Traditional Chinese medicine composition for treating insomnia with syndrome of deficiency of heart-liver yin blood as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating insomnia caused by heart-liver yin blood deficiency and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following raw material medicines: semen boitae, fried jujube kernels, angelica sinensis, longan aril, poria with hostwood, semen cuscutae, radix ophiopogonis, radix morindae officinalis, fried radix paeoniae alba, schisandra chinensis and dens draconis. The traditional Chinese medicine composition disclosed by the invention has the effects of tonifying heart blood, nourishing liver blood, nourishing yin and suppressing yang, and tranquilizing by heavy prescription, and is especially suitable for treating insomnia caused by deficiency syndromes such as heart and liver yin blood deficiency syndromes. Therefore, the traditional Chinese medicine composition disclosed by the invention is particularly suitable for preparing medicines for treating insomnia caused by heart-liver yin blood deficiency, and has wide clinical application prospects and commercial values.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating insomnia caused by deficiency of heart and liver yin and blood, and a preparation method and use thereof. Background Art

[0002] Insomnia is a common disease with the main symptoms of difficulty falling asleep, waking up easily when asleep, difficulty falling asleep when waking up, and short sleep at night. If people do not get enough sleep for a long time, they will become more and more anxious and depressed, and it will have a huge impact on the cardiovascular system. Western medicine drugs for the treatment of insomnia mainly include first-generation barbiturates, second-generation benzodiazepines, and third-generation non-benzodiazepines. Among them, benzodiazepines are the most widely used hypnotic drugs in clinical practice. However, Western medicine has great limitations in the treatment of insomnia. It only treats the symptoms but not the root cause. Long-term use can easily lead to adverse reactions such as psychomotor damage, memory disorders, drug addiction, and recurrence of the disease after stopping the drug. It has large side effects and is limited in clinical application.

[0003] Insomnia is called "insomnia" in traditional Chinese medicine, also known as "eyes cannot close", "cannot sleep", etc. Traditional Chinese medicine believes that the causes and pathogenesis of insomnia include various factors such as overthinking, fatigue, internal damage to the heart and spleen, yang not communicating with yin, heart and kidney not communicating, yin deficiency and fire, liver yang disturbance, heart and gallbladder qi deficiency and stomach disharmony, all of which can affect the mind and cause insomnia. Its location is always related to the spleen, liver, heart and kidney, involving yin and blood deficiency; its pathological changes are always yang excess and yin deficiency, yin and yang not communicating, both deficiency and excess, but mostly deficiency syndrome. Deficiency syndrome is yin and blood deficiency, heart and brain not nourishing, manifested as thin physique, dull complexion, fatigue, lazy speech, palpitations and forgetfulness, mostly due to spleen failure to transform, liver failure to store blood, kidney failure to store essence, and empty mind. The positive syndrome is characterized by excessive fire disturbing the heart or blood stasis, manifested as irritability, bitter taste in the mouth and dry throat, constipation, red urine, chest tightness and pain, which are mostly caused by excessive heart fire, liver depression turning into fire, stagnation of phlegm and fire, and blockage of Qi and blood.

[0004] Generally speaking, most insomnia is caused by improper diet that damages the spleen and stomach, weakening the spleen's transportation and transformation function, resulting in phlegm, which turns into fire after a long period of time, and the combination of phlegm and fire, which disturbs the mind and emotions, liver depression turns into fire, phlegm and heat disturb the mind, yin deficiency and fire excess, heart and spleen deficiency, and heart and gallbladder qi deficiency. Traditional Chinese medicine believes that insomnia is related to the five internal organs, mainly the heart, spleen, and kidney, and is also related to the liver and lungs. The main principles of treatment are to balance yin and yang, replenish qi and blood, strengthen the spleen and kidney, and calm the mind. As one of the traditional treatment methods, Chinese medicine has unique advantages in the clinical application of treating insomnia, with its overall conditioning, syndrome differentiation and treatment, treating both the symptoms and the root causes, good efficacy, and few adverse reactions.

