A traditional Chinese medicine composition for treating chronic insomnia, a preparation method thereof and application thereof

Abstract

The application belongs to the field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating chronic insomnia and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 6-18 parts of mimusops elengi, 6-18 parts of lotus seed, 6-18 parts of lily, 9-30 parts of clematis, and 0.25-1 part of safflower. According to the pathogenesis of yang failing to enter yin in traditional Chinese medicine, the plant medicine with the characteristic of night movement is used for treating insomnia. The clinical curative effect of the traditional Chinese medicine composition presents multilink, can shorten the sleep latency of chronic insomnia patients, prolong the sleep time, reduce the number of night awakenings, improve the daytime function, has no obvious adverse reactions, is high in safety, and is worthy of clinical popularization and application.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, specifically relating to a traditional Chinese medicine composition for treating chronic insomnia, its preparation method, and its application. Background Technology

[0002] Insomnia is a common and prevalent clinical condition, affecting up to 35% of the population, with 10-13% suffering from chronic insomnia. It severely impacts quality of life and health, imposing a significant economic burden and social pressure. The mechanisms of insomnia are complex, and there is currently a lack of clearly defined and effective pharmacological targets for treatment-resistant or intractable insomnia.

[0003] Currently, clinical treatment for insomnia primarily relies on sedative-hypnotic drugs and antidepressants / anxiety medications, most of which are single-target drugs. For example, while benzodiazepine receptor agonists (BZRAs) have been proven to be relatively safe and effective hypnotics, their effect on prolonging sleep time mainly occurs in the light sleep phase of non-rapid eye movement (NREM) sleep 2 and the rapid eye movement (REM) sleep phase, failing to truly improve sleep quality. Furthermore, many drugs suffer from problems such as drug tolerance, dependence, and cutoff effects, especially showing poor efficacy in treatment-resistant insomnia, and thus failing to meet the dual needs of insomnia patients for both effectiveness and safety.

[0004] Traditional Chinese medicine (TCM) compositions, based on TCM theory, are characterized by syndrome differentiation and treatment combined with disease differentiation and treatment in disease treatment. Multi-target effects and solid, extensive clinical practice are inherent characteristics of TCM, enabling comprehensive improvement of clinical symptoms through multiple pathways and providing broader research opportunities for insomnia research. However, current research on the treatment of insomnia with nocturnal plants has been limited to single-herb studies, without treating them as a special category of nocturnal plant TCM. Summary of the Invention

[0005] The inventors conducted systematic theoretical research on chronic insomnia, proposed that herbal medicines with nymphogenic properties can be used to treat insomnia, and after nearly six years of clinical research, summarized a herbal composition that can effectively and safely treat chronic insomnia.

[0006] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating chronic insomnia, which is made from the following raw materials in parts by weight:

[0007] Albizia bark 6-18 parts, lotus seeds 6-18 parts, lily bulbs 6-18 parts, Polygonum multiflorum 9-30 parts, saffron 0.25-1 part.

[0008] A second aspect of the present invention provides a method for preparing a traditional Chinese medicine composition for treating chronic insomnia, comprising the following steps:

[0009] S1. Weigh each ingredient according to the weight proportions, mix the ingredients and add 9-11 times the amount of water, bring to a boil over high heat, then simmer over low heat for 50-60 minutes, filter, and obtain the first decoction.

[0010] S2. Add 8-10 times the amount of water to the dregs obtained in S1 and decoct. First, bring to a boil over high heat, then simmer over low heat for 20-30 minutes. Filter to obtain the second decoction.

[0011] S3. Combine the two decoctions, filter, and concentrate to obtain the decoction.

[0012] Furthermore, in S3, the two decoction liquids are combined, filtered, and concentrated to obtain a dry extract. The dry extract is then pulverized, mixed with an appropriate amount of sucrose and dextrin, granulated with ethanol as a wetting agent, dried, and sized to obtain granules.

[0013] Further, in S3, the two decoctions are combined, filtered, and concentrated to obtain a dry extract. The dry extract is pulverized, and an appropriate amount of micronized silica gel and α-galactose are added and mixed. Ethanol is used as a wetting agent to granulate, dry, granulate, and encapsulate to obtain a capsule.

[0014] Further, in S3, the two decoction liquids are combined, filtered, and concentrated to obtain a dry extract. The dry extract is pulverized, and an appropriate amount of sucrose and dextrin are added and mixed. Ethanol is used as a wetting agent to granulate, dry, granulate, and compress into tablets to obtain tablets.

[0015] Furthermore, in S3, the two decoctions are combined, filtered, concentrated, and centrifuged. An appropriate amount of sucrose and flavoring are added to the concentrated liquid after centrifugation, and the mixture is sterilized and bottled to obtain an oral liquid.

[0016] A third aspect of the present invention provides the use of the traditional Chinese medicine composition in the preparation of a medicament for treating chronic insomnia.

[0017] Furthermore, the treatment includes shortening the sleep latency of patients with chronic insomnia, prolonging sleep time, reducing the number of nighttime awakenings, and improving daytime function.

[0018] The present invention has the following beneficial effects:

[0019] Based on the traditional Chinese medicine understanding of insomnia as "Yang failing to enter Yin," the inventor believes that the core pathogenesis of insomnia is the disruption of the rhythm of Yang Qi entering and exiting the Yin aspect of the body. In nature, there are some plants whose growth characteristics are similar to the sleep-wake rhythm of the human body, such as lilies (Lilium spp.), lotus (Nymphaeaceae), mimosa (Albizia julibrissin), Polygonum multiflorum (Polygonum multiflorum), and saffron (Iridaceae). The leaves, flowers, and vines of these plants exhibit diurnal rhythmic movements; for example, the leaves of mimosa "close at dusk"; lilies "open during the day and close at night"; and Polygonum multiflorum "closes at night." In modern botany, this diurnal rhythmic movement phenomenon of plants is called "nocturnal movement," and these plants are also known as "nocturnal plants." Based on this, a systematic study of this type of drug for treating insomnia was conducted, and after repeated experiments, the traditional Chinese medicine composition of this invention was proposed. All five herbs exhibit a rhythmic pattern of being active during the day and sparse at night. Among them, saffron, which cools the blood, relieves depression, and calms the mind, serves as the principal herb; lily bulb clears the heart and calms the mind; Polygonum multiflorum nourishes the blood and calms the mind; and Albizia julibrissin bark relieves depression and calms the mind—these three act as assistant herbs. This combination addresses insomnia caused by yin deficiency and excessive fire disturbing the mind, as well as insomnia caused by insufficient qi and blood failing to nourish the mind. It can also be used for insomnia caused by emotional distress and liver fire disturbing the heart, embodying the treatment philosophy of combining symptom and syndrome differentiation. Lotus seed is added as the guiding herb; its sweet and astringent properties soothe and calm the mind, coordinating the effects of all the herbs to guide yang into yin, calm the mind, and aid sleep.

[0020] Animal experiments have shown that the traditional Chinese medicine composition of the present invention can effectively inhibit the amount of spontaneous activity in mice, shorten the sleep latency of sodium pentobarbital, prolong the sleep duration, reduce the frequency of wakefulness-insomnia transition in PCPA-induced insomnia rats, prolong the occurrence of long NREM and REM sleep cycles and thus prolong sleep time, and improve sleep structure.

[0021] Clinical studies have shown that the composition of this invention can shorten the sleep latency of patients with chronic insomnia, prolong sleep time, reduce the number of nighttime awakenings, and improve daytime function. Attached Figure Description

[0022] Figure 1 The diurnal activity of rats on day 3 of drug administration in the efficacy experiment is shown. (AD) represents the activity trajectory of long-term spontaneous activity; (E) represents the activity distance of long-term spontaneous activity. All data are expressed as MEAN±SEM, n=4. **: P<0.001: Vehicle-Control and PCPA-Control, PCPA-NHD, PCPA-DZP; ##: P<0.01, ###: P<0.001: PCPA-Control and PCPA-NHP, PCPA-DZP.

[0023] Figure 2The temporal variation of NREM and REM sleep in rats on day 3 after drug administration in the efficacy experiment is shown in Figure (A), and the hourly sleep duration during light and dark periods is shown in Figure (B). All data are expressed as MEAN±SEM, n=4. ***: P<0.001, **: P<0.01, *: P<0.05, Vehicle-Control vs. PCPA-Control, PCPA-NHD, PCPA-DZP; ###: P<0.001, ##: P<0.01, #: P<0.05: PCPA-Control vs. PCPA-NHP, PCPA-DZP.

[0024] Figure 3 The values ​​represent the number of occurrences (A), average duration (B), and number of transitions (C) of different sleep stages during the 24-hour period on day 3 after drug administration in the efficacy experiment. All data are expressed as MEAN±SEM, n=4. ***: P<0.001, **: P<0.01, *: P<0.05, Vehicle-Control and PCPA-Control, PCPA-NHD, PCPA-DZP; ###: P<0.001, ##: P<0.01, #: P<0.05: PCPA-Control and PCPA-NHP, PCPA-DZP

[0025] Figure 4 The changes in neurotransmitter levels in rats after 3 days of drug administration in a pharmacodynamic experiment are shown in (A) the levels of 5-HT, 5-HIAA, and 5-HIAA / 5-HT, and (B) the levels of NE, DA, and ACh. All data are expressed as MEAN±SEM, n=4–5, ***: P<0.001, **: P<0.01, *: P<0.05, Vehicle-Control and PCPA-Control, PCPA-NHD, PCPA-DZP; ###: P<0.001, ##: P<0.01, #: P<0.05: PCPA-Control and PCPA-NHP, PCPA-DZP; 5-HT, serotonin; 5-HIAA, 5-hydroxyindoleacetic acid; NE, norepinephrine; DA, dopamine; ACh, acetylcholine.

[0026] Figure 5This study depicts the spontaneous activity of mice before modeling, 30 min after treatment, and 24 h after treatment in a synergistic effect experiment. (A) Spontaneous activity trajectory of mice; (B) Spontaneous activity distance of mice. All data are expressed as MEAN±SEM, n=6. ***: P<0.001, **: P<0.01, *: P<0.05, Before Modeling and 30 min After Treatment; ###: P<0.001, 30 min After Treatment and 24 h After Treatment.

[0027] Figure 6 Immobility time in mice after drug administration during the synergistic effect experiment. (A) Immobility time in the forced swimming experiment; (B) Immobility time in the tail suspension experiment. All data are expressed as MEAN±SEM, n=6. ***: P<0.001, Vehicle versus PCPA, NHD(S+), Saffron, NHD(S-), Diazepam; ###: P<0.001: PCPA versus NHD(S+), Saffron, NHD(S-), Diazepam.

[0028] Figure 7 To detect the sleep latency and sleep duration induced by sodium pentobarbital in normal mice during the synergistic effect experiment, the following data were obtained. (A) Sodium pentobarbital sleep latency; (B) Sodium pentobarbital sleep duration. All data are expressed as MEAN±SEM, n=6. ***: P<0.001, **: P<0.01, *: P<0.05, Vehicle vs. NHD(S+), NHD(S-), Saffron. Detailed Implementation

[0029] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments, but this should not be construed as limiting the invention. Unless otherwise specified, the technical means used in the following embodiments are conventional means well known to those skilled in the art, and the materials, reagents, etc. used in the following embodiments are commercially available unless otherwise specified.

[0030] The raw materials used in the following examples—Albizia bark, lotus seeds, lily bulbs, Polygonum multiflorum stem, and saffron—all comply with the relevant provisions of the Chinese Pharmacopoeia 2020 edition, Volume I, under the respective medicinal materials section. Each medicinal material underwent cleaning, cutting, processing, and pulverizing. Before being added to the Pharmacopoeia, each material was identified to ensure that its actual appearance matched its name, and its quality met the national Pharmacopoeia standards (specific identification methods for medicinal materials were implemented according to the Pharmacopoeia standards).

[0031] Example 1

[0032] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0033] Weigh out 150g of Albizia bark, 150g of lotus seeds, 150g of lily bulbs, 300g of Polygonum multiflorum stem, and 10g of saffron. Add 7.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 6.0L of water to the dregs from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to 4L to obtain the decoction.

[0034] Example 2

[0035] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0036] Weigh out 180g of Albizia bark, 180g of lotus seeds, 180g of lily bulbs, 90g of Polygonum multiflorum stem, and 2.5g of saffron. Add 6.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour to extract. Filter to obtain the first decoction. Add 5.70L of water to the dregs obtained from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes to extract. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to 3.5L to obtain the decoction.

[0037] Example 3

[0038] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0039] Weigh out 100g of Albizia bark, 100g of lotus seeds, 100g of lily bulbs, 200g of Polygonum multiflorum stem, and 5g of saffron. Add 5.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 4.60L of water to the dregs obtained from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to 3.2L to obtain the decoction.

[0040] The decoctions prepared in Examples 1-3 can be used flexibly according to changes in the patient's condition. The drugs can promote and restrain each other, which can enhance the therapeutic effect, moderate the drug properties, and reduce side effects.

[0041] Example 4

[0042] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0043] Weigh out 150g of Albizia bark, 150g of lotus seeds, 150g of lily bulbs, 300g of Polygonum multiflorum stem, and 10g of saffron. Add 7.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 6.0L of water to the residue from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to an extract with a relative density of 1.40 at 20℃. Centrifuge at 3000 rpm for 10 minutes; spray dry at 60℃ to obtain the dry extract.

[0044] The dry extract is pulverized, and the dry extract, sucrose, and dextrin (mass ratio 1:3:1) are mixed, granulated with 70% ethanol as a wetting agent, dried, and sized to obtain granules.

[0045] Example 5

[0046] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0047] Weigh out 180g of Albizia bark, 180g of lotus seeds, 180g of lily bulbs, 90g of Polygonum multiflorum stem, and 2.5g of saffron. Add 6.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 5.70L of water to the residue from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to an extract with a relative density of 1.40 at 20℃. Centrifuge at 3000 rpm for 10 minutes; spray dry at 60℃ to obtain the dry extract.

[0048] The dry extract is pulverized, and the dry extract, sucrose, and dextrin (mass ratio 1:3:1) are mixed, granulated with 70% ethanol as a wetting agent, dried, and sized to obtain granules.

[0049] Example 6

[0050] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0051] Weigh out 100g of Albizia bark, 100g of lotus seeds, 100g of lily bulbs, 200g of Polygonum multiflorum stem, and 5g of saffron. Add 5.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 4.60L of water to the residue from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to an extract with a relative density of 1.40 at 20℃. Centrifuge at 3000 rpm for 10 minutes; spray dry at 60℃ to obtain the dry extract.

[0052] The dry extract is pulverized, and the dry extract, sucrose, and dextrin (mass ratio 1:3:1) are mixed, granulated with 70% ethanol as a wetting agent, dried, and sized to obtain granules.

[0053] The granules prepared in Examples 4-6 can be taken by simply adding boiling water before use, making them convenient to take.

[0054] Example 7

[0055] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0056] Weigh out 150g of Albizia bark, 150g of lotus seeds, 150g of lily bulbs, 300g of Polygonum multiflorum stem, and 10g of saffron. Add 7.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 6.0L of water to the dregs from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to a relative density of 1.40 at 20℃. Centrifuge at 3000 rpm for 10 minutes. Spray dry at 60℃ to obtain a dry extract.

[0057] The dry extract is pulverized, mixed with an appropriate amount of micronized silica gel and α-galactose, granulated with ethanol as a wetting agent, dried, sized, and encapsulated to obtain capsules.

[0058] Example 8

[0059] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0060] Weigh out 180g of Albizia bark, 180g of lotus seeds, 180g of lily bulbs, 90g of Polygonum multiflorum stem, and 2.5g of saffron. Add 6.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 5.70L of water to the dregs from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to a relative density of 1.40 at 20℃. Centrifuge at 3000 rpm for 10 minutes. Spray dry at 60℃ to obtain a dry extract.

[0061] The dry extract is pulverized, mixed with an appropriate amount of micronized silica gel and α-galactose, granulated with ethanol as a wetting agent, dried, sized, and encapsulated to obtain capsules.

[0062] Example 9

[0063] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0064] Weigh out 100g of Albizia bark, 100g of lotus seeds, 100g of lily bulbs, 200g of Polygonum multiflorum stem, and 5g of saffron. Add 5.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 4.60L of water to the residue from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to a relative density of 1.40 at 20℃. Centrifuge at 3000 rpm for 10 minutes. Spray dry at 60℃ to obtain a dry extract.

[0065] The dry extract is pulverized, mixed with an appropriate amount of micronized silica gel and α-galactose, granulated with ethanol as a wetting agent, dried, sized, and encapsulated to obtain capsules.

[0066] The capsules prepared in Examples 7-9 are not only neat and aesthetically pleasing and easy to swallow, but they can also mask the unpleasant odor of the drug and rapidly disintegrate and release the drug after ingestion to exert its therapeutic effect.

[0067] Example 10

[0068] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0069] Weigh out 150g of Albizia bark, 150g of lotus seeds, 150g of lily bulbs, 300g of Polygonum multiflorum stem, and 10g of saffron. Add 7.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 6.0L of water to the dregs from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to a relative density of 1.40 at 20℃. Centrifuge at 3000 rpm for 10 minutes. Spray dry at 60℃ to obtain a dry extract.

[0070] The dry extract is pulverized, mixed with an appropriate amount of sucrose and dextrin, granulated with ethanol as a wetting agent, dried, sized, and compressed into tablets to obtain tablets.

[0071] Example 11

[0072] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0073] Weigh out 180g of Albizia bark, 180g of lotus seeds, 180g of lily bulbs, 90g of Polygonum multiflorum stem, and 2.5g of saffron. Add 6.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 5.70L of water to the dregs from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to a relative density of 1.40 at 20℃. Centrifuge at 3000 rpm for 10 minutes. Spray dry at 60℃ to obtain a dry extract.

[0074] The dry extract is pulverized, mixed with an appropriate amount of sucrose and dextrin, granulated with ethanol as a wetting agent, dried, sized, and compressed into tablets to obtain tablets.

[0075] Example 12

[0076] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0077] Weigh out 100g of Albizia bark, 100g of lotus seeds, 100g of lily bulbs, 200g of Polygonum multiflorum stem, and 5g of saffron. Add 5.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 4.60L of water to the residue from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to a relative density of 1.40 at 20℃. Centrifuge at 3000 rpm for 10 minutes. Spray dry at 60℃ to obtain a dry extract.

[0078] The dry extract is pulverized, mixed with an appropriate amount of sucrose and dextrin, granulated with ethanol as a wetting agent, dried, sized, and compressed into tablets to obtain tablets.

[0079] The tablets prepared in Examples 10-12 have advantages such as accurate dosage, low cost, and convenient administration, storage, and transportation.

[0080] Example 13

[0081] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0082] Weigh out 150g of Albizia bark, 150g of lotus seeds, 150g of lily bulbs, 300g of Polygonum multiflorum stem, and 10g of saffron. Add 7.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 6.0L of water to the dregs from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to a relative density of 1.40 at 20℃. Centrifuge at 3000 rpm for 10 minutes.

[0083] Add appropriate amounts of sucrose and flavoring to the concentrated liquid after centrifugation, mix, sterilize, and fill to obtain an oral liquid.

[0084] Example 14

[0085] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0086] Weigh out 180g of Albizia bark, 180g of lotus seeds, 180g of lily bulbs, 90g of Polygonum multiflorum stem, and 2.5g of saffron. Add 6.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 5.70L of water to the dregs from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to a relative density of 1.40 at 20℃. Centrifuge at 3000 rpm for 10 minutes.

[0087] Add appropriate amounts of sucrose and flavoring to the concentrated liquid after centrifugation, mix, sterilize, and fill to obtain an oral liquid.

[0088] Example 15

[0089] A traditional Chinese medicine composition for treating chronic insomnia, prepared as follows:

[0090] Weigh out 100g of Albizia bark, 100g of lotus seeds, 100g of lily bulbs, 200g of Polygonum multiflorum stem, and 5g of saffron. Add 5.50L of water to the first decoction, bring to a boil over high heat, then simmer over low heat for 1 hour. Filter to obtain the first decoction. Add 4.60L of water to the dregs from the first decoction, bring to a boil over high heat, then simmer over low heat for 30 minutes. Filter to obtain the second decoction. Combine the two decoctions, filter, and concentrate the filtrate to a relative density of 1.40 at 20℃. Centrifuge at 3000 rpm for 10 minutes.

[0091] Add appropriate amounts of sucrose and flavoring to the concentrated liquid after centrifugation, mix, sterilize, and fill to obtain an oral liquid.

[0092] The oral liquids prepared in Examples 13-15 are based on decoctions with the addition of sucrose and flavorings, making them easy to take and able to mask the unpleasant odor of the medicine.

[0093] The different dosage forms of traditional Chinese medicine compositions prepared in Examples 1-15 each have their own characteristics and all have significant therapeutic effects on chronic insomnia. The efficacy of the traditional Chinese medicine compositions of the present invention will be verified below using the decoction prepared in Example 1 as an example.

[0094] Experimental Example 1: Pharmacodynamic Study of Sedative-Hypnotic Effects of Traditional Chinese Medicine Composition

[0095] 1) Drug efficacy experiment

[0096] Methods: A Wistar rat model of insomnia was established by intraperitoneal injection of 400 mg / kg p-chlorophenylalanine (PCPA) for 2 days. Water was used as a control, and a traditional Chinese medicine combination (NHD) and diazepam (DZP) were administered by gavage at 1 ml / 100 g once a day for 3 consecutive days. The diurnal activity, electroencephalogram (EEG) and neurotransmitter content were observed on the 24-hour period of the third day.

[0097] Results: The traditional Chinese medicine composition (NHD) was used to intervene in PCPA-induced insomnia in rats and was found to effectively inhibit the increase in spontaneous activity distance induced by PCPA. Figure 1 In EEG analysis, NHD can reduce the cumulative amount during the WAKE phase and increase the cumulative amount during the NREM and REM phases. Figure 2 This reduces the frequency of sleep-wake transitions, prolongs the average duration of sleep, and improves sleep structure in rats. Figure 3 Detection of changes in hypothalamic neurotransmitters revealed that it can increase 5-HT synthesis and utilization, and inhibit excitatory neurons such as NE, ACh, and DA. Figure 4 This helps regulate sleep.

[0098] 2) Synergistic effect experiment

[0099] Methods: C57BBL / 6 mice were induced to develop chlorophenylalanine (PCPA) by intraperitoneal injection of 400 mg / kg for 2 days. The mice were then administered water (Control), NHD(S-) (the herbal composition did not contain saffron), Saffron, NHD(S+) (the herbal composition contained saffron), and Diazepam (Diazepam) by gavage at a dose of 0.1 ml / 10 g.

[0100] Spontaneous activity was assessed before modeling, 30 minutes after treatment, and 24 hours after treatment.

[0101] The immobility time of forced swimming and tail suspension tests was measured after interventional drug administration.

[0102] Sleep was induced by 1% sodium pentobarbital (45 mg / kg), and the disappearance of the righting reflex for more than 1 minute was used as the marker of sleep. The sleep latency and sleep duration were observed in mice. Sleep latency refers to the time from the start of sodium pentobarbital injection to the disappearance of the righting reflex for more than 1 minute, and sleep duration refers to the time from the disappearance of the righting reflex for more than 1 minute to the recovery of the righting reflex.

[0103] Result: As Figure 5-7 As shown, through short-term behavioral experiments and pentobarbital sodium sleep cooperation experiments, it is clear that the traditional Chinese medicine composition has a sedative effect, can reduce the activity of spontaneous activities of mice, shorten the sleep latency of pentobarbital sodium, prolong the sleep maintenance time, improve the depressive state caused by PCPA, and this medicine combination has synergistic effects. The traditional Chinese medicine composition containing saffron has more obvious curative effects compared with single saffron and the traditional Chinese medicine composition without saffron. At the same time, its sedative effect does not affect the activity behavior on the second day and has no obvious residual effect, showing certain safety.

[0104] Test Example 2: Clinical Study on the Sedative and Hypnotic Effects of Traditional Chinese Medicine Composition

[0105] A total of 450 patients from Fengxian District Traditional Chinese Medicine Hospital in Shanghai were included in the study, including 150 in the control group and 300 in the observation group. The control group was given Tianwang Buxin Pills, and the observation group was given the traditional Chinese medicine composition for treatment. The decoction was uniformly decocted by the hospital's decoction room. One dose per day (400 ml of the decoction obtained in Example 1, divided into 2 bags), orally administered twice at 4 pm and 2 hours before bedtime respectively, and the course of treatment was 8 weeks. The sleep curative effect, traditional Chinese medicine syndrome curative effect and adverse reactions of the two groups of patients were observed. During the research process, 10 patients dropped out in the control group and 8 patients dropped out in the observation group. Finally, 140 people were included in the control group and 292 people were included in the observation group. After 8 weeks of treatment, the sleep curative effects of both groups were improved (Tables 1 - Table 5). In terms of the improvement degree, the traditional Chinese medicine composition can effectively shorten the sleep latency and has a more obvious improvement in daytime function. However, in terms of prolonging the deep sleep time and reducing the number of nocturnal awakenings, Tianwang Buxin Pills have more advantages. It can be seen that the traditional Chinese medicine composition has multi-link curative effects on improving insomnia, has no obvious adverse reactions, has high safety, and is worthy of clinical promotion and application.

[0106] Table 1 Improvement of Modified SPIEGEL Sleep Scale Score and Sleep Curative Effect Evaluation before and after Treatment [Case (%)]

[0107]

[0108] Table 2 Changes in Sleep Latency before and after Treatment [Case (%)]

[0109]

[0110]

[0111] Note: A: 10 - 30 minutes, B: 30 - 60 minutes, C: 1 - 2 hours, D: more than 2 hours.

[0112] Table 3 Changes in Sleep Duration before and after Treatment [Case (%)]

[0113]

[0114] Note: A: 7-8 hours, B: 6-7 hours, C: 5-6 hours, D: 3-5 hours, E: <3 hours.

[0115] Table 4. Changes in sleep maintenance before and after treatment [n(%)]

[0116]

[0117] Table 5. Changes in sleep maintenance before and after treatment in the two groups of patients [n(%)]

[0118]

[0119] It should be noted that when numerical ranges are mentioned in the claims of this invention, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected. To avoid redundancy, the present invention describes preferred embodiments.

[0120] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

[0121] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A traditional Chinese medicine composition for treating chronic insomnia, characterized in that, Made from the following raw materials by weight: 150g of Albizia bark, 150g of lotus seeds, 150g of lily bulbs, 300g of Polygonum multiflorum stem, and 10g of saffron.

2. The method for preparing the traditional Chinese medicine composition for treating chronic insomnia according to claim 1, characterized in that, Includes the following steps: S1. Weigh each ingredient according to the weight proportions, mix the ingredients and add 9-11 times the amount of water, bring to a boil over high heat, then simmer over low heat for 50-60 minutes, filter, and obtain the first decoction. S2. Add 8-10 times the amount of water to the dregs obtained in S1 and decoct. First, bring to a boil over high heat, then simmer over low heat for 20-30 minutes. Filter to obtain the second decoction. S3. Combine the two decoctions, filter, and concentrate to obtain the decoction.

3. The preparation method according to claim 2, characterized in that, In step S3, the two decoction liquids are combined, filtered, and concentrated to obtain a dry extract. The dry extract is then pulverized, mixed with an appropriate amount of sucrose and dextrin, granulated with ethanol as a wetting agent, dried, and sized to obtain granules.

4. The preparation method according to claim 2, characterized in that, In step S3, the two decoctions are combined, filtered, and concentrated to obtain a dry extract. The dry extract is then pulverized, mixed with an appropriate amount of micronized silica gel and α-galactose, granulated with ethanol as a wetting agent, dried, sized, and encapsulated to obtain capsules.

5. The preparation method according to claim 2, characterized in that, In step S3, the two decoctions are combined, filtered, and concentrated to obtain a dry extract. The dry extract is then pulverized, mixed with an appropriate amount of sucrose and dextrin, granulated with ethanol as a wetting agent, dried, sized, and compressed into tablets.

6. The preparation method according to claim 2, characterized in that, In step S3, the decoctions from the two decoctions are combined, filtered, concentrated, and centrifuged. An appropriate amount of sucrose and flavoring are added to the concentrated liquid after centrifugation, the mixture is sterilized, and then bottled to obtain an oral liquid.

7. The use of the traditional Chinese medicine composition according to claim 1 in the preparation of a medicament for treating chronic insomnia.

8. The application according to claim 7, characterized in that, The treatment includes shortening the sleep latency of patients with chronic insomnia, prolonging sleep time, reducing the number of nighttime awakenings, and improving daytime function.

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