Traditional Chinese medicine composition for treating liver blood deficiency type insomnia and application thereof

Abstract

The invention belongs to the field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating liver blood deficiency type insomnia and a preparation method and application thereof. The invention provides a traditional Chinese medicine composition. The traditional Chinese medicine composition comprises Chinese angelica, parched white peony root, prepared rhizome of rehmannia or radix rehmanniae, cistanche, blighted wheat, honey-fried licorice root, jujube, ligusticum wallichii, pawpaw, bighead atractylodes rhizome, rhizoma acori graminei, spina date seed, tuber fleeceflower stem, oyster, nacre mother of pearl and radix curcumae. By taking the traditional Chinese medicine composition disclosed by the invention, the liver-blood deficiency type insomnia can be effectively treated, or the symptoms of patients with the liver-blood deficiency type insomnia can be improved.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating insomnia of liver blood deficiency type, a preparation method thereof and an application thereof. Background Art

[0002] Chronic insomnia refers to nocturnal symptoms such as difficulty falling asleep, difficulty maintaining sleep or early awakening that last for at least 3 months, and sleep disorders that affect daytime functions such as life, work, and social activities. Long-term insufficient sleep efficiency is an independent risk factor for inducing chronic diseases such as coronary heart disease, acute myocardial infarction, heart failure, hypertension, diabetes, depression, and dementia. At the same time, it will also cause daytime fatigue, cognitive impairments such as attention, memory, and executive ability in patients, induce negative emotions, and affect the quality of life of patients.

[0003] The short-term efficacy of hypnotic drugs in treating insomnia has been confirmed, but most hypnotic drugs have side effects such as causing daytime dysfunction, sleep driving, behavioral abnormalities and worsening depression. Long-term use has addictive properties, and it will also cause patients to have resistance, thereby reducing patient compliance. Due to reasons such as cultural background and lack of specialist physicians in China, the psychological treatment (cognitive behavioral therapy) of insomnia has a low implementation quality and non-standard content in primary hospitals and general hospitals, and it is difficult to carry out or even not carried out.

[0004] The treatment of chronic insomnia with traditional Chinese medicine has a long history. Because of its unique advantages, definite curative effect, fewer adverse reactions, and no addictive properties and drug resistance, it is accepted and recognized by more patients. Traditional Chinese medicine believes that "the liver stores blood and the blood houses the soul". When the soul can be housed, one can sleep soundly at night. The brain is the residence of the primordial spirit. Only when the yin blood is abundant can the brain orifices be nourished, so as to normally exert its spiritual function.

[0005] Therefore, there is an urgent need in this field to provide a traditional Chinese medicine composition to effectively treat insomnia of liver blood deficiency type and overcome the deficiencies of existing treatment methods. Summary of the Invention

[0006] In view of this, in the first aspect, the present invention provides a traditional Chinese medicine composition, which comprises: Angelica sinensis, stir-fried Paeonia lactiflora, Rehmannia glutinosa or Rehmannia glutinosa recen, Cistanche deserticola, Fructus Tritici Levis, Radix Glycyrrhizae Preparata, Fructus Jujubae, Rhizoma Chuanxiong, Fructus Chaenomelis, Rhizoma Atractylodis Macrocephalae, Rhizoma Acori Tatarinowii, Semen Ziziphi Spinosae, Caulis Polygoni Multiflori, Concha Ostreae, Concha Margaritifera Usta, Radix Curcumae.

[0007] In the second aspect, the present invention provides a decoction prepared from the traditional Chinese medicine composition according to the first aspect of the present invention.

[0008] In the third aspect, the present invention provides an application of the traditional Chinese medicine composition according to the first aspect of the present invention or the decoction according to the second aspect of the present invention in the preparation of a drug for treating insomnia.

[0009] The traditional Chinese medicine composition or decoction of the present invention can effectively treat insomnia of the liver blood deficiency type or improve the symptoms of patients with insomnia of the liver blood deficiency type, and at the same time has fewer adverse reactions and no addiction and drug resistance. Detailed implementation manners

[0010] The present invention will be clearly and completely described below in conjunction with the implementation manners of the present invention. Obviously, the described implementation manners are only a part of the implementation manners of the present invention, rather than all of the implementation manners. All other implementation manners that can be obtained by those of ordinary skill in the art based on the implementation manners in the present invention belong to the scope protected by the present invention.

[0011] As described above, the prior art lacks a traditional Chinese medicine composition for treating insomnia, especially insomnia of the liver blood deficiency type.

[0012] The purpose of the present invention is to provide a traditional Chinese medicine composition, which can overcome the deficiencies of the existing treatment methods, effectively treat insomnia of the liver blood deficiency type, and at the same time has fewer adverse reactions and no addiction and drug resistance.

