A Chinese herbal medicine composition and its use in the preparation of a medicament for the treatment of chronic functional constipation

Abstract

The present application provides a Chinese herbal medicine composition and its application in preparing a medicine for treating chronic functional constipation. The Chinese herbal medicine composition comprises the following components in mass parts: 2.3-2.7 parts of radix rehmanniae, 1.2-1.5 parts of angelica sinensis, 1.5-1.7 parts of persicae semen, 1-1.4 parts of radix bupleuri, 0.8-1 part of citri reticulatae pericarpium, 0.3-0.4 part of aurantii fructus, and 0.3-0.6 part of glycyrrhizae radix. The Chinese herbal medicine composition can effectively improve defecation, improve the peristalsis of the intestinal tract, and repair the morphology of the colon, and is very suitable for treating chronic functional constipation.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology. More specifically, it relates to a traditional Chinese herbal composition and its application in the preparation of a medicine for treating chronic functional constipation. Background Technology

[0002] Chronic functional constipation (CFC) is a chronic digestive system disorder characterized by difficulty in defecation, reduced frequency of bowel movements, and hard, dry stools. It is often accompanied by symptoms such as abdominal distension and discomfort, frequent flatulence, loss of appetite, fatigue, dry mouth, and lack of thirst. A diagnosis can be made after a course of illness exceeding 6 months and after examinations (such as colonoscopy and blood tests) have ruled out organic lesions (such as tumors, inflammation, metabolic abnormalities, etc.) or drug-induced effects. Currently, the main Western medical treatments for CFC include dietary regulation, biofeedback therapy, and the use of Western medications. However, dietary regulation and biofeedback therapy rely on the patient's own actions, leading to limited adherence and a high likelihood of symptom recurrence. Long-term use of Western medications may also cause dependence or other adverse reactions. Traditional Chinese medicine, on the other hand, is often used for long-term symptom management due to its convenience for patients, low recurrence rate, and fewer side effects, making it well-suited for chronic functional constipation. For example, Tongyou Decoction (1.5 parts raw Rehmannia root, 1.5 parts prepared Rehmannia root, 3.0 parts Angelica sinensis root, 0.3 parts peach kernel, 0.3 parts safflower, 3.0 parts Cimicifuga rhizome, and 3.0 parts prepared licorice root) from Li Dongyuan's "Treatise on the Spleen and Stomach" is often used in clinical practice to treat chronic functional constipation, but its therapeutic effect is limited. Summary of the Invention

[0003] This invention addresses the shortcomings of existing technologies by providing a traditional Chinese medicine composition based on Tongyou Decoction, a classic formula from Li Dongyuan's "Treatise on the Spleen and Stomach." It is modified by combining the principles of "nourishing blood and yin, moistening the intestines and relieving constipation" with "regulating qi and strengthening the spleen, breaking up qi stagnation." The effect of this composition in treating chronic functional constipation is significantly improved compared to Tongyou Decoction.

[0004] The first objective of this invention is to provide a traditional Chinese medicine composition.

[0005] A second objective of this invention is to provide a method for preparing the above-mentioned traditional Chinese medicine composition.

[0006] A third objective of this invention is to provide the application of the above-mentioned herbal composition in the preparation of a medicine for treating chronic functional constipation.

[0007] The above-mentioned objective of this invention is achieved through the following technical solution: This invention provides a traditional Chinese medicine composition comprising the following components in parts by weight: 2.3-2.7 parts of Rehmannia glutinosa, 1.2-1.5 parts of Angelica sinensis, 1.5-1.7 parts of Prunus persica, 1-1.4 parts of Atractylodes macrocephala, 0.8-1 part of Citrus reticulata peel, 0.3-0.4 parts of Citrus aurantium, and 0.3-0.6 parts of Glycyrrhiza uralensis.

[0008] The properties, flavors, and effects of each herbal component in this invention are as follows: Rehmannia glutinosa: Sweet in taste and cold in nature. It enters the heart, liver, and kidney meridians. It has the effects of clearing heat and cooling blood, nourishing yin and promoting body fluids. It is mainly used to treat heat entering the blood level, febrile rashes, hematemesis and epistaxis, yin deficiency due to febrile diseases, red tongue with thirst, constipation due to fluid depletion, yin deficiency fever, bone steaming fever, and internal heat with thirst. Huang Yuanyu's "Changsha Yaoxie" states: "Rehmannia glutinosa is moistening and cold, and is most effective in lubricating the large intestine. It is suitable for those with excessive fire and dryness. In typhoid fever with Yangming disease, dryness of the intestines and constipation, taking more concentrated Rehmannia glutinosa juice can nourish the kidneys and lubricate the intestines, which is better than using Chengqi Decoction. Fresh Rehmannia glutinosa is even more effective." Modern research shows that its active ingredient, rehmannia glutinosa glycoside A, has the effects of enhancing humoral immunity and nourishing yin.

[0009] Angelica sinensis: sweet and pungent in taste, warm in nature. It enters the liver, heart, and spleen meridians. It has the effects of nourishing blood and promoting blood circulation, regulating menstruation and relieving pain, and moistening the intestines and promoting bowel movements. It is commonly used for blood deficiency and chlorosis, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, rheumatic arthralgia, traumatic injuries, carbuncles and sores, and constipation due to intestinal dryness. Angelica sinensis infused with wine promotes blood circulation and regulates menstruation. It is used for amenorrhea and dysmenorrhea, rheumatic arthralgia, and traumatic injuries. Classical medical texts record the use of Angelica sinensis in combination with other herbs to treat constipation due to blood deficiency, such as the "Run Chang Wan" and "Dao Zhi Tong You Tang" recorded in *Shen Shi Zun Sheng Shu* and *Pi Wei Lun*. Angelica sinensis contains volatile oil, polysaccharides, flavonoids, amino acids, and trace elements. The volatile oil has the effect of relaxing uterine smooth muscle, tracheal smooth muscle, and gastrointestinal smooth muscle. In addition, Angelica sinensis can improve the atrophy of the colonic mucosa and intestinal glands in mice, increase the thickness of the mucosal layer, and increase mucus secretion, thus exerting the effect of moistening the intestines and promoting bowel movements.

[0010] Peach kernel: Bitter and sweet in taste, neutral in nature. It enters the heart, liver, and large intestine meridians. It has the functions of promoting blood circulation and removing blood stasis, moistening the intestines and relieving constipation, and stopping cough and asthma. It is used for amenorrhea and dysmenorrhea, abdominal masses, lung abscess and intestinal abscess, traumatic injuries, constipation due to intestinal dryness, and cough and asthma. Studies have shown that peach kernel can promote intestinal peristalsis in constipated mice, improve defecation function, and relieve constipation symptoms.

[0011] Raw Atractylodes macrocephala: Bitter and sweet in taste, warm in nature. It enters the spleen and stomach meridians. It has the functions of strengthening the spleen and replenishing qi, drying dampness and promoting diuresis, stopping sweating, and calming the fetus. It is used for spleen deficiency with poor appetite, abdominal distension and diarrhea, phlegm retention with dizziness and palpitations, edema, spontaneous sweating, and threatened abortion. Raw Atractylodes macrocephala can improve the secretion of intestinal neurotransmitters and regulate intestinal flora, thereby restoring intestinal motility and improving intestinal water absorption.

[0012] Tangerine Peel: Bitter and pungent in taste, warm in nature. It enters the lung and spleen meridians. It has the effects of regulating qi and strengthening the spleen, drying dampness and resolving phlegm. It is used for symptoms such as abdominal distension, reduced food intake, vomiting and diarrhea, and excessive cough with phlegm. The volatile oil contained in tangerine peel can gently stimulate the gastrointestinal tract, promote the secretion of digestive juices and expel the accumulated gas in the gastrointestinal tract. Nobiletin is a flavonoid compound isolated from tangerine peel, which has biological activities such as antifungal and anti-inflammatory effects, can bidirectionally regulate the contraction function of the smooth muscle of the jejunum segment of rats, and promote gastrointestinal motility.

[0013] Immature Bitter Orange: Bitter, pungent and sour in taste, slightly cold in nature. It enters the spleen and stomach meridians. It has the effects of breaking qi to eliminate accumulation and resolving phlegm to disperse stagnation. It is mainly used for internal retention of accumulation, fullness and distending pain, tenesmus after diarrhea and dysentery, constipation, phlegm stagnation and qi obstruction, chest obstruction, knotted chest, and visceral ptosis. The volatile oil components (D-limonene) and flavonoid components (hesperidin, naringin) contained in immature bitter orange can regulate gastrointestinal motility by acting on the gastrointestinal smooth muscle. Its main active ingredient, total flavonoids of immature bitter orange, can also reduce calcium overload and apoptosis of interstitial cells of Cajal in constipated mice, regulate the content of neurotransmitters, and improve constipation symptoms.

[0014] Licorice Root: Sweet in taste, neutral in nature. It enters the heart, lung, spleen and stomach meridians. It has the effects of invigorating the spleen and replenishing qi, clearing heat and detoxifying, resolving phlegm and relieving cough, relieving spasm and pain, and harmonizing various medicinal herbs. It is used for spleen and stomach weakness, fatigue and weakness, palpitations and shortness of breath, excessive cough with phlegm, abdominal and limb spasmodic pain, carbuncles and sores, and relieving the toxicity and potency of drugs. For qi-deficiency type or spleen-deficiency type constipation, licorice root can enhance the transportation and transformation function of the spleen and stomach and the intestinal peristalsis ability by invigorating the spleen and replenishing qi.

[0015] This formula is based on Tongyou Decoction, a classic formula from Li Dongyuan's *Treatise on the Spleen and Stomach*, and is adapted using a combination of "nourishing blood and yin, moistening the intestines and relieving constipation" and "regulating qi and strengthening the spleen, breaking up qi stagnation and promoting bowel movement." Rehmannia glutinosa and Angelica sinensis are the principal herbs. Rehmannia glutinosa is cold in nature and sweet in taste, moist and juicy, excelling at nourishing yin and blood, generating fluids and moistening dryness, targeting the pathogenesis of yin deficiency, blood deficiency, and intestinal dryness. Angelica sinensis is sweet, warm, and moistening, a key herb for replenishing and activating blood, and also has the effect of moistening the intestines and relieving constipation. The two herbs work synergistically to nourish yin and blood, moisten dryness and relieve constipation, forming the core of the formula's blood-nourishing, yin-nourishing, and intestinal-moistening effects. Peach kernel is the assistant herb, bitter and sweet in taste and neutral in nature, entering the blood to activate blood and remove blood stasis, moist and oily, also moistening dryness and lubricating the intestines, assisting the principal herbs in enhancing their laxative effect, and also having the effect of removing blood stasis and generating new blood. Atractylodes macrocephala, Citrus reticulata peel, and Citrus aurantium are the adjuvant herbs. Raw Atractylodes macrocephala strengthens the spleen and replenishes Qi. Unlike stir-fried Atractylodes macrocephala, which stops diarrhea, raw Atractylodes macrocephala, when used in large doses, can relieve constipation. It utilizes the spleen's ability to "strengthen transportation and replenish Qi to propel the bowels," targeting symptoms of spleen deficiency, weak Qi, and impaired transport function. Immature Bitter Orange (Citrus aurantium) and Tangerine Peel (Citrus reticulata) are a classic Qi-regulating pair: Immature Bitter Orange is pungent and bitter, breaking up stagnation, resolving phlegm, and dispersing masses; its nature is strong and it effectively descends to clear the bowels. Tangerine Peel is pungent and warm, regulating Qi, strengthening the spleen and stomach, drying dampness, and resolving phlegm; its nature is mild. The combination of these two herbs, one strong and one mild, not only regulates the Qi mechanism of the middle Jiao but also breaks up stagnation and dissipates fullness, allowing Qi to flow, thus distributing body fluids and blood, and clearing the bowels, thereby relieving constipation. Licorice root (Glycyrrhiza uralensis) is the guiding herb, sweet and neutral in nature. Firstly, it harmonizes the other herbs, mitigating the strong Qi-breaking effect of Immature Bitter Orange and preventing it from harming the body's vital energy; secondly, it replenishes Qi and strengthens the middle Jiao, assisting Atractylodes macrocephala in its spleen-strengthening effect. This formula features a meticulously balanced combination of principal, assistant, and adjuvant herbs, employing both purgative and tonifying methods. It effectively improves intestinal motility and promotes the distribution of body fluids, while simultaneously supporting the body's vital energy and facilitating bowel movements. It is suitable for chronic functional constipation, especially deficiency-type constipation due to yin deficiency and blood deficiency, or spleen deficiency and qi stagnation. This formula not only focuses on purging the bowels but also emphasizes restoring the ascending and descending functions of the spleen and stomach, as well as the biochemical circulation of qi, blood, and body fluids. It addresses both the root cause and the symptoms, avoiding the drawbacks of solely purgative methods that deplete qi and damage body fluids. Therefore, it provides an effective and safe treatment option for chronic functional constipation.

[0016] More preferably, the components include the following parts by weight: 2.3-2.5 parts of Rehmannia glutinosa, 1.2-1.5 parts of Angelica sinensis, 1.5 parts of Prunus persica, 1-1.2 parts of Atractylodes macrocephala, 0.8-1 part of Citrus reticulata peel, 0.3-0.4 parts of Citrus aurantium, and 0.3-0.5 parts of Glycyrrhiza uralensis.

[0017] Most preferably, the components include the following parts by weight: 2.3 parts Rehmannia glutinosa, 1.2 parts Angelica sinensis, 1.5 parts Prunus persica, 1 part Atractylodes macrocephala, 0.8 parts Citrus reticulata, 0.3 parts Citrus aurantium, and 0.3 parts Glycyrrhiza uralensis.

[0018] Based on this, the present invention also provides a method for preparing the above-mentioned traditional Chinese medicine composition, namely: the components in the prescribed amounts are mixed evenly and then extracted with water.

[0019] Preferably, the water extraction is a stepwise water extraction.

[0020] More preferably, the stepwise water extraction is as follows: S1. Add the mixed product to water and heat at 95-100 °C for 1.8-2.2 h to extract. Separate the solid and liquid components to obtain the extract and residue. S2. Add the residue obtained in S1 to water and heat at 95-100 °C for 1.3-1.7 h to extract. Separate the solid and liquid components to obtain the extract. S3. Combine the extracts obtained from S1 and S2, and concentrate them to obtain the herbal composition.

[0021] More preferably, the mass of the water in S1 is 10 to 14 times the mass of the mixed product, and most preferably 12 times.

[0022] More preferably, the heating temperature described in S1 is 100 °C.

[0023] More preferably, the heating time in S1 is 2 hours.

[0024] More preferably, the solid-liquid separation described in S1 is filtration.

[0025] More preferably, the mass of the water in S2 is 8 to 12 times the mass of the dregs, and most preferably 10 times.

[0026] More preferably, the heating temperature described in S2 is 100 °C.

[0027] More preferably, the heating time in S2 is 1.5 h.

[0028] More preferably, the solid-liquid separation in S2 is filtration.

[0029] More preferably, the concentration described in S3 is carried out at -0.08 to -0.03 MPa, and most preferably at -0.05 MPa.

[0030] More preferably, the endpoint of the concentration described in S3 is a solids content of 15% ( w / v ) ~25% w / v ).

[0031] The herbal composition of this invention can effectively improve defecation, enhance intestinal motility, and repair colon morphology, making it highly suitable for treating chronic functional constipation. Therefore, the application of the above-mentioned herbal composition in the preparation of medicines for treating chronic functional constipation should be within the scope of protection of this invention.

[0032] Preferably, the drug is one of the following: granules, capsules, tablets, pills, oral liquids, suppositories, liniments, powder inhalers, aerosols, tinctures, sterile powders for injection, and injections.

[0033] More preferably, the drug further contains excipients.

[0034] More preferably, the excipient is one or more of dextrin, lactose, starch, sucrose, glucose, mannose, steviol glycosides, or micronized silica gel.

[0035] The present invention has the following beneficial effects: 1. The herbal composition of the present invention can effectively improve defecation, enhance intestinal motility, and repair colon morphology, and is very suitable for treating chronic functional constipation.

[0036] 2. In the herbal composition of the present invention, peach kernel and angelica, raw atractylodes macrocephala and angelica, angelica and immature bitter orange, angelica and licorice, peach kernel and raw atractylodes macrocephala, peach kernel and licorice, raw atractylodes macrocephala and immature bitter orange, raw atractylodes macrocephala and licorice, tangerine peel and immature bitter orange, immature bitter orange and licorice all play a synergistic role in promoting intestinal peristalsis. Attached Figure Description

[0037] Figure 1 A fluorescent image of the intestinal contents (Nile Red) of a zebrafish.

[0038] Figure 2 This is a photograph of the gastrointestinal tract.

[0039] Figure 3 This is a microscope image of the colon. Detailed Implementation

[0040] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0041] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0042] Ink: Accurately weigh 100 g of gum arabic (Aladdin Reagent (Shanghai) Co., Ltd., product batch number A2405121), add 800 mL of distilled water, heat to boiling until the solution becomes transparent, then add 50 g of activated carbon powder (Tianjin Baishi Chemical Co., Ltd., product batch number 20241019), continue to boil 3 times, and after the solution temperature drops to 25 ℃, add distilled water to make up to 1000 mL, store in a refrigerator at 4 ℃, and shake well before use.

[0043] Example 1: A Traditional Chinese Medicine Composition I. The components comprising the following parts by mass 2.5 parts Rehmannia glutinosa, 1.5 parts Angelica sinensis, 1.5 parts Prunus persica, 1.2 parts Atractylodes macrocephala, 1.0 part Citrus reticulata, 0.4 parts Citrus aurantium, and 0.5 parts Glycyrrhiza uralensis.

[0044] II. Preparation Method Mix all components according to the formula, add 12 times their weight of water, and heat at 100 ℃ for 2 h. Filter to obtain extract 1 and residue. Add the residue to 10 times its weight of water and heat at 100 ℃ for 1.5 h. Filter to obtain extract 2. Combine extract 1 and extract 2, and concentrate at -0.05 MPa to a solids content of 20%. w / v That is, the herbal medicine composition is obtained.

[0045] Example 2: A Traditional Chinese Medicine Composition I. The components comprising the following parts by mass 2.7 parts Rehmannia glutinosa, 1.2 parts Angelica sinensis, 1.7 parts Prunus persica, 1.4 parts Atractylodes macrocephala, 0.8 parts Citrus reticulata, 0.3 parts Citrus aurantium, and 0.6 parts Glycyrrhiza uralensis.

[0046] II. Preparation Method Same as Example 1.

[0047] Example 3: A Traditional Chinese Medicine Composition I. The components comprising the following parts by mass 2.3 parts Rehmannia glutinosa, 1.2 parts Angelica sinensis, 1.5 parts Prunus persica, 1.0 part Atractylodes macrocephala, 0.8 parts Citrus reticulata, 0.3 parts Citrus aurantium, and 0.3 parts Glycyrrhiza uralensis.

[0048] II. Preparation Method Same as Example 1.

[0049] Comparative Example 1 I. Tongyou Decoction comprises the following components in parts by weight. 1.5 parts raw Rehmannia root, 1.5 parts prepared Rehmannia root, 3.0 parts Angelica sinensis root, 0.3 parts peach kernel, 0.3 parts safflower, 3.0 parts Cimicifuga rhizome, and 3.0 parts prepared licorice root.

[0050] II. Preparation Method Same as Example 1.

[0051] Comparative Example 2 I. The components comprising the following parts by mass 2.5 parts Rehmannia glutinosa, 1.5 parts Angelica sinensis, 1.5 parts Prunus persica, 1.2 parts Atractylodes macrocephala, 1.0 part Citrus medica, 0.4 parts Citrus aurantium, and 0.5 parts Glycyrrhiza uralensis.

[0052] That is, the same as in Example 1, except that the dried tangerine peel is replaced with Buddha's hand.

[0053] II. Preparation Method Same as Example 1.

[0054] Comparative Examples 3–18 I. As shown in Table 1, the components include the following parts by mass (for ease of comparison, the complete formula of Example 1 is also presented in Table 1). Table 1

[0055] II. Preparation Method Same as Example 1.

[0056] Test Example 1: Zebrafish Intestinal Peristalsis Experiment Zebrafish developed to day 4 were exposed to Nile red solution (20.0 ng / mL) and incubated for 24 h at 28.5 ℃, 0 mg / L chlorine, 5–8 mg / L dissolved oxygen, 0.25‰–0.50‰ salinity, 500 μS / cm conductivity, and pH 7.4 (at which point fluorescence microscopy confirmed that the intestines were filled with Nile red). After washing three times with E3 culture water, they were then divided into the following groups: (1) Model group: zebrafish were placed in 10 mL of E3 culture water; (2) Sample group: zebrafish were placed in 10 mL of solution containing 0.1% ( v / v E3 culture water containing the herbal compositions obtained in Examples 1-3 and Comparative Examples 1-18.

[0057] All groups were incubated for 24 h at a temperature of 28.5 ℃, a chlorine content of 0 mg / L, a dissolved oxygen content of 5–8 mg / L, a salinity of 0.25‰–0.50‰, a conductivity of 500 μS / cm, and a pH of 7.4. Fluorescent images of the zebrafish intestinal contents (Nile red) were then captured using a fluorescence microscope (e.g., Figure 1 As shown), the fluorescence intensity S of the zebrafish intestinal contents was analyzed using ImageJ image processing software, and the fluorescence intensity S was calculated according to the formula: "Promotion rate (%) = (S) / (S)". 模型组 - S 样品组 ) / S 模型组 The ×100% method was used to evaluate the promoting effect of the sample on intestinal peristalsis in zebrafish. Ten parallel samples were set up in each group, and the results were averaged, as shown in Table 2.

[0058] Table 2

[0059] visible: (1) The herbal composition obtained in Examples 1 to 3 has a high rate of promoting intestinal peristalsis in zebrafish of 48.83% to 51.39%, indicating that the herbal composition of the present invention can effectively improve intestinal peristalsis and promote the efficiency of intestinal contents propulsion, and is suitable for the treatment of chronic functional constipation.

[0060] (2) The herbal composition obtained in Examples 1-3 significantly promoted the intestinal peristalsis of zebrafish, which was significantly higher than that in Comparative Example 1, indicating that the herbal composition of the present invention has a significantly improved therapeutic effect on chronic functional constipation compared with Tongyou Decoction.

[0061] (3) The herbal composition obtained in Example 1 has a significantly higher rate of promoting intestinal peristalsis in zebrafish than that in Comparative Example 2, indicating that it is precisely because the herbal composition of the present invention specifically selected herbal medicines such as tangerine peel that it was able to exert such an excellent effect on promoting intestinal peristalsis.

[0062] (4) Compared with Comparative Example 9, Comparative Example 3, which increased the amount of peach kernel and the same weight, increased the rate of promoting intestinal peristalsis in zebrafish by 3.5%, Comparative Example 4, which increased the amount of angelica and the same weight, increased it by 16.45%, and Example 1, which increased the amount of peach kernel and angelica and the same weight, increased it by 27.89% (>3.5%+16.45%=19.95%). This indicates that in the herbal composition of the present invention, peach kernel and angelica play a synergistic role in promoting intestinal peristalsis. Compared to Comparative Example 10, Comparative Example 3, with an equal mass of added raw Atractylodes macrocephala, showed a 13.98% decrease in the rate of promoting intestinal peristalsis in zebrafish; Comparative Example 5, with an equal mass of added Angelica sinensis, showed a 10.28% decrease; while Example 1, with an equal mass of added raw Atractylodes macrocephala and Angelica sinensis, not only did not show a decrease, but actually increased by 10.41% (>(-13.98%) + (-10.28%) = -24.26%), indicating that in the herbal composition of the present invention, raw Atractylodes macrocephala and Angelica sinensis play a synergistic role in promoting intestinal peristalsis. Similarly, in the herbal composition of the present invention, Angelica sinensis with Citrus aurantium, Angelica sinensis with Glycyrrhiza uralensis, Prunus persica with raw Atractylodes macrocephala, Prunus persica with Glycyrrhiza uralensis, raw Atractylodes macrocephala with Citrus aurantium, raw Atractylodes macrocephala with Glycyrrhiza uralensis, Citrus reticulata with Citrus aurantium, and Citrus aurantium with Glycyrrhiza uralensis all play a synergistic role in promoting intestinal peristalsis.

[0063] Test Example 2: Chronic Functional Constipation in Rats I. Experimental Grouping and Treatment Eighteen SPF-grade SD rats (weighing 180–220 g) were acclimatized for one week and then randomly divided into a blank control group, a model group, and a sample group, and then subjected to the following treatments: (1) Days 1-4: No treatment was given to the blank group, while the model group and the sample group were subjected to tail clamping provocation treatment (the tail of the rat was clamped at 1 / 3 of the length with a long tail clamp wrapped in sterile gauze, twice a day for 30 minutes each time, with an interval of more than half an hour between the two tail clamps). (2) Day 5: The blank group was given physiological saline by gavage at a dose of 1 mL / kg·bw; the model group and the sample group were given loperamide by gavage at a dose of 7 mg / kg·bw (loperamide was dissolved in physiological saline to make the concentration of loperamide 0.7 mg / mL), thus completing the construction of the chronic functional constipation model. (3) Days 6-12: The blank group and the model group were given physiological saline by gavage at a dose of 1 mL / kg·bw every day, and the sample group was given the herbal composition obtained in Example 1 by gavage at a dose of 1.717 g / kg·bw every day (the gavage dose for rats was converted from the human dose of 16.703 g / d).

[0064] II. Testing Methods (1) Statistics on food intake of rats From day 1 to day 12, the amount of food consumed by the rats was recorded each day, and the average daily amount of food consumed by each rat was calculated.

[0065] (2) Rat fecal test On day 12, feces from rats were collected throughout the day. The characteristics, number of pellets, and wet weight of the feces were recorded. The feces were dried at a constant temperature of 60 °C for 24 hours and then weighed. The fecal moisture content was calculated according to the formula "fecal moisture content (%) = (fecal wet weight - fecal dry weight) / fecal wet weight × 100%". The result was the average value of each rat.

[0066] (3) 9-hour black stool test in rats Starting from the end of gavage on day 10, all rats were fasted for 12 hours but allowed free access to water. On the second day, the following treatments were administered: the blank group and the model group were gavaged with 1 mL / 100 g·bw ink; the sample group was gavaged with 1 mL / 100 g·bw ink containing 1.717 g / mL of the herbal composition obtained in Example 1.

[0067] After gavage, each rat was housed individually, with unrestricted access to food and water. Precise timing was started at the point when each rat finished receiving the ink (using the same model of timer). The time when each rat expelled its first black feces was recorded, along with the number of black feces expelled within 9 hours. The results were taken as the average for each rat.

[0068] (4) Small intestine motility test Starting from the end of gavage on day 12, all rats were fasted for 12 hours but allowed free access to water. The following treatments were then administered on the second day: the blank group and the model group were gavaged with 1 mL / 100 g·bw ink; the sample group was gavaged with 1 mL / 100 g·bw ink containing 1.717 g / mL of the herbal composition obtained in Example 1.

[0069] Thirty minutes after gavage, the rats were sacrificed, and the entire gastrointestinal tract was removed via laparotomy. (Photos are shown below.) Figure 2 As shown. The distance (cm) from the tip of the ink to the pyloric sphincter and the distance (cm) from the pyloric sphincter to the end of the small intestine were measured. The ink propulsion rate was calculated according to the formula "Ink propulsion rate (%) = distance from the tip of the ink to the pyloric sphincter / distance from the pyloric sphincter to the end of the small intestine × 100%". The result was the average value of each rat.

[0070] (5) Changes in rat colon weight and morphological observation Starting from the end of gavage on day 12, all rats were fasted for 12 hours but allowed free access to water. The following day, the rats were dissected, the colon was removed and weighed, and a 1 cm section was rinsed with physiological saline at 4 °C. The colon was then fixed in 4 wt% paraformaldehyde solution and soaked for 24 hours. The tissue was then dehydrated, cleared, paraffin-embedded, and prepared into paraffin blocks. Paraffin sections were prepared, stained with hematoxylin and eosin (H&E), and mounted. Finally, the colon morphology of each group was observed under a microscope (e.g., ...). Figure 3 As shown in the figure (arrows indicate inflammatory infiltration), the thickness of smooth muscle was statistically analyzed.

[0071] III. Test Results The test results are shown in Table 3.

[0072] Table 3

[0073] visible: (1) Compared with the control group, the model group showed a significant reduction in daily food intake, number of fecal particles, fecal weight, fecal water content, number of black fecal particles within 9 hours, ink propulsion rate, colon weight, and smooth muscle thickness, indicating that the chronic functional constipation model was successfully constructed. Compared with the model group, the sample group showed a significant increase in daily food intake, number of fecal particles, fecal weight, fecal water content, number of black fecal particles within 9 hours, ink propulsion rate, colon weight, and smooth muscle thickness, and some indicators were even better than those of the control group, indicating that the herbal composition of the present invention can significantly improve the quality of defecation and thus effectively treat chronic functional constipation.

[0074] (2) Compared with the control group, the time to first black stool in the model group was significantly prolonged, indicating that the chronic functional constipation model was successfully constructed; compared with the model group, the time to first black stool in the sample group was significantly shortened, indicating that the herbal composition of the present invention can promote intestinal peristalsis and thus effectively treat chronic functional constipation.

[0075] (3) The fecal particles of the control group rats were larger, smoother, and softer. In contrast, the fecal particles of the model group rats were smaller, beaded, rougher, and harder. This indicates that the chronic functional constipation model was successfully established compared to the control group. Compared to the model group, the fecal characteristics of the sample group were significantly improved, and the probability of beaded feces decreased significantly, indicating that the herbal composition of this invention can significantly improve defecation quality and thus effectively treat chronic functional constipation.

[0076] (4) No pathological changes were observed in the intestines of the control group rats. The number of goblet cells in the colon of the model group rats decreased, the number of inflammatory cells increased, and the smooth muscle layer was significantly thinned, indicating that the morphology of the rat colon was significantly damaged and the chronic functional constipation model was successfully constructed. Compared with the model group, the number of goblet cells in the colon of the sample group rats increased, the glands were arranged more neatly, and the number of inflammatory cells decreased, indicating that the herbal composition of the present invention can effectively repair the colonic mucosa and smooth muscle structure, improve the morphology and functional integrity of the colon, and thus effectively treat chronic functional constipation.

[0077] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition, characterized in that, The components include the following parts by weight: 2.3-2.7 parts of Rehmannia glutinosa, 1.2-1.5 parts of Angelica sinensis, 1.5-1.7 parts of Prunus persica, 1-1.4 parts of Atractylodes macrocephala, 0.8-1 part of Citrus reticulata, 0.3-0.4 parts of Citrus aurantium, and 0.3-0.6 parts of Glycyrrhiza uralensis.

2. The herbal composition according to claim 1, characterized in that, The components include the following parts by weight: 2.3-2.5 parts of Rehmannia glutinosa, 1.2-1.5 parts of Angelica sinensis, 1.5 parts of Prunus persica, 1-1.2 parts of Atractylodes macrocephala, 0.8-1 part of Citrus reticulata peel, 0.3-0.4 parts of Citrus aurantium, and 0.3-0.5 parts of Glycyrrhiza uralensis.

3. The method for preparing the herbal composition according to claim 1 or 2, characterized in that, The product is obtained by mixing the components in the specified amounts, followed by water extraction.

4. The preparation method according to claim 3, characterized in that, The water extraction is a step-by-step water extraction.

5. The preparation method according to claim 4, characterized in that, The stepwise water extraction is as follows: S1. Add the mixed product to water and heat at 95-100 °C for 1.8-2.2 h to extract. Separate the solid and liquid components to obtain the extract and residue. S2. Add the residue obtained in S1 to water and heat at 95-100 °C for 1.3-1.7 h to extract. Separate the solid and liquid components to obtain the extract. S3. Combine the extracts obtained from S1 and S2, and concentrate them to obtain the herbal composition.

6. The preparation method according to claim 5, characterized in that, The mass of water in S1 is 10 to 14 times the mass of the mixed product.

7. The preparation method according to claim 5, characterized in that, The mass of the water mentioned in S2 is 8 to 12 times the mass of the medicinal residue.

8. The use of the herbal composition according to claim 1 or 2 in the preparation of a medicament for treating chronic functional constipation.

9. The application according to claim 8, characterized in that, The drug is one of the following: granules, capsules, tablets, pills, oral liquids, suppositories, liniments, powder inhalers, aerosols, tinctures, sterile powders for injection, and injections.

10. The application according to claim 8, characterized in that, The drug also contains excipients.

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