[0005] For example, Chinese patent CN103816467B discloses a Chinese medicine for treating insomnia due to deficiency of both heart and spleen, which is made of the following medicinal materials in weight ratio: 10 parts of ginseng, 20 parts of longan pulp, 20 parts of white hyacinth bean, 10 parts of rhizoma dahliae, 15 parts of genista chinensis, 10 parts of stir-fried immature bitter orange, 6 parts of chuanxiong, 10 parts of donkey hide gelatin, 6 parts of licorice, 10 parts of amomum, 24 parts of kudzu root, 10 parts of gardenia, 10 parts of polygala, 10 parts of lodestone, and 10 parts of valerian. The Chinese medicine has the effects of invigorating qi and blood, strengthening spleen and nourishing heart, and can effectively treat insomnia due to deficiency of both heart and spleen. Chinese patent CN116139236B discloses a Chinese medicine composition for treating insomnia of liver depression type, including a day prescription and a night prescription, wherein the day prescription is made of the following raw materials in parts by weight: 6-12 parts of bupleurum, 15-21 parts of stir-fried white peony root, 25-35 parts of calcined dragon bone, 2-4 parts of amomum villosum, 6-12 parts of processed cyperus, 6-12 parts of calamus, 4-8 parts of cicada slough, 4-8 parts of angelica dahurica, 6-12 parts of sophora flavescens , 6-12 parts of Bombyx Batryticatus, 6-12 parts of Ligusticum chuanxiong, and 4-8 parts of licorice; the Yefang is made of the following raw materials in parts by weight: 6-12 parts of Scutellaria baicalensis, 2-4 parts of cinnamon bark, 6-12 parts of Curcuma aromatica, 25-35 parts of Salvia miltiorrhiza, 6-12 parts of processed Cyperus rotundus, 6-12 parts of charred Gardenia, 10-20 parts of Polygonum multiflorum, 15-21 parts of Albizzia julibrissin, 6-12 parts of Polygala tenuifolia, 10-20 parts of Ganoderma lucidum, and 4-8 parts of licorice.

[0006] Although there are many traditional Chinese medicine prescriptions for the treatment of insomnia in clinical practice, there are relatively few prescriptions that are effective for the syndrome of heart and liver yin and blood deficiency and have been confirmed through efficacy experiments. Many prescriptions are only determined by traditional Chinese medicine practitioners based on their experience and have not been tested by recognized pharmacodynamic research models, which often leads to problems such as poor efficacy.

[0007] In view of this, the present invention uses modern pharmacological research methods, through in-depth research and screening of classical prescriptions of traditional Chinese medicine for treating insomnia, to develop a Chinese medicine composition that can effectively treat insomnia (especially insomnia of heart and liver yin and blood deficiency syndrome). Summary of the invention

[0008] The purpose of the present invention is to overcome the deficiencies in the prior art and provide a Chinese medicine composition that can effectively treat insomnia (especially insomnia of heart-liver yin-blood deficiency syndrome) and a preparation method and use thereof.

[0009] Specifically, the present invention is realized through the following technical solutions:

[0010] In the first aspect, the present invention provides a traditional Chinese medicine composition for treating insomnia, which is prepared from the following raw materials in parts by weight: 5-40 parts of pine nuts, 1-20 parts of stir-fried jujube seeds, 5-40 parts of angelica sinensis, 10-50 parts of longan pulp, 10-40 parts of poria, 10-50 parts of dodder seeds, 1-25 parts of ophiopogon japonicus, 5-40 parts of Morinda officinalis, 5-40 parts of stir-fried white peony root, 1-20 parts of schisandra chinensis, and 10-50 parts of dragon teeth.

[0011] As an optional method, in the above-mentioned traditional Chinese medicine composition, the traditional Chinese medicine composition is made of the following raw materials in parts by weight: 15-25 parts of pine nuts, 5-15 parts of fried jujube seeds, 15-25 parts of angelica, 25-35 parts of longan pulp, 20-30 parts of poria, 25-35 parts of dodder seeds, 10-20 parts of ophiopogon, 15-25 parts of Morinda officinalis, 15-25 parts of fried white peony root, 5-15 parts of schisandra, and 25-35 parts of dragon teeth.

[0012] As an optional method, in the above-mentioned traditional Chinese medicine composition, the traditional Chinese medicine composition is made of the following raw materials in parts by weight: 20 parts of pine nuts, 10 parts of fried jujube seeds, 20 parts of angelica, 30 parts of longan pulp, 25 parts of poria, 30 parts of dodder seeds, 15 parts of ophiopogon, 20 parts of Morinda officinalis, 20 parts of fried white peony root, 10 parts of schisandra, and 30 parts of dragon teeth.

[0013] As an optional mode, in the above-mentioned traditional Chinese medicine composition, the traditional Chinese medicine composition has the effects of replenishing heart blood, nourishing liver blood, nourishing yin and suppressing yang, and calming the mind.

[0014] In the second aspect, the present invention provides a method for preparing the traditional Chinese medicine composition described in the first aspect, the preparation method comprising the following steps: crushing pine nuts, fried jujube seeds, angelica, longan pulp, poria, dodder seeds, ophiopogon japonicus, Morinda officinalis, fried white peony root, schisandra chinensis, and dragon teeth, adding water for decoction, mixing the filtrate, and concentrating to obtain a concentrated solution.

[0015] As an optional manner, in the above preparation method, the decoction is performed twice, and after the first decoction for 1-3 hours, a primary filtrate is obtained by filtering, the filter residue is further decocted with water for 1-3 hours, and a secondary filtrate is obtained by filtering, and the primary filtrate and the secondary filtrate are combined.

[0016] As an optional manner, in the above preparation method, the material-liquid ratio of the first decoction and the second decoction is 1:3, the decoction time of the first decoction and the second decoction is 1.5 hours, and the water used for the first decoction and the second decoction is distilled water.

[0017] Preferably, the concentration is concentration under reduced pressure.