[0013] Insomnia was called "insomnia", "inability to lie down", "inability to sleep", "inability to close eyes" in ancient Chinese medical literature. The indication targeted by the present invention is insomnia of the liver blood deficiency type, and the specific information is as follows:

[0014] Main symptoms: insomnia with many dreams, difficulty in falling asleep, restlessness and random thoughts in the mind before going to bed, irritability and anger. Concurrent symptoms: dry eyes, blurred vision, muscle twitching, palpitations and forgetfulness, hair loss and white hair, scanty menstruation in women, pale red tongue, thin white or white and greasy tongue coating, deep and thready pulse, or stringy and thready pulse.

[0015] Etiology and pathogenesis: deficiency of liver blood, loss of nourishment of the heart and liver, loss of the spirit, yang not entering yin, and vexation disturbing upward.

[0016] Differentiation information: congenital endowment deficiency or long-term staying up late, excessive use of eyes, irregular work and rest lead to deficiency of liver blood. The liver opens into the eyes, so there are dry eyes and blurred vision; the tendons and vessels lose nourishment, so there is muscle twitching; the liver and kidney are homologous, and the kidney essence is deficient, resulting in hair loss and white hair, and scanty menstruation in women; the mother disease affects the son, and the deficiency of liver blood leads to the loss of nourishment of the heart spirit, resulting in insomnia at night, palpitations and forgetfulness; the deficiency of yin and blood, the loss of the spirit, yang not entering yin lead to difficulty in falling asleep, random thoughts before going to bed, restlessness in the mind, and excessive floating of deficient yang lead to many dreams, irritable and angry personality, pale red tongue, thin white or white and greasy tongue coating, deep and thready pulse, or stringy and thready pulse, which is differentiated as insomnia disease and liver blood deficiency syndrome.

[0017] Therefore, in the first aspect, the present invention provides a traditional Chinese medicine composition, which comprises: Angelica sinensis, stir-fried Paeonia lactiflora, Rehmannia glutinosa or Rehmannia glutinosa var. procumbens, Cistanche deserticola, Fructus Tritici Levis, roasted Glycyrrhiza uralensis, Jujube, Ligusticum chuanxiong, Chaenomeles sinensis, Atractylodes macrocephala, Acorus tatarinowii, Semen Ziziphi Spinosae, Caulis Polygoni Multiflori, Oyster, Concha Margaritifera Usta, Curcuma aromatica.

[0018] The following is a detailed description of the Chinese medicinal materials in the Chinese medicinal composition of the present invention:

[0019] Angelica sinensis: The dried root of the umbelliferous plant Angelica sinensis (Oliv.) Diels. It is sweet for tonifying, pungent for dispersing, bitter for purging and warm for dredging, entering the liver, heart and spleen meridians. It can both enrich blood and activate blood circulation, promote qi movement and relieve pain, and has the functions of nourishing and harmonizing blood, regulating menstruation by enriching blood, promoting blood circulation to relieve pain, and moistening the intestines for defecation. Angelica sinensis is pungent, fragrant and spreading, tonifying the heart blood and nourishing the liver blood. Clinically, it can be combined with qi-regulating drugs to treat qi stagnation and blood stasis syndrome, and can also treat various diseases caused by blood deficiency and blood stasis.

[0020] Stir-fried white peony root: The dried root of the ranunculaceous plant Paeonia lactiflora Pall, which is stir-fried. White peony root is sour for astringency, bitter and cool for purging pathogenic heat, entering the liver and spleen meridians, and has the functions of enriching blood and astringing yin, soothing the liver and relieving pain, nourishing yin and suppressing the hyperactive liver. It can be applied to all syndromes such as blood deficiency, liver depression, insufficiency of liver yin and hyperactivity of liver yang.

[0021] Prepared rehmannia root: The tuberous root of the scrophulariaceae plant Rehmannia glutinosa Libosch, which is processed by roasting. Prepared rehmannia root is sweet, slightly warm, entering the liver and kidney meridians, and has the effects of enriching blood and nourishing yin, replenishing essence and marrow. It is used to treat yin deficiency and blood deficiency, weakness of waist and knees, consumptive cough with hectic fever, spermatorrhea, metrorrhagia and metrostaxis, irregular menstruation, polydipsia, frequent urination, deafness, and dim vision.

[0022] Fresh rehmannia root: The fresh or dried tuberous root of the scrophulariaceae plant Rehmannia glutinosa Libosch. It tastes sweet and bitter, and is cold in nature. It belongs to the heart, liver and kidney meridians. Fresh rehmannia root is superior to prepared rehmannia root in terms of the effects of stopping bleeding, clearing heat and promoting fluid production.

[0023] Cistanche deserticola: The dried fleshy stem with scale leaves of the cistanche family plant Cistanche deserticola Y.C.Ma or Cistanche tubulosa. It is sweet, salty and warm in nature, belonging to the kidney and large intestine meridians, and can tonify the kidney yang, benefit essence and blood, and moisten the intestines for defecation.

