CN108434287B - Traditional Chinese medicine composition and preparation method and application thereof - Google Patents

Abstract

The invention provides a traditional Chinese medicine composition and a preparation method and application thereof, wherein the traditional Chinese medicine composition comprises the following components in parts by weight: 32-45 parts of raw bighead atractylodes rhizome, 32-45 parts of raw astragalus, 5-25 parts of whole angelica, 32-40 parts of cistanche, 5-20 parts of snakegourd seed, 11-20 parts of almond, 3-18 parts of dried orange peel, 16-25 parts of immature bitter orange, 5-20 parts of betel nut, 5-15 parts of white paeony root, 5-20 parts of divaricate saposhnikovia root, 5-30 parts of radix rehmanniae, 16-25 parts of cynomorium songaricum and 1-12 parts of liquorice. The traditional Chinese medicine composition disclosed by the invention has the advantages that various traditional Chinese medicines are compatible and the components are synergistic, so that the constipation symptom score is effectively reduced, the anorectal kinetic index is improved, the life quality of patients with chronic functional constipation is improved, the constipation recurrence rate is reduced, the long-term clinical curative effect is exact, and the popularization is worthy.

Description

Traditional Chinese medicine composition and preparation method and application thereof

Technical Field

The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating chronic functional constipation and a preparation method thereof.

Background

Functional constipation is a common gastrointestinal dysfunction disease in clinic and is manifested by constipation, obstruction, prolonged defecation interval, and difficulty in defecation. In the rapid economic development era, due to the fact that the conditions of different degrees of pressure, irregular work and rest, improper diet and the like of learning, work, life and the like affect the hormone secretion level and gastrointestinal motility of a human body, and functional constipation is easy to cause, according to related research results, the incidence rate of senile chronic constipation in Western Europe and America countries can reach 20% -30%, and the incidence rate of senile chronic constipation in Asian countries is 11.6%. According to related data, the prevalence rate of chronic constipation in China is 3% -17%, the prevalence rate of women is obviously higher than that of men, and the prevalence rate of women is increased continuously with the increase of age, the prevalence rate of the chronic constipation is obviously increased after the age of 60, and the prevalence rate of the chronic constipation is increased more quickly after the age of 70. With the increasing aging of cities, senile constipation is very common, and the prevalence rate is obviously increased with the increase of age. The prevalence rate of constipation of old people over 60 years old in Beijing, Tianjin and Xian is as high as 15-20%. Dyschezia can induce severe events such as angina pectoris, acute myocardial infarction, cerebrovascular diseases, etc. of the elderly. Constipation not only causes gastrointestinal dysfunction, but also causes gastrointestinal and anal diseases such as intestinal inflammation, hemorrhoids, anal fissure, abdominal pain and the like, and patients with intractable constipation show various obvious psychological problems, often accompanied by anxiety, depression and sleep disorder, while serious patients can induce other critical diseases such as heart diseases, cerebrovascular accidents, even colorectal cancer and even death, which brings great influence to the daily life of people and becomes the key point of domestic and foreign research. Therefore, finding a method for effectively relieving the pain of constipation is a direct problem in modern medicine.

The onset of chronic functional constipation is influenced by a plurality of factors, and although the research on the chronic functional constipation is more, no uniform treatment principle and effective treatment scheme exist. The treatment aim of chronic functional constipation is to eliminate the cause of chronic functional constipation as much as possible, relieve the symptoms of chronic functional constipation, enhance the intestinal transmission capacity and promote the defecation. At present, two methods, namely non-operation and operation, are mainly used for treating the chronic functional constipation. Non-surgical treatments include: general therapy, drug therapy, behavioral and psychological therapies, and other treatment modalities. The general therapy requires long time and can not achieve satisfactory effect in a short period. The treatment of chronic functional constipation is still mostly drug dependent, among which laxatives and prokinetic drugs are used more often. However, if the laxatives are taken for a long time, especially for the laxatives such as rhubarb and senna, not only intestinal function and electrolyte disorder are easily formed, but also dependence is generated, and the colon melanosis may occur. Prokinetic drugs have some effects, but symptoms are more likely to be repeated. The colon diversion operation and the colon partial resection operation with pathological changes have large trauma to the organism, more complications and sequelae and higher recurrence rate, and the clinical application is difficult to grasp the operation indications and indications; sacral nerve stimulation is used as a new means for treating mixed constipation, and foreign research shows that the clinical effect is good; domestic research shows that the technology has complex operation, high cost and general clinical treatment effect.

The constipation is called as 'posterior disorder' in the "internal classic" of traditional Chinese medicine, and the constipation is called as 'spleen about', 'yin knot' and 'yang knot' in the "middle energizer". The pathogenesis of the disease is the dysfunction of the large intestine in conduction, but the pathogenesis is closely related to the dysfunction of the viscera, the intermingled deficiency and excess, blood stasis and the like. The traditional Chinese medicine for treating constipation has various methods, obvious advantages, definite curative effect, safety, low price and no toxic or side effect, and eliminates pathogenic factors without damaging vital qi and simultaneously treats both principal and secondary aspects. The traditional Chinese medicine compound adopts specific treatment methods of heat release, warm powder, dredging, qi tonifying, yin nourishing, blood stasis removing and the like, and relieves constipation and improves disordered gastrointestinal functions. The traditional Chinese medicine composition is low in price, has small adverse reaction, can be taken for a long time, is obviously superior to western medicines in curative effect, disease recurrence, symptom improvement, adverse reaction and recurrence rate, and fully embodies the characteristics and advantages of traditional Chinese medicine for treating diseases.

CN102698161A discloses a traditional Chinese medicine composition for treating senile constipation, which comprises the following components in parts by weight: 15-30 parts of cistanche, 30-60 parts of caulis spatholobi, 30-60 parts of raw astragalus membranaceus, 30-60 parts of raw bighead atractylodes rhizome, 30-60 parts of angelica sinensis, 15-30 parts of prepared polygonum multiflorum, 15-30 parts of cynomorium songaricum, 10-25 parts of radix stemonae, 10-25 parts of houttuynia cordata, 10-25 parts of perillaseed, 10-25 parts of almond, 10-15 parts of immature bitter orange, 10-15 parts of perillaseed and 10-15 parts of. CN102698162A discloses a traditional Chinese medicine composition for treating constipation, which comprises the following components in parts by weight: 15-30 parts of cistanche, 30-60 parts of caulis spatholobi, 30-60 parts of raw astragalus membranaceus, 30-60 parts of raw bighead atractylodes rhizome, 30-60 parts of angelica sinensis, 15-30 parts of prepared polygonum multiflorum, 15-30 parts of cynomorium songaricum, 10-25 parts of radix stemonae, 10-25 parts of houttuynia cordata, 10-25 parts of perillaseed, 10-25 parts of black sesame, 10-15 parts of immature bitter orange, 10-15 parts of perillaseed, 10-15 parts of platycodon grandiflorum, 5-8 parts of luffa flower, 10-15 parts of asparagus, 20-35 parts of pine nut. The adjuvant and the conductant drugs in the formula can not be well matched with monarch and minister drugs, the drug properties of the medicinal materials in each component are unbalanced, and the liver load is large when the adjuvant and the conductant drugs are taken excessively.

Therefore, the traditional Chinese medicine composition for treating chronic functional constipation, which is safe, has no side effect and obvious curative effect, has important significance and broad prospect.

Disclosure of Invention

Aiming at the defects and actual requirements of the prior art, the traditional Chinese medicine composition and the preparation method and application thereof are provided by the invention, the traditional Chinese medicine composition is reasonable in formula, the components are synergistic, the score of constipation symptoms can be effectively reduced, the anorectal kinetic index can be improved, the life quality of patients with chronic functional constipation can be improved, the recurrence rate of constipation can be reduced, the long-term curative effect can be maintained, and the traditional Chinese medicine composition has wide application prospect and market value.

In order to achieve the purpose, the invention adopts the following technical scheme:

in a first aspect, the invention provides a traditional Chinese medicine composition, which comprises the following components in parts by weight: 32-45 parts of raw bighead atractylodes rhizome, 32-45 parts of raw astragalus, 5-25 parts of whole angelica, 32-40 parts of cistanche, 5-20 parts of snakegourd seed, 11-20 parts of almond, 3-18 parts of dried orange peel, 16-25 parts of immature bitter orange, 5-20 parts of betel nut, 5-15 parts of white paeony root, 5-20 parts of divaricate saposhnikovia root, 5-30 parts of radix rehmanniae, 16-25 parts of cynomorium songaricum and 1-12 parts of liquorice.

The nature and the taste and the efficacy of the traditional Chinese medicines are as follows:

raw rhizoma atractylodis macrocephalae: sweet and bitter in taste, warm in nature, entering spleen and stomach channels, has the effects of tonifying spleen and benefiting qi, eliminating dampness and diuresis, consolidating superficial resistance and arresting sweating, activating spleen and moistening dryness, and is mainly used for treating fullness and diarrhea, phlegm retention and edema caused by spleen dysfunction and water retention and qi failure; restlessness and disinclination to talk due to deficiency of middle qi, metrorrhagia, metrostaxis, chronic dysentery and rectocele; due to spleen deficiency and qi weakness with symptoms of insecurity in the interior, sweating due to deficiency, etc., Atractylodis rhizoma can promote gastric secretion, enhance absorption of small intestine, and regulate gastrointestinal function. The atractylodes macrocephala koidz can promote gastrointestinal motility by increasing the distribution of cholinergic nerves of the myenteric plexus and promoting the release of acetylcholine. The rhizoma Atractylodis Macrocephalae also has the effects of promoting the proliferation of beneficial bacteria bifidobacteria and lactic acid bacteria in intestinal flora, improving the flora condition in intestinal tract, and promoting defecation.

Raw astragalus root: sweet in nature and taste, slightly warm, entering spleen and lung meridians, raw Huang Qi is mostly used for consolidating exterior, supporting sore, inducing diuresis, etc.; radix astragali processed with honey is often used for tonifying middle-jiao and Qi; stir-baked Huang Qi is mostly used for tonifying qi and spleen. Astragalus membranaceus is a holy medicine for tonifying qi, is good for tonifying qi of the whole body, and has the characteristic of tonifying but not greasy, and the chemical components of astragalus membranaceus mainly comprise glycosides, polysaccharides, flavones, amino acids, trace elements and the like. Radix astragali has effects of promoting metabolism, relieving fatigue, and improving anemia; can enhance immunity.

Whole Chinese angelica: it is warm in nature, sweet and pungent in flavor, and can enter heart, liver and spleen meridians. Enriching the blood; promoting blood circulation; regulating menstruation and relieving pain; moistening dryness and smoothing intestine. The main symptoms are blood deficiency; menoxenia; amenorrhea; dysmenorrhea; the accumulation of symptoms; (ii) metrorrhagia and metrostaxis; abdominal pain due to deficiency-cold; flaccidity and paralysis; numbness of the skin; intestinal dryness and difficult defecation; severe dysentery with diarrhea; carbuncle, cellulitis, sore and ulcer; injury from falling. Modern researches show that the angelica volatile oil can relax gastrointestinal smooth muscles and reduce muscle tension. There may be a bi-directional modulating effect on gastrointestinal motility.

Cistanche deserticola: it is warm in nature, bitter and salty in taste, and enters kidney and large intestine meridians. Has effects of invigorating kidney yang, replenishing essence and blood, loosening bowel to relieve constipation, etc. The active ingredients are inorganic salts and hydrophilic colloid polysaccharide.

Semen trichosanthis: sweet, slightly bitter and cold. It enters lung, stomach and large intestine meridians. Clear heat and resolve phlegm, relieve chest stuffiness and dissipate nodulation, moisten intestines and relax bowels.

Almond: has the main functions of depressing qi, relieving cough and asthma, and relaxing bowel. Can be used for treating cough, asthma, chest fullness, excessive phlegm, blood deficiency, dry body fluid, intestinal dryness, and constipation. The almond is bitter in taste and smells sweet, and is rich in fatty oil. The fatty oil can improve the lubricating effect of intestinal contents on mucous membrane, and the amygdalin can be decomposed to generate hydrocyanic acid and benzyl vinegar, so that benzyl has an inhibiting effect on the digestion function of pepsin. The semen Armeniacae amarum extract has effects in resisting histamine and acetylcholine on smooth muscle, and enhancing intestinal peristalsis.

Dried orange peel: bitter and pungent in flavor and warm in nature. It enters lung and spleen meridians. Regulate qi to invigorate spleen, dry dampness and resolve phlegm. Can be used for treating abdominal distention, anorexia, vomiting, diarrhea, cough, and excessive phlegm. The pericarpium citri reticulatae volatile oil can directly act on intestinal smooth muscle; the tangerine peel water decoction, the volatile oil and the total flavone have obvious inhibiting effect on the contraction of normal isolated intestinal muscles of the rabbits, can antagonize the spastic contraction of isolated duodenum of the rabbits caused by acetylcholine, and can further relax the isolated intestinal muscles of the rabbits with reduced tension by using atropine and further weaken the amplitude.

Immature bitter orange: bitter, pungent and sour in taste, slightly cold in nature, entering spleen and stomach channels, and has the effects of breaking qi, removing food retention, eliminating phlegm and relieving distension and fullness. It is often combined with other herbs to treat gastroptosis, food retention, constipation, abdominal pain, cough with excessive phlegm, wind-phlegm vertigo. Zhi Shi can relieve intestinal spasm caused by acetylcholine or barium chloride, increase gastrointestinal contraction rhythm, and promote intestinal peristalsis. Flavonoid components in fructus Aurantii Immaturus mainly include hesperidin, hesperetin, naringin, naringenin, neohesperidin, narirutin, tangeretin, rhoifolin, loniceran, poncirin, eriocitrin, hesperetin 7-O-beta-D-glucoside and other flavanone components, and hesperetin, nobiletin, 5,7,8, 4' -tetramethoxyflavone, 5-demethyltangeritin and other polymethoxyflavone components, and can enhance gastrointestinal motility, and promote gastrointestinal motility of rats with spleen deficiency model by promoting secretion of rat Gastrin (GAS), plasma acetylcholine (ACh) and Motilin (MTL) and inhibiting secretion of Vasoactive Intestinal Peptide (VIP).

Betel nut: bitter and pungent taste, warm in nature, entering stomach and large intestine, good at promoting qi stagnation in stomach and intestine, removing food stagnation and resolving food stagnation, and relaxing bowels. Arecoline promotes the contraction of gastrointestinal smooth muscle, and enhances gastrointestinal motility and digestive juice secretion.

White peony root: slightly cold in nature, bitter, sour and sweet in flavor, entering liver and spleen channels, entering liver with sweet and sour taste, tonifying liver blood, astringing liver yin, and has effects of nourishing blood, regulating menstruation, astringing yin, arresting sweating, replenishing blood, softening liver, and relieving spasm and pain. Radix Paeoniae alba has effects of astringing with acid, relieving diarrhea, relieving constipation and regulating. Paeoniflorin studies have also shown that paeoniflorin has an inhibitory effect on the cerebral cortex, for example, to prolong the sleep time of mice caused by a threshold dose of sodium pentobarbital.

Wind prevention: it is warm in nature, pungent and sweet in flavor, and enters bladder, liver and spleen meridians. Has the effects of dispersing pathogenic wind, relieving exterior syndrome, eliminating dampness, relieving pain, dispelling pathogenic wind, and relieving spasm. The windproof part has the function of bidirectional adjustment of lifting: it can not only ascend clear yang to stop diarrhea, but also can relieve constipation by qi stagnation. The divaricate saposhnikovia root can inhibit the small intestine propulsion and the gastric emptying of a mouse and inhibit the colon smooth muscle contraction of an isolated rat, and the mechanism is related to adrenergic alpha-receptors and M choline receptors and unrelated to opioid receptors and beta receptors; ledebouriella seseloides can reduce the concentration of intracellular free calcium ion, and its mechanism is related to the inhibition of extracellular calcium ion influx.

Dried rehmannia root: sweet and cold in nature. It enters heart, liver and kidney meridians. Clear heat and cool blood, nourish yin, promote the production of body fluid. Can be used for treating fever with deep-red tongue, polydipsia, yin deficiency, internal heat, bone steaming, internal heat, diabetes, hematemesis, epistaxis, macula, and eruption. The rhizome of rehmannia contains beta-sitosterol and mannitol, and the extract of the rhizome of rehmannia has the effect of relaxing bowel on constipation model mice.

And (3) locking the positive: sweet in flavor and warm in nature. It enters liver, kidney and large intestine meridians. Originally recorded in Ben Cao Yan Yi Bu Yi and Ben Cao gang mu, it has the actions of tonifying kidney yang, benefiting essence and blood, moistening intestines and relaxing bowels, and is mainly used for treating diseases such as kidney yang deficiency, soreness and weakness of waist and knees, essence and blood deficiency, impotence, spermatorrhea, constipation due to intestinal dryness, etc. The water-soluble inorganic ions in the cynomorium songaricum form known salt cathartics such as magnesium sulfate, sodium phosphate and the like to play a role in relaxing the bowel.

Licorice root: sweet in flavor and neutral in nature. It enters heart, lung, spleen and stomach meridians. Invigorating spleen and replenishing qi, clearing away heat and toxic material, eliminating phlegm and relieving cough, relieving spasm and pain, and harmonizing the drugs. Can be used for treating weakness of spleen and stomach, asthenia, palpitation, short breath, cough, excessive phlegm, abdominal and limb spasm, pain, carbuncle, swelling, sore, and drug toxicity and strong nature.

The traditional Chinese medicine composition is used for prescription dispatching according to the principle of monarch, minister, assistant and guide.

The constipation belongs to the categories of 'spleen restriction' and 'constipation' in traditional Chinese medicine, the purgative can consume the vital qi of a human body and aggravate the disease, the slow-transit constipation of the type belongs to 'deficient constipation', symptoms of yin deficiency and intestine dryness such as intestine dryness, constipation due to dry mouth and drinking preference and the like are common symptoms, the key pathological core is spleen deficiency and transportation failure, the spleen deficiency and kidney deficiency, large intestine conduction weakness, dregs of rice wine can not go down, qi stagnation, turbid qi ascending, lung orifice obstruction, qi dispersing and descending, qi transportation failure of the whole body, kidney yang deficiency loss for a long time, large intestine deficiency in warm body, qi stagnation and qi stagnation, and the disease is developed. According to the data mining result of the experience of Wumen medical department in Mingqing period in distinguishing and treating constipation, the prescription is prepared by using a treatment method of freeing lung and inducing resuscitation, enriching blood and nourishing yin, and tonifying spleen and warming kidney based on the treatment principle of 'treating the constipation with Tong as shun'. In the formula, raw astragalus and raw bighead atractylodes rhizome, which are sweet in taste, have the effects of tonifying lung and spleen, invigorating spleen and promoting the production of body fluid, are monarch drugs; dry stool and defecation with less frequency are caused by the loss of nourishment of yin and blood in the intestinal tract, the loss of body fluid in the large intestine and the absence of water for moving the boat, which are the symptoms of yin and blood deficiency, so the angelica is used for enriching the blood and moistening dryness, and relaxing the bowel; cynomorium songaricum and cistanche salsa have the effects of tonifying kidney and replenishing vital essence and relaxing bowel; bing Lang, Zhi Shi and Chen Pi, acting as ministerial drugs, act together to break qi and remove stagnation. Bai Shao can nourish blood and astringe yin, and soften liver, relieve spasm and alleviate pain; semen trichosanthis has the functions of moistening lung and reducing phlegm, and relaxing bowel; apricot kernel, semen Armeniacae amarum, the herb of formula Praeparata, acts as an adjuvant drug in the aspect of dispersing lung qi, lifting the pot and uncovering the lid, and clearing yang and ascending turbidity and yin can descend to supplement each other to help defecation. Ledebouriella root, radix Saposhnikoviae, in one aspect, raises yang qi of spleen, and in the other aspect, combines with raw Bai Zhu to eliminate dampness. Ledebouriella root, radix Ledebouriellae raises the clear yang, clears the yang, lowers turbid yin, removes dampness stagnation, and is easy to get through. Licorice root, radix Glycyrrhizae coordinates the effects of the other drugs in the recipe, and acts as a guiding drug in combination with Fang Feng.

Preferably, the weight portion of the raw white atractylodes rhizome is 32 to 45 portions, for example, 32 portions, 33 portions, 34 portions, 35 portions, 36 portions, 37 portions, 38 portions, 39 portions, 40 portions, 41 portions, 42 portions, 43 portions, 44 portions or 45 portions, preferably 35 to 40 portions, and more preferably 35 portions.

Preferably, the raw astragalus membranaceus accounts for 32-45 parts by weight, and can be 32 parts, 33 parts, 34 parts, 35 parts, 36 parts, 37 parts, 38 parts, 39 parts, 40 parts, 41 parts, 42 parts, 43 parts, 44 parts or 45 parts by weight, preferably 35-40 parts by weight, and more preferably 35 parts by weight.

Preferably, the total angelica is 5 to 25 parts by weight, for example, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, 21 parts, 22 parts, 23 parts, 24 parts or 25 parts, preferably 10 to 20 parts, and more preferably 18 parts.

Preferably, the cistanche salsa is 32-40 parts by weight, for example, 32 parts, 33 parts, 34 parts, 35 parts, 36 parts, 37 parts, 38 parts, 39 parts, 40 parts, 41 parts, 42 parts, 43 parts, 44 parts or 45 parts by weight, preferably 35-40 parts by weight, and more preferably 35 parts by weight.

Preferably, the parts by weight of the snakegourd fruit kernel are 5-20 parts, such as 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts, preferably 10-18 parts, and more preferably 18 parts.

Preferably, the weight part of the almond is 11 to 20 parts, such as 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts, preferably 6 to 15 parts, and more preferably 14 parts.

Preferably, the part by weight of the dried orange peel is 3 to 18 parts, for example, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts or 18 parts, preferably 5 to 13 parts, and more preferably 12 parts.

Preferably, the weight portion of the immature bitter orange is 16 to 25 portions, such as 16 portions, 17 portions, 18 portions, 19 portions, 20 portions, 21 portions, 22 portions, 23 portions, 24 portions or 25 portions, preferably 16 to 20 portions, and more preferably 18 portions.

Preferably, the weight portion of the betel nut is 5 to 20 portions, such as 5 portions, 6 portions, 7 portions, 8 portions, 9 portions, 10 portions, 11 portions, 12 portions, 13 portions, 14 portions, 15 portions, 16 portions, 17 portions, 18 portions, 19 portions or 20 portions, preferably 10 to 20 portions, and more preferably 18 portions.

Preferably, the white peony root is 5 to 15 parts by weight, for example, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts or 15 parts by weight, preferably 6 to 12 parts by weight, and more preferably 12 parts by weight.

Preferably, the weight portion of the divaricate saposhnikovia root is 5 to 20 parts, such as 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts, preferably 10 to 15 parts, and more preferably 12 parts.

Preferably, the weight portion of the raw rehmannia root is 5 to 30 portions, for example, 5 portions, 6 portions, 7 portions, 8 portions, 9 portions, 10 portions, 11 portions, 12 portions, 13 portions, 14 portions, 15 portions, 16 portions, 17 portions, 18 portions, 19 portions, 20 portions, 21 portions, 22 portions, 23 portions, 24 portions, 25 portions, 26 portions, 27 portions, 28 portions, 29 portions or 30 portions, preferably 15 to 25 portions, and more preferably 24 portions.

Preferably, the weight part of the cynomorium songaricum is 16-25 parts, for example, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, 21 parts, 22 parts, 23 parts, 24 parts or 25 parts, preferably 16-20 parts, and more preferably 18 parts.

Preferably, the weight part of the licorice is 1 to 12 parts, for example, 1 part, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts or 12 parts, preferably 4 to 10 parts, and more preferably 7 parts.

According to the traditional Chinese medicine composition, a plurality of traditional Chinese medicinal materials are added, the components are synergistic, the medicinal properties and the medicinal effects of the components are coordinated under the weight parts, so that the traditional Chinese medicine composition has the effects of moistening intestines, relaxing bowels, nourishing viscera, reducing the load on the liver, comprehensively and comprehensively conditioning the internal circulation system of a patient, and effectively antagonizing the release of inflammatory mediators and endotoxin.

Preferably, the composition further comprises an adjuvant.

Preferably, the adjuvant comprises any one of dextrin, lactose, starch, sucrose, glucose, mannose, stevioside or aerosil or a combination of at least two thereof, which may be, for example, a combination of dextrin and lactose, a combination of starch and sucrose, a combination of stevioside and aerosil, a combination of dextrin, glucose and aerosil or a combination of starch, mannose and aerosil, preferably a combination of dextrin, glucose and aerosil.

In a second aspect, the present invention provides a method for preparing the Chinese medicinal composition according to the first aspect, comprising the following steps:

(1) mixing raw bighead atractylodes rhizome, snakegourd seed, dried orange peel and immature bitter orange in parts by weight, then soaking in water, distilling to extract volatile oil, adding an inclusion compound and water, preparing the volatile oil into an inclusion compound, and drying for later use;

(2) mixing radix astragali, radix Paeoniae alba, Glycyrrhrizae radix and radix Saposhnikoviae in parts by weight, adding ethanol, reflux extracting, filtering, and concentrating to obtain ethanol extract concentrate and residue;

(3) adding the whole Chinese angelica, the cistanche, the almond, the betel nut, the radix rehmanniae recen and the cynomorium songaricum into the dregs obtained in the step (2) according to the parts by weight, mixing, adding water for decoction, filtering and concentrating, adding ethanol, stirring uniformly, standing, filtering to obtain a water extraction and alcohol precipitation concentrated solution;

(4) and (3) uniformly mixing the concentrated solutions obtained in the step (2) and the step (3), concentrating and drying to obtain a dry extract, uniformly mixing the dry extract, the inclusion compound obtained in the step (1) and auxiliary materials, and granulating to obtain the traditional Chinese medicine composition granules.

Preferably, the weight ratio of the water addition amount in the step (1) to the mixed medicinal materials is (8-15) to 1, and can be 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1 or 15:1, for example.

Preferably, the soaking time in step (1) is 20-60min, such as 20min, 30min, 40min, 50min or 60min, preferably 30 min.

Preferably, the distillation of step (1) is steam distillation.

Preferably, the distillation time in step (1) is 4-8h, for example 4h, 5h, 6h, 7h or 8h, preferably 6 h.

Preferably, the inclusion agent of step (1) is beta-cyclodextrin.

Preferably, the weight ratio of the volatile oil, the inclusion agent and the water in the step (1) is 1 (4-8) to (20-30), and can be 1:6:24, 1:4:20, 1:8:30, 1:5:26, 1:7:28 or 1:5: 22.

Preferably, the time for inclusion in step (1) is 60-120min, such as 60min, 70min, 80min, 90min, 100min, 110min or 120 min.

Preferably, the drying of step (1) is vacuum drying.

Preferably, the drying temperature in step (1) is 35-45 deg.C, such as 35 deg.C, 36 deg.C, 37 deg.C, 38 deg.C, 39 deg.C, 40 deg.C, 41 deg.C, 42 deg.C, 43 deg.C, 44 deg.C or 45 deg.C.

The invention discovers that the volatile oil can be effectively improved by extracting the volatile oil after mixing the raw rhizoma atractylodis macrocephalae, the snakegourd seed, the dried orange peel and the immature bitter orange according to the weight part, the loss of the volatile oil can be prevented by performing cyclodextrin inclusion on the volatile oil, and the invention is suitable for various dosage forms and has wide application.

Preferably, the weight ratio of the ethanol dosage in the step (2) to the mixed medicinal materials is (11-15):1, and can be 11:1, 12:1, 13:1, 14:1 or 15:1, for example.

Preferably, the ethanol concentration in step (2) is 60-70%, for example, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69% or 70%.

Preferably, the reflux extraction in step (2) is performed 1 to 3 times, for example, 1, 2 or 3 times.

Preferably, the reflux extraction time of step (2) is 1-3h each time, for example, 1h, 2h or 3 h.

The invention discovers that the extraction of effective components can be improved by using alcohol extraction after mixing the astragalus, the white paeony root, the liquorice and the divaricate saposhnikovia root, and the more effective components of the obtained alcohol extraction concentrated solution are in the weight part ratio.

Preferably, the weight ratio of the water addition amount in the step (3) to the mixed medicinal materials in the step (3) is (10-13):1, and can be, for example, 10:1, 11:1, 12:1 or 13: 1.

Preferably, the number of times of decoction in step (3) is 1-4, and may be, for example, 1, 2, 3 or 4.

In the invention, the filtrate obtained by multiple times of decoction is uniformly mixed and then concentrated.

Preferably, the time for decocting in step (3) is 1-3h each time, and may be 1h, 2h or 3 h.

Preferably, the filtrate of step (3) is concentrated to a relative density of 1.02-1.10, which may be, for example, 1.02, 1.03, 1.04, 1.05, 1.06, 1.07, 1.08, 1.09 or 1.10, preferably 1.05-1.08.

The method for measuring the relative density comprises the following steps: taking a clean, dry and precisely weighed pycnometer, filling the pycnometer with a sample, then installing a thermometer (no air bubbles should be in the bottle), placing the bottle in a water bath at 50-60 ℃ for 10-20 minutes to ensure that the temperature of the content reaches 50-60 ℃, removing the liquid overflowing the side tube by using filter paper, and immediately covering the bottle with a cover. Taking out the pycnometer from the water bath, wiping the outer surface of the pycnometer with filter paper, precisely weighing, subtracting the weight of the pycnometer to obtain the weight of the sample, pouring the sample, cleaning the pycnometer, filling with newly boiled cold water, measuring the weight of water at the same temperature according to the method, and calculating according to the following formula, namely the relative density of the sample is the weight of the sample/the weight of water.

The invention discovers that the effect of the water extraction concentrated solution obtained in the step (2) is optimal when the concentrated solution is concentrated to the relative density of 1.02-1.10, the ethanol raw material is wasted due to over dilution, and the precipitation effect is influenced due to over concentration, so that the relative density of 1.02-1.10 is selected as the concentration condition of the water extraction concentrated solution in the invention.

Preferably, the ethanol of step (3) is added to an alcohol content of 40-60%, for example 40%, 42%, 45%, 48%, 50%, 53%, 55%, 58% or 60%.

According to the invention, the active ingredients are extracted more favorably by water extraction and alcohol precipitation after the whole angelica, the cistanche, the almond, the betel nut, the radix rehmanniae recen and the cynomorium songaricum are mixed, the dosage of the ethanol is 40-60% of the alcohol content added into the concentrated solution, and the active ingredients of the medicine can be dissolved out to the maximum extent under the condition of the alcohol content.

Preferably, the standing time in step (3) is 20-30h, such as 20h, 21h, 22h, 23h, 24h, 25h, 26h, 27h, 28h, 29h or 30 h.

The invention discovers that the impurities can be more completely precipitated after the ethanol is added and stirred uniformly and placed for 20-30h, and the obtained concentrated solution has higher quality.

Preferably, the concentration of step (4) is to a relative density of 1.10-1.15, which may be, for example, 1.10, 1.11, 1.12, 1.13, 1.14 or 1.15.

The invention discovers that the alcohol precipitation concentrated solution has the best effect when being concentrated to the relative density of 1.10-1.15, and is beneficial to the subsequent spray drying process.

Preferably, the temperature at which the relative density is measured in step (4) is 50 to 60 ℃, and may be, for example, 50 ℃, 51 ℃, 52 ℃, 53 ℃, 54 ℃, 55 ℃, 56 ℃, 57 ℃, 58 ℃, 59 ℃ or 60 ℃.

The invention finds that the concentrated solution has the best fluidity when the testing temperature is controlled to be 50-60 ℃, and is convenient to measure.

Preferably, the granulation mode in the step (4) is spray granulation.

Preferably, the temperature of the inlet air for spray drying is 165-175 ℃, for example 165 ℃, 166 ℃, 167 ℃, 168 ℃, 169 ℃, 170 ℃, 171 ℃, 172 ℃, 173 ℃, 174 ℃ or 175 ℃.

Preferably, the temperature of the outlet air of the spray drying is 85-90 ℃, for example 85 ℃, 86 ℃, 87 ℃, 88 ℃, 89 ℃ or 90 ℃.

After the thin material is atomized in the drying chamber, the water content is quickly vaporized in the contact of the thin material and hot air, and then the dried product is obtained. The method can directly dry the solution and emulsion into powder or granular products, can omit the procedures of evaporation, crushing and the like, and can well form granules under the spray drying condition.

Preferably, the method specifically comprises the following steps:

(1) mixing raw rhizoma atractylodis macrocephalae, semen trichosanthis, dried orange peel and immature bitter orange in parts by weight, adding water, wherein the weight ratio of the added water to the mixed medicinal materials is (8-15):1, soaking for 20-60min, performing steam distillation for 4-8h to extract volatile oil, adding beta-cyclodextrin and water, wherein the weight ratio of the volatile oil to the inclusion compound to the water is 1 (4-8): 20-30, including for 60-120min, preparing the volatile oil into an inclusion compound, and performing vacuum drying at 35-45 ℃ for later use;

(2) mixing radix astragali, radix Paeoniae alba, Glycyrrhrizae radix and radix Saposhnikoviae in parts by weight, adding ethanol at a weight ratio of (11-15):1, ethanol concentration of 60-70%, reflux-extracting for 1-3 times, refluxing for 1-3 hr each time, recovering ethanol, concentrating, and filtering to obtain ethanol extract concentrate and residue;

(3) adding the whole Chinese angelica, the cistanche, the almond, the betel nut, the radix rehmanniae recen and the cynomorium songaricum into the dregs obtained in the step (2) according to the weight part, mixing, adding water for decoction, wherein the weight ratio of the added water to the mixed medicinal materials is (10-13):1, decocting for 1-4 times and 1-3h each time, filtering, concentrating the filtrate until the relative density is 1.02-1.10, then adding ethanol until the alcohol content is 40-60%, uniformly stirring, standing for 20-30h, filtering, recovering the ethanol from the filtrate, and obtaining a water extraction and ethanol precipitation concentrated solution;

(4) and (3) uniformly mixing the concentrated solutions obtained in the steps (2) and (3), concentrating until the relative density is 1.10-1.15, testing the relative density at 50-60 ℃, drying to obtain a dry extract, uniformly mixing the dry extract, the inclusion compound obtained in the step (1) and auxiliary materials, and performing spray granulation, wherein the inlet air temperature is 165-175 ℃, and the outlet air temperature is 85-90 ℃ to obtain the traditional Chinese medicine composition particles.

In a third aspect, a use of the Chinese medicinal composition of the first aspect in preparing a medicament and/or a preparation for treating functional constipation and gastrointestinal dysfunction diseases.

Preferably, the formulation comprises any one of granules, capsules, tablets or pills or a combination of at least two thereof.

Compared with the prior art, the invention has the following beneficial effects:

(1) according to the invention, through compatibility of various traditional Chinese medicines and synergistic interaction of the components, the score of constipation symptoms is effectively reduced, the anorectal kinetic index is improved, the life quality of patients with chronic functional constipation is improved, the recurrence rate of constipation is reduced, and the long-term clinical curative effect is definite;

(2) the traditional Chinese medicine composition has a reasonable formula, treats both lung, spleen and kidney, and can promote the expression of Myosin Light Chain Kinase (MLCK) of colon smooth muscle, promote the movement of colon, improve the barrier function of intestinal mucosa, and increase the water content and the quantity of excrement;

(3) the preparation method of the traditional Chinese medicine composition can effectively increase the extraction rate of the active ingredients of the medicine, has high bioavailability and obvious curative effect compared with the traditional decoction, can recycle the ethanol in the process conditions, and reduces the production cost.

Drawings

FIG. 1A is a graph showing the resting anal pressures of two groups of patients in clinical trials of the present invention before and after treatment and during follow-up, respectively, with example 1 and comparative example 5; FIG. 1B is a graph showing the maximum systolic anal pressure for clinical trials of the present invention before and after treatment and during follow-up visits with the administration of example 1 and comparative example 5, respectively; FIG. 1C is a graph showing the rectal initial sensation threshold before and after treatment and during follow-up for the clinical trial of the present invention with example 1 and comparative example 5, respectively; FIG. 1D is a graph showing the maximum rectal tolerance of the clinical trial of the present invention before and after treatment and during follow-up with example 1 and comparative example 5, respectively;

FIG. 2A is a graph of the change in PAC-QOL physical discomfort score before and after treatment and during follow-up in clinical trials of the present invention using example 1 and comparative example 5, respectively; FIG. 2B is a graph showing the change in PAC-QOL psychosocial discomfort score before and after treatment and during follow-up in clinical trials of the present invention using example 1 and comparative example 5, respectively; FIG. 2C is a graph of PAC-QOL fear and anxiety score changes before and after treatment and during follow-up for clinical trials of the present invention using example 1 and comparative example 5, respectively; FIG. 2D is a graph of the change in PAC-QOL satisfaction score before and after treatment and during follow-up for clinical trials in the present invention, respectively, using example 1 and comparative example 5;

FIG. 3A is a graph showing the change in fecal number of rats administered different doses of STC of example 1 in the rat experiment of the present invention, wherein group A is the normal group, group B is the model group, group C is the low dose group of example 1, group D is the medium dose group of example 1, and group E is the high dose group of example 1; FIG. 3B is a graph showing the change in fecal moisture content of rats administered different doses of STC of example 1 in a rat experiment of the present invention, wherein group A is the normal group, group B is the model group, group C is the low dose group of example 1, group D is the medium dose group of example 1, and group E is the high dose group of example 1;

FIG. 4 shows the change of the organ index of the rat after administration in the rat experiment of the present invention;

FIG. 5A is a colon histopathological change of normal group STC rats in a rat experiment of the present invention; FIG. 5B shows colon histopathological changes of model group STC rat in rat experiments according to the present invention; FIG. 5C is a graph showing colon histopathological changes in rats administered the low dose group STC of example 1 in a rat experiment of the present invention; FIG. 5D is a graph showing colon histopathological changes in rats treated with the dose group STC of example 1 in a rat experiment of the present invention; FIG. 5E is a graph of colon histopathological changes in rats administered the high dose group STC of example 1 in a rat study of the present invention; FIG. 5F shows colon histopathological changes of STC rats of comparative example 5 administered in rat experiments of the present invention;

FIG. 6A shows the expression of normal group STC rat colon tissue MLCK protein in rat experiments according to the present invention; FIG. 6B shows the expression of MLCK protein in rat colon tissue of model group STC rat in rat experiment of the present invention; FIG. 6C shows the expression of MLCK protein in colon tissue of rats administered with STC of example 1 low dose group in rat experiments according to the present invention; FIG. 6D shows the expression of MLCK protein in colon tissue of rats administered with the dose group STC of example 1 in a rat experiment of the present invention; FIG. 6E shows the expression of MLCK protein in colon tissue of rats administered with STC of example 1 high dose group in rat experiments according to the present invention; FIG. 6F shows the expression of MLCK protein in rat colon tissue of rats treated with STC from comparative example 5 in the rat experiment of the present invention.

Detailed Description

To further illustrate the technical means and effects of the present invention, the following embodiments further illustrate the technical solutions of the present invention, but the present invention is not limited to the scope of the embodiments.

Example 1

A traditional Chinese medicine composition comprises the following components in parts by weight: 35g of raw bighead atractylodes rhizome, 35g of raw astragalus, 18g of whole angelica, 35g of cistanche, 18g of snakegourd seed, 14g of almond, 12g of dried orange peel, 18g of immature bitter orange, 18g of betel nut, 12g of white paeony root, 12g of divaricate saposhnikovia root, 24g of radix rehmanniae, 18g of cynomorium songaricum and 7g of liquorice.

The preparation method comprises the following steps:

(1) mixing raw rhizoma atractylodis macrocephalae, semen trichosanthis, pericarpium citri reticulatae and fructus aurantii immaturus according to the weight part, adding water, soaking for 30min, distilling for 6h by steam to extract volatile oil, adding beta-cyclodextrin and water, preparing the volatile oil, the inclusion agent and the water according to the weight part ratio of 1:6:24, including for 90min, preparing the volatile oil into an inclusion compound, and performing vacuum drying at 40 ℃ for later use;

(2) mixing radix astragali, radix Paeoniae alba, Glycyrrhrizae radix and radix Saposhnikoviae in parts by weight, adding ethanol at a weight ratio of ethanol to mixed medicinal materials of 12:1 and ethanol concentration of 65%, reflux-extracting for 2 times, refluxing for 1.5 hr each time, recovering ethanol, concentrating, and filtering to obtain ethanol extractive concentrate and residue;

(3) adding the whole Chinese angelica, the cistanche, the almond, the betel nut, the radix rehmanniae recen and the cynomorium songaricum into the dregs obtained in the step (2) according to the parts by weight, mixing, adding water for decoction, decocting for 3 times, each time for 1.5 hours, filtering, concentrating the filtrate until the relative density is 1.06, then adding ethanol until the alcohol content is 50%, uniformly stirring, standing for 24 hours, filtering, and recovering the ethanol from the filtrate to obtain a water extraction and ethanol precipitation concentrated solution;

(4) and (3) uniformly mixing the concentrated solutions obtained in the steps (2) and (3), concentrating until the relative density is 1.12, testing the relative density at 60 ℃, drying to obtain a dry extract, uniformly mixing the dry extract, the inclusion compound obtained in the step (1), dextrin, glucose and aerosil, and performing spray granulation, wherein the inlet air temperature is 170 ℃, and the outlet air temperature is 90 ℃, so as to obtain the traditional Chinese medicine composition particles.

Example 2

A traditional Chinese medicine composition comprises the following components in parts by weight: 35g of raw bighead atractylodes rhizome, 40g of raw astragalus root, 10g of whole angelica, 32g of cistanche, 18g of snakegourd seed, 15g of almond, 13g of dried orange peel, 20g of immature bitter orange, 10g of betel nut, 5g of white paeony root, 10g of divaricate saposhnikovia root, 15g of raw rehmannia root, 20g of cynomorium songaricum and 10g of liquorice.

The preparation method comprises the following steps:

(1) mixing raw rhizoma atractylodis macrocephalae, semen trichosanthis, pericarpium citri reticulatae and fructus aurantii immaturus in parts by weight, adding water, soaking for 20min, distilling with water vapor for 4h to extract volatile oil, adding beta-cyclodextrin and water, including for 60min, preparing the volatile oil into an inclusion compound, and performing vacuum drying at 35 ℃ for later use, wherein the weight ratio of the added water to the mixed medicinal materials is 15: 1;

(2) mixing radix astragali, radix Paeoniae alba, Glycyrrhrizae radix and radix Saposhnikoviae in parts by weight, adding ethanol at a weight ratio of 11:1 to the mixed materials, with ethanol concentration of 60%, reflux-extracting for 1 time, refluxing for 3 hr each time, recovering ethanol, concentrating, and filtering to obtain ethanol extractive concentrate and residue;

(3) adding the whole Chinese angelica, the cistanche, the almond, the betel nut, the radix rehmanniae recen and the cynomorium songaricum into the dregs obtained in the step (2) according to the weight part, mixing, adding water, decocting for 2 times, 2 hours each time, filtering, concentrating the filtrate until the relative density is 1.02, then adding ethanol until the alcohol content is 40%, uniformly stirring, standing for 20 hours, filtering, recovering the ethanol from the filtrate, and obtaining a water extraction and ethanol precipitation concentrated solution;

(4) and (3) uniformly mixing the concentrated solutions obtained in the steps (2) and (3), concentrating until the relative density is 1.10, testing the relative density at 50 ℃, drying to obtain a dry extract, uniformly mixing the dry extract, the inclusion compound obtained in the step (1), stevioside and aerosil, and performing spray granulation, wherein the inlet air temperature is 165 ℃, and the outlet air temperature is 85 ℃, so as to obtain the traditional Chinese medicine composition particles.

Example 3

A traditional Chinese medicine composition comprises the following components in parts by weight: 40g of raw bighead atractylodes rhizome, 32g of raw astragalus, 25g of whole angelica, 40g of cistanche, 10g of snakegourd seed, 11g of almond, 5g of dried orange peel, 16g of immature bitter orange, 20g of betel nut, 6g of white paeony root, 15g of divaricate saposhnikovia root, 5g of raw rehmannia root, 16g of cynomorium songaricum and 4g of liquorice.

The preparation method comprises the following steps:

(1) mixing raw rhizoma atractylodis macrocephalae, semen trichosanthis, pericarpium citri reticulatae and fructus aurantii immaturus in parts by weight, adding water, soaking for 40min, distilling with water vapor for 7h to extract volatile oil, adding beta-cyclodextrin and water, including for 100min, preparing the volatile oil into an inclusion compound, and performing vacuum drying at 40 ℃ for later use, wherein the weight ratio of the added water to the mixed medicinal materials is 13: 1;

(2) mixing radix astragali, radix Paeoniae alba, Glycyrrhrizae radix and radix Saposhnikoviae in parts by weight, adding ethanol at a weight ratio of 14:1 to the mixed materials, reflux-extracting for 3 times (1 hr each time), recovering ethanol, concentrating, and filtering to obtain ethanol extractive concentrate and residue;

(3) adding the whole Chinese angelica, the cistanche, the almond, the betel nut, the radix rehmanniae recen and the cynomorium songaricum into the dregs obtained in the step (2) according to the weight part, mixing, adding water, decocting for 2 times, 2 hours each time, filtering, concentrating the filtrate until the relative density is 1.05, then adding ethanol until the alcohol content is 60%, uniformly stirring, standing for 26 hours, filtering, recovering the ethanol from the filtrate, and obtaining a water extraction and ethanol precipitation concentrated solution;

(4) and (3) uniformly mixing the concentrated solutions obtained in the steps (2) and (3), concentrating until the relative density is 1.14, testing the relative density at 55 ℃, drying to obtain a dry extract, uniformly mixing the dry extract, the inclusion compound obtained in the step (1), starch, mannose and aerosil, and performing spray granulation, wherein the inlet air temperature is 175 ℃, and the outlet air temperature is 90 ℃, so as to obtain the traditional Chinese medicine composition particles.

Example 4

A traditional Chinese medicine composition comprises the following components in parts by weight: 45g of raw bighead atractylodes rhizome, 32g of raw astragalus, 20g of whole angelica, 35g of cistanche, 20g of snakegourd seed, 20g of almond, 18g of dried orange peel, 25g of immature bitter orange, 15g of betel nut, 12g of white paeony root, 5g of divaricate saposhnikovia root, 25g of raw rehmannia root, 25g of cynomorium songaricum and 11g of liquorice.

The preparation method comprises the following steps:

(1) mixing raw rhizoma atractylodis macrocephalae, semen trichosanthis, pericarpium citri reticulatae and fructus aurantii immaturus according to the weight part, adding water, soaking for 60min, distilling for 4h by steam to extract volatile oil, adding beta-cyclodextrin and water, including for 110min, preparing the volatile oil into an inclusion compound, and drying in vacuum at 40 ℃ for later use, wherein the weight ratio of the added water to the mixed medicinal materials is 8: 1;

(2) mixing radix astragali, radix Paeoniae alba, Glycyrrhrizae radix and radix Saposhnikoviae in parts by weight, adding ethanol at a weight ratio of 15:1 to the mixed materials, with ethanol concentration of 60%, reflux-extracting for 2 times, each reflux for 1.5 hr, recovering ethanol, concentrating, and filtering to obtain ethanol extractive concentrate and residue;

(3) adding the whole Chinese angelica, the cistanche, the almond, the betel nut, the radix rehmanniae recen and the cynomorium songaricum into the dregs obtained in the step (2) according to the weight part, mixing, adding water, decocting, adding water and mixing the medicinal materials according to the weight ratio of 13:1, decocting for 2 times, 3 hours each time, filtering, concentrating the filtrate until the relative density is 1.08, then adding ethanol until the alcohol content is 55%, uniformly stirring, standing for 22 hours, filtering, recovering the ethanol from the filtrate, and obtaining an ethanol precipitation concentrated solution;

(4) and (3) uniformly mixing the concentrated solutions obtained in the steps (2) and (3), concentrating until the relative density is 1.15, testing the relative density at 55 ℃, drying to obtain a dry extract, uniformly mixing the dry extract, the inclusion compound obtained in the step (1), dextrin and lactose, and performing spray granulation, wherein the inlet air temperature is 165 ℃, and the outlet air temperature is 85 ℃, so as to obtain the traditional Chinese medicine composition granules.

Example 5

A traditional Chinese medicine composition comprises the following components in parts by weight: 32g of raw bighead atractylodes rhizome, 45g of raw astragalus root, 5g of whole angelica, 38g of cistanche, 5g of snakegourd fruit kernel, 6g of almond, 3g of dried orange peel, 20g of immature bitter orange, 5g of betel nut, 15g of white paeony root, 20g of divaricate saposhnikovia root, 30g of raw rehmannia root, 20g of cynomorium songaricum and 12g of liquorice.

The preparation method comprises the following steps:

(1) mixing raw rhizoma atractylodis macrocephalae, semen trichosanthis, pericarpium citri reticulatae and fructus aurantii immaturus in parts by weight, adding water, soaking for 60min, distilling with water vapor for 8h to extract volatile oil, adding beta-cyclodextrin and water, including for 120min, preparing the volatile oil into an inclusion compound, and performing vacuum drying at 40 ℃ for later use, wherein the weight ratio of the added water to the mixed medicinal materials is 15: 1;

(2) mixing radix astragali, radix Paeoniae alba, Glycyrrhrizae radix and radix Saposhnikoviae in parts by weight, adding ethanol at a weight ratio of 15:1 to the mixed materials, reflux-extracting for 2 times with ethanol concentration of 70%, refluxing for 1.5 hr each time, recovering ethanol, concentrating, and filtering to obtain ethanol extractive concentrate and residue;

(3) adding the whole Chinese angelica, the cistanche, the almond, the betel nut, the radix rehmanniae recen and the cynomorium songaricum into the dregs obtained in the step (2) according to the parts by weight, mixing, adding water, decocting for 4 times, 1 hour each time, filtering, concentrating the filtrate until the relative density is 1.10, then adding ethanol until the alcohol content is 50%, uniformly stirring, standing for 30 hours, filtering, recovering the ethanol from the filtrate, and obtaining an ethanol precipitation concentrated solution;

(4) and (3) uniformly mixing the concentrated solutions obtained in the steps (2) and (3), concentrating until the relative density is 1.15, testing the relative density at 60 ℃, drying to obtain a dry extract, uniformly mixing the dry extract, the inclusion compound obtained in the step (1), dextrin, glucose and aerosil, and performing spray granulation, wherein the inlet air temperature is 175 ℃, and the outlet air temperature is 90 ℃, so as to obtain the traditional Chinese medicine composition particles.

Example 6

Compared with example 1, the process is the same as example 1 except that the decoction and concentration of raw white atractylodes rhizome, snakegourd fruit kernel, dried orange peel and immature bitter orange are added with water, and the volatile oil extraction and inclusion process is not carried out.

Example 7

The procedure of example 1 was repeated except that the concentrated solution was prepared by decocting Astragalus membranaceus, Paeonia lactiflora pall, Glycyrrhiza uralensis Fisch and Saposhnikovia divaricata with water.

Example 8

The procedure of example 1 was repeated except that the concentrated solution was extracted from Angelica sinensis, cistanche, apricot kernel, Areca catechu, rehmannia glutinosa and Cynomorium songaricum with ethanol, and the other conditions were the same as those of example 1.

Comparative example 1

The procedure of example 1 was followed except that areca catechu and tangerine peel were not added, as compared with example 1.

Comparative example 2

The procedure is as in example 1 except that the weight parts of Astragalus membranaceus and Atractylodes macrocephala are 50g and 50g, respectively, as compared with example 1.

Comparative example 3

The procedure of example 1 was repeated except that the total weight of Angelica gigas nakai was changed to 30g, as compared with example 1.

Comparative example 4

Compared with the example 1, the conditions are the same as the example 1 except that the snakegourd seed, the almond, the radix rehmanniae recen, the white paeony root, the divaricate saposhnikovia root and the liquoric root are not added, namely, adjuvant drugs and guiding drugs are not added.

Comparative example 5

The commercially available mosapride was used as a therapeutic drug (5mg × 20 tablets/box, Chengdu Kanghong pharmaceutical industry group GmbH, product batch number: H20031110)10 mg.

Crowd test

Preliminary screening experiment, 240 patients with constipation symptoms are selected, the age is 18-60 years old, the patients are randomly divided into 12 groups, the traditional Chinese medicine composition granules of examples 1-8 and comparative examples 1-4 are respectively taken twice a day, 30g is taken each time, the curative effect is graded, 5 points are 5, the defecation is less than 2 days, the stool character is normal, and the defecation is smooth; 4-defecation interval is 2-3 days, the defecation is dry and then soft, and the defecation needs labor; 3-defecation interval is 3-5 days, and the excrement is dry and has no sense of incomplete defecation; 2-no significant change compared to before treatment, the results are shown in Table 1.

Table 1 population test results

	Defecation time interval	Stool character	Sense of smooth defecation
				Example 1	4.8	4.9	4.9
Example 2	4.7	4.9	4.8
				Example 3	4.7	4.8	4.8
Example 4	4.6	4.6	4.7
				Example 5	4.5	4.5	4.6
Example 6	4.3	4.3	4.2
				Example 7	4.1	4.3	4.2
Example 8	4.1	4.2	4.2
				Comparative example 1	3.8	3.9	4.2
Comparative example 2	4.1	4.1	4.2
				Comparative example 3	4.1	4.3	4.2
Comparative example 4	3.3	3.5	3.8

As can be seen from table 1, in comparative example 1 and comparative example 1, the traditional Chinese medicine composition provided by the invention has a synergistic effect, ministerial drugs and monarch drugs supplement each other, and pericarpium citri reticulatae and areca catechu play an important role in the drug effect of the monarch drugs, and in comparative example 1 and comparative examples 2-3, the components have the best effect within the weight part range, and the raw rhizoma atractylodis macrocephalae and the raw radix astragali are used as the monarch drugs, so that the weight parts are particularly important and too late, and the whole drug effect of the traditional Chinese medicine composition is influenced when the weight parts are exceeded; comparing the example 1 with the comparative example 4, it can be seen that the traditional Chinese medicine composition provided by the invention has the advantages that each component is compatible according to the monarch, minister, assistant and guide, and none is available, and the adjuvant and guide play an important role in exerting the drug effects of the monarch and minister drugs; comparing example 1 with example 6, it can be seen that the extraction of volatile oil from semen Trichosanthis, pericarpium Citri Tangerinae and fructus Aurantii Immaturus and the inclusion with cyclodextrin can effectively improve the absorption and utilization of effective components and prevent the loss of effective components; comparing example 1 with examples 7-8, it can be seen that the use of different extraction solvents for different herbs has an important effect on the dissolution of the active ingredients of the drugs, and a preliminary screening experiment shows that the effect of the traditional Chinese medicine composition in the formula of example 1 is the best, so that the traditional Chinese medicine compositions used in subsequent clinical experiments are all the traditional Chinese medicine compositions described in example 1.

Clinical testing

The patients are 110 patients who are treated by anorectal department outpatient service and ward collection of chronic functional constipation in the hospital 2015 from 11 months to 2017 from 12 months. 42 men and 58 women all meet the diagnosis standard of chronic functional constipation. Patients were randomized into 2 groups: the medicines of example 1 and comparative example 5 are respectively taken, and example 1 is taken 30g each time, twice a day, morning and evening; comparative example 5 was administered 3 times a day, with the usage amounts being referred to the description. After the patient is admitted, the general data and the disease data of the patient are collected and recorded, and the disease degree of the patient is evaluated by adopting the grading standard of the constipation symptom. There was no significant difference between the baseline data such as sex, age and disease course of the two groups of patients and the score of constipation symptom (P > 0.05).

Diagnosis and inclusion criteria: meeting functional constipation roman IV diagnosis standards (see table 2); ② those aged 18-60 years old; and thirdly, people who are willing to cooperate with clinicians to treat and observe and sign informed consent.

TABLE 2 diagnosis criteria for functional constipation in Roman III criteria

^*The symptoms appear for at least 6 months before diagnosis, and the symptoms meet the diagnosis standards in nearly 3 months

Exclusion criteria

Those who do not meet the diagnosis and incorporate the standard; secondly, the patients with digestive tract organic pathological changes (such as tumor, Crohn's disease, colon polyp and the like) and intestinal obstruction are verified by electronic fibercolonoscopy, pathological biopsy or related imaging examination; ③ patients with other diseases such as cardiovascular diseases, urinary diseases, hematopoietic diseases, mental diseases, etc. or serious diseases of the heart, liver and kidney; (iv) patients with history of laxative use and abdominal operation; patients allergic to the test medicine and women in pregnancy and lactation; sixthly, patients with psychosis; and seventhly, the patients are not treated according to the research scheme.

During the treatment period, patients are ordered to eat more food which is easy to digest and rich in nutrition, eat more vegetables and fruits with higher cellulose content, and fast spicy and pungent food, so as to regulate mood, pay attention to rest and exercise properly. The treatment course of the two groups is 30 days, the clinical curative effect is judged by the clinical symptom score after the treatment course is finished, the two groups stop taking the medicines related to the treatment in the observation period, normally drink, make a double-check every 7 days or make a follow-up call, and record the information and the symptom sign integral in detail.

Observation indexes are as follows: integrating clinical symptoms and signs: scoring criteria were prepared by reference to literature and are detailed in table 3. Secondly, a digestive tract dynamic detection system is used for monitoring resting pressure of the anal canal, maximum contraction pressure of the anal canal, an initial rectal sensation threshold value and maximum rectal tolerance in real time, and the results are shown in the figures 1A-D. And thirdly, evaluation is carried out on the conditions before and after two groups of treatments by using the satisfaction degree related item scores in a constipation symptom self-evaluation questionnaire (PAC-SYM) and a constipation patient life quality questionnaire (PAC-QOL score scale), and the results are shown in the figures 2A-D.

TABLE 3 functional Constipation clinical symptom Scoring Standard

The statistical method comprises the following steps: all data are statistically analyzed by SPSS18.0 statistical software, and each group of measured data conforming to normal distribution will be analyzed

Performing statistical description, and performing paired t test for comparison (with uniform variance) in the measurement data set; the comparison of the count data adopts chi²And (4) testing, wherein non-parameter independent sample rank sum testing is adopted for the grade data.

The evaluation standard of the curative effect is as follows: refer to the therapeutic standard formulated in the guideline of clinical research of new Chinese medicine. The clinical cure is as follows: stools were normal, or returned to pre-disease levels, >3 times per week, with all other symptoms disappeared. The effect is shown: constipation is obviously improved, and the defecation interval time and the stool quality are close to normal; or stool is slightly dry and the time interval between defecations is less than 3d, and other symptoms mostly disappear. The method has the following advantages: the defecation interval time is shortened by 1d, or the dry feces is improved, and other symptoms are improved. And (4) invalidation: constipation and other symptoms were not improved. The results are shown in Table 4.

TABLE 4 clinical effects

TABLE 5 comparison of symptom and sign scores before and after treatment and during follow-up

Note: in-group and post-treatment comparisons with this group,^ΔP<0.05，^*P＜0.01。

as can be seen from tables 4 and 5, after treatment and during follow-up visit, the stool characteristics, the stool interval time, the difficulty in defecation, the defecation time, the feeling of incomplete defecation, the feeling of anus obstruction, shortness of breath and abdominal distension and chest distress score of two groups are all obviously lower than that before the same group of treatment (P is less than 0.01), and the improvement condition of the example 1 is better than that of the comparative example 5, which indicates that the traditional Chinese medicine composition provided by the invention has better treatment effect than that of the traditional western medicine. As can be seen from FIGS. 1A-D, the resting anal pressure, resting rectal pressure, maximum systolic anal pressure, initial sensation threshold, defecation distress sensation threshold and maximum rectal tolerance in the two groups were all significantly lower than those before the same group treatment (P <0.05) after treatment and during follow-up, and some of the indices of example 1 improved better than those of comparative example 5. As can be seen from FIGS. 2A-D, the difference in PAC-QOL scores in the four dimensions of the patients in the two groups before treatment was not statistically significant (P >0.05), and the scores in the 4 dimensions of physical discomfort, psychosocial discomfort, anxiety and satisfaction in the two groups after treatment were significantly reduced (P < 0.01).

Slow transit constipation rat experiment

(I) determination of intestinal transport function of rat

The test was carried out with the Chinese medicinal composition prepared in example 1 above. The test was as follows:

after 24 hours of fasting after the last administration, water is not forbidden, each group of rats is drenched with 2 ml/one of 10% activated carbon suspension, animals are killed by dislocation after 40 minutes, the abdominal cavity is rapidly opened, all intestinal tracts from the pylorus to the end of the rectum are removed, the intestinal tracts are placed in a tray, the intestinal tracts are gently straightened, the total length of the intestinal tracts and the distance from the pylorus to the front edge of the carbon end are measured in a relaxed state, and the percentage of the activated carbon propulsion length to the total length of the intestinal tracts is calculated. Carbon dust propulsion test to detect intestinal transmission function: percent (%) carbon end advancement (distance of the carbon end from the pylorus (cm)/total length of pylorus to rectum end (cm)) x 100%. The results are shown in Table 6.

TABLE 6 comparison of the Change in Pushing Rate of traditional Chinese medicinal compositions against STC rat activated carbon

As can be seen from Table 6, after molding, the active carbon push rate of rats in the low, medium and high dose groups of example 1 and the control 5 group after administration were significantly different (P < 0.05); compared with the model group, the intestinal canal activated carbon propulsion rate of rats in each dose group of the traditional Chinese medicine composition is increased to different degrees (P <0.001), and is obviously increased in the high dose group in example 1 (P < 0.05). Compared with the model group, the carbon ink propelling rate of each treatment group is obviously accelerated, and the difference has statistical significance (P <0.05), wherein the effect is obvious when the high dose is used in example 1. The traditional Chinese medicine composition is shown to enhance or recover the colon motility to improve the constipation.

(II) Experimental rat stool test

After the molding is finished and after the medication, about 10 grains of excrement of rats are collected every other day, the wet weight of the excrement of the rats is firstly weighed, the excrement is put into an oven and baked for 15 minutes at the temperature of 150 ℃, and then the weight is weighed, namely the dry weight of the excrement, and then the water content of the excrement ((wet excrement weight-dry excrement weight)/wet excrement weight) is calculated. The results are shown in FIGS. 3A-B.

As can be seen from FIGS. 3A and 3B, the number of stools and water contents of rats in the low, medium and high dose groups of example 1 were significantly increased and statistically significant (P <0.05) compared to the model group after molding. In conclusion, the traditional Chinese medicine composition may not absolutely improve the slow transit constipation by increasing the water content of the excrement.

(III) pathological changes of rat viscera

And (3) fixing the tissues of the stomach, the heart, the liver and the kidney in 10% formalin solution for 12 hours by using an optical microscope, then carrying out conventional paraffin embedding, slicing and HE staining, and observing pathological changes by using the optical microscope. The results are shown in FIG. 4.

As can be seen from FIG. 4, the gastric mucosa was not stained in the normal (stomach) group and the group of example 1, and chronic inflammatory changes of the mucosa were observed in the model group and the group of comparative example 5; the (heart) shows that the myocardial cells of the normal group and the group of example 1 have no obvious degeneration and inflammatory cell infiltration, and the model group and the group of comparative example 5 have fibroblast infiltration; the liver cells of the normal group and the group of example 1 had no swelling, clear boundaries, clear liver lobules boundaries, and no congestion in blood sinuses; mild edema of hepatocytes was observed in both the model group and the comparative example 5 group; another observation in the model group is hepatocyte cord disorders; the (kidney) normal group, the group of example 1 and the group of comparative example 5 have no abnormal change of the renal corpuscle capillary vessels, no swelling of the cells on the vessel wall and clear balloon boundary. The boundaries of the proximal and distal convoluted tubules are clear, and the cell on the wall of the duct has no swelling phenomenon; whereas the model group showed neutrophil infiltration.

(IV) Experimental pathological changes of rat colon tissue

After the rats die, respectively taking the ascending colon tissue and the transverse colon tissue about 4cm, repeatedly washing the ascending colon tissue and the transverse colon tissue with PBS buffer solution for 4 times, taking the middle 2cm tissue, fixing the middle 2cm tissue with 10% formaldehyde solution, preparing pathological sections according to the steps of dehydration, wax dipping, embedding, slicing, dyeing and the like, observing under an optical microscope, and measuring colon intestinal villi or basal layers of different groups of rats by adopting an ImageJ software analysis processing system, wherein the specific method comprises the following steps: randomly pick 100 times of field for photographing. When taking a picture, the tissues are filled in the whole visual field as much as possible, and the background light of each picture is ensured to be consistent. The results of measuring the intestinal villus length and basal layer thickness (setting the corresponding scale, selecting the measurement needed, and analyzing the data) using ImageJ software are shown in fig. 5A-F and table 7.

TABLE 7 variation of Colon villus length and muscular layer thickness of traditional Chinese medicine composition example 1 to STC rats

Note: in comparison to the set of models,^ΔP<0.05。

as shown in FIGS. 5A-F and Table 7, the Chinese medicinal composition provided by the invention can increase the villus length and the muscular layer thickness of the colon mucosa, increase the digestive absorption area of the intestinal tract, promote the differentiation and maturation of cells, facilitate the renewal and repair of the mucosa, and effectively improve the barrier function of the intestinal mucosa.

(V) immunohistochemical staining experiment

The immunohistochemical Staining (SP) method is used for determining the expression condition of the colon smooth muscle Myosin Light Chain Kinase (MLCK) protein, and each group of specimens are subjected to conventional dewaxing and hydration, endogenous peroxidase activity is eliminated, boiling is carried out for repair, normal goat serum working solution is sealed, and incubation is carried out for 10min at 37 ℃. Sequentially dropwise adding 50 μ l of rabbit anti-rat MLCK primary antibody, biotin goat anti-rabbit IgG secondary antibody and horseradish peroxidase labeled streptavidin working solution, performing DAB color development, hematoxylin counterstain and dehydrating transparent sealing sheets. The observation index shows that the MLCK immunoreactive positive cells are yellow or brown yellow particles in colon tissues. All the obtained pictures are subjected to image analysis by adopting medical professional image analysis software (MIAS), at least 5 non-overlapping high power visual fields (400 x) are observed in a positive expression area by utilizing the static gray level analysis function of the pictures, the positive expression area is compared with a normal group slice to reduce errors, and the number of positive cells is counted by a double-blind method and is subjected to statistical analysis. The results are shown in FIGS. 6A-F and Table 8.

TABLE 8 Effect of Chinese medicinal compositions on expression of MLCK protein in STC rat colon tissue

Note: in comparison to the set of models,^ΔP<0.05。

combining FIGS. 6A-F and Table 8 the constipation model group showed significantly lower MLCK immunoreactivity in colon tissue than the normal group (P < 0.05); in example 1, the immunoreactivity of the high dose group was significantly higher than that of the model group (P <0.05), but lower than that of the normal group (P < 0.05). The Chinese medicinal composition is suggested to relieve the inhibition of gastrointestinal functions of constipation rats by regulating the expression of MLCK in colon tissues.

In conclusion, the traditional Chinese medicine composition provided by the invention has an obvious curative effect on constipation, is safe, does not have side effects, is high in patient satisfaction degree, is compatible with various traditional Chinese medicines, is synergistic with various components, effectively reduces the integral of constipation symptoms, improves anorectal kinetic indexes, improves the life quality score of patients with chronic functional constipation, and has great medical significance and broad prospects.

The applicant states that the present invention is illustrated in detail by the above examples, but the present invention is not limited to the above detailed methods, i.e. it is not meant that the present invention must rely on the above detailed methods for its implementation. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.

Claims (15)

1. The traditional Chinese medicine composition is characterized by being prepared from the following components in parts by weight: 32-45 parts of raw bighead atractylodes rhizome, 32-45 parts of raw astragalus, 5-25 parts of whole angelica, 32-40 parts of cistanche, 5-20 parts of snakegourd seed, 11-20 parts of almond, 3-18 parts of dried orange peel, 16-25 parts of immature bitter orange, 5-20 parts of betel nut, 5-15 parts of white paeony root, 5-20 parts of divaricate saposhnikovia root, 5-30 parts of radix rehmanniae, 16-25 parts of cynomorium songaricum and 1-12 parts of liquorice.

2. The traditional Chinese medicine composition according to claim 1, wherein the composition is prepared from the following components in parts by weight: 35-40 parts of raw bighead atractylodes rhizome, 35-40 parts of raw astragalus, 10-20 parts of whole angelica, 35-40 parts of cistanche, 10-18 parts of snakegourd seed, 6-15 parts of almond, 5-13 parts of dried orange peel, 16-20 parts of immature bitter orange, 10-20 parts of betel nut, 6-12 parts of white paeony root, 10-15 parts of divaricate saposhnikovia root, 15-25 parts of dried rehmannia root, 16-20 parts of cynomorium songaricum and 4-10 parts of liquorice.

3. The traditional Chinese medicine composition according to claim 2, wherein the composition is prepared from 35 parts by weight of raw bighead atractylodes rhizome, 35 parts by weight of raw astragalus membranaceus, 18 parts by weight of whole angelica, 35 parts by weight of cistanche, 18 parts by weight of snakegourd seed, 14 parts by weight of almond, 12 parts by weight of dried orange peel, 18 parts by weight of immature bitter orange, 18 parts by weight of areca seed, 12 parts by weight of white peony root, 12 parts by weight of divaricate saposhnikovia root, 24 parts by weight of raw rehmannia root, 18 parts by weight.

4. The traditional Chinese medicine composition according to any one of claims 1 to 3, wherein the composition further comprises an adjuvant;

the auxiliary materials comprise any one or the combination of at least two of dextrin, lactose, starch, sucrose, glucose, mannose, stevioside or aerosil.

5. The traditional Chinese medicine composition according to claim 4, wherein the auxiliary material is a combination of dextrin, glucose and aerosil.

6. A method of preparing the traditional Chinese medicine composition of any one of claims 1-5, comprising the steps of:

(1) mixing raw bighead atractylodes rhizome, snakegourd seed, dried orange peel and immature bitter orange in parts by weight, then soaking in water, distilling to extract volatile oil, adding an inclusion compound and water, preparing the volatile oil into an inclusion compound, and drying for later use;

(2) mixing radix astragali, radix Paeoniae alba, Glycyrrhrizae radix and radix Saposhnikoviae in parts by weight, adding ethanol, reflux extracting, filtering, and concentrating to obtain ethanol extract concentrate and residue;

(3) adding the whole Chinese angelica, the cistanche, the almond, the betel nut, the radix rehmanniae recen and the cynomorium songaricum into the dregs obtained in the step (2) according to the parts by weight, mixing, adding water for decoction, filtering and concentrating, adding ethanol, stirring uniformly, standing, filtering to obtain a water extraction and alcohol precipitation concentrated solution;

(4) and (3) uniformly mixing the concentrated solutions obtained in the step (2) and the step (3), concentrating and drying to obtain a dry extract, uniformly mixing the dry extract, the inclusion compound obtained in the step (1) and auxiliary materials, and granulating to obtain the traditional Chinese medicine composition granules.

7. The method according to claim 6, wherein the weight ratio of the water addition amount in the step (1) to the mixed medicinal materials is (8-15): 1;

the soaking time in the step (1) is 20-60 min;

the distillation in the step (1) is steam distillation;

the distillation time in the step (1) is 4-8 h;

the inclusion agent in the step (1) is beta-cyclodextrin;

the weight ratio of the volatile oil, the inclusion agent and the water in the step (1) is 1 (4-8) to 20-30;

the inclusion time of the inclusion compound in the step (1) is 60-120 min;

the drying in the step (1) is vacuum drying;

the drying temperature in the step (1) is 35-45 ℃.

8. The method of claim 7, wherein the soaking time of step (1) is 30 min;

the distillation time in the step (1) is 6 h.

9. The method according to any one of claims 6 to 8, wherein the weight ratio of the ethanol amount in the step (2) to the mixed medicinal materials is (11-15): 1;

in the step (2), the concentration of the ethanol is 60-70%;

the reflux extraction frequency of the step (2) is 1-3 times;

the reflux extraction time in the step (2) is 1-3h each time.

10. The method according to claim 9, wherein the weight ratio of the water addition amount in the step (3) to the mixed medicinal material in the step (3) is (10-13): 1;

the number of times of decoction in the step (3) is 1-4;

the decoction time in the step (3) is 1-3h each time;

the relative density of the concentrated solution in the step (3) is 1.02-1.10;

adding ethanol in the step (3) until the content of the ethanol is 40-60%;

the standing time in the step (3) is 20-30 h.

11. The method of claim 10, wherein the concentrate of step (3) has a relative density of 1.05 to 1.08.

12. The method of claim 10, wherein said concentrating of step (4) is to a relative density of 1.10 to 1.15;

the temperature of the relative density of the concentrated liquid in the testing step (4) is 50-60 ℃;

the granulating mode in the step (4) is spray granulation;

the inlet air temperature of the spray drying is 165-175 ℃;

the outlet air temperature of the spray drying is 85-90 ℃.

13. The method according to any of claims 6-8, 10-12, characterized in that it comprises in particular the steps of:

(1) mixing raw rhizoma atractylodis macrocephalae, semen trichosanthis, dried orange peel and immature bitter orange in parts by weight, adding water, wherein the weight ratio of the added water to the mixed medicinal materials is (8-15):1, soaking for 20-60min, performing steam distillation for 4-8h to extract volatile oil, adding beta-cyclodextrin and water, wherein the weight ratio of the volatile oil to the inclusion compound to the water is 1 (4-8): 20-30, including for 60-120min, preparing the volatile oil into an inclusion compound, and performing vacuum drying at 35-45 ℃ for later use;

(2) mixing radix astragali, radix Paeoniae alba, Glycyrrhrizae radix and radix Saposhnikoviae in parts by weight, adding ethanol at a weight ratio of (11-15):1, ethanol concentration of 60-70%, reflux-extracting for 1-3 times, refluxing for 1-3 hr each time, recovering ethanol, concentrating, and filtering to obtain ethanol extract concentrate and residue;

(3) adding the whole Chinese angelica, the cistanche, the almond, the betel nut, the radix rehmanniae recen and the cynomorium songaricum into the dregs obtained in the step (2) according to the weight part, mixing, adding water for decoction, wherein the weight ratio of the added water to the mixed medicinal materials is (10-13):1, decocting for 1-4 times and 1-3h each time, filtering, concentrating the filtrate until the relative density is 1.02-1.10, then adding ethanol until the alcohol content is 40-60%, uniformly stirring, standing for 20-30h, filtering, recovering the ethanol from the filtrate, and obtaining a water extraction and ethanol precipitation concentrated solution;

(4) and (3) uniformly mixing the concentrated solutions obtained in the steps (2) and (3), concentrating until the relative density is 1.10-1.15, testing the relative density at 50-60 ℃, drying to obtain a dry extract, uniformly mixing the dry extract, the inclusion compound obtained in the step (1) and auxiliary materials, and performing spray granulation, wherein the inlet air temperature is 165-175 ℃, and the outlet air temperature is 85-90 ℃ to obtain the traditional Chinese medicine composition particles.

14. Use of a Chinese medicinal composition according to any one of claims 1 to 5 for the preparation of a medicament and/or formulation for the treatment of chronic functional constipation, gastrointestinal dysfunction disease.

15. The use according to claim 14, wherein the formulation comprises any one of granules, capsules, tablets or pills or a combination of at least two thereof.

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