep quality - Google Patents
Pharmaceutical composition for improving sleep quality Download PDFInfo
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- CN113952408B CN113952408B CN202111409504.5A CN202111409504A CN113952408B CN 113952408 B CN113952408 B CN 113952408B CN 202111409504 A CN202111409504 A CN 202111409504A CN 113952408 B CN113952408 B CN 113952408B
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Abstract
The invention aims to provide a pharmaceutical composition for improving sleep quality. The medicinal composition is prepared from the raw materials of spina date seed, cistanche, poria cocos, rhizoma anemarrhenae, rose, platycladi seed and lily, and is prepared into the medicament or the health-care product for improving sleep.
Description
Technical Field
The invention belongs to the field of pharmacy, and relates to a pharmaceutical composition for improving sleep quality.
Background
Insomnia is a common sleep disorder in modern society, and generally refers to a subjective experience that a patient does not meet sleep time or quality and affects social functions in the daytime, and the physical and mental health of people is seriously affected. Clinically, the symptoms of difficult falling asleep, easy waking after sleeping, no longer sleeping after waking up, waking up during sleep and no sleeping all over night are characterized by the difficulty falling asleep, and the symptoms of absentmindedness, slow response, tiredness, hypodynamia, chagrin and the like in the daytime are often accompanied. With the rapid development of economy in China, the pace of life is continuously accelerated, the pressure of life and the working pressure of people are increased sharply, so that the incidence rate of epidemic diseases related to sleep disorder is increased day by day, and the Chinese sleep quality report in 2018 indicates that 83.81% of visitors in China have sleep troubles, wherein the difficulty in falling asleep accounts for 25.83%, and the light sleep accounts for 26.49%. According to the survey of the world health organization, about 27 percent of people all over the world have sleep disorder, the incidence rate of insomnia of adults in China is as high as 38.2 percent, and the sleep disorder becomes an important health problem of global concern.
Modern medicine considers that sleep disorder is often related to neurotransmitters, immunoregulation, intestinal flora, environmental and psychological factors, and the like, and a treatment mode mainly based on drug treatment and assisted by psychological behavior intervention is usually adopted clinically. The continuous sleep disorder can cause various related diseases such as human body chronic fatigue, hypomnesis, low immunity, cardiovascular damage, metabolic disturbance and the like, and even lead to suicide in severe cases. Therefore, improving sleep plays a key role in conditioning sub-health of human bodies, reducing occurrence of related epidemic diseases and improving life quality of people. At present, the clinical chemical drugs for treating sleep disorder mainly comprise barbiturates, benzodiazepines, non-benzodiazepines and the like, the drugs have quick response and definite action mechanism, but the drugs are easy to generate side effects such as residual effect, amnesia effect, drug withdrawal effect and the like after long-term administration.
Insomnia is also recorded in traditional Chinese medicine, and there are related records of sleeping disorders such as "contemplational for the eye", "insomnia", "decubitus", and the like in the yellow emperor's internal classic. In the traditional Chinese medicine practice, natural medicinal materials are usually used or are prepared with daily food in a compound way to improve sleep, so that the traditional Chinese medicine has the advantage of being difficult to generate drug resistance and dependence, is a sustainable slow conditioning mode, and finally enables people to sleep normally.
Along with the increase of insomnia rate, the demand of health care products for improving sleep is continuously increased. Meanwhile, in recent years, the development of the health industry is also very important in China, and the development of the sleep improvement health product industry is promoted to a certain extent by the coming of a plurality of related policies of the health product industry and the health industry. In 7 months 2019, 15 major special actions are proposed to be developed around the centers of disease prevention and health in "health Chinese actions (2019-2030)", so as to promote the conversion from treating diseases to human health, and try to prevent the people from getting ill or getting ill less; the goals related to sleep are: the prevalence rate of insomnia patients is gradually reduced, and the daily average sleeping time of adults is increased to 7-8 hours, and the like. According to data, the market scale of the Chinese sleep improvement health care product industry in 2018 is 128 hundred million yuan, and the market scale is increased by 3.1% in year. Therefore, the health care product for improving sleep has a huge market in China, and the current product can not meet the requirement.
At present, 635 sleep improvement health-care foods are inquired by a special food supervision department website of the State market supervision and administration, wherein most of the imported sleep improvement health-care foods are prepared by taking melatonin as a raw material, and nearly 1/5 of the domestic health-care foods are also prepared by taking the melatonin as the raw material. Melatonin is also called Melatonin, and pineal hormone (Melatonin, MT is commonly called Melatonin) is a bioactive factor secreted by the pineal body of the brain. It has been reported that long-term administration of melatonin-containing nutraceuticals may affect gonadal development in children. Experts point out that the elderly are also cautious to take melatonin. If insomnia in the elderly is not associated with insufficient melatonin secretion, blindly taking such products is not only ineffective, but may even be harmful. Because long-term melatonin supplementation can inhibit normal melatonin secretion to cause pineal atrophy. Researchers at the diabetes center at the university of londer, sweden, found that increased melatonin signaling in islet cells decreased insulin secretion, possibly leading to hyperglycemia and increased risk of type 2 diabetes.