[0024] Floating wheat: The shriveled and floating glume grains of the gramineous plant Triticum aestivum L. It is sweet and cool in nature, entering the heart meridian, and functions to replenish qi, remove heat and stop sweating, and relieve vexation. It can be used for night sweating, spontaneous sweating, consumptive fever and other symptoms.

[0025] Honey-fried licorice root: The dried root and rhizome of the leguminous plant Glycyrrhiza uralensis Fisch, which is fried with honey. It tastes sweet and is neutral in nature, belonging to the heart, lung, spleen and stomach meridians, and has the functions of invigorating the spleen and replenishing qi, clearing heat and detoxifying, resolving phlegm and relieving cough, relieving spasm and pain, and coordinating various drugs. It is used to treat spleen and stomach weakness, lassitude and weakness, palpitation and shortness of breath, cough with profuse phlegm, abdominal pain and spasm of the extremities, carbuncles and sores, etc., and can also relieve the toxicity and potency of drugs.

[0026] Chinese Date: It is the dried ripe fruit of Ziziphus jujuba Mill of the family Rhamnaceae. It is sweet in flavor and warm in nature, entering the spleen, stomach, heart, and liver meridians. It has the effects of tonifying the spleen and regulating nutrient qi, nourishing blood and stopping bleeding, calming the mind and soothing the nerves, and moderating the properties of other drugs. It is commonly used to treat weakness of the spleen and stomach, anorexia and lassitude, deficiency of qi and blood, restlessness and insomnia due to deficiency, and the syndrome of zangzao with mental disorders.

[0027] Chuanxiong Rhizome: It is the dried rhizome of Ligusticum chuanxiong Hort of the family Umbelliferae. It is pungent in flavor and warm in nature, entering the liver, gallbladder, and pericardium meridians. It has the effects of promoting blood circulation and qi movement, dispelling wind and relieving pain. It is mainly used for distending pain in the hypochondrium due to stagnation of liver qi, stabbing pain in the chest and hypochondrium due to stasis of liver blood, injuries from falls and bruises due to blood stasis obstruction, swelling and pain of sores and ulcers, irregular menstruation, amenorrhea and dysmenorrhea, stasis pain after childbirth, retention of lochia, various headaches, and rheumatic arthralgia.

[0028] Chaenomeles Fruit: It is the dried nearly ripe fruit of Chaenomeles speciosa (Sweet) Nakai of the family Rosaceae. It is warm in nature, pungent and sour in flavor. It has the effects of relaxing muscles and tendons, regulating the stomach and resolving dampness. It is mainly used to treat rheumatic arthralgia, beriberi edema, vomiting and diarrhea with cramps, food retention, and gastric distension and vomiting.

[0029] Atractylodes Rhizome: It is the dried rhizome of Atractylodes macrocephala Koidz of the family Compositae. It is bitter, sweet, and warm in nature, entering the spleen and stomach meridians. It has the effects of invigorating qi and strengthening the spleen, drying dampness and promoting diuresis, stopping sweating, and preventing miscarriage. Atractylodes rhizome is mainly used to treat qi deficiency of the spleen and stomach, edema due to spleen deficiency, phlegm retention, spontaneous sweating due to deficiency of the exterior, and restlessness of the fetus.

[0030] Grassleaf Sweetflag Rhizome: It is the dried rhizome of Acorus tatarinowii Schott of the family Araceae. It is pungent, warm, fragrant, and dispersing. It has the effects of opening orifices and resolving phlegm, waking up the mind and improving intelligence, and promoting digestion by eliminating dampness.

[0031] Sour Jujube Seed: It is the dried ripe seed of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow of the family Rhamnaceae. It is sweet, sour, and neutral in flavor, entering the heart, liver, gallbladder, and spleen meridians. It has the effects of calming the mind and soothing the nerves, astringing yin and stopping sweating. It is used for syndromes such as insufficiency of heart blood, disharmony between the heart and kidney, deficiency of heart and gallbladder qi, and excessive sweating due to yin deficiency.

[0032] Caulis Polygoni Multiflori: It is the dried vine stem of Fallopia multiflora (Thunb.) Harald of the family Polygonaceae. It is sweet and neutral in flavor, entering the heart and liver meridians. It has the effect of calming the mind and soothing the nerves. It is used for restlessness and insomnia due to deficiency, dreaminess, itchy skin rash, and limb soreness caused by deficiency of qi and blood and malnutrition of the tendons and vessels.

[0033] Oyster: It is the shell of Ostrea gigas Thunberg, Ostrea talienwhanensis Crosse or Ostrea rivularis Gould of the family Ostreidae. It astringes yin, subdues yang, stops sweating, astringes essence, resolves phlegm, and softens hardness. It is used to treat infantile convulsion, dizziness, spontaneous sweating, night sweating, spermatorrhea, stranguria, metrorrhagia and leukorrhea, scrofula, goiter. It is used for palpitation and insomnia, dizziness and tinnitus, scrofula and phlegm nodes, abdominal mass, spontaneous sweating and night sweating, spermatorrhea, metrorrhagia and leukorrhea, stomachache and acid regurgitation.