[0018] In a third aspect, the present invention provides use of the Chinese medicine composition described in the first aspect or the Chinese medicine composition prepared by the preparation method described in the second aspect in preparing a drug for treating insomnia.

[0019] As an optional mode, in the above use, the insomnia is deficiency-syndrome type insomnia.

[0020] Preferably, the insomnia is of the heart-liver yin-blood deficiency syndrome.

[0021] Also preferably, the insomnia is chronic insomnia, refractory insomnia, primary insomnia, menopausal insomnia or senile insomnia.

[0022] More preferably, the medicament shortens sleep latency and prolongs sleep duration.

[0023] As an optional mode, in the above-mentioned use, the dosage form of the drug is granules, tablets, oral liquid or capsules.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] (1) The Chinese medicine composition of the present invention has the effects of replenishing heart blood, nourishing liver blood, nourishing yin and suppressing yang, and calming the mind, and is particularly suitable for treating insomnia caused by deficiency syndromes such as heart and liver yin and blood deficiency.

[0026] (2) The results of pharmacological experiments showed that the Chinese medicine composition of the present invention significantly improved the sleep latency and sleep test of PCPA insomnia model rats and the body weight of rats. In addition, the preliminary clinical trial results showed that compared with other Chinese patent medicines commonly used in the clinic for the treatment of insomnia (e.g., Baizi Yangxin Pills), the Chinese medicine composition of the present invention is more suitable for the treatment of insomnia caused by deficiency syndromes such as heart and liver yin and blood deficiency.

[0027] (3) The Chinese medicine composition of the present invention is based on the traditional Chinese medicine formula, uses modern preparation technology and is deeply optimized. The preparation method is simple, and the Chinese medicine composition of the present invention can be made into various dosage forms such as granules, tablets, oral liquids or capsules. DETAILED DESCRIPTION

[0028] The Chinese medicine composition of the invention has the effects of replenishing heart blood, nourishing liver blood, nourishing yin and suppressing yang, and calming the mind, and is particularly suitable for treating insomnia caused by deficiency syndromes such as heart and liver yin and blood deficiency syndrome.

[0029] The efficacy and main treatment of each medicinal ingredient in the Chinese medicine composition of the present invention are as follows:

[0030] "Platycladus orientalis" is the dried mature kernel of the plant Platycladus orientalis (L.) Franco of the Cupressaceae family. It tastes sweet and is neutral in nature. It enters the heart, kidney, and large intestine meridians. It has the effects of nourishing the heart and calming the mind, moistening the intestines and relieving constipation. It is mainly used to treat palpitations, insomnia, and constipation caused by dry intestines.

[0031] "Zhao Ren" is also known as "Suanzaoren", which is the name of a Chinese medicine. It has the effects of nourishing the heart and liver, calming the mind, astringing sweat, and promoting body fluid. It is used for insomnia, palpitations, dreaminess, physical weakness, sweating, and thirst due to loss of body fluid.

[0032] "Danggui" is the root of Angelica sinensis (Oliv) Diels., a plant of the Umbelliferae family. It is sweet and pungent in taste and warm in nature. It enters the liver, heart and spleen meridians. It has the effects of nourishing blood and regulating menstruation, promoting blood circulation and relieving pain, and moistening the intestines and relieving constipation. It is mainly used to treat chlorosis due to blood deficiency, irregular menstruation, amenorrhea and dysmenorrhea, blood deficiency, blood stasis, pain caused by cold blood, injuries caused by falls, rheumatic arthralgia, carbuncle sores, dry intestines and constipation, etc.

[0033] "Longan" refers to the root, leaf, aril (longan flesh) and seed (longan kernel) of the plant Dimocarpus longans Lour. [Euphorialongans (Lour.) Steud.] of the Sapindaceae family. Root: diuretic, dredges the meridians. Mainly used for chyluria, leucorrhea, rheumatic joint pain. Leaf: clears away heat and detoxifies, relieves the symptoms and diuretics. Mainly used for preventing influenza, epidemic cerebrospinal meningitis, colds, enteritis; externally used for treating scrotal eczema. Aril: nourishes the heart and spleen, nourishes blood and calms the mind. Mainly used for treating physical weakness after illness, neurasthenia, forgetfulness, palpitations, insomnia. Seed: stops bleeding and relieves pain. Mainly used for treating stomachache, burns, bleeding from knife wounds, hernia pain; externally used for treating bleeding from external injuries.

[0034] "Fu Shen" is the white part of the sclerotium of the fungus Poria cocos (Schw.) Wolf., which has a pine root (i.e. "Fu Shen wood") in the middle. It tastes sweet and light, and is neutral in nature. It enters the heart and spleen meridians. It has the effects of calming the mind, tranquilizing the nerves, and promoting diuresis. It is mainly used to treat palpitations, restlessness, forgetfulness, insomnia, epilepsy, and difficulty urinating.

