A traditional Chinese medicine composition for treating insomnia, and a preparation method and application thereof
This traditional Chinese medicine composition, consisting of Prunella vulgaris, Acorus tatarinowii, Cirsium japonicum, Platycladus orientalis seed, and Bambusa textilis, addresses the shortcomings of existing Chinese medicine insomnia preparations for patients with deficiency syndromes. It provides an effective treatment for insomnia caused by liver stagnation transforming into fire and phlegm-heat disturbing the interior, achieving significant calming effects and safety.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- BEIJING UNIV OF CHINESE MEDICINE
- Filing Date
- 2024-12-13
- Publication Date
- 2026-05-12
Smart Images
Figure CN119746005B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for treating insomnia, its preparation method, and its application. Background Technology
[0002] Insomnia is very common in clinical practice. Good sleep is a basic guarantee for the normal operation of various essential physiological functions such as maintaining immunity, protecting the brain, repairing the body, replenishing energy, and relieving fatigue. Insomnia can lead to cognitive decline, depression, obesity, decreased reproductive function, and a series of cardiovascular and cerebrovascular diseases.
[0003] While Western medicines used to treat insomnia have definite sedative and hypnotic effects, they often exhibit numerous side effects and are prone to addiction and tolerance. Traditional Chinese medicine (TCM) has a long history of treating insomnia, with reliable clinical efficacy and good safety. With the increasing demand for insomnia treatment, the development of TCM preparations with more definitive clinical effects and clearer mechanisms of action has significant clinical value and market demand.
[0004] Traditional Chinese medicine (TCM) theory holds that sleep is a process of transitioning from Yang to Yin, from movement to stillness, and from opening to closing, thus requiring a state of calm and tranquility. From a TCM perspective, insomnia may be caused by liver Qi stagnation, phlegm-fire disturbing the heart, Yin deficiency with excessive fire, deficiency of both heart and spleen, or disharmony between the heart and kidneys. Modern life, with its fast pace, high work pressure, and irregular eating habits, coupled with climate factors, easily leads to heat syndromes. Heat, being a Yang evil, is easily dissipated and agitated; therefore, internal heat most easily depletes the heart and spirit, causing insomnia, and further leading to excess-type insomnia. Currently, pharmaceutical companies mainly produce TCM insomnia preparations targeting patients with deficiency-type insomnia, focusing on nourishing the heart and calming the mind, tonifying Qi and replenishing the kidneys (such as Ziziphus jujuba seed paste, Wuling capsules, Bailuomian capsules, and Liuwei Anshen capsules). According to the clinical experience of Professor Wang Qingguo, a master of traditional Chinese medicine, more than one-third of insomnia patients suffer from excess-type insomnia due to liver Qi stagnation transforming into fire and phlegm-heat disturbing the mind, but there is still a lack of effective and fast-acting TCM preparations for excess-type insomnia on the market. Summary of the Invention
[0005] To overcome the problems existing in the prior art, one objective of this invention is to provide a traditional Chinese medicine composition. A second objective is to provide a method for preparing the aforementioned traditional Chinese medicine composition. A third objective is to provide applications of the traditional Chinese medicine composition.
[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:
[0007] The first aspect of the present invention provides a traditional Chinese medicine composition, which is prepared from the following raw materials in parts by weight: 12-17 parts of Prunella vulgaris, 7-11 parts of Acorus tatarinowii, 4-8 parts of Cirsium japonicum, 7-13 parts of Platycladus orientalis seed, and 4-8 parts of Bambusa textilis.
[0008] Based on the TCM theories of "supplementing what is deficient and purging what is excessive" and "treating the root cause of the disease," this invention cleverly utilizes the complementary properties of different drugs to target the cause of the disease from multiple aspects. It adopts the principle of "pungent, sweet, bitter, and cold" to create a TCM preparation for treating insomnia. This preparation combines Prunella vulgaris, which has the effect of clearing liver fire, Acorus tatarinowii, which has the effects of opening the orifices, resolving phlegm, refreshing the mind, and improving intelligence, with other Chinese herbs that enhance the clearing of liver fire and nourish the heart and calm the mind, along with Bambusa textilis, which is sweet and cold.