Traditional Chinese medicine considers that the cause of sleep disorder is caused by emotional, dietary or internal injury such as deficiency of qi and blood, and the sleep disorder is easy to cause disharmony of qi and blood and imbalance of yin and yang of heart, liver, gallbladder, spleen, stomach, kidney and the like. Ling Shu & kou Wen (Ling Shu & kou Wen) mentions that "Yang Qi is exhausted, yin Qi is preponderant, and contemplational for contemplational moment; the treatment of deficiency of yin qi and preponderance of yang qi is good. Elucidating the relationship between yin-yang qi and yin-qi of the human body. Lingshu-evil-Gu (Lingshu-Xie-Gu) says that the wei-defensive qi can move outside only when it is in the five zang-organs and six fu-organs, while yang can not enter yin when it is in yang, yang qi can be preponderant when it is in yang, yang qi can collapse when it is in yang, and yin deficiency can not be used for contemplational women. Su Wen & Sheng Qi Tong Tian Lun also points out "Yin Ping Yang secret, shen Zhi, yin Yang separation and Jing Qi Zhi Ke". Therefore, imbalance of yin and yang, disharmony of ying and wei and visceral disorder are the main pathogenesis of insomnia, the etiology includes external pathogen attack, seven-emotion internal injury, improper diet, congenital deficiency, old age and asthenia, etc., and the disease is localized in the heart and relates to the liver, spleen and kidney. The traditional Chinese medicine also thinks that insomnia mostly belongs to deficiency of yin and blood of liver and kidney, and is often caused by liver depression and qi stagnation, deficiency yang and stagnated fire disturbing heart spirit. The book of "Puji Benshi Fang" (prescription of general relief): "pacify the liver without being attacked by pathogen, so lying down would cause the spirit to fall to the liver and calm the mind to cause sleep. Liver has pathogenic factors, and spirit can not return, but spirit can be raised when lying down and separated when lying down. The "blood syndrome treatise" is characterized by: yang floating outside, failing to enter the liver, insomnia. The facial Qian Ling is considered that the liver depression is most apt to cause fire for a long time, the liver fire is reversed to rush the liver spirit, the spirit shakes to make sleep restless, the syndrome is manifested as restlessness at night, difficulty in falling asleep, irritability and the like. Wangping considers that insomnia is caused by liver depression as the first disease, liver qi stagnation is formed by liver loss and catharsis, which disturbs the mind, and insomnia is caused by hidden spirit. Cuochulins thinks that the stagnation of the liver-qi transforms into fire, consumes blood and injures yin, causes imbalance of yin and yang, finally damages liver and kidney, disturbs heart spirit and leads to insomnia. "Jingyue full book, insomnia" cloud: its general indications include deficiency of essence and blood, disharmony between yin and yang, and insecurity of the ears. Su Wen, chapter VI Tibetan elephant treaty, cloud: the kidney governs hibernation, seals the root and stores essence. Book of Ling Shu & Ben Shen cloud: "liver stores blood and blood is rounded off. The theory of "the theory of redundancy of yang and deficiency of yin" is recorded: the kidney is the dominant one in occlusion and the liver is the dominant one in excretion. Both of them are involved in fire, which is attributed to the heart.
The traditional Chinese medicine can improve sleep disorder, follow the traditional Chinese medicine syndrome differentiation theory, and restore the normal state of the organism by regulating qi, blood and yin and yang of viscera. Roc thinks that insomnia and anxiety cause the conflagration along with external objective stimulation on the one hand and various fire-heat symptoms appear; on the other hand, fire-heat consuming essence and blood causes hyperactivity of yang and deficiency of yin, the fire-heat condition is manifested in the exterior, while deficiency of yin and essence and blood changes in the interior. The pathogenesis of insomnia and anxiety is fire heat, the pathology is ministerial fire, and the treatment should clear heat and purge fire, and take the qi and yin deficiency into consideration. The Liwenlong considers that the kidney stores essence and is the water organ; the heart governs mind, and pertains to yang, when kidney water is deficient, it cannot go up to heart, water and fire are not in harmony, and heart fire is hyperactivity, resulting in insomnia and anxiety, the key points of treatment are nourishing kidney yin, lowering heart fire, and nourishing heart spirit.
Therefore, the formula of the sleep-improving health-care product is developed from the traditional Chinese medicine theory, and a safe health-care food with the sleep-improving function is developed. The health product with the function of improving sleep is prepared by taking spina date seeds, cistanche, poria cocos, rhizoma anemarrhenae, roses, platycladi seeds and lily as raw materials. The spina date seed is sweet and sour in taste and neutral in nature, enters liver, gallbladder and heart channels, and has the effects of nourishing the heart, tonifying the liver, calming the heart, soothing the nerves, arresting sweating and promoting the secretion of saliva or body fluid. Cistanchis herba is sweet, salty, warm in nature, and enters kidney and large intestine channels, and has effects of invigorating kidney yang, replenishing essence and blood, loosening bowel to relieve constipation. Poria has sweet and light taste, neutral nature, and effects of benefiting heart, lung, spleen, and kidney channels, promoting diuresis, eliminating dampness, invigorating spleen, and calming heart. Rhizoma anemarrhenae is bitter and sweet in taste and cold in nature, enters lung, stomach and kidney channels, and has the effects of clearing heat and purging fire, and nourishing yin and moistening dryness. The rose flower is sweet in taste, slightly bitter in taste and warm in nature, enters liver and spleen channels, and has the effects of promoting qi circulation, relieving depression, regulating blood and relieving pain. The arborvitae seed is sweet in taste and neutral in nature, enters heart, kidney and large intestine channels, and has the effects of nourishing heart, soothing nerves, moistening intestines, relaxing bowels and arresting sweating. Lily has sweet taste and cold nature, and has the effects of nourishing yin, moistening lung, clearing away heart-fire and tranquilizing mind. In the whole formula, the spina date seed is a monarch drug, has sweet and mild nature and taste, enters heart and liver channels, and has the effects of nourishing blood, tonifying liver, calming heart and soothing nerves; poria has sweet and light flavor and mild nature, and can calm heart and tranquilize mind; rhizoma anemarrhenae is cold in nature, and has the effects of nourishing yin and clearing heat; the arborvitae seed is sweet in taste and neutral in nature, and can nourish heart and calm mind; the lily is sweet in taste and cold in nature, and has the effects of nourishing yin, moistening lung, clearing away heart-fire and tranquilizing; the four medicines are used as ministerial medicines; cistanche deserticola is sweet and salty in taste and warm in nature, can tonify kidney yang, benefit essence and blood, assists in treating cold nature such as rhizoma anemarrhenae, lily and the like, and prevents excessive clearing of heat and clearing away heart-fire; rose is sweet and slightly bitter in taste, warm in nature, and has the effects of promoting qi circulation, resolving stagnation, regulating blood, and regulating yin and yang. The medicines are used in combination, not only can nourish liver blood to calm heart spirit, but also can clear internal heat to remove deficient restlessness, has the effects of nourishing blood to calm nerves, clearing heat to relieve restlessness, promoting qi circulation to relieve depression and harmonizing yin and yang, and can help the yin and yang to sleep.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition for improving sleep quality.
The pharmaceutical composition is prepared from the raw materials of fried spina date seed, cistanche, poria cocos, rhizoma anemarrhenae, rose, platycladi seed and lily, and is prepared into the medicine or health-care product capable of improving sleep.