[0035] "Dodder" is the mature seed of Cuscuta chinensis Lam., a plant of the genus Cuscuta in the family Convolvulaceae. It has the functions of nourishing the kidney, strengthening the essence, nourishing the liver, improving eyesight, stopping diarrhea, and calming the fetus. It tastes sweet and is warm in nature; it enters the liver, kidney, and spleen meridians. It is mainly used to treat soreness of the waist and knees, impotence and spermatorrhea, enuresis and frequent urination, liver and kidney deficiency, blurred vision, spleen and kidney yang deficiency, loose stools and diarrhea, restless fetuses, and bleeding during pregnancy.

[0036] "Maidong" is the dried root of the plant Ophiopogon japonicus (Ophiopogon japonicus) of the Liliaceae family. It has the effects of nourishing yin and moistening the lungs, benefiting the stomach and producing body fluid, clearing the heart and relieving restlessness. It is often used for dry cough due to lung dryness, lung abscess, cough due to yin deficiency, thirst due to loss of body fluid, thirst, restlessness and insomnia, sore throat, dry intestines and constipation, and vomiting and bleeding due to blood heat.

[0037] "Bajitian" is the root of Morinda officinalis How. It is pungent and sweet, slightly warm in nature, and enters the kidney and liver meridians. It has the effects of tonifying the kidney and yang, dispelling wind and removing dampness. It is mainly used to treat impotence, infertility due to cold uterus, frequent urination, rheumatic pain in the waist and knees, and soreness of the waist and knees due to kidney deficiency.

[0038] White peony root is the root of Paeonia lactiflora Pall., a plant of the genus Paeonia in the family Ranunculaceae. It tastes bitter and sour, and is slightly cold in nature. It enters the liver and spleen meridians. It has the effects of nourishing blood and restraining yin, softening the liver and relieving pain, and calming liver yang. It is mainly used to treat liver blood deficiency, irregular menstruation, liver-spleen disharmony, chest and flank abdominal pain, cramps and pain in the limbs, hyperactivity of liver yang, headache and dizziness, etc.

[0039] "Schisandra chinesis" is the mature fruit of Schisandra chinesis (Turcz.) Ball or Schisandra sphenanthera rehd.et Wils. of the Schisandra family. It tastes sour and sweet, and is warm in nature. It enters the lung, heart, and kidney meridians. It has the effects of astringing, strengthening qi, promoting body fluid, and nourishing the kidney and calming the mind. It is mainly used to treat chronic cough, asthenia, spontaneous sweating, night sweats, spermatorrhea, spermatorrhea, chronic diarrhea, thirst due to loss of body fluid, polydipsia, palpitations, insomnia, and dreaminess.

[0040] "Dragon teeth" are fossilized teeth of ancient mammals such as elephants, rhinoceroses, and three-toed horses. They are sweet and astringent, cool in nature, and enter the heart and liver meridians. They have the effects of calming the nerves, clearing away heat and relieving restlessness. They are mainly used to treat epilepsy, mania, palpitations, insomnia, fever and restlessness.

[0041] Torreya grandis seed: nourishes the heart and calms the mind; Angelica sinensis: nourishes the liver and blood and calms the mind; Stir-fried jujube seed: nourishes the heart and liver and calms the mind; Longan meat: combined with torreya grandis seed, nourishes the heart and calms the mind; Ophiopogon japonicus: nourishes the heart and stomach; Poria: calms the mind; Cuscuta australis: benefits the essence and blood; Morinda officinalis: guides the yang into the yin; Stir-fried white peony root: astringes and descends, softens the liver; Schisandra chinensis: astringes and descends, calms the mind; Dragon tooth: calms and calms the mind.

[0042] The present invention will be further described with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the scope of the present invention.

[0043] If no specific techniques or conditions are specified in the examples, the techniques or conditions described in the literature in the field or the product instructions are used. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0044] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0045] Preparation Example:

[0046] Embodiment 1:

[0047] A traditional Chinese medicine composition for treating insomnia, the traditional Chinese medicine composition is prepared from the following raw materials: 20g of cypress seed, 10g of fried jujube seed, 20g of angelica, 30g of longan pulp, 25g of poria, 30g of dodder seed, 15g of ophiopogon, 20g of Morinda officinalis, 20g of fried white peony root, 10g of schisandra chinensis, and 30g of dragon tooth.

[0048] The preparation method of the traditional Chinese medicine composition comprises the following steps: crushing cypress seeds, fried jujube seeds, angelica, longan pulp, poria, dodder seeds, ophiopogon japonicus, Morinda officinalis, fried white peony root, schisandra chinensis, and dragon tooth, adding water for decoction, decocting twice, the material-liquid ratio of the first decoction and the second decoction is 1:3, the decoction time of the first decoction and the second decoction is 1.5 hours, the water used for the first decoction and the second decoction is distilled water, mixing the filtrates after decoction, and concentrating under reduced pressure to obtain 80 mL of concentrated solution.