[0034] Mother-of-Pearl: It is the shell of Hyriopsis cumingii (Lea), Cristaria plicata (Leach) of the family Unionidae or Pinctada martensii (Dunker) of the family Pteriidae. Its nature and flavor are salty and cold, and it pertains to the liver and heart meridians. It has the effects of suppressing the hyperactive liver and subsiding yang, clearing the liver and improving eyesight, and calming the mind and tranquilizing the nerves.

[0035] Turmeric Root-Tuber: It is the dried tuberous root of Curcuma wenyujin Y.H.Chen et C.Ling, Curcuma longa L, Curcuma kwangsiensis S.G.Lee et C.F.Liang or Curcuma phaeocaulis Val of the family Zingiberaceae. Its nature and flavor are pungent, bitter and cold, and it pertains to the liver, heart and lung meridians. It has the effects of promoting qi circulation to remove stasis, clearing the heart and relieving depression, and promoting bile drainage to remove jaundice. It is used to treat qi stagnation and blood stasis, coma due to febrile disease, epilepsy with phlegm obstruction, hematuria, jaundice due to damp-heat in the liver and gallbladder, etc.

[0036] Among the above traditional Chinese medicine ingredients, the monarch drugs are Angelica sinensis, stir-fried White Peony Root, Rehmannia glutinosa or Rehmannia glutinosa Libosch mainly for tonifying liver blood; the ministerial drugs include three groups: ① "tonify the mother when deficiency occurs", the liver and kidney share the same origin, and Cistanche deserticola for tonifying the kidney and benefiting essence and blood; ② the mother disease affecting the son, liver blood deficiency, heart spirit loss of nourishment, restlessness disturbing upward, and Fructus Tritici Levis, Radix Glycyrrhizae Preparata and Fructus Jujubae for nourishing the heart and relieving restlessness; ③ drugs for nourishing the heart and calming the mind heavily: Semen Ziziphi Spinosae, Caulis Polygoni Multiflori, Oyster, Mother-of-Pearl; the adjuvant drugs are Ligusticum chuanxiong, Chaenomeles sinensis, Atractylodes macrocephala and Acorus tatarinowii for resolving phlegm and promoting blood circulation and preventing the greasy nature of the drugs for tonifying the liver and kidney; the guiding drug is Turmeric Root-Tuber (liver meridian).

[0037] In some embodiments, the traditional Chinese medicine composition comprises, by weight: 10 - 15 parts of Angelica sinensis, 10 - 30 parts of stir-fried White Peony Root, 10 - 20 parts of Rehmannia glutinosa or 10 - 20 parts of Rehmannia glutinosa Libosch, 10 - 30 parts of Cistanche deserticola, 15 - 30 parts of Fructus Tritici Levis, 6 parts of Radix Glycyrrhizae Preparata, 10 parts of Fructus Jujubae, 6 - 12 parts of Ligusticum chuanxiong, 6 - 18 parts of Chaenomeles sinensis, 10 - 15 parts of Atractylodes macrocephala, 10 - 15 parts of Acorus tatarinowii, 6 - 30 parts of Semen Ziziphi Spinosae, 15 - 30 parts of Caulis Polygoni Multiflori, 15 - 30 parts of Oyster, 15 - 30 parts of Mother-of-Pearl, 10 - 12 parts of Turmeric Root-Tuber.

[0038] Further, in some embodiments, the traditional Chinese medicine composition comprises, by weight: 15 parts of Angelica sinensis, 30 parts of stir-fried white peony root, 20 parts of prepared rehmannia root or raw rehmannia root, 30 parts of cistanche deserticola, 30 parts of floating wheat, 6 parts of roasted licorice root, 10 parts of Chinese date, 9 parts of chuanxiong rhizome, 15 parts of papaya, 10 parts of atractylodes macrocephala, 15 parts of acorus tatarinowii, 30 parts of wild jujube seed, 30 parts of polygonum multiflorum thunb., 30 parts of oyster, 30 parts of mother-of-pearl, and 10 parts of turmeric root-tuber.

[0039] In a second aspect, the present invention provides a decoction prepared from the traditional Chinese medicine composition according to the first aspect of the present invention.

[0040] In some embodiments, the decoction is prepared by the following method:

[0041] 1) Add oyster and mother-of-pearl to an appropriate amount of clear water, first decoct with strong fire for the first period of time, then add Angelica sinensis, stir-fried white peony root, prepared rehmannia root or raw rehmannia root, cistanche deserticola, floating wheat, roasted licorice root, Chinese date, chuanxiong rhizome, papaya, atractylodes macrocephala, acorus tatarinowii, wild jujube seed, polygonum multiflorum thunb., and turmeric root-tuber, continue to decoct with strong fire, turn to slow fire after boiling and decoct for the second period of time, and filter to obtain the first decoction liquid and the residue;

[0042] 2) Add clear water in an amount that can submerge the residue again, bring to a boil with strong fire and then turn to slow fire for the third period of time, and filter to obtain the second decoction liquid;

[0043] 3) Combine the first decoction liquid and the second decoction liquid to obtain the final decoction.