The spina date seed is sweet and sour in taste and neutral in nature, enters liver, gallbladder and heart channels, and has the effects of nourishing heart and liver, calming heart and soothing nerves, arresting sweating and promoting fluid production. Cistanchis herba is sweet and salty in taste and warm in nature, enters kidney and large intestine channels, and has the effects of invigorating kidney yang, replenishing essence and blood, and loosening bowel to relieve constipation. Poria has sweet and light taste, neutral nature, and has effects of promoting diuresis, eliminating dampness, invigorating spleen, and calming heart. Rhizoma anemarrhenae is bitter and sweet in taste and cold in nature, enters lung, stomach and kidney channels, and has the effects of clearing heat and purging fire, and nourishing yin and moistening dryness. The rose flower is sweet in taste, slightly bitter in taste and warm in nature, enters liver and spleen channels, and has the effects of promoting qi circulation, relieving depression, regulating blood and relieving pain. The arborvitae seed is sweet in taste and neutral in nature, enters heart, kidney and large intestine channels, and has the effects of nourishing heart, soothing nerves, moistening intestines, relaxing bowels and arresting sweating. Lily has sweet taste and cold nature, enters heart and lung channels, and has the effects of nourishing yin, moistening lung, clearing heart and tranquilizing mind. In the whole formula, the spina date seed is a monarch drug, has sweet and mild nature and taste, enters heart and liver channels, and has the effects of nourishing blood, tonifying liver, calming heart and soothing nerves; poria has sweet and light flavor and mild nature, and can calm heart and tranquilize mind; rhizoma anemarrhenae is cold in nature, and has the effects of nourishing yin and clearing heat; the semen boitae is sweet in taste and neutral in nature, and can nourish heart and calm nerves; the lily is sweet in taste and cold in nature, and has the effects of nourishing yin, moistening lung, clearing away heart-fire and tranquilizing; the four medicines are used as ministerial medicines; cistanche deserticola is sweet and salty in taste and warm in nature, can tonify kidney yang, can replenish essence and blood, can assist in treating cold nature such as rhizoma anemarrhenae, lily and the like, and can prevent excessive heat clearing and heart fire clearing; rose is sweet and slightly bitter in taste, warm in nature, and has the effects of promoting qi circulation, resolving stagnation, regulating blood, and regulating yin and yang. The medicines are used together, so that the traditional Chinese medicine composition can nourish liver blood to calm heart and spirit, clear internal heat to remove deficient restlessness, nourish blood to calm nerves, clear heat to remove restlessness, promote qi circulation to relieve depression, and harmonize yin and yang, and the sleep can be achieved when the yin and yang harmonize.
The pharmaceutical composition is prepared from the following traditional Chinese medicine raw materials in parts by weight:
preferably, the pharmaceutical composition is prepared from the following traditional Chinese medicine raw materials in parts by weight:
most preferably, the pharmaceutical composition is prepared from the following traditional Chinese medicine raw materials in parts by weight:
another object of the present invention is to provide a process for the preparation of the pharmaceutical composition.
The preparation method comprises the following steps:
extracting the above Chinese medicinal materials with 6-10 times of ethanol for 1-4 times (1-2 hr for each time), concentrating the extractive solution, drying under reduced pressure to obtain solid, pulverizing, and sieving.
Preferably, the preparation method comprises the following steps:
extracting decoction pieces or coarse powder of the above Chinese medicinal materials with 6-10 times volume of 30-70% ethanol for 1-4 times (each for 1-2 hr), concentrating the extractive solution, drying under reduced pressure to obtain solid, pulverizing into powder, and sieving.
Most preferably, the preparation method comprises the following steps:
extracting decoction pieces or coarse powder of the above Chinese medicinal materials with 8 times volume of 50% ethanol twice, each for 1.5 hr, concentrating the extractive solution at 50-70 deg.C to density of 1.20-1.40, drying at 50-70 deg.C under reduced pressure to obtain solid, pulverizing, and sieving.
The pharmaceutical composition of the invention can be in any form of medicine which can be taken: such as: tablets, sugar-coated tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, buccal agents, granules, pills, powders, ointments, pellets, suspensions, powders, solutions, injections, suppositories, ointments, plasters, creams, sprays, drops, patches.
The pharmaceutical preparation composition of the present invention is preferably in the form of a unit dose pharmaceutical preparation, for example, when the pharmaceutical preparation composition is prepared into a medicament, the unit dose medicament can contain the pharmaceutical composition of the present invention, and the rest is pharmaceutically acceptable auxiliary materials. The pharmaceutically acceptable adjuvant may be 0.01-99.99% by weight of the total weight of the preparation.
The pharmaceutical preparation composition of the present invention is used in an amount determined according to the condition of the patient, for example, 1 to 3 times a day. 1-20 tablets at a time, and the like.
Preferably, the pharmaceutical preparation composition of the present invention is an oral preparation or an injection. Wherein the oral preparation is selected from one of capsule, tablet, dripping pill, granule, concentrated pill and oral liquid. Wherein, the injection is selected from one of liquid, semisolid, solid and powder, preferably injection and powder injection.
The pharmaceutical preparation composition of the present invention, which is a preparation for oral administration, may contain auxiliary materials such as binders, fillers, diluents, tabletting agents, lubricants, disintegrants, coloring agents, flavoring agents and wetting agents, and the tablet may be coated if necessary.
Suitable fillers include cellulose, mannitol, lactose and other similar fillers. Suitable disintegrants include starch, polyvinylpyrrolidone and starch derivatives such as sodium starch glycolate. Suitable lubricants include, for example, magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulphate.
The pharmaceutical preparation of the present invention can be prepared into solid oral compositions by conventional methods such as mixing, filling, tabletting and the like. Repeated mixing can distribute the active throughout those compositions that use large amounts of filler.
Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethyl cellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agents, for example lecithin, sorbitan monooleate or acacia; non-aqueous carriers (which may include edible oils), for example almond oil, fractionated coconut oil, oily esters such as esters of glycerine, propylene glycol or ethyl alcohol; preservatives, for example p-hydroxybenzyl or propyl p-hydroxybenzoate or sorbic acid, and, if desired, conventional flavouring or colouring agents.
For injections, liquid unit dosage forms are prepared containing the active agents of the invention and a sterile carrier. Depending on the carrier and concentration, the compound may be suspended or dissolved. Solutions are generally prepared by dissolving the active substance in a carrier, filter sterilising before filling it into a suitable vial or ampoule, and then sealing. Adjuvants such as a local anaesthetic, preservatives and buffering agents may also be dissolved in the vehicle. To improve its stability, the composition can be frozen after filling into vials and the water removed under vacuum.
Another object of the present invention is to provide the use of the pharmaceutical composition of the present invention for the preparation of a medicament for treating or improving sleep quality.
The health product is prepared according to the traditional Chinese medicine theory, takes spina date seed, cistanche deserticola, tuckahoe, rhizoma anemarrhenae, rose, platycladi seed and lily as raw materials, and is prepared into the health product with the function of improving sleep. The spina date seed is a monarch drug, has sweet and mild nature and flavor, enters heart and liver channels, and has the effects of nourishing blood, tonifying liver, calming heart and soothing nerves; poria has sweet and light flavor and mild nature, and can calm heart and tranquilize mind; rhizoma anemarrhenae is cold in nature, and has the effects of nourishing yin and clearing heat; the semen boitae is sweet in taste and neutral in nature, and can nourish heart and calm nerves; lily is sweet in taste and cold in nature, and has the effects of nourishing yin, moistening lung, clearing away heart-fire and tranquilizing mind; the four medicines are used as ministerial medicines; cistanche deserticola is sweet and salty in taste and warm in nature, can tonify kidney yang, benefit essence and blood, assists in treating cold nature such as rhizoma anemarrhenae, lily and the like, and prevents excessive clearing of heat and clearing away heart-fire; rose is sweet and slightly bitter in taste, warm in nature, and has the effects of promoting qi circulation, resolving stagnation, regulating blood, and regulating yin and yang. The traditional Chinese medicine composition has the effects of nourishing liver and blood to calm heart spirit, clearing internal heat to eliminate deficient restlessness, nourishing blood and tonifying liver, calming heart and soothing nerves, nourishing yin and moistening lung, tonifying kidney and boosting essence, clearing heat and relieving restlessness, promoting qi circulation and relieving depression, and harmonizing yin and yang, has the effects of improving sleep, clearing damp, invigorating spleen, beautifying, nourishing yin and moistening lung, can comprehensively condition body, and can keep yin and yang of body secret, sufficient qi and blood and full energy. The raw materials of the product are mostly medicinal and edible materials, can be taken for a long time, and have the advantages of small side effect, good taste and good compliance of patients. No damage to memory, no obvious adverse reaction and no drug resistance. Compared with the prior sedative hypnotic drugs for treating insomnia, such as barbiturates, benzodiazepines and non-benzodiazepines, the sedative hypnotic drugs do not cause visual activity, visual ability reduction, memory reduction, drug resistance, drug dependence, drug withdrawal rebound and memory reduction, and adverse effects such as psychomotor damage and withdrawal response syndrome.
Detailed Description
The invention is further illustrated and described by the following specific examples, which are not intended to be limiting.
Experimental example 1 screening of extraction Process
1. Selection of survey indicators
The spina date seed is the main medicinal ingredient in the prescription, and the contained saponin components (main spina date seed saponins A and B) and flavonoid component (spinosin) are the medicinal components with the sedative-hypnotic function and are also the content determination index components specified by pharmacopeia; in addition, the effective components of Bulbus Lilii, semen Platycladi, and rhizoma anemarrhenae are saponins. Therefore, the research indexes for researching the extraction process are the content of the spinosad and total saponin and the yield of solid matters.
2. Research on extraction Process
2.1 screening of extraction methods
The extraction method of the traditional Chinese medicine comprises water decoction, ethanol reflux method and the like, in order to fully utilize the active ingredients of the medicinal materials in the prescription and ensure complete extraction of the active ingredients by considering the physicochemical properties of the active ingredients contained in each medicinal material and the original ancient method, the extraction solvent of the whole formula extraction process is firstly investigated, and the optimal extraction method is selected from the solvent.
2.2 Experimental materials and Equipment
2.2.1 Experimental materials
Table 1 Experimental materials information table
2.2.2 formula of the sleep-improving health food:
TABLE 2 sleep improving health food formula table
2.2.3 Experimental facilities
TABLE 3 Experimental facility information Table
2.3 Experimental procedures and results
2.3.1 selection of assay methods for indices
2.3.1.1 determination of Total Saponin content
Taking the jujuboside A as a standard substance, and determining total saponins by reference.
2.3.1.2 determination of the content of the functional ingredient spinosin
The Spanish-Nafion is measured by high performance liquid chromatography (0512, the four Ming Dynasty rules of 2020 edition).
In chromatographic condition and system adaptability test, octadecylsilane chemically bonded silica is used as a filler; taking acetonitrile as a mobile phase A, taking water as a mobile phase B, and eluting according to the following ratio of A: B = 15; the detection wavelength is 340nm; the theoretical plate number is not less than 3000 calculated according to the peak of the Spiromone.
The determination method comprises precisely sucking 10 μ l of each of the reference solution and the sample solution, injecting into liquid chromatograph, and determining.
2.3.2 extraction solvent screening and results
In order to fully utilize the effective components of the medicinal materials in the prescription and ensure the complete extraction of the effective components, the extraction solvent of the whole formula extraction process is examined firstly, and the optimal extraction method is selected from the solvent.
Taking 5 times of daily dosage of medicinal materials, and respectively using a solvent with 8 times of crude drug quantity: extracting with water (pulverized semen Ziziphi Spinosae), water, 50% ethanol (pulverized semen Ziziphi Spinosae), and 50% ethanol for 2 times, each for 1.5 hr. The results are shown in Table 4.
TABLE 4 measurement results of respective indices
As can be seen from the above table, alcohol extraction is selected because it has higher total saponin content than water extraction and higher breaking ratio than no breaking. And the grinding degree needs to be inspected.
2.3.3 examination of grinding degree and results
The previous experiments show that the crushing treatment of the medicinal materials has influence on the extraction of the components, so the crushing degree is investigated. The medicinal materials are respectively divided into decoction pieces, coarse powder and coarse powder, 15g of semen Ziziphi Spinosae and 10g of the rest medicinal materials are extracted with 50% ethanol 8 times of the crude drug for 2 times and 1.5 hr each time. The results are shown in tables 5 and 6.
TABLE 5 measurement results of respective indices
TABLE 6 measurement results of respective indices
The particle size of the platycladi seed decoction pieces is the same as that of the coarsest powder, the decoction pieces are the coarsest powder, and as can be seen from the table above, the contents of effective components and total saponins in the coarsest powder and the coarse powder are higher than those in the decoction pieces directly, the coarsest powder and the coarse powder are similar, and because the platycladi seed is not suitable for sieving after being crushed, flower medicinal materials basically have no crushing treatment steps. Selecting decoction pieces in combination with pharmacopeia application mode. Finally, selecting decoction pieces: rhizoma anemarrhenae, flos Rosae Rugosae, bulbus Lilii, and semen Platycladi; coarse powder: cistanche, spina date seed and tuckahoe.
2.3.4 verification of the degree of Omnidirectional comminution and results
Taking 5 times daily dosage of medicinal materials, and dividing into three groups: extracting the whole decoction pieces, mixed decoction pieces (rhizoma anemarrhenae, flos Rosae Rugosae, bulbus Lilii, semen Platycladi; coarse powder: cistanchis herba, semen Ziziphi Spinosae, poria), and whole coarse powder respectively with 50% ethanol 8 times of the crude drug amount for 2 times, each for 1.5 hr. The results are shown in Table 7.
TABLE 7 measurement results of respective indices
As can be seen from the above table, the contents of the effective components of the mixed type, namely the spinosad and the total saponin are higher, and are consistent with the single medicine investigation result, so that the mixed type feeding is adopted in the follow-up research.
2.3.5 ethanol concentration screening and results
Extracting 5 times daily dosage of the medicinal materials with 8 times crude drug amount of 30% ethanol, 50% ethanol, and 70% ethanol for 2 times, each for 1.5 hr. The results are shown in Table 8.
TABLE 8 measurement results of respective indices
As can be seen from the above table, the extraction of the total saponins and the spinosyns in 50% ethanol is relatively good.
2.3.6 examination of extraction frequency and results
Taking 5 times daily dosage of medicinal materials, respectively using 8 times crude drug amount of 50% ethanol, extracting for 1.5h each time, detecting corresponding index of extractive solution extracted each time, and examining influence of extraction times. The results are shown in Table 9.
TABLE 9 measurement results of respective indices
From the above table, it is known that the extraction of the spinosad once is relatively complete, the content of the spinosad three times and later is low, and the total saponin content is gradually reduced. Considering production practice, 2 extractions were selected.
2.3.7 investigation and results of the Material-to-liquid ratio
Taking 5 times daily dosage of the medicinal materials, adding 6 times, 8 times, 10 times and 12 times crude drug amount of 50% ethanol, extracting twice, each time for 1.5 hr, the results are shown in Table 10.
TABLE 10 measurement results of respective indices
As can be seen from the above table, the content of the spinosyns extracted by the solvent with the amount of 8 times, 10 times and 12 times is similar, and the total saponin content increases gradually, but increases more slowly after 8 times. In consideration of production practice and energy conservation, the material-liquid ratio is selected to be 1.
2.3.8 examination of extraction time and results
The 5 times daily dosage of the medicinal materials are respectively added with 8 times of 50% ethanol of crude drug, and the extraction is carried out twice, the extraction time of each group is 1 h/time of the first group extraction, 1.5 h/time of the second group extraction, 2 h/time of the third group extraction, and 3 h/time of the fourth group extraction, and the result is shown in Table 11.
TABLE 11 measurement results of each index
As can be seen from the above table, the results of all indexes are similar when the extraction time is 1.5h or more, and the time of about 1.5h can be selected as the level of the orthogonal experiment.
2.3.9 orthogonal experiments of extraction Process
According to the test results, 3 factors of ethanol concentration, feed-liquid ratio and extraction time are selected on the basis, and L is adopted 9 (3 4 ) The orthogonal design method is used for carrying out orthogonal test, and the optimal extraction process is preferably selected by comprehensively comparing and taking the solid content, the total saponin content and the spinosin content as evaluation indexes. As shown in tables 12, 13, 14 below.
TABLE 12 factor level table
TABLE 13 statistical table of orthogonal experimental design results of extraction process
TABLE 14 SPSS variance data analysis Table
a.R side =.731 (adjusting R side = -. 077)
The comprehensive scoring is carried out by taking the content of the spinosad, the content of the total saponin and the yield of the solid as indexes, different weights are set after the data are normalized by taking the maximum value of each index as a reference during scoring, the weight coefficients of the content of the spinosad, the content of the total saponin and the yield of the solid are respectively set to be 0.4, 0.4 and 0.2, and the maximum value of each index is taken as a reference to carry out standardization treatment on each data of the same index so as to obtain the weight analysis integral of each test. The orthogonal test design and results are shown in Table 13, and the results of the ANOVA are shown in Table 14. Combining tables 13 and 14, we can see that the influence of the 3 factors of this experiment is mainly B (solvent volume) > a (ethanol concentration) > C (extraction time), respectively. Then obtaining the optimal extraction process condition B from K1, K2 and K3 3 A 2 C 2 Namely, the optimal process conditions are as follows: the ethanol concentration is 50%, the extraction time is 1.5 h/time, and the solvent volume is 10 times. Because the result that the volume of the solvent is 10 times that of the solvent is 8 times that of the solvent is not obviously increased, and the practical and energy-saving aspects of mass production are considered, the optimal extraction process conditions are corrected as follows: the extraction ethanol concentration is 50%, the time is 1.5 h/time, and the solvent volume is 8 times.
3. Three groups of verification tests and results
The three groups are prepared by extracting 35 times of daily prescription amount of crude drug with 8 times of 50% ethanol for 2 times, each for 1.5 hr, and mixing the two extractive solutions. The results are shown in Table 15 below (content 5 times the amount of crude drug).
Table 15 measurement results of respective indices
The results show that the contents of the spinosad and the total saponin in the three verification tests are higher and similar; RSD values are all below 5%, so that the optimal scheme has good reproducibility and proper conditions.
4. Research and results of concentration process
4.1 examination of concentration temperature
The extract from the first set of experiments under "4" was taken. Respectively taking three parts of extracting solution with the same volume, and respectively carrying out vacuum concentration at the temperature of 60 ℃,70 ℃ and 80 ℃ to obtain crude drugs: and when the extracting solution is about 1. The results are shown in Table 16 below (results were obtained in a unified manner to give a content of 5 times the crude drug amount).
TABLE 16 results of concentration temperature under reduced pressure
The results show that different decompression concentration temperatures have little influence on the ingredients of the spinosad and the total saponin, and the concentration temperature below 80 ℃ can be generally applied.
4.2 examination of the degree of concentration
Concentrating to obtain a concentrate with good fluidity, and measuring relative density with densimeter to obtain a density of 1.200 or more.
5. Drying process and results
Collecting three parts of 60 deg.C reduced pressure concentrated solution under item 5, drying at 60 deg.C, 70 deg.C and 80 deg.C under reduced pressure, and detecting the content of spina date seed saponin A, spinosin and total saponin. The results are shown in Table 17 below (results were combined to 5 times the amount of crude drug).
TABLE 17 drying temperature results
The results show that different drying temperatures have little influence on the ingredients of the spinosad and the total saponin, and the drying is carried out under reduced pressure below 70 ℃ in combination with energy consumption and timeliness.
6. Research on preparation process
6.1 prescription design
5260 times of daily prescription amount of crude drug is extracted with 50% ethanol 8 times of the amount of crude drug for 2 times, each for 1.5 hr. Concentrating under reduced pressure at 70 deg.C, drying under reduced pressure at 70 deg.C to obtain dry extract, pulverizing, and sieving with 60 mesh sieve to obtain raw material powder. The formulation was designed as in Table 18 below and made into 0.70g tablets.
Table 18 formulation Process screening study
As can be seen from the above table, the formulas 1-3 all have a splinter, and the splinter problem can be solved by properly increasing the pressure because sodium carboxymethyl starch only has the disintegration effect and the low-substituted hydroxypropyl cellulose also has the disintegration effect and the adhesion effect. In summary, formula 6 was chosen as the formulation process condition.
6.2 coating
The tablet color was selected as purple to aid sleep and the purple coating powder of the Callerkang company under the color number material designation 150K600002-CN was selected. Specific parameters are shown in Table 19 below.
TABLE 19 coating parameter settings results
| Name(s) | Parameter(s) |
| Name of Material | 150K600002-CN |
| The temperature of the inlet air is lower | 75 |
| Temperature of the tablet bed | 38-42 |
| Air discharge temperature DEG C | 40-45 |
| Solvent(s) | Water (W) |
| Atomization pressure bar | 1.0-2.0 |
| Solid content of coating liquid | 16.7％ |
| Theoretical weight gain% | 3.5％ |
| Coating pan rotating speed rpm | 2.0％ |
| Flow rate of material g/min | 20-40％ |
In summary, combining the feasibility of mass production during filtration and the insignificant increase of total saponins before and after the pulverization of cistanche and poria, only spina date seeds are pulverized, and the coarsest powder is packaged by decoction bags. The process research result is as follows: extracting with 8 times volume of 50% ethanol twice, each for 1.5 hr, concentrating the extractive solution at 70 deg.C to density of 1.200 (measured by heat), drying at 70 deg.C under reduced pressure to obtain solid, pulverizing, sieving with 60 mesh sieve, and adding adjuvants at the following ratio: 7 percent of low-substituted hydroxypropyl cellulose (LH-11), 2 percent of SiO2, 0.3 percent of magnesium stearate and microcrystalline cellulose are mixed uniformly in proper amount to prepare 0.68 g/tablet of plain tablets, the rotating speed is slow during coating, the material flow rate is increased in the later period, the weight is increased by 3.5 percent after coating, and the tablet weight is 0.70 g/tablet.
Experimental example 2, and the influence of the spina date seed lily tablets in the experimental example and the comparative example on the sleep latency and the sleep time of the mice are observed.
Experimental methods experimental groups 1/2/3/4/5 samples, comparative examples 1/2/3 samples.
The sample preparation method comprises the following steps: according to the earlier stage process research, a certain amount of fried spina date seed (crushed into coarse powder) and poria cocos, rhizoma anemarrhenae, lily, platycladi seed, cistanche and rose (all prepared into decoction pieces) are taken, extracted by 8 times of solvent, concentrated, dried under reduced pressure, uniformly mixed with a proper amount of auxiliary materials, tabletted and coated to obtain the traditional Chinese medicine.
Experimental group 1 extraction with 20% ethanol: taking 3 parts of fried spina date seed, 1 part of tuckahoe, 1 part of rhizoma anemarrhenae, 1 part of lily, 1 part of platycladi seed, 1 part of cistanche, 0.5 part of rose and water as a solvent, and preparing a sample 1 according to a sample preparation method.
Experimental group 2% ethanol extraction: taking 3 parts of fried spina date seed, 1 part of tuckahoe, 1 part of rhizoma anemarrhenae, 1 part of lily, 1 part of platycladi seed, 1 part of cistanche, 0.5 part of rose and 30% ethanol as solvents, and preparing a sample 2 according to a sample preparation method.
Experimental group 3% ethanol extraction: taking 3 parts of fried spina date seed, 1 part of tuckahoe, 1 part of rhizoma anemarrhenae, 1 part of lily, 1 part of platycladi seed, 1 part of cistanche, 0.5 part of rose and 50% ethanol as a solvent, and preparing a sample 3 according to a sample preparation method.
Experimental group 4% ethanol extraction: taking 3 parts of fried spina date seed, 1 part of tuckahoe, 1 part of rhizoma anemarrhenae, 1 part of lily, 1 part of platycladi seed, 1 part of cistanche, 0.5 part of rose and 70% ethanol as a solvent, and preparing a sample 4 according to a sample preparation method.
Experimental group 5 ethanol extraction: taking 3 parts of fried spina date seeds, 1 part of poria cocos, 1 part of rhizoma anemarrhenae, 1 part of lily, 1 part of platycladi seeds, 1 part of cistanche, 0.5 part of rose and ethanol as a solvent, and preparing a sample 5 according to a sample preparation method.
Comparative example 1 a comparative sample 1 was prepared by using 3 parts of fried spina date seed, 1 part of poria cocos, 1 part of rhizoma anemarrhenae, 1 part of lily, 1 part of platycladi seed, 1 part of cistanche deserticola and 50% ethanol as solvents according to a sample preparation method.
Comparative example 2 a comparative sample 2 was prepared by using 3 parts of fried spine date seed, 1 part of poria cocos, 1 part of rhizoma anemarrhenae, 1 part of lily, 1 part of platycladi seed, 1 part of cistanche, 0.5 part of rose, 3 parts of arillus longan and 50% ethanol as solvents according to a sample preparation method.
Comparative example 3 a comparative sample 3 was prepared by a sample preparation method using 3 parts of arillus longan, 1 part of poria cocos, 1 part of rhizoma anemarrhenae, 1 part of lily, 1 part of platycladi seed, 1 part of cistanche, 0.5 part of rose, and 50% ethanol as a solvent.
Grouping and administration modes A traditional Chinese medicine control group is administered with sweet dream capsule (10.9 g crude drug/(kg.d)), a western medicine control group is administered with diazepam (4 mg/(kg.d)), and a blank control group is administered with distilled water. According to the requirements of the usage and dosage of the spina date seed lily tablet product specification, the tablet is orally taken 1-2 times a day, 3 tablets (0.70 g/tablet, each tablet contains 2.83g of crude drug, namely each gram of spina date seed lily tablet contains 4.04g of crude drug), and the dosage of the tablet is 1.10g of crude drug/(kg.d) calculated by 70kg for each person converted into a mouse. Grinding and pulverizing the control drug and sample drug to obtain medicinal liquid of 1.1g crude drug/mL (sweet dream capsule), 0.1g crude drug/mL (experimental and comparative samples), and 0.4mg/mL (diazepam), respectively, and intragastrically administering to each mouse at a weight of 0.1mL/10 g.
Experimental method 110 mice were randomly divided into 11 groups of 10 mice each, and each group of mice was fasted (without water) for 12h, and then gavaged for 1/d at the same volume for 30 consecutive days according to the above grouping and administration dose, and a threshold dose of sodium pentobarbital was intraperitoneally injected 1h after the last administration (39 mg/kg as determined in the preliminary experiment). The mice were immediately observed for sleep latency and sleep time, and the experiment was performed at night. ( Judging that the index (1) righting reflection disappears: the mice are not turned over within 1min after lying on the back, which indicates that the turning reflection disappearance stage is started; (2) righting reflection recovery: the mouse can automatically turn over from the supine position and does not turn over within 1min, which indicates that the righting reflex is recovered; (3) sleep latency: the time taken from the start of injection until the righting reflex disappears; (4) sleep time: the time taken from disappearance of the righting reflection to restoration of the righting reflection. )
The results are shown below:
TABLE 20 sleep latency and sleep time of pentobarbital sodium in each group of mice
Note: p < 0.05, P < 0.01, compared to blank control
The experimental result shows that compared with a blank control group, the sleep latency of a traditional Chinese medicine control (sweet dream capsule) group is obviously shortened (P is less than 0.05), the sleep latency of mice can be obviously shortened (P is less than 0.01) by a western medicine control (diazepam) group and an experimental group 1-5, wherein the western medicine control (diazepam) group has the same effect as the experimental group 1-5, the experimental group 3 has the best effect, the experimental group is the traditional Chinese medicine control (sweet dream capsule) group, and the comparative examples 1-3 slightly improve the sleep latency, but have no obvious difference compared with the blank control group. The spina date seed and lily tablet can shorten the sleep latency of mice, wherein the sleep improvement effect of each experimental group is better than that of a traditional Chinese medicine sweet dream capsule, but the sleep improvement effect of each experimental group is slightly worse than that of diazepam, and the effect of the experimental group 3 is the best.
In conclusion, the experiment that sodium pentobarbital induces the sleep of mice shows that the spina date seed and lily tablet compound for improving the sleep can obviously prolong the sleep duration of the mice, shorten the sleep latency and have the function of improving the sleep, the function of the compound is stronger than that of a traditional Chinese medicine control (sweet dream capsules) group and slightly weaker than that of a western medicine control (diazepam), most of the formula of the compound consists of medicinal and edible medicinal materials, and the compound has no side effect. The product has the function of improving sleep remarkably, has stronger effect than that of common traditional Chinese medicines, has similar effect to diazepam, and has no side effect of diazepam.
Example 1 Chinese medicinal composition
Example 2 Chinese medicinal composition
Example 3 Chinese medicinal composition
Example 4 tablet
Taking rhizoma anemarrhenae decoction pieces, rose decoction pieces, lily decoction pieces and platycladi seed decoction pieces according to the formula shown in the embodiment 1; pulverizing Cistanchis herba, semen Ziziphi Spinosae and Poria into coarse powder; extracting with 8 times volume of 50% ethanol twice, each for 1.5 hr, concentrating the extractive solution at 50-70 deg.C to density of 1.200-1.400 (measured by heat), drying at 50-70 deg.C under reduced pressure to obtain solid, pulverizing, sieving with 60 mesh sieve, adding adjuvants at a ratio of: mixing 7% low-substituted hydroxypropyl cellulose (LH-11), 2% SiO2, 0.3% magnesium stearate and microcrystalline cellulose, and making into 0.68 g/tablet, wherein the rotation speed is slow, the material flow rate is increased in the later stage, and the weight is increased by 3.5% after coating, thereby obtaining 0.70 g/tablet.
Example 5 Chinese medicinal composition
The formula shown in example 2 is that decoction pieces or coarse powder of the traditional Chinese medicine raw materials are taken, 30% ethanol with 6 times of volume is added for extraction for 1 time, each time is 1 hour, the extract is concentrated, the solid is obtained by decompression drying, and the solid is obtained by powdering and sieving.
Example 6 Chinese medicinal composition
The formula shown in example 2 is that decoction pieces or coarse powder of the traditional Chinese medicine raw materials are taken, 70% ethanol with 10 times of volume is added for extraction, the extraction is carried out for 4 times, each time lasts for 2 hours, the extract is concentrated, the solid is obtained by decompression drying, and the solid is obtained by powdering and sieving.
Example 7 Chinese medicinal composition
The formula shown in example 3 is that decoction pieces or coarse powder of the traditional Chinese medicine raw materials are taken, 30% ethanol with 6 times of volume is added for extraction for 1 time and 1 hour each time, the extract is concentrated, the solid is obtained by decompression and drying, and the solid is ground and sieved, thus obtaining the traditional Chinese medicine preparation.
Example 8 Chinese medicinal composition
The formula shown in example 3 is that decoction pieces or coarse powder of the traditional Chinese medicine raw materials are taken, 70% ethanol with 10 times of volume is added for extraction for 4 times, each time is 2 hours, the extract is concentrated, the solid is obtained by decompression and drying, and the solid is ground and sieved, thus obtaining the traditional Chinese medicine preparation.
Example 9 Chinese medicinal composition
The formula shown in the embodiment 1 is that decoction pieces or coarse powder of the traditional Chinese medicine raw materials are taken, ethanol with the volume 10 times of the decoction pieces or coarse powder is added for extraction for 4 times, each time lasts for 2 hours, the extract is concentrated, the solid is obtained by decompression and drying, and the solid is ground and sieved, thus obtaining the traditional Chinese medicine.
Example 10 tablet
Taking rhizoma anemarrhenae decoction pieces, rose decoction pieces, lily decoction pieces, platycladi seed decoction pieces, cistanche decoction pieces and poria cocos decoction pieces according to the formula shown in the embodiment 1; pulverizing parched semen Ziziphi Spinosae into coarse powder; extracting with 6 times volume of 50% ethanol twice, each time for 1.5 hr, concentrating the extractive solution at 60 deg.C to density of 1.200 (measured by heat), drying at 60 deg.C under reduced pressure to obtain solid, pulverizing, sieving with 60 mesh sieve, and adding adjuvants at the following ratio: 7 percent of low-substituted hydroxypropyl cellulose (LH-11), 2 percent of silicon dioxide, 0.3 percent of magnesium stearate and microcrystalline cellulose are mixed uniformly in proper amount to prepare 0.68 g/tablet of plain tablets, the rotating speed is slow during coating, the material flow rate is increased in the later period, the weight is increased by 3.5 percent after coating, and the tablet weight is 0.70 g/tablet.
Example 11 tablet
Taking rhizoma anemarrhenae decoction pieces, rose decoction pieces, lily decoction pieces, platycladi seed decoction pieces, cistanche decoction pieces and poria cocos decoction pieces according to the formula shown in the embodiment 1; pulverizing parched semen Ziziphi Spinosae into coarse powder; extracting with 10 times volume of 50% ethanol twice, each for 1.5 hr, concentrating the extractive solution at 60 deg.C to density of 1.300 (measured thermally), adding 7% low-substituted hydroxypropyl cellulose (LH-11), 2% silicon dioxide, and appropriate amount of microcrystalline cellulose, granulating, drying, adding 0.3% magnesium stearate, mixing, making into 0.68 g/tablet, and coating to obtain 0.70 g/tablet.
Example 12 Capsule
Taking rhizoma anemarrhenae decoction pieces, rose decoction pieces, lily decoction pieces, platycladi seed decoction pieces, cistanche decoction pieces and poria cocos decoction pieces according to the formula shown in the embodiment 1; pulverizing parched semen Ziziphi Spinosae into coarse powder; extracting with 12 times volume of 50% ethanol twice, each for 1.5 hr, concentrating the extractive solution at 70 deg.C to density of 1.200 (measured by heat), drying at 70 deg.C under reduced pressure to obtain solid, pulverizing, sieving with 60 mesh sieve, and adding adjuvants at the following ratio: mixing 7% low-substituted hydroxypropyl cellulose (LH-11), 2% silicon dioxide, 0.3% magnesium stearate, and microcrystalline cellulose, and making into capsule with a loading amount of 0.68 g.
Example 13 granules
Taking rhizoma anemarrhenae decoction pieces, rose decoction pieces, lily decoction pieces, platycladi seed decoction pieces, cistanche decoction pieces and poria cocos decoction pieces according to the formula shown in the embodiment 1; pulverizing parched semen Ziziphi Spinosae into coarse powder; extracting with 10 times volume of 50% ethanol twice, each for 1.5 hr, concentrating the extractive solution at 70 deg.C to density of 1.200 (measured thermally), drying at 70 deg.C under reduced pressure to obtain solid, pulverizing, sieving with 60 mesh sieve, adding appropriate amount of dextrin and starch, granulating, drying, and making into granule.
Claims (10)
1. The pharmaceutical composition for improving sleep quality is characterized by being prepared from the following traditional Chinese medicine raw materials in parts by weight:
2. the pharmaceutical composition according to claim 1, which is prepared from the following traditional Chinese medicine raw materials in parts by weight:
3. a process for preparing a pharmaceutical composition according to claim 1, comprising the steps of:
extracting the above Chinese medicinal materials with 6-10 times volume of ethanol for 1-4 times (each for 1-2 hr), concentrating the extractive solution, drying under reduced pressure to obtain solid, pulverizing into powder, and sieving.
4. A process for preparing a pharmaceutical composition according to claim 1, comprising the steps of:
extracting decoction pieces or coarse powder of the above Chinese medicinal materials with 6-10 times volume of 30-70% ethanol for 1-4 times (each for 1-2 hr), concentrating the extractive solution, drying under reduced pressure to obtain solid, pulverizing into powder, and sieving.
5. A process for preparing a pharmaceutical composition according to claim 1, comprising the steps of:
extracting decoction pieces or coarse powder of the above Chinese medicinal materials with 8 times volume of 50% ethanol twice, each for 1.5 hr, concentrating the extractive solution at 50-70 deg.C to density of 1.20-1.40, drying at 50-70 deg.C under reduced pressure to obtain solid, pulverizing, and sieving.
6. A process for preparing a pharmaceutical composition according to claim 1, comprising the steps of:
the raw material medicines are as follows: 5g of cistanche, 15g of fried spina date seed, 5g of poria cocos, 5g of rhizoma anemarrhenae, 2.5g of rose and 5g of platycladi seed; the preparation method comprises the following steps: taking rhizoma anemarrhenae decoction pieces, flos Rosae Rugosae decoction pieces, bulbus Lilii decoction pieces, semen Platycladi decoction pieces, herba cistanches decoction pieces, and Poria decoction pieces; pulverizing parched semen Ziziphi Spinosae into coarse powder; mixing, extracting with 8 times volume of 50% ethanol twice, each for 1.5 hr, concentrating the extractive solution at 60 deg.C to density of 1.200, drying at 60 deg.C under reduced pressure to obtain solid, pulverizing, and sieving with 60 mesh sieve.
7. The pharmaceutical composition of claim 1, in any ingestible pharmaceutical form.
8. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated as tablets, capsules, buccal formulations, granules, pills, powders, ointments, pellets, suspensions, solutions, injections, suppositories, ointments, plasters, creams, sprays, drops, patches.
9. A pharmaceutical preparation comprising the pharmaceutical composition of claim 1, further comprising pharmaceutically acceptable excipients, wherein the pharmaceutically acceptable excipients may be 0.01 to 99.99% by weight of the total weight of the preparation.
10. The use of the pharmaceutical composition of claim 1 in the preparation of a medicament or health product for improving sleep quality.
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| CN107349321A (en) * | 2017-06-23 | 2017-11-17 | 天津金匮堂生物科技有限公司 | A kind of Chinese medicine for improving sleep |
| CN111743968A (en) * | 2019-03-28 | 2020-10-09 | 太和康美(北京)中医研究院有限公司 | Plant composition, preparation method and application thereof |
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