[0049] Embodiment 2:

[0050] A traditional Chinese medicine composition for treating insomnia, the traditional Chinese medicine composition is prepared from the following raw materials: 25g of cypress seed, 15g of stir-fried jujube seed, 20g of angelica, 30g of longan pulp, 20g of poria, 30g of dodder seed, 15g of ophiopogon, 20g of Morinda officinalis, 20g of stir-fried white peony root, 10g of schisandra chinensis, and 25g of dragon tooth.

[0051] The preparation method of the Chinese medicine composition is the same as that of Example 1.

[0052] Comparative Example 1:

[0053] A traditional Chinese medicine composition is prepared from the following raw materials: 30g of cypress seed, 20g of fried jujube seed, 30g of angelica, 30g of longan pulp, 25g of poria, 30g of dodder seed, 15g of ophiopogon, 20g of Morinda officinalis, 20g of fried white peony root, and 10g of schisandra chinensis.

[0054] The preparation method of the Chinese medicine composition is the same as that of Example 1.

[0055] Comparative Example 2:

[0056] A traditional Chinese medicine composition is prepared from the following raw materials: 20g of cypress seed, 10g of fried jujube seed, 20g of angelica, 30g of longan pulp, 25g of poria, 30g of dodder seed, 15g of ophiopogon, 20g of cistanche, 20g of fried white peony root, 10g of schisandra chinensis, and 30g of dragon tooth.

[0057] The preparation method of the Chinese medicine composition is the same as that of Example 1.

[0058] Comparative Example 3 (the main active ingredient is the same as that of Baizi Yangxin Pills):

[0059] A traditional Chinese medicine composition is prepared from the following traditional Chinese medicines in parts by weight: 10g of cypress seed, 10g of codonopsis pilosula, 40g of roasted astragalus, 40g of chuanxiong, 40g of angelica, 40g of poria, 10g of polygala (processed), 10g of spiny jujube seed, 10g of cinnamon bark, 10g of schisandra (steamed), 40g of pinellia (cured), 4g of roasted liquorice, and 12g of cinnabar.

[0060] The preparation method of the Chinese medicine composition is the same as that of Example 1.

[0061] Effect embodiment:

[0062] Effect Example 1: Effect of the Chinese medicine composition of the present invention on treating insomnia

[0063] 1. Animal grouping and modeling

[0064] Healthy male SD rats (10 weeks old, weighing 220-240 g) were obtained (purchased from the Experimental Animal Center of Heilongjiang University of Traditional Chinese Medicine) and fed normally for 1 week. These SD rats were randomly divided into 8 groups (blank group, model group, positive drug group, Example 1-2 group, Comparative Example 1-3 group), 8 rats in each group.

[0065] The preparation methods of Examples 1-2 and Comparative Examples 1-3 are as shown in the above-mentioned preparation examples. Each administration group was intragastrically administered once a day. The dosage of Examples 1-2 and Comparative Examples 1-3 was 10 g of the original medicinal material·kg -1 The dosage was calculated to be 15 g / kg. The blank group and the model group were gavaged with an equal volume of saline once a day. After the rat model was successfully established, the drug was continuously gavaged for 7 days. The dosage of Estazolam tablets for rats was calculated to be 0.18 mg / kg according to the adult dosage.

[0066] The insomnia model was established by intraperitoneal injection of parachlorophenoxyacetic acid (PCPA): PCPA is an inhibitor of tryptophan hydroxylase (TDH). By blocking 5-HT synthesis, the 5-HT content in the rat brain is reduced, thereby eliminating the circadian rhythm. PCPA suspension was intraperitoneally injected at a fixed time in the morning, once a day, for 2 consecutive days.

[0067] 2. Evaluation indicators

[0068] 2.1 Pentobarbital sodium synergistic hypnosis time

[0069] After the treatment intervention, a synergistic hypnosis test was conducted with sodium pentobarbital 40 mg / kg, and parameters such as sleep latency and sleep time were used to determine the model replication and the effect of the treatment intervention on the synergistic sleep of rats at the threshold dose of sodium pentobarbital, so as to determine whether the treatment intervention had an inducing effect on sleep.

[0070] In the experiment, the disappearance of the righting reflex of the animal for 1 minute was regarded as the indicator of falling asleep, and turning over 3 times within 30 seconds was regarded as the indicator of the end of sleep. The time from the disappearance of the righting reflex to the recovery of each mouse was recorded as the sleep time.

[0071] 2.2 Weight

[0072] The body weights of rats in each group were measured before and after modeling and after the intervention.

[0073] 3. Statistical methods

[0074] The results were analyzed using SPSS 27.0 statistical software, and the data were expressed as mean ± standard deviation. One-way analysis of variance was used for comparison among multiple groups, and t-test was used for comparison between two groups. P < 0.05 indicated statistically significant differences.