[0044] Specifically, in some embodiments, the first period of time is 10 - 20 minutes.

[0045] In some embodiments, the second period of time and the third period of time are each independently 20 - 30 minutes.

[0046] In some embodiments, before step 1), Angelica sinensis, stir-fried white peony root, prepared rehmannia root or raw rehmannia root, cistanche deserticola, floating wheat, roasted licorice root, Chinese date, chuanxiong rhizome, papaya, atractylodes macrocephala, acorus tatarinowii, wild jujube seed, polygonum multiflorum thunb., oyster, mother-of-pearl, and turmeric root-tuber are soaked in clear water for 20 - 30 minutes.

[0047] In a third aspect, the present invention provides the use of the traditional Chinese medicine composition according to the first aspect of the present invention or the decoction according to the second aspect of the present invention in the preparation of a drug for treating insomnia.

[0048] The main efficacy of the traditional Chinese medicine composition according to the first aspect of the present invention or the decoction according to the second aspect of the present invention is: nourishing blood and nourishing the liver, calming the mind and tranquilizing the nerves. Therefore, it is applicable to insomnia mainly caused by deficiency of liver blood, loss of nourishment of the heart and liver, loss of the mind, yang not entering yin, and restlessness disturbing the upper part.

[0049] Therefore, in some embodiments, the insomnia is liver-blood deficiency type insomnia, and its main symptoms are: insomnia with many dreams, difficulty in falling asleep, restlessness and random thoughts in the mind before going to bed, irritability and anger; the concurrent symptoms are: dry eyes, blurred vision, muscle twitching, palpitations and forgetfulness, hair loss and white hair, scanty menstruation in women, pale red tongue, thin white or white and greasy tongue coating, deep and thready pulse, or stringy and thready pulse.

[0050] The present invention will be further described through the following examples. The test methods used in the following examples are all conventional methods unless otherwise specified; the materials, reagents, etc. used in the following examples can be obtained from commercial channels unless otherwise specified.

[0051] Example

[0052] Preparation of Decoction

[0053] ① Take 15 parts of Angelica sinensis, 30 parts of stir-fried Paeonia lactiflora, 20 parts of Rehmannia glutinosa or 20 parts of Rehmannia glutinosa recens, 30 parts of Cistanche deserticola, 30 parts of Fructus Tritici Levis, 6 parts of roasted Glycyrrhiza uralensis, 10 parts of Chinese date, 9 parts of Ligusticum chuanxiong, 15 parts of Chaenomeles sinensis, 10 parts of Atractylodes macrocephala, 15 parts of Acorus tatarinowii, 30 parts of Semen Ziziphi Spinosae, 30 parts of Caulis Polygoni Multiflori, 30 parts of Concha Ostreae, 30 parts of Concha Margaritifera Usta, and 10 parts of Curcuma aromatica in the formula amount, mix them evenly, add clear water to submerge the above raw medicinal materials and soak them, and then wash and filter the mixture. Separately soak and wash an appropriate amount of Concha Ostreae and Concha Margaritifera Usta for later use.

[0054] ② Add clear water that can submerge all the raw material amounts into the decocting pot, then first add Concha Ostreae and Concha Margaritifera Usta and decoct them with strong fire for 20 minutes. After boiling, add the remaining raw medicinal materials and continue to decoct with strong fire. After boiling, turn to slow fire and continue to decoct for 20 - 30 minutes, and filter to obtain the first decoction liquid and the residue.

[0055] ③ Add clear water that can submerge the residue amount again, bring to a boil with strong fire and then continue to decoct with slow fire for 20 - 30 minutes, filter to obtain the second decoction liquid, and mix the two decoction liquids evenly to obtain the traditional Chinese medicine decoction for treating insomnia.

[0056] Clinical Trial

[0057] 1. Clinical Trial Research Design

[0058] 1.1 Study design type

[0059] This part adopts a randomized parallel control and interventional research design type.

[0060] 1.2 Sample size

[0061] No similar literature was found in this study, and no pre-experiment was conducted temporarily. The sample size was taken as the minimum number of cases in clinical trials, which is 30 cases. Considering a 20% dropout rate, in this study, N1 = N2 = 36 cases, totaling 72 cases.

[0062] 1.3 Randomization method

[0063] Using the computer random method, a random number is assigned to each of 1 - 72 through the randbetween function in the excel table. Enter "auxiliary column" in the first row of column C, such as, and enter the header "Generate random non - repeating data" in another column, such as column B; Secondly, enter the function formula "=RAND()*RAND()" in the second row of column C and drag the mouse down to the 73rd row to generate numbers; Finally, enter the function formula "=RANK(C2,$C$2:$C$73)" in the second row of column B to sort the numbers in the auxiliary column, and 72 random integers can be generated. According to the order of medical treatment, the odd numbers are assigned to the experimental group and the even numbers are assigned to the control group.

[0064] 1.4 Concealment grouping method and process

[0065] The random grouping scheme is saved in an airtight and light - proof envelope, and the envelopes are opened in sequence according to the order of enrollment. The grouping of patients is determined according to the allocation scheme in the envelope.

[0066] 1.5 Blinding method

[0067] This study is not blinded, and both the researchers and the subjects are aware of the grouping and treatment plan. The researchers participating in the clinical outcome evaluation are kept in a blinded state as much as possible during the trial, and the "three - separation principle" of the trial designer, operator, and evaluator is implemented.

[0068] 2. Research subjects in clinical trials

[0069] 2.1 Subject recruitment

[0070] 72 cases of chronic insomnia were recruited by posting recruitment advertisements at the outpatient department of the Encephalopathy Hospital of Shaanxi Provincial Traditional Chinese Medicine Hospital and posting them on WeChat Moments.

[0071] Recruitment time: from August 2020 to February 2021.

[0072] 2.2 Diagnostic criteria

[0073] According to the diagnostic description of insomnia disorder in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM - 5):

[0074] ① The main complaint is dissatisfaction with the quantity or quality of sleep, accompanied by the following (or more) related symptoms:

[0075] A. Difficulty falling asleep

[0076] B. Difficulty maintaining sleep, characterized by frequent awakenings or difficulty falling back asleep after waking up

[0077] C. Early awakening and inability to fall back asleep

[0078] ②The sleep disorder causes clinically significant distress or leads to impairment in social, occupational, educational, academic, behavioral, or other important functions;

[0079] ③Sleep difficulties occur at least 3 nights per week;

[0080] ④Sleep difficulties have been present for at least 3 months;

[0081] ⑤Sleep difficulties occur despite having adequate opportunities for sleep;

[0082] ⑥The insomnia cannot be better explained by another sleep - wake disorder and does not occur exclusively during the course of another sleep - wake disorder (e.g., narcolepsy, sleep - related breathing disorders, circadian rhythm sleep - wake disorders, parasomnias);

[0083] ⑦The insomnia cannot be attributed to the physiological effects of a substance (e.g., abused drugs, medications);

[0084] ⑧Co - existing mental disorders and medical conditions do not adequately explain the complaint of insomnia.

[0085] 2.3 Inclusion criteria

[0086] ①Meet the diagnostic criteria for chronic insomnia in the above - mentioned DSM - 5;

[0087] ②Meet the diagnostic criteria of the syndrome of liver blood deficiency in traditional Chinese medicine;

[0088] ③Aged 18 - 45 years old, regardless of gender;

[0089] ④Insomnia Severity Index (ISI) > 7;

[0090] ⑤Chinese Handedness Inventory ≥ 7;

[0091] ⑥Years of education ≥ 12 years;

[0092] ⑦Sign the informed consent form.

[0093] 2.4 Exclusion criteria

[0094] ①Insomnia associated with other mental illnesses (depression, anxiety disorder, schizophrenia, bipolar disorder, etc.), physical illnesses (pain, stroke, coronary heart disease, tumor, etc.);

[0095] ②Combined with severe depression and anxiety (PHQ - 9 depression screening ≥ 20; GAD - 7 anxiety screening ≥ 19);

[0096] ③Insomnia caused by other reasons such as poor sleep hygiene, jet lag, shift work, etc.;

[0097] ④High-risk individuals for sleep apnea (a positive result in ≥3 items of the Stop Bang questionnaire is considered high-risk);

[0098] ⑤Individuals with severe, unstable, or poorly controlled chronic diseases;

[0099] ⑥History of central nervous system diseases such as epilepsy, brain tumor, hemangioma, encephalitis, acute brain injury, etc.

[0100] 3. Clinical trial research methods

[0101] 3.1 Intervention measures

[0102] 3.1.1 Grouping

[0103] ①Experimental group: Take the decoction, once in the morning and once in the evening every day, about 200 ml each time, for 2 weeks continuously.

[0104] ②Blank control group: No intervention.

[0105] 3.1.2 Basic treatment

[0106] Both groups were given sleep hygiene education and cognitive therapy in cognitive behavioral therapy for insomnia (CBT-I).

[0107] At the first treatment, the therapist distributed a "Sleep Hygiene Education + Cognitive Therapy" brochure to the patients, and conducted about 30 minutes of education and communication by the therapist, trying to make the patients understand the education content as much as possible, and asking them to try to implement it according to the education content during the research period.

[0108] 3.1.3 Course of treatment

[0109] Both groups were given 2 weeks of treatment.

[0110] 3.1.4 Emergency plan

[0111] During the research period, any benzodiazepines, antidepressants, antipsychotics, and mood stabilizers were prohibited. When intolerable insomnia occurred during the research period, according to ethical requirements, alternative treatment: orally take eszopiclone tablets 3 mg / time (manufacturer: Jiangsu Tianshili Diyi Pharmaceutical Co., Ltd.; product batch number: h20070212; specification: 3 mg * 6). If the subjects used alternative drugs during the research period, the number of times and dosage of the alternative plan used needed to be recorded in detail.

[0112] 3.2 Observation indicators

[0113] 3.2.1 General information collection

[0114] This part of the research collected general information on chronic insomnia: gender, age, years of education, course of disease (months).

[0115] 3.2.2 Sleep symptom assessment

[0116] Insomnia Severity Index (ISI)

[0117] The ISI is a self-rating scale consisting of 7 questions, which is more commonly used for insomnia screening and evaluating the treatment response of insomnia. Each question has five options from 0 to 4, and the total score ranges from 0 to 28 points. The degree of insomnia of the subject can be evaluated through the total score obtained by the subject.

[0118] 3.2.3 Emotional symptom assessment

[0119] ① Beck Depression Inventory (BDI)

[0120] The Beck Depression Inventory is specifically used to evaluate the degree of depression. The entire scale includes the following 21 groups of items. Each group has 4 statements, and the Arabic numerals marked before each statement are the rating scores. According to the feeling, circle the number in front of the statement that best suits your situation. After completing all 21 groups, add up the circled scores of each group to obtain the total score. Based on the total score, the degree of depression of the subject can be evaluated.

[0121] ② Beck Anxiety Inventory (BAI)

[0122] The Beck Anxiety Inventory is an anxiety self-assessment questionnaire containing 21 items compiled in 1988, which can reflect the severity of the anxiety status of the subject. The severity of different anxiety symptoms is used as the evaluation index in the scale, and a 4-level scoring method is adopted. The standard is that "1" means none; "2" means mild, without much trouble; "3" means moderate, feeling uncomfortable but still tolerable; "4" means severe, barely tolerable. Measurement method: Add up the 21 self-rating scores of the subject to get the raw score, and then use the formula Y = INT(1.19x) to round up to convert the raw score into a standard score. Generally, BAI ≥ 45 is used as the judgment standard for positive anxiety.

[0123] 3.2.4 Assessment time

[0124] All subjects in both groups were evaluated once for the above-mentioned sleep and emotional indicators before treatment (day 0 of enrollment) and after treatment (day 14 of enrollment).

[0125] 3.3 Statistical analysis

[0126] SPSS 22.0 software was used for data analysis. With a two-sided α = 0.05 as the test level, P < 0.05 was considered statistically significant.

[0127] Descriptive analysis of baseline data: Calculation of measurement data Median, interquartile range (P75 - P25), minimum and maximum values; for count data, calculate the constituent ratio and rate.

[0128] Analysis of effect indicators: For measurement data, calculate the mean and standard deviation of each detection index. Paired t-tests (or Wilcoxon Signed Ranks Test for paired sign rank test) are used for within-group pre- and post-treatment comparisons in the treatment and control groups. For between-group comparisons of measurement data, t-tests (or calculation of 95% confidence intervals) are used. When the data is non-normally distributed and the variances are heterogeneous, the rank sum test (Mann-Whitney U) method is used.

[0129] 4. Research Results

[0130] 4.1 Baseline data analysis

[0131] A total of 72 subjects were included in this study, and finally 65 subjects completed all the tests.

[0132] Among them, Group 1: 33 cases in the experimental group (taking decoction); Group 2: 32 cases in the blank control group.

[0133] Table 1. Baseline data

[0134]

[0135] The results of the chi-square test showed that there was no statistically significant difference in gender distribution between the two groups.

[0136] The results of the two independent sample t-tests showed that there was no statistically significant difference in age between the two groups.

[0137] The results of the rank sum test (Mann-Whitney U) showed that there were no statistically significant differences in years of education and disease duration between the two groups.

[0138] 4.2 Effects on sleep and mood of insomnia

[0139] 4.2.1 Comparison of insomnia symptoms between the two groups

[0140] Table 2. Analysis of ISI before and after treatment and change values

[0141]

[0142] Using the two independent sample t-test method, the results showed that the ISI baselines of the two groups were homogeneous, and there was a statistically significant difference in the difference between pre- and post-treatment ISI in the two groups.

[0143] 4.2.2 Comparison of depressive symptoms between the two groups

[0144] Table 3. Analysis of BDI before and after treatment and change values

[0145]

[0146] The rank sum test (Mann-Whitney U) method was used, and the results showed that the baselines of the two groups in terms of BDI were homogeneous, and the difference in BDI before and after treatment was statistically significant.

[0147] 4.2.3 Comparison of anxiety symptoms between the two groups

[0148] Table 4. Analysis of BAI before and after treatment and the change values

[0149]

[0150] The rank sum test (Mann-Whitney U) method was used, and the results showed that the baselines of the two groups in terms of BAI were homogeneous, and the difference in BAI before and after treatment was statistically significant.

[0151] 5. Summary and discussion of the results

[0152] 5.1 Baseline data

[0153] The baseline characteristics of the experimental group (the group taking the decoction) included in this study were as follows: 12 males (36.4%), 21 females (63.6%), with an average age of 35.8 ± 7.0 years, a median education years of 16 (12.0 - 16.0), a median insomnia duration of 15 (6.5 - 72.0); the average score of ISI was 16.1 ± 4.0; the median of BDI was 7.0 (2.5 - 13.5); the median of BAI was 37.0 (30.5 - 52.0). The baseline characteristics of the blank control group for chronic insomnia were: 14 males (43.8%), 18 females (56.3%), with an average age of 35.7 ± 6.9 years, a median education years of 15 (15.0 - 15.7), a median insomnia duration of 36 (12.0 - 60.0); the average score of ISI was 15.9 ± 5.0; the median of BDI was 6.0 (3.0 - 12.7); the median of BAI was 37.0 (32.0 - 44.5).

[0154] 5.2 Efficacy indicators

[0155] The clinical trial results showed that the decoction of the present invention could significantly decrease the values of ISI, BDI and BAI in the subjects within the experimental group. Therefore, the decoction of the present invention can improve the sleep quality and anxiety and depressive moods of patients with chronic insomnia.

Claims

1. A Chinese medicine composition, comprising: angelica, stir-fried white peony root, cooked or raw rehmannia root, Cistanche deserticola, floating wheat, roasted liquorice, jujube, chuanxiong, papaya, atractylodes, calamus, spiny jujube seed, smilax china, oyster, mother of pearl, and curcuma.

2. The Chinese medicine composition according to claim 1, wherein The Chinese medicine composition comprises, by weight, 10-15 parts of angelica sinensis, 10-30 parts of stir-fried white peony root, 10-20 parts of cooked rehmannia root or 10-20 parts of raw rehmannia root, 10-30 parts of Cistanche deserticola, 15-30 parts of floating wheat, 6 parts of roasted liquorice root, 10 parts of jujube, 6-12 parts of chuanxiong, 6-18 parts of papaya, 10-15 parts of atractylodes macrocephala, 10-15 parts of calamus, 6-30 parts of spiny jujube seeds, 15-30 parts of tuberose, 15-30 parts of oyster, 15-30 parts of mother-of-pearl, and 10-12 parts of curcuma.

3. The Chinese medicine composition according to claim 2, wherein The Chinese medicine composition comprises, by weight, 15 parts of angelica sinensis, 30 parts of stir-fried white peony root, 20 parts of cooked rehmannia root or 20 parts of raw rehmannia root, 30 parts of cistanche deserticola, 30 parts of floating wheat, 6 parts of roasted licorice root, 10 parts of jujube, 9 parts of chuanxiong, 15 parts of papaya, 10 parts of atractylodes macrocephala, 15 parts of calamus, 30 parts of spiny jujube seeds, 30 parts of polyphylla, 30 parts of oyster, 30 parts of mother-of-pearl, and 10 parts of curcuma.

4. A decoction, wherein the decoction is prepared from the Chinese medicine composition according to any one of claims 1 to 3.

5. The decoction according to claim 4, wherein the decoction is prepared by the following method: 1) Add oysters and mother of pearl to appropriate amount of water, first boil over high heat for a first period of time, then add angelica, stir-fried white peony root, cooked rehmannia or raw rehmannia, Cistanche deserticola, floating wheat, roasted licorice, jujube, chuanxiong, papaya, atractylodes, calamus, spiny jujube seed, smilax glabra, and curcuma, continue to boil over high heat, boil over low heat for a second period of time, and filter to obtain the first decoction and residue; 2) adding clean water in an amount sufficient to submerge the filter residue again, boiling over high heat, then decocting over low heat for a third period of time, and filtering to obtain a second decoction; 3) combining the first decoction and the second decoction to obtain a final decoction.

6. The decoction according to claim 5, wherein The first time period is 10-20 minutes.

7. The decoction according to claim 5 or 6, wherein The second time period and the third time period are each independently 20-30 minutes.

8. The decoction according to any one of claims 5 to 7, wherein Before performing step 1), soak Chinese angelica, stir-fried white peony root, cooked or raw rehmannia root, Cistanche deserticola, floating wheat, roasted liquorice, jujube, chuanxiong, papaya, atractylodes, calamus, spiny jujube seed, smilax china, oyster, mother of pearl, and turmeric in clean water for 20-30 minutes.

9. Use of the Chinese medicine composition according to any one of claims 1 to 3 or the decoction according to any one of claims 4 to 8 in the preparation of a medicament for treating insomnia.

10. The use according to claim 9, wherein The insomnia is liver-blood deficiency type insomnia.

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