[0009] In the traditional Chinese medicine formula of this invention, Prunella vulgaris is the principal herb, Acorus tatarinowii and Cirsium japonicum are the assistant herbs, and Platycladus orientalis seed and Bambusa textilis are the adjuvant herbs. Prunella vulgaris, as the principal herb, clears liver fire and nourishes liver blood; Acorus tatarinowii, as the assistant herb, calms the mind and improves intelligence; Cirsium japonicum, as the assistant herb, cools the blood and removes blood stasis; Platycladus orientalis seed, as the adjuvant herb, calms the mind and soothes the nerves; and Bambusa textilis, as the adjuvant herb, clears heat and eliminates phlegm, calms the mind and relieves depression, and harmonizes the effects of the other herbs.
[0010] Prunella vulgaris: pungent, bitter, and cold in nature, it clears liver heat, improves eyesight, disperses nodules, and reduces swelling. It is the dried fruit spike of Prunella vulgaris L., a plant of the Lamiaceae family.
[0011] Sweet flag (Acorus tatarinowii): pungent, bitter, and warm in nature, it opens the orifices, clears phlegm, refreshes the mind and improves intelligence, and resolves dampness and stimulates the appetite. It is the dried rhizome of the plant Acorus tatarinowii (scientific name: Acrorus tatarinowii Schott) in the Araceae family.
[0012] Small thistle: sweet, bitter, cool, cool blood and stop bleeding, disperse blood stasis, detoxify and eliminate carbuncles. It is the dried aerial part of Cirsium setosum (Willd.) MB., a plant of the Asteraceae family.
[0013] Arborvitae seed kernel: sweet and neutral, nourishes the heart and calms the mind, moistens the intestines and promotes bowel movement, stops sweating, and is mainly used to treat wind-cold headache, sinusitis, phlegm, cough, and nasal congestion due to cold. It is the dried mature seed kernel of the arborvitae plant (scientific name Platycladus orientalis (L.) Franco).
[0014] Bamboo shavings: sweet, slightly cold, clears heat and resolves phlegm, relieves irritability, stops vomiting. It is the dried middle layer of the stems of the grass plants Bambusatuldoides Munro, Sinocalamus beecheyanus (Munro) McClure var. Pubescens PFLi, or Phyllostachys nigra (Lodd.) Munro var. hennis (Mitf.) Stapf ex Rendle.
[0015] Preferably, the active ingredient is prepared from the following raw materials in parts by weight: 13-16 parts of Prunella vulgaris, 8-10 parts of Acorus tatarinowii, 5-7 parts of Cirsium japonicum, 8-12 parts of Platycladus orientalis seed, and 5-7 parts of Bambusa textilis.
[0016] Preferably, it also includes pharmaceutically acceptable excipients.
[0017] For those skilled in the art, the aforementioned pharmaceutically acceptable uses of excipients are to improve drug stability or to give drugs appropriate dosage forms for easy transport, carrying, storage, or administration, such as surfactants, lubricants, and preservatives. The types of pharmaceutically acceptable excipients, as well as the selection criteria and methods, are well known to those skilled in the art. Through orthogonal experimental design methods, those skilled in the art can select suitable excipients, their proportions, and preparation processes through a limited number of experiments without inventive effort. For pharmaceutically acceptable excipients in traditional Chinese medicine compound preparations, see *Pharmaceutics* (edited by Cui Lide, Beijing: People's Medical Publishing House, 2007) and *Traditional Chinese Medicine Pharmaceutics* (edited by Zhang Zhaowang, Beijing: China Traditional Chinese Medicine Press, 2007), etc. For oral granules of traditional Chinese medicine, commonly used excipients include starch, lactose, microcrystalline silica gel, and microcrystalline cellulose. Their uses and methods of application in formulations are well known to those skilled in the art, and their dosages can be obtained directly through a limited number of experiments without inventive effort.