[0075] 4. Experimental Results

[0076] 4.1 Results of the measurement of sodium pentobarbital synergistic hypnosis time

[0077] The experimental results are shown in Table 1. Compared with the blank group, the sleep latency of the rats in the model group was significantly prolonged (P < 0.001), while the sleep time was shorter (P < 0.001). In addition, the rats in the model group had a disordered circadian rhythm, were active during the day, had increased sensitivity to external stimuli such as sound and light, and had increased excitability and aggression. At the same time, the rats in the model group had increased diet and defecation, and the stool color was grayish white, which was significantly different from the blank group, indicating that the model was successfully established.

[0078] Compared with the model group, the sleep latency of rats in Example 1, Example 2 and the positive drug group was significantly shortened (P < 0.001) and the sleep time was significantly prolonged (P < 0.001), and the shortening of sleep latency in Example 1 and Example 2 was better than that in the positive drug group. In addition, the Baizi Yangxin Pills (see Comparative Example 3), which is commonly used in the clinic to treat insomnia, did not shorten the sleep latency of rats, and its effect on prolonging sleep time was not as good as that of the Chinese medicine composition of the present invention.

[0079] It can be seen from the experimental results of Comparative Example 1 and Comparative Example 2 that when the medicinal flavors in the Chinese medicine composition of the present invention are replaced or removed, the effects of the Chinese medicine composition on shortening sleep latency and prolonging sleep time are significantly weakened, which indicates that the improvement effect of the Chinese medicine composition of the present invention on rat sleep is closely related to the types of medicinal flavors in the Chinese medicine composition.

[0080] Table 1: Effect of the Chinese medicine composition of the present invention on the hypnotic effect of pentobarbital sodium-induced rats

[0081]

[0082] Note: Compared with the blank group, ### P<0.001; compared with the model group, * P<0.05, *** P<0.001.

[0083] 4.2 Body weight measurement results

[0084] The rats in the blank group were in good mental state, quick response, shiny fur, normal diet, water intake and body weight. The sleep rhythm was obvious, showing nocturnal activity. Compared with the rats in the blank group, the rats in the model group began to show poor spirits, dull fur, shrill voices, and sometimes manic and irritable, aggressive, upright confrontation, and increased biting times after PCPA injection. The circadian rhythm disappeared, the food intake decreased, and the body weight decreased significantly. It can be seen that the body weight of rats injected with PCPA after modeling basically did not increase or slightly decreased compared with that before modeling.

[0085] However, compared with the model group, the number of confrontations and bites of rats in the positive drug group, Example 1 group and Example 2 group decreased, the cleaning behavior was basically flexible, the call was soft, the hair was shiny, the food intake increased, the circadian rhythm was basically restored, and the body weight increased significantly (P < 0.01, P < 0.001). The weight gain of rats in Example 1 group and Example 2 group was better than that in the positive drug group. The above results show that the Chinese medicine composition of the present invention can effectively regulate the mental state and behavioral performance of insomnia rats and increase the body weight of model rats. In addition, the Baizi Yangxin Pills (see Comparative Example 3 group) commonly used in the clinic for the treatment of insomnia can also significantly increase the body weight of experimental rats (P < 0.01).

[0086] From the experimental results of Comparative Example 1 and Comparative Example 2, it can be seen that when the medicinal flavors in the Chinese medicine composition of the present invention are replaced or removed, the effect of the Chinese medicine composition on increasing the body weight of rats is significantly weakened, which indicates that the improvement effect of the Chinese medicine composition of the present invention on the body weight of rats is closely related to the types of medicinal flavors in the Chinese medicine composition.

[0087] Table 2: Effect of the Chinese medicine composition of the present invention on the body weight of rats

[0088]

[0089] Note: Compared with the blank group, ### P<0.001; compared with the model group, ** P<0.01, *** P<0.001. Effect Example 2: Preliminary clinical trial results of the Chinese medicine composition of the present invention in treating insomnia caused by deficiency of heart and liver yin and blood

[0090] 1. Case selection criteria

[0091] The diagnostic criteria for insomnia refer to the "Guidelines for Diagnosis and Treatment of Common Diseases in Traditional Chinese Medicine" and the "Guidelines for Clinical Practice of Insomnia in Traditional Chinese Medicine":

[0092] (1) Anyone with difficulty falling asleep, waking up easily during sleep, or even having trouble sleeping all night can be diagnosed with insomnia;

[0093] (2) Insomnia often causes symptoms such as fatigue, listlessness, weakness, loss of appetite, and decreased work ability;

[0094] (3) Clinical examination revealed no organic lesions, and polysomnography revealed signs of sleep structure disorder, which was confirmed by combining the sleep quality questionnaire and relevant biochemical tests.

[0095] Diagnostic criteria for insomnia due to deficiency of heart-liver yin and blood:

[0096] The main symptoms are palpitations, insomnia, forgetfulness, dizziness, blurred vision, etc.

[0097] Patients with heart and liver yin blood deficiency often experience symptoms of palpitations and restlessness. This is because the heart is not adequately nourished due to insufficient heart blood, which leads to weakened heart function and irregular heartbeat. Due to heart blood deficiency and restlessness, patients often have difficulty falling asleep, and even if they fall asleep, they are prone to dreaming and have poor sleep quality. The heart governs the mind, and the liver governs catharsis. When the heart and liver are deficient in blood, the mind is not nourished, memory will be significantly reduced, and symptoms of forgetfulness will appear. The liver opens up to the eyes, and liver blood deficiency will cause the eyes to lose nourishment. Therefore, patients will experience symptoms of dizziness and blurred vision, and in severe cases, it may even lead to night blindness.

[0098] Anyone with the above symptoms will be used as the criteria for case selection.

[0099] 2. Inclusion and Exclusion Criteria

[0100] 2.1 Inclusion criteria

[0101] (1) Meet the diagnostic criteria for insomnia and the duration of illness is more than 3 months;

[0102] (2) Meet the diagnostic criteria of insomnia of heart and liver yin and blood deficiency syndrome in traditional Chinese medicine;

[0103] (3) 6 points ≤ PSQI ≤ 15 points;

[0104] (4) Age 20-65 years old;

[0105] (5) No psychotropic drugs or vasoactive drugs had been taken in the past month;

[0106] (6) The informed consent form has been signed.

[0107] 2.2 Exclusion criteria

[0108] (1) Self-rating Anxiety Scale (SAS) ≥ 50 points and / or Self-rating Depression Scale (SDS) ≥ 53 points;

[0109] (2) Pregnant and lactating women;

[0110] (3) Those who are allergic to the test drug;

[0111] (4) Alcoholics and psychotropic drug abusers;

[0112] (5) Those who are also participating in other clinical trials.

[0113] 2.3 Elimination criteria

[0114] (1) Patients who have poor compliance and fail to return for follow-up visits on time;

[0115] (2) those who dropped out naturally during the observation process and could not be followed up;

[0116] (3) Incomplete data make it impossible to judge the efficacy of the treatment.

[0117] 3. Dosage regimen

[0118] Zopiclone group: Specification: 3 mg, taken 30 minutes before bedtime, once a day.

[0119] Group 1 of Example: On the basis of zopiclone treatment, the patients took the Chinese medicine prepared in Example 1, once a day, 80 mL each time, after dinner.

[0120] Comparative Example 3 Group: On the basis of zopiclone treatment, the patients took the Chinese medicine prepared in Comparative Example 3, once a day, 80 mL each time, after dinner.

[0121] Duration of treatment: 4 weeks.

[0122] Main outcome measure: Pittsburgh Sleep Quality Index (PSQI).

[0123] Secondary outcome measure: Quantitative score of TCM symptom grading.

[0124] 4. Efficacy evaluation criteria

[0125] 4.1 Pittsburgh Sleepiness Scale Assessment

[0126] The PSQI score before and after treatment was compared within and between groups, and the treatment effect was evaluated by calculating the score reduction rate. Score reduction rate = (pre-treatment score - post-treatment score) / pre-treatment score × 100%. 1 Clinical cure: score reduction ≥ 75% or PSQI < 6 points; 2 Significant effect: score reduction ≥ 50%; 3 Effective: score reduction ≥ 30% is considered improvement; 4 Ineffective: score reduction < 30%.

[0127] 4.2 TCM Syndrome Scale Assessment

[0128] The scoring standard was formulated with reference to the "Guidelines for Clinical Research of New Chinese Medicines". Each main symptom was scored as 0, 2, 4, or 6 points according to the severity, and each secondary symptom was scored as 0, 1, 2, or 3 points according to the severity. The TCM symptom scores before and after treatment were compared to determine the changes.

[0129] 4.3 Safety evaluation

[0130] All three groups of patients underwent routine blood, urine, stool, liver and kidney function tests and electrocardiogram before and after treatment.

[0131] 5. Statistical analysis

[0132] The results were analyzed using SPSS27.0 statistical software, and the non-parametric rank sum test or chi-square test was used for count treatment. The dosage data were expressed as mean ± standard deviation. The differences were analyzed using t-test for those that met the normal distribution, and the median and interquartile range (Md, (P25, P75)) for those that were not normally distributed. The non-parametric rank sum test was used for analysis, and P < 0.05 indicated that the difference was statistically significant.

[0133] 6. Test results

[0134] A total of 90 patients were included in this study, 1 patient dropped out in the zopiclone group, 0 patients dropped out in the example 1 group, and 2 patients dropped out in the comparative example 3 group. Finally, 29 patients were included in the zopiclone group, 30 patients were included in the example 1 group, and 28 patients were included in the comparative example 3 group. The basic data of the three groups of patients were not statistically different after testing.

[0135] 6.1 Comparison of PSQI scores between and within groups

[0136] The test results are shown in Table 3. The PSQI score shows that both zopiclone and zopiclone combined with Example 1 or Comparative Example 3 can improve the patient's sleep. However, it can be seen that the efficacy of zopiclone combined with Example 1 in improving the patient's sleep is more significant than that of zopiclone combined with Comparative Example 3.

[0137] Table 3: Comparison of total PSQI scores among the three groups before and after treatment (Md, (P25, P75))

[0138] Group Number of cases Before treatment After treatment Zopiclone group 29 13(11，14) 7(7，10) Example 1 Group 30 13(11，14) 4(3，5) Comparative Example 3 28 13(11，14) 6(6，8)

[0139] 6.2 Clinical efficacy evaluation

[0140] The test results are shown in Table 4. After 4 weeks of treatment, all three groups of patients had significant clinical efficacy, but the effective rate of Example 1 group was significantly higher than that of the zopiclone group and the comparative example 3 group. According to the rank sum test, Z=-2.562, P=0.01.

[0141] Table 4: Comparison of clinical efficacy among three groups of patients

[0142] Group get well Significant effect efficient invalid Total Effectiveness Zopiclone group 4 8 9 9 72.41％ Example 1 Group 14 12 3 1 96.67％ Comparative Example 3 6 7 9 6 78.57％

[0143] 6.3 Comparison between and within groups of the TCM symptom grading and quantitative table

[0144] The test results are shown in Table 5. P<0.05 for intra-group comparison before and after treatment and inter-group comparison after treatment, the differences were statistically significant. It can also be seen that compared with Comparative Example 3, Example 1 has a better therapeutic effect on patients with insomnia due to deficiency of heart and liver yin and blood.

[0145] Table 5: Comparison of TCM symptom grading scale scores among the three groups of patients before and after treatment

[0146] Group Number of cases Before treatment After treatment Zopiclone group 29 21.38±3.05 9.88±1.93 Example 1 Group 30 22.07±2.98 5.62±1.27 Comparative Example 3 28 21.86±3.14 8.16±2.04

[0147] 6.4 Safety evaluation

[0148] During the entire preliminary clinical trial, no obvious adverse reactions were observed in any group.

[0149] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A Chinese medicine composition for treating insomnia, characterized in that: The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 5-40 parts of pine nuts, 1-20 parts of fried jujube seeds, 5-40 parts of angelica sinensis, 10-50 parts of longan pulp, 10-40 parts of poria, 10-50 parts of dodder seeds, 1-25 parts of ophiopogon japonicus, 5-40 parts of Morinda officinalis, 5-40 parts of fried white peony root, 1-20 parts of schisandra chinensis, and 10-50 parts of dragon teeth.

2. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition is prepared from the following raw materials in parts by weight: 15-25 parts of cypress seeds, 5-15 parts of fried jujube seeds, 15-25 parts of angelica sinensis, 25-35 parts of longan pulp, 20-30 parts of poria, 25-35 parts of dodder seeds, 10-20 parts of ophiopogon japonicus, 15-25 parts of Morinda officinalis, 15-25 parts of fried white peony root, 5-15 parts of schisandra chinensis, and 25-35 parts of dragon teeth.

3. The Chinese medicine composition according to claim 2, characterized in that: The Chinese medicine composition is prepared from the following raw materials in parts by weight: 20 parts of pine nuts, 10 parts of fried jujube seeds, 20 parts of angelica sinensis, 30 parts of longan pulp, 25 parts of poria, 30 parts of dodder seeds, 15 parts of ophiopogon japonicus, 20 parts of Morinda officinalis, 20 parts of fried white peony root, 10 parts of schisandra chinensis, and 30 parts of dragon teeth.

4. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition has the effects of nourishing heart blood, nourishing liver blood, nourishing yin and suppressing yang, and calming the mind.

5. The method for preparing the Chinese medicine composition according to any one of claims 1 to 4, characterized in that: The preparation method comprises the following steps: crushing cypress seeds, fried jujube seeds, angelica, longan pulp, poria, dodder seeds, ophiopogon japonicus, Morinda officinalis, fried white peony root, schisandra chinensis and dragon tooth, adding water for decoction, mixing filtrate and concentrating to obtain concentrated solution.

6. The preparation method according to claim 5, characterized in that: The decoction is performed twice. After the first decoction for 1-3 hours, a primary filtrate is obtained by filtering. The filter residue is then decocted with water for 1-3 hours, and a secondary filtrate is obtained by filtering. The primary filtrate and the secondary filtrate are combined.

7. The preparation method according to claim 6, characterized in that: The material-liquid ratio of the first decoction and the second decoction was 1:3, the decoction time of the first decoction and the second decoction was 1.5 hours, and the water used in the first decoction and the second decoction was distilled water.

8. Use of the Chinese medicine composition according to any one of claims 1 to 4 or the Chinese medicine composition prepared by the preparation method according to any one of claims 5 to 7 in preparing a medicine for treating insomnia.

9. The use according to claim 8, characterized in that: The insomnia is deficiency syndrome insomnia, preferably, the insomnia is heart-liver yin-blood deficiency syndrome, and also preferably, the insomnia is chronic insomnia, refractory insomnia, primary insomnia, menopausal insomnia or senile insomnia.

10. The use according to claim 8, characterized in that: The dosage form of the medicine is granules, tablets, oral liquid or capsules.

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