Traditional Chinese medicine composition for tonifying spleen and moistening intestines and application method of traditional Chinese medicine composition in functional constipation

Abstract

The invention relates to the field of traditional Chinese medicine, and particularly discloses a spleen-tonifying intestine-moistening traditional Chinese medicine composition and an application method thereof in functional constipation. The spleen-tonifying intestine-moistening traditional Chinese medicine composition comprises the following components in parts by weight: roasted rhizoma atractylodis macrocephalae, codonopsis pilosula, poria cocos, pericarpium citri reticulatae, fructus cannabis and bunge cherry seeds; the formula is accurately matched with the core pathogenesis of spleen dysfunction in transportation and intestine dysfunction in moistening, the roasted rhizoma atractylodis macrocephalae, the codonopsis pilosula and the like are used for invigorating the spleen and replenishing qi to consolidate the root, the fructus cannabis and the bunge cherry seeds are used for relaxing bowel to treat the symptoms, the defect of emphasizing a single effect is avoided, and the formula is suitable for multi-subtype constipation, and has the advantages of no toxic or side effect, no toxic or side effect, no toxic or side effect, no toxic or side effect, no toxic or side effect, no toxic or side effect, no toxic or side effect, no toxic or side effect, no toxic or side effect, no toxic or side effect and the like. The traditional Chinese medicine is especially suitable for patients with spleen-stomach deficiency with intestinal dryness type functional constipation.

Description

Technical Field

[0001] This application relates to the field of traditional Chinese medicine, and specifically discloses a traditional Chinese medicine composition for strengthening the spleen and moistening the intestines and its application method in functional constipation. Background Technology

[0002] Functional constipation (FC) is a common functional bowel disorder of the digestive system, falling under the categories of "constipation," "spleen deficiency," and "intestinal obstruction" in Traditional Chinese Medicine. Its core characteristic is the presence of abnormal bowel symptoms such as difficulty in defecation, reduced frequency of bowel movements, and hard, dry stools, after ruling out clear causes such as organic intestinal lesions, endocrine and metabolic diseases, and drug side effects. These symptoms are persistent and significantly impact the patient's quality of life. With changes in modern lifestyles, the incidence of functional constipation is increasing year by year, becoming a global public health problem that seriously endangers human physical and mental health. Therefore, the development of safe and effective treatments has significant clinical value and social importance.

[0003] Regarding functional constipation: According to the Rome IV diagnostic criteria, the diagnosis of functional constipation requires meeting the following conditions, with symptoms present for at least 6 months, and symptoms meeting the following criteria in the past 3 months: ① Spontaneous bowel movements ≤ 2 times per week; ② Straining during bowel movements ≥ 25% of the time; ③ Hard or dry stools ≥ 25% of the time; ④ Feeling of incomplete bowel movements ≥ 25% of the time; ⑤ Manual assistance during bowel movements (e.g., using fingers, pelvic floor support) ≥ 25% of the time; ⑥ A feeling of anorectal obstruction or blockage during bowel movements ≥ 25% of the time. Simultaneously, the patient does not have any organic or systemic diseases that could explain the constipation symptoms, and has not been using medications that may cause constipation for a long period. Furthermore, patients with functional constipation often experience systemic or psychological symptoms such as abdominal distension, abdominal pain, loss of appetite, anxiety, and depression, which further exacerbate the patient's suffering.

[0004] Epidemiological characteristics: Globally, the incidence of functional constipation varies geographically and among different population groups, with an overall prevalence of approximately 10%–20%. In my country, with accelerated urbanization, changes in dietary structure, faster pace of life, and an aging population, the prevalence of functional constipation has reached 15%–20%, with significantly higher rates among the elderly, women, sedentary office workers, and those under high stress. For example, due to physiological changes such as decreased intestinal motility, reduced pelvic floor muscle function, and decreased digestive fluid secretion, the prevalence in the elderly can be as high as 30% or more; women, due to hormonal fluctuations and the unique structure of the pelvic floor, have a prevalence approximately 2–3 times higher than men. Functional constipation not only affects patients' daily life and work efficiency but may also induce anorectal diseases such as hemorrhoids, anal fissures, and rectal prolapse. Long-term chronic constipation is also associated with an increased risk of colorectal cancer and negatively impacts patients' mental health, increasing the probability of anxiety and depression.