[0018] Preferably, the dosage form of the traditional Chinese medicine composition is an oral preparation or a transdermal absorption agent; wherein the oral preparation is selected from granules, powders, tablets, pills, oral liquids or capsules.
[0019] More preferably, the dosage form of the traditional Chinese medicine composition is a granule, specifically a solid granule of traditional Chinese medicine, which is obtained by mixing and granulating the following raw materials: volatile oil of Acorus tatarinowii, volatile oil of Platycladus orientalis seed, dry extract, and other pharmaceutical excipients; the dry extract is prepared from Acorus tatarinowii residue, Platycladus orientalis seed residue, Prunella vulgaris, Cirsium japonicum and Bambusa textilis.
[0020] More preferably, the volatile oils of Acorus tatarinowii and Platycladus orientalis are prepared into inclusion complexes by β-cyclodextrin inclusion.
[0021] The second aspect of this invention provides a method for preparing the traditional Chinese medicine composition described in the first aspect, comprising the following steps:
[0022] S1. The volatile oils of Acorus tatarinowii and Platycladus orientalis seeds were extracted by steam distillation to obtain volatile oils, residues and liquids.
[0023] S2. Combine the residue with Prunella vulgaris, Cirsium japonicum, and Bambusa textilis for water extraction and / or alcohol extraction 1, then combine the medicinal liquid and extract for concentration to obtain an extract; the water extraction may be performed once or multiple times.
[0024] S3. Combine the volatile oil and extract to obtain the traditional Chinese medicine composition;
[0025] Alternatively, the method may include the following steps: combining the raw materials and performing single or multiple alcohol extractions to obtain the traditional Chinese medicine composition.
[0026] The volatile oil contained in Acorus tatarinowii has a certain central nervous system depressant effect, and the volatile oil of Platycladus orientalis seed has the effect of nourishing the heart and calming the mind, and has a good effect on insomnia. In addition, the water extracts of both also contain components with sleep-inducing effects. Therefore, in the preparation process of this invention, the volatile oils of Acorus tatarinowii and Platycladus orientalis seed are first extracted, and the residue is mixed with other raw materials, decocted with water, and the water-soluble effective components are extracted and combined to obtain the Chinese medicine composition.
[0027] Preferably, the mass ratio of the water used in the steam distillation to the total mass of Acorus tatarinowii and Platycladus orientalis seeds is (15-20):1.
[0028] Preferably, the steam distillation time is 5-7 hours.
[0029] Preferably, the mass ratio of the amount of water used in the water extraction to the total mass of the medicinal residue and other raw materials is (15-25):1.
[0030] Preferably, the water extraction time is 1-2 hours.
[0031] Preferably, the temperature of the water extraction is 90-100℃.
[0032] Preferably, the water extraction is performed 2-3 times.
[0033] More preferably, step S2 is: combining the residue with Prunella vulgaris, Cirsium japonicum and Bambusa textilis for 2-3 water extractions, then combining the medicinal liquid and the extract for concentration to obtain an extract.
[0034] Preferably, the method further includes the following steps: preparing the volatile oil into an inclusion complex and then combining it with the extract.
[0035] More preferably, the inclusion complex is prepared by including the volatile oil with β-cyclodextrin using a saturated aqueous solution method.
[0036] Preferably, the concentration involves concentrating the combined liquid of the drug solution and the aqueous extract to a relative density of 1.10-1.15.
[0037] Preferably, step S2 further includes: concentrating the combined medicinal solution and extract, and performing alcohol precipitation to obtain an extract.
[0038] More preferably, the alcohol precipitation is achieved by adding ethanol dropwise to the concentrated liquid obtained from the concentration process until the alcohol content reaches 60%-80%.
[0039] Preferably, the mass ratio of alcohol used in the alcohol extraction 2 to the total mass of the residue and other raw materials is (15-25):1;
[0040] Preferably, the alcohol extraction time is 1-2 hours.
[0041] Preferably, the temperature of the alcohol extraction 2 is 70-80°C.
[0042] Preferably, the alcohol extraction 2 is performed 2-3 times.
[0043] Preferably, the alcohol extraction 2 uses an aqueous ethanol solution with a concentration of 40%-60%.
[0044] The third aspect of this invention provides the use of the traditional Chinese medicine composition described in the first aspect in the preparation of a medicament for treating insomnia.
[0045] Preferably, the insomnia is an insomnia disorder diagnosed by traditional Chinese medicine as liver stagnation transforming into fire and / or phlegm-fire disturbing the heart.
[0046] The beneficial effects of this invention are:
[0047] This invention provides a traditional Chinese medicine composition consisting of five specific herbs, with *Prunella vulgaris* as the principal herb, *Acorus tatarinowii* and *Cirsium japonicum* as assistant herbs, and *Platycladus orientalis* seed and *Bamboo shavings* as adjuvant herbs. *Prunella vulgaris*, which clears liver fire, and *Acorus tatarinowii*, which opens the orifices, resolves phlegm, and refreshes the mind, along with *Cirsium japonicum* and *Platycladus orientalis* seed, which further enhance liver fire clearing and heart-nourishing and calming effects, are combined with the sweet and cold *Bamboo shavings* to create a traditional Chinese medicine preparation for treating insomnia. This herbal composition has the effects of soothing the liver and clearing heat, relieving irritability and calming the mind, and has a significant therapeutic effect on sleep disorders caused by excessive liver fire, phlegm-heat, and yin deficiency. It can help patients alleviate insomnia symptoms and improve sleep quality through endogenous treatment. Attached Figure Description
[0048] Figure 1 The preparation method of the traditional Chinese medicine granules in Example 1 is as follows;
[0049] Figure 2 The results of the sleep-inducing experiment with sodium pentobarbital are shown; (a) shows the results of the sleep latency experiment, and (b) shows the results of the sleep duration experiment.
[0050] Figure 3 The results of the repeated synergistic sleep-inducing experiment with sodium pentobarbital are shown; (a) shows the results of the sleep latency experiment, and (b) shows the results of the sleep duration experiment.
[0051] Figure 2 and Figure 3 In the study, compared with the control group, *P<0.05, **P<0.01, *P<0.001, n=10. Detailed Implementation
[0052] The present invention will be further described in detail below through specific embodiments. Unless otherwise specified, the raw materials used in the following embodiments can be obtained from conventional commercial channels or prepared and isolated through simple synthesis; unless otherwise specified, the processes employed are conventional processes in the art.
[0053] Example 1
[0054] This embodiment provides a traditional Chinese medicine granule (solid granule), the effective ingredients of which are in the following mass ratio: 15 parts of Prunella vulgaris, 9 parts of Acorus tatarinowii, 6 parts of Cirsium japonicum, 10 parts of Platycladus orientalis seed, and 6 parts of Bambusa textilis. Figure 1 The preparation method of the traditional Chinese medicine granules in Example 1 is as follows:
[0055] S1. Take Acorus tatarinowii and Platycladus orientalis seeds, and extract volatile oil by steam distillation. The mass ratio of water used in steam distillation to the total mass of Acorus tatarinowii and Platycladus orientalis seeds is 16:1. The steam distillation time is 6 hours. The resulting liquid, residue and volatile oil are stored separately for later use.
[0056] S2. Mix Prunella vulgaris, Cirsium japonicum, and bamboo shavings with the dregs, add 18 times the amount of deionized water, soak for 1 hour, heat to 100℃ and reflux for 1.5 hours, filter to obtain filtrate 2; add 18 times the amount of deionized water again, heat to 100℃ and reflux for 1.5 hours, filter to obtain filtrate 3. Combine filtrate 1, filtrate 2, and filtrate 3, and concentrate the filtrate to a relative density of 1.10-1.15. Add ethanol dropwise to the above concentrate until the alcohol content reaches 70%, let stand for a certain period of time, centrifuge, collect the supernatant, recover the solvent, dry under reduced pressure to obtain a dry extract for later use.
[0057] S3. Add an appropriate amount of β-cyclodextrin to the volatile oils of Acorus tatarinowii and Platycladus orientalis seeds for encapsulation. Prepare a saturated aqueous solution of β-cyclodextrin. Dissolve the volatile oil in 95% ethanol at the same weight ratio. Add the volatile oil to the saturated aqueous solution at a ratio of 1:8 (volatile oil: β-cyclodextrin). Stir at 50°C for 2 hours at a stirring speed of 800 rpm. Let stand at 4°C for 24 hours. Filter the solution. Wash the filter layer with an appropriate amount of water and petroleum ether respectively. Evaporate the petroleum ether. Dry the solution in a vacuum drying oven at 40°C for 4 hours to prepare the inclusion complex. Mix the inclusion complex evenly with the above-mentioned dry extract of traditional Chinese medicine. Add an appropriate amount of dextrin, granulate, dry, and package to obtain the traditional Chinese medicine granule product.
[0058] Example 2
[0059] This embodiment provides a traditional Chinese medicine granule (solid granule), with the following mass ratio of active ingredients: 15 parts Prunella vulgaris, 9 parts Acorus tatarinowii, 6 parts Cirsium japonicum, 10 parts Platycladus orientalis seed, and 6 parts Bambusa textilis. The specific preparation steps are as follows:
[0060] S1. Take Acorus tatarinowii and Platycladus orientalis seeds, and extract volatile oil by steam distillation. The mass ratio of water used in steam distillation to the total mass of Acorus tatarinowii and Platycladus orientalis seeds is 16:1. The steam distillation time is 6 hours. Store the liquid, residue and volatile oil separately for later use.
[0061] S2. Mix Prunella vulgaris, Cirsium japonicum, and bamboo shavings with the dregs, add 20 times the amount of 50% ethanol (2200ml), heat to 80℃ and reflux for 1.5h, filter to obtain filtrate 2; add 18 times the amount of deionized water, heat to 80℃ and reflux for 1.5h, filter to obtain filtrate 3, combine filtrate 1, filtrate 2 and filtrate 3, concentrate the filtrate to a relative density of 1.10-1.15, recover the solvent, dry under reduced pressure to obtain dry extract for later use.
[0062] S3. Add an appropriate amount of β-cyclodextrin to the volatile oils of Acorus tatarinowii and Platycladus orientalis seeds for encapsulation. The encapsulation method is the same as in Example 1. Then mix the mixture evenly with the above-mentioned dry extract of traditional Chinese medicine, add an appropriate amount of dextrin, granulate, dry, and package to obtain the traditional Chinese medicine granule product.
[0063] Example 3
[0064] This embodiment provides a traditional Chinese medicine composition (i.e., a traditional Chinese medicine extract), wherein the effective components are in the following mass ratio: 15 parts of Prunella vulgaris, 9 parts of Acorus tatarinowii, 6 parts of Cirsium japonicum, 10 parts of Platycladus orientalis seed, and 6 parts of Bambusa textilis. The preparation steps are as follows:
[0065] Take Prunella vulgaris, Acorus tatarinowii, Cirsium japonicum, Platycladus orientalis seed, and bamboo shavings, place them in a 5000ml round-bottom flask, add 20 times the amount of 50% ethanol (2200ml), and reflux extract twice at 80℃, 1.5h each time. Filter, combine the filtrates, concentrate the decoction to a relative density of 1.10-1.15, recover the solvent, dry under reduced pressure to obtain a dry extract, add an appropriate amount of dextrin, granulate, dry, and package to obtain the traditional Chinese medicine granule product.
[0066] Experimental Analysis
[0067] The pentobarbital-induced sleep assay in mice is a widely accepted behavioral method for evaluating the sedative-hypnotic effects of drugs. This experiment used a suprathreshold dose-synergistic sleep assay with sodium pentobarbital to observe sleep latency and sleep duration. The disappearance of the righting reflex was used as the criterion for initiation of sleep. After administration, when the animal had essentially stopped moving, its position was turned over to a supine position. If the animal remained supine for more than 60 seconds, the righting reflex was considered to have disappeared and the animal had entered a sleep state. After a period of time, when the righting reflex first returned, the animal was immediately turned back to a supine position. If the righting reflex returned again within 30 seconds, the animal was considered to have awakened, and the time of the first return of the righting reflex was recorded as the sleep termination time.
[0068] The team used the classic method of the pentobarbital sodium-induced sleep assay (PIST) to verify the sedative-hypnotic efficacy of the compound. Based on previous research, the suprathreshold dose of pentobarbital sodium in ICR mice was determined to be 50 mg / kg, and this dose was continued in this experiment. The dosage was 55 g of the Prunella vulgaris compound orally per 70 kg adult, which is equivalent to 0.86 g / kg in mice. Fifty male ICR mice (8 weeks old, 20-25 g, SPF grade) were randomly divided into 5 groups: blank group, diazepam group, water extract group, alcohol extract group, and oil group, with 10 mice in each group. The oil group is Example 1, the water extract group is Example 2, and the alcohol extract group is Example 3. Pharmacodynamic studies were conducted using sleep latency and sleep onset time as indicators. Figure 2 and 3 The results of two repeated experiments showed that the formulations of Examples 1-3 had a good synergistic effect with sodium pentobarbital in inducing sleep in animals, effectively shortening the time for mice to fall asleep and increasing the duration of sleep in mice, and the formulation of Example 1 had a more significant effect.
[0069] The product of this invention is safe. Acute toxicity or maximum tolerated dose experiments were conducted using the powder from Example 1. Twelve male mice were administered the drug by gavage at the maximum test concentration (6.88 g / kg) and the maximum test volume. The maximum tolerated dose was equivalent to eight times the clinical dose, and no obvious abnormal reactions or gross pathological changes were observed.
[0070] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.
Claims
1. The application of a traditional Chinese medicine composition in the preparation of a drug for treating insomnia, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 12-17 parts of Prunella vulgaris, 7-11 parts of Acorus tatarinowii, 4-8 parts of Cirsium japonicum, 7-13 parts of Platycladus orientalis seed, and 4-8 parts of Bambusa textilis.
2. The application according to claim 1, characterized in that, It also includes pharmaceutically acceptable excipients.
3. The application according to claim 1, characterized in that, The dosage form of the traditional Chinese medicine composition is an oral preparation; wherein the oral preparation is selected from granules, powders, tablets, pills, oral liquids or capsules.
4. The application according to claim 1, characterized in that, The preparation method of the traditional Chinese medicine composition includes the following steps: S1. The volatile oils of Acorus tatarinowii and Platycladus orientalis seeds were extracted by steam distillation to obtain volatile oils, residues and liquids. S2. Combine the residue with Prunella vulgaris, Cirsium japonicum and Bambusa textilis for water extraction and / or alcohol extraction, then combine the liquid and extract for concentration to obtain an extract. S3. Combine the volatile oil and extract to obtain the traditional Chinese medicine composition.
5. The application according to claim 4, characterized in that, The mass ratio of water used in the steam distillation to the total mass of Acorus tatarinowii and Platycladus orientalis seeds is 15-20:1; And / or, the steam distillation time is 5-7 hours.
6. The application according to claim 4, characterized in that, The mass ratio of water used in the water extraction to the total mass of the medicinal residue and other raw materials is 15-25:
1. And / or, the water extraction time is 1-2 hours; And / or, the temperature of the water extraction is 90-100℃.
7. The application according to claim 4, characterized in that, It also includes the following steps: preparing the volatile oil into an inclusion complex and then combining it with the extract.
8. The application according to claim 1, characterized in that, The insomnia mentioned is a sleep disorder diagnosed by Traditional Chinese Medicine as liver stagnation transforming into fire and / or phlegm-fire disturbing the heart.