[0005] Etiology and Pathogenesis: The etiology of functional constipation is complex and not fully understood. Currently, it is believed to be related to multiple factors, including intestinal motility disorders, visceral hypersensitivity, gut microbiota dysbiosis, psychological factors, dietary and lifestyle habits, and pelvic floor dysfunction. From the perspective of intestinal motility, patients experience a decrease in the frequency and intensity of intestinal smooth muscle contractions, leading to prolonged fecal transit time in the colon, excessive water absorption, and the formation of hard, dry stools, causing difficulty in defecation. Visceral hypersensitivity causes patients to have abnormal perception of intestinal stimuli from feces; even small amounts of feces can cause intense bloating and abdominal pain, and may also inhibit intestinal peristalsis, exacerbating constipation. When the gut microbiota is imbalanced, the number of beneficial bacteria decreases while harmful bacteria increase, leading to a reduction in short-chain fatty acids produced by the fermentation of dietary fiber in the intestine. Short-chain fatty acids can promote intestinal peristalsis and regulate gut microbiota. The lack of mucosal barrier function further exacerbates constipation; psychological factors can regulate intestinal function through the brain-gut axis, inhibiting intestinal peristalsis and affecting patients' defecation behavior, leading to disordered defecation habits; insufficient intake of dietary fiber and water in the diet cannot effectively stimulate intestinal peristalsis and increase stool volume, while prolonged sitting and lack of exercise slow down intestinal peristalsis. These dietary and lifestyle habits are important causes of functional constipation; in addition, some patients have pelvic floor dysfunction, such as abnormal coordinated contraction of pelvic floor muscles during defecation, which leads to obstruction of stool expulsion and forms outlet obstruction type functional constipation.

[0006] Clinical classification: Based on the results of colonic transit tests and pelvic floor function examinations, functional constipation can be divided into three main subtypes: ① Slow Transit Constipation (STC): The most common subtype, accounting for about 40% to 50% of functional constipation. It is mainly characterized by significantly prolonged intestinal transit time, infrequent bowel movements, hard stools, and often accompanied by abdominal distension. It is more common in the elderly and women. ② Outlet Obstructive Constipation (OOC): Accounting for about 30% to 40%, it is mainly due to pelvic floor muscle dysfunction leading to obstruction of stool expulsion. Although patients have a frequent urge to defecate, they experience difficulty in defecation, a significant feeling of incomplete evacuation, and prolonged defecation time. ③ Mixed Constipation: This type involves both slow transit and outlet obstruction mechanisms. Patients exhibit symptoms of both subtypes, making treatment relatively more difficult.

[0007] Currently, clinical treatments for functional constipation mainly include basic treatment, drug therapy, and surgical treatment. Basic treatment focuses on adjusting diet, improving lifestyle habits, and regulating mental and psychological state; however, due to the difficulty in correcting long-standing bad habits, the effectiveness of basic treatment is limited. Drug therapy is a commonly used clinical approach, mainly including bulk-forming laxatives, osmotic laxatives, stimulant laxatives, prokinetic drugs, and probiotics. Bulk-forming laxatives require drinking large amounts of water, which may worsen abdominal distension in some patients; osmotic laxatives, while relatively safe, have a slow onset of action and are ineffective for patients with severe constipation; stimulant laxatives have a rapid onset of action, but long-term use may lead to intestinal nerve damage, drug dependence, and even electrolyte imbalances, posing significant safety risks; the therapeutic effects of prokinetic drugs and probiotics vary greatly among individuals and cannot meet the treatment needs of all patients. Surgical treatment is only suitable for a very small number of patients with severe functional constipation who do not respond to strict conservative treatment, and its clinical application is limited due to high surgical risks and numerous postoperative complications.

[0008] Traditional Chinese medicine (TCM) believes that the core pathogenesis of functional constipation lies in "spleen dysfunction, intestinal dryness, and stagnation of Qi." The spleen governs transformation and transportation, and is the foundation of acquired constitution. If dietary indiscretions, overwork, or old age lead to spleen and stomach weakness, the spleen's function will be impaired, preventing the proper transformation and distribution of nutrients. This results in dry, hard stools that are difficult to pass. Simultaneously, spleen dysfunction can also cause Qi stagnation and impaired large intestine function, further aggravating constipation. Therefore, TCM treatment for functional constipation focuses on "strengthening the spleen and replenishing Qi, moistening the intestines and promoting bowel movements, and regulating Qi and relieving stagnation." By regulating spleen and stomach function, nourishing intestinal fluids, and restoring large intestine function, TCM addresses the root cause of constipation symptoms and offers advantages such as stable efficacy, minimal side effects, and low recurrence rate.

[0009] While existing TCM formulas and prepared medicines for treating functional constipation have some efficacy, they still have many shortcomings. Combining these with publicly available technologies can further clarify the limitations of existing solutions. For example, Chinese patent CN202311070720.0 discloses a TCM composition for strengthening the spleen, nourishing the stomach, moistening the intestines, and relieving constipation. This composition includes spleen-strengthening ingredients such as deer blood powder, chicken gizzard lining, and coix seed, as well as intestinal-moistening ingredients such as inulin. Although it balances both spleen-strengthening and intestinal-moistening effects, the composition contains approximately 15 ingredients across multiple categories. This complexity leads to cumbersome preparation processes and high production costs. The efficacy of these treatments is relatively high, and they are not tailored to different subtypes of functional constipation, such as slow transit constipation and outlet obstruction constipation, resulting in limited universality of efficacy. Furthermore, studies have shown that current patented traditional Chinese medicine compound formulas for treating functional constipation primarily use herbs such as Atractylodes macrocephala, Glycyrrhiza uralensis, and Cistanche deserticola-Angelica sinensis-Atractylodes macrocephala, focusing on tonifying deficiency, regulating qi, and purging to achieve bowel movement. However, their mechanisms of action are mostly focused on simply restoring intestinal motility or regulating intestinal flora, without fully considering the synergistic treatment of the core pathogenesis of "spleen deficiency and intestinal dryness," leading to limited improvement in efficacy for patients with spleen and stomach weakness accompanied by intestinal dryness.

[0010] From the perspective of commonly used traditional Chinese medicines, while Ma Ren Run Chang Wan can lubricate the intestines and relieve constipation, its spleen-strengthening ingredients, such as bitter almond, have a low proportion. Long-term use may lead to recurrence of constipation due to unresolved spleen deficiency, and it is not suitable for those with spleen deficiency and dampness. Shen Ling Bai Zhu San focuses on strengthening the spleen and eliminating dampness with core ingredients such as ginseng and poria. Although it can indirectly relieve constipation by improving the digestive function of the spleen and stomach, it lacks lubricating ingredients and has a slow onset of action for patients with acute constipation and dry stools, and cannot quickly relieve the symptoms of difficulty in defecation. Xiang Sha Liu Jun Wan takes into account both strengthening the spleen and regulating qi, but its lubricating effect is weak and it is not suitable for functional constipation of the intestinal dryness and fluid deficiency type.

[0011] Furthermore, most existing traditional Chinese medicine (TCM) prescriptions either exacerbate abdominal distension due to their rich and nourishing properties (e.g., containing large amounts of spleen-tonifying ingredients) or increase the risk of adverse reactions due to their complex formulations. These limitations fail to meet the comprehensive needs of patients with different subtypes of functional constipation who require rapid symptom relief, long-term efficacy consolidation, and high safety. Therefore, based on the core pathogenesis of "spleen dysfunction and intestinal dryness" in TCM, developing a scientifically simplified and precisely formulated TCM composition that can effectively strengthen the spleen and replenish qi to consolidate the root cause, quickly lubricate the intestines and relieve constipation to address the symptoms, and is suitable for multiple subtypes of functional constipation with higher safety is of significant clinical demand and application potential.

[0012] This invention provides a traditional Chinese medicine composition for strengthening the spleen and moistening the intestines, and its application method in functional constipation, in order to solve the above-mentioned problems. Summary of the Invention

[0013] The purpose of this invention is to solve one or more of the technical problems mentioned in the background art.

[0014] To achieve the above objectives, the present invention provides the following basic solution: A traditional Chinese medicine composition for strengthening the spleen and moistening the intestines, comprising, by weight, stir-fried Atractylodes macrocephala, Codonopsis pilosula, Poria cocos, Citrus reticulata peel, Cannabis sativa seed, and Prunus japonica seed; wherein stir-fried Atractylodes macrocephala is 13-18 parts, Codonopsis pilosula is 10-15 parts, Poria cocos is 8-13 parts, Citrus reticulata peel is 4-8 parts, Cannabis sativa seed is 13-18 parts, and Prunus japonica seed is 8-12 parts.

[0015] Furthermore, according to the weight ratio, there are 15 parts of stir-fried Atractylodes macrocephala, 12 parts of Codonopsis pilosula, 10 parts of Poria cocos, 6 parts of dried tangerine peel, 15 parts of hemp seed, and 10 parts of Prunus japonica seed.

[0016] Furthermore, according to the weight ratio, there are 18 parts of stir-fried Atractylodes macrocephala, 15 parts of Codonopsis pilosula, 13 parts of Poria cocos, 8 parts of dried tangerine peel, 18 parts of hemp seed, and 12 parts of Prunus japonica seed.

[0017] Furthermore, according to the weight ratio, there are 13 parts of stir-fried Atractylodes macrocephala, 10 parts of Codonopsis pilosula, 8 parts of Poria cocos, 4 parts of dried tangerine peel, 13 parts of hemp seed, and 8 parts of Prunus japonica seed.

[0018] Based on a traditional Chinese medicine composition for strengthening the spleen and moistening the intestines, this invention also discloses a clinical formulation of the traditional Chinese medicine composition for strengthening the spleen and moistening the intestines. Those skilled in the art can add various pharmaceutically acceptable excipients, such as disintegrants, lubricants, emulsifiers, and binders, to the traditional Chinese medicine composition according to the needs of different patients. The clinical formulation can be prepared by directly or indirectly adding pharmaceutically acceptable excipients through conventional traditional Chinese medicine preparation methods and conventional processing.

[0019] Furthermore, the clinical preparations are tablets, granules, capsules, decoctions, pills, oral liquids, and syrups.

[0020] Based on a traditional Chinese medicine composition for strengthening the spleen and moistening the intestines, this invention also discloses a method for preparing the composition. The dosage and method of use of the pharmaceutical composition of this invention depend on many factors, including the patient's age, weight, gender, natural health condition, nutritional status, the activity intensity of the compound, the duration of administration, metabolic rate, severity of the disease, and the subjective judgment of the treating physician. Those skilled in the art can easily determine the dosage and method of use of the pharmaceutical composition based on the above factors.

[0021] A method for preparing a traditional Chinese medicine composition for strengthening the spleen and moistening the intestines includes the following steps: Step S01: Raw material pretreatment: Take the above-mentioned medicinal materials and clean them according to the pharmacopoeia standards. Remove impurities and non-medicinal parts from stir-fried Atractylodes macrocephala, Codonopsis pilosula, Poria cocos and tangerine peel. Screen the hemp seeds and Prunus japonica seeds to remove shriveled grains and mud, and rinse them quickly with water several times. Drain the water. Grind the cleaned stir-fried Atractylodes macrocephala, Codonopsis pilosula, Poria cocos and tangerine peel into coarse powder; grind the hemp seeds and Prunus japonica seeds into medium powder separately. Step S02: Using the water decoction extraction method, put the above four crude powders into the extraction tank, add 10 times the amount of purified water, and soak for 20-30 minutes; heat to 95℃-100℃ and maintain decoction for 50-60 minutes, and collect the first decoction; add 7-8 times the amount of purified water to the residue, heat to 95℃-100℃ and decoct for 40-45 minutes, and collect the second decoction; combine the two decoctions, filter through a 200-mesh sieve to remove the medicinal residue and impurities, and obtain the water extract of the spleen-strengthening components; Step S03: Using a combined method of low-temperature pressing and solvent-assisted extraction, the crushed hemp seeds and apricot kernels are put into a low-temperature press and pressed at 40℃-45℃ to collect the virgin oil. The pressed cake is then added to 5-6 times the amount of anhydrous ethanol and refluxed in a water bath at 45℃-50℃ for 5-30 minutes. The ethanol extract is collected by filtration. The ethanol extract is then distilled under reduced pressure to recover the ethanol and obtain the concentrated oil. The virgin oil and the concentrated oil are combined to obtain the extract of the laxative components, which is stored away from light. Step S04: Thoroughly mix the water extract of the spleen-strengthening component and the extract of the bowel-moistening component, add 0.1% chitosan solution, stir evenly, and let stand for 2 hours; then use plate and frame filter press at a pressure of 0.35MPa-0.5MPa to obtain a clear mixed extract; Step S05: Put the clear mixed extract into a vacuum concentration tank and concentrate it under vacuum at a vacuum degree of 0.07-0.09MPa and a temperature of 60-65℃ to obtain a clear extract with a relative density of 1.15-1.20; Step S06: Dry the ointment, set the inlet air temperature to 160-170℃, the outlet air temperature to 80-85℃, and the feed rate to 10-15mL / min to obtain dried Chinese herbal extract powder. The moisture content of the Chinese herbal extract powder is controlled below 5.0%. This Chinese herbal extract powder is the spleen-strengthening and bowel-moistening Chinese herbal composition.

[0022] Furthermore, in step S01, all medicinal materials meet the processing requirements. Among them, stir-fried Atractylodes macrocephala must be either stir-fried with soil or stir-fried with wheat bran, and hemp seeds must be dried at a low temperature of less than or equal to 60°C. Stir-fried Atractylodes macrocephala, Codonopsis pilosula, Poria cocos and tangerine peel are pulverized into coarse powder and passed through a 20-mesh sieve. Hemp seeds and Prunus japonica seeds are pulverized separately into medium powder and passed through a 40-mesh sieve.

[0023] Furthermore, regarding the decoction: Take the powdered Chinese herbal extract, add an appropriate amount of purified water to dissolve it, and adjust the volume to the volume corresponding to the daily dose. The volume of the decoction should be 150-300mL. After dispensing, sterilize it. The dosage for adults is 250mL-300mL, and for children it is 150mL-250mL. Regarding granules: Take Chinese herbal extract powder, add dextrin and sucrose powder to the Chinese herbal extract powder. The amount of dextrin is 30% of the mass of the Chinese herbal extract powder, and the amount of sucrose powder is 20% of the mass of the Chinese herbal extract powder. Make soft material with ethanol, granulate through a 16-mesh sieve, dry at 60℃, and package after granulation. Regarding capsules: Take the Chinese herbal extract powder and fill it directly into enteric-coated capsules. The daily dosage for adults is 0.5g per capsule, and the daily dosage for children is 0.35g per capsule.

[0024] In another aspect, the present invention provides a method for preparing a traditional Chinese medicine composition for strengthening the spleen and moistening the intestines, and the application of the prepared composition for functional constipation.

[0025] The principle and effect of this solution are as follows: 1. Compared with existing technologies, the formulation is simplified and the preparation is simple: it contains only 6 standard medicinal materials. Compared with the complex formulations of existing formulas with many different ingredients, it greatly simplifies the preparation process, reduces production costs, and reduces the risk of potential adverse reactions between multiple components.

[0026] 2. Compared with existing technologies, the treatment focuses on synergistic regulation of the pathogenesis: It accurately matches the core pathogenesis of spleen deficiency and intestinal dryness. It strengthens the spleen and replenishes qi by using stir-fried Atractylodes macrocephala and Codonopsis pilosula to consolidate the foundation, and lubricates the intestines and promotes bowel movement by using hemp seed and Prunus japonica seed to treat the symptoms. It avoids the shortcomings of existing solutions that focus on a single effect, and is especially suitable for patients with functional constipation of spleen and stomach weakness accompanied by intestinal dryness.

[0027] 3. Compared with existing technologies, it is suitable for multiple subtypes of constipation: slow transit type: the spleen-strengthening ingredients can enhance intestinal motility and shorten colonic transit time, while the laxative ingredients soften the stool; outlet obstruction type: the laxative ingredients reduce the resistance to stool expulsion, and the tangerine peel regulates qi and relieves the obstruction sensation related to pelvic floor muscle spasms; mixed type: it takes into account both mechanisms, improving the universality of efficacy.

[0028] 4. Compared with existing technologies, it is safer and less prone to recurrence: All medicinal materials are commonly used and mild medicinal materials included in the pharmacopoeia. There are no cold, purgative or greasy ingredients that can harm the stomach. This avoids damage to the intestinal nerves, drug dependence or damage to the spleen and stomach yang caused by long-term use, and meets the clinical needs of "rapidly relieving symptoms and consolidating the curative effect in the long term". Detailed Implementation

[0029] The present disclosure will now be described in further detail with reference to the embodiments. It should be understood that the specific embodiments described herein are for illustrative purposes only and are not intended to limit the scope of the disclosure.

[0030] It should be noted that, unless otherwise specified, the embodiments and features described in this disclosure can be combined with each other.

[0031] Unless otherwise stated, the exemplary implementations / embodiments shown are to be understood as providing exemplary features of various details that provide ways in which the technical concepts of this disclosure can be implemented in practice. Therefore, unless otherwise stated, the features of various implementations / embodiments may be additionally combined, separated, interchanged and / or rearranged without departing from the technical concepts of this disclosure.

[0032] The terminology used herein is for the purpose of describing particular embodiments and is not intended to be limiting. As used herein, unless the context clearly indicates otherwise, the singular forms “a” and “the” are intended to include the plural forms as well. Furthermore, when the terms “comprising” and / or “including” and variations thereof are used in this specification, it indicates the presence of the stated features, integrals, steps, operations, parts, components, and / or groups thereof, but does not exclude the presence or addition of one or more other features, integrals, steps, operations, parts, components, and / or groups thereof. It should also be noted that, as used herein, the terms “substantially,” “about,” and other similar terms are used as approximate terms rather than as terms of degree, thus explaining the inherent biases in measurements, calculated values, and / or provided values ​​that would be recognized by one of ordinary skill in the art.

[0033] If the embodiments of the present invention involve descriptions such as "first" or "second", such descriptions are for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated.

[0034] Unless otherwise specified, one day in this invention is 24 hours, for example, 7 days is 168 hours, and 14 days is 336 hours.

[0035] It should be noted that this composition uses standard medicinal materials listed in the Chinese Pharmacopoeia as raw materials. The Chinese Pharmacopoeia refers to the 2025 edition of the Pharmacopoeia of the People's Republic of China. Unless otherwise specified or required, all raw materials used are commercially available raw materials that meet the standards of the Chinese Pharmacopoeia, and all methods used are conventional experimental methods in this field.

[0036] A traditional Chinese medicine composition for strengthening the spleen and moistening the intestines includes stir-fried Atractylodes macrocephala, Codonopsis pilosula, Poria cocos, Citrus reticulata peel, Cannabis sativa seed, and Prunus japonica seed; wherein stir-fried Atractylodes macrocephala is 13-18 parts, Codonopsis pilosula is 10-15 parts, Poria cocos is 8-13 parts, Citrus reticulata peel is 4-8 parts, Cannabis sativa seed is 13-18 parts, and Prunus japonica seed is 8-12 parts.

[0037] Stir-fried Atractylodes macrocephalae Rhizoma Preparata: Principal herb: Stir-fried Atractylodes macrocephalae. Core effects: Strengthens the spleen and replenishes qi, dries dampness and promotes diuresis. After processing, stir-fried Atractylodes macrocephalae has enhanced spleen-strengthening effects and reduced coldness. Targeting the core pathogenesis of spleen deficiency, it can promote the transformation and transportation of food essence, fundamentally improving the problem of insufficient intestinal lubrication and avoiding the risk of recurrence caused by simply lubricating the intestines.

[0038] Codonopsis Radix (Dang Shen) + Poria (Fu Ling), assistant herbs: Synergistic effects: Strengthening the spleen, eliminating dampness and promoting digestion. Codonopsis pilosula tonifies qi and strengthens the spleen, and when combined with stir-fried Atractylodes macrocephala, it enhances the spleen-strengthening and qi-boosting effects; Poria cocos strengthens the spleen and eliminates dampness, resolving water retention caused by spleen deficiency, preventing cloying and cloying substances from hindering stomach function, and simultaneously helping to improve intestinal motility disorders. Together with the principal herbs, these two herbs address the issue of insufficient synergy between strengthening the spleen and moistening the intestines.

[0039] Pruni Semen and Cannabis Fructus: Adjuvant herbs; Synergistic effects: Moisturizes the intestines and promotes bowel movements, relieves dryness and generates fluids. Cannabis Fructus is sweet and neutral in nature, moisturizing the intestines without being cold, making it a key herb for promoting bowel movements. Pruni Semen is sweet and bitter in nature, also neutral, moisturizing the intestines and promoting bowel movements while also reducing swelling, assisting Cannabis Fructus in enhancing its laxative effect. It can also relieve abdominal distension symptoms in patients with functional constipation. The combination of these two herbs targets intestinal dryness, quickly softening stool and promoting excretion, addressing the problem of weak or slow-acting laxative effects in existing traditional Chinese medicine preparations.

[0040] Example 1: According to the weight ratio, the ingredients are: 15 parts stir-fried Atractylodes macrocephala, 12 parts Codonopsis pilosula, 10 parts Poria cocos, 6 parts dried tangerine peel, 15 parts hemp seed, and 10 parts Prunus japonica seed.

[0041] Example 2: According to the weight ratio, the ingredients are: 18 parts stir-fried Atractylodes macrocephala, 15 parts Codonopsis pilosula, 13 parts Poria cocos, 8 parts dried tangerine peel, 18 parts hemp seed, and 12 parts Prunus japonica seed.

[0042] Example 3: According to the weight ratio, the weight is g, there are 13 parts of stir-fried Atractylodes macrocephala, 10 parts of Codonopsis pilosula, 8 parts of Poria cocos, 4 parts of tangerine peel, 13 parts of hemp seed, and 8 parts of Prunus japonica seed.

[0043] Examples 1-3 all need to be prepared into clinical formulations, which are tablets, granules, capsules, decoctions, pills, oral liquids, and syrups.

[0044] Examples 1-3 were prepared using a specific method, comprising the following steps: Step S01: Raw material pretreatment: Take the above-mentioned medicinal materials and clean them according to the pharmacopoeia standards. Remove impurities and non-medicinal parts from stir-fried Atractylodes macrocephala, Codonopsis pilosula, Poria cocos and tangerine peel. Screen the hemp seeds and Prunus japonica seeds to remove shriveled grains and mud, and rinse them quickly with water several times. Drain the water. Grind the cleaned stir-fried Atractylodes macrocephala, Codonopsis pilosula, Poria cocos and tangerine peel into coarse powder; grind the hemp seeds and Prunus japonica seeds into medium powder separately. Step S02: Using the water decoction extraction method, put the above four crude powders into the extraction tank, add 10 times the amount of purified water, and soak for 20-30 minutes; heat to 95℃-100℃ and maintain decoction for 50-60 minutes, and collect the first decoction; add 7-8 times the amount of purified water to the residue, heat to 95℃-100℃ and decoct for 40-45 minutes, and collect the second decoction; combine the two decoctions, filter with a 200-mesh sieve to remove the medicinal residue and impurities, and obtain the water extract of the spleen-strengthening components.

[0045] Step S03: Using a combination of low-temperature pressing and solvent-assisted extraction, the crushed hemp seeds and apricot kernels are put into a low-temperature press and pressed at 40℃-45℃ to collect the virgin oil. The pressed cake is then added to 5-6 times the amount of anhydrous ethanol and refluxed in a water bath at 45℃-50℃ for 5-30 minutes. The ethanol extract is then filtered and collected. The ethanol extract is then distilled under reduced pressure to recover the ethanol, yielding a concentrated oil solution. The virgin oil and the concentrated oil solution are combined to obtain an extract of the laxative components, which is stored away from light.

[0046] Step S04: Thoroughly mix the water extract of the spleen-strengthening component and the extract of the bowel-regulating component, add 0.1% chitosan solution, stir evenly and let stand for 2 hours; then use plate and frame filter press at a pressure of 0.35MPa-0.5MPa to obtain a clear mixed extract.

[0047] Step S05: The clarified mixed extract is put into a vacuum concentration tank and concentrated under vacuum conditions of 0.07-0.09 MPa and 60-65℃ to obtain a clear extract with a relative density of 1.15-1.20.

[0048] Step S06: Dry the extract, setting the inlet air temperature to 160-170℃, the outlet air temperature to 80-85℃, and the feed rate to 10-15mL / min to obtain a dried Chinese herbal extract powder. The moisture content of the Chinese herbal extract powder is controlled below 5.0%. This Chinese herbal extract powder is the spleen-strengthening and bowel-moistening Chinese herbal composition. In step S01, all medicinal materials meet the processing requirements. Among them, stir-fried Atractylodes macrocephala must be either stir-fried with soil or stir-fried with wheat bran. Hemp seeds must be dried at a low temperature of less than or equal to 60℃. Stir-fried Atractylodes macrocephala, Codonopsis pilosula, Poria cocos, and Citrus reticulata peel are pulverized into coarse powder and passed through a 20-mesh sieve. Hemp seeds and Prunus japonica seeds are separately pulverized into medium powder and passed through a 40-mesh sieve.

[0049] Regarding decoctions: Take the herbal extract powder, add an appropriate amount of purified water to dissolve it, and adjust the volume to the volume corresponding to the daily dose. The volume of the decoction should be 150-300mL. After dispensing, sterilize. The dosage for adults is 250mL-300mL, and for children it is 150mL-250mL. Regarding granules: Take the herbal extract powder, add dextrin and sucrose powder to it. The amount of dextrin is 30% of the mass of the herbal extract powder, and the amount of sucrose powder is 20% of the mass of the herbal extract powder. Prepare the granules with ethanol, granulate them through a 16-mesh sieve, dry them at 60℃, and then package them after granulation. Regarding capsules: Take the herbal extract powder and directly fill it into enteric-coated capsules. The daily dosage for adults is 0.5g per capsule, and the daily dosage for children is 0.35g per capsule.

[0050] Comparative example: The dried tangerine peel in the formulas of Experimental Examples 1-3 above was removed and replaced with a placebo that had no effect or influence. The weight of the placebo was the same as that of the dried tangerine peel in the formulas of Experimental Examples 1-3 above.

[0051] Experiment Example 1: Pharmacodynamic Experiment First, a mouse model was used to verify the therapeutic efficacy of this formula on mice with functional constipation, clarify its effect on improving defecation function, intestinal motility and intestinal mucosal secretion in mice, and provide pharmacodynamic evidence for clinical application.

[0052] Next, the experimental materials were prepared: Experimental animals: 60 SPF-grade Kunming mice, half male and half female, weighing 18-22g, purchased from an experimental animal center, animal license number: SCXK-2024-0001. Housing environment: temperature 22-25℃, relative humidity 55%-65%, 12h diurnal rhythm, free access to water and food. The experiment was started after 3 days of acclimatization. Experimental drugs: traditional Chinese medicine extract powder; positive control drug: polyethylene glycol 4000 powder, a commonly used clinical drug for functional constipation.

[0053] Next, prepare the reagents and instruments: compound diphenoxylate for modeling, ink for detecting intestinal propulsion rate, mouse MUC2 and SPELISA kits; electronic balance, high-speed refrigerated centrifuge, enzyme reader, etc.

[0054] Grouping: 60 mice were randomly divided into 6 groups of 10 each: blank control group, comparative experimental group, positive control group, low-dose group, medium-dose group, and high-dose group. The low-dose, medium-dose, and high-dose groups corresponded to the formulation dosages of Examples 1-3, respectively. The comparative experimental group used the formulation of the medium-dose group, but replaced it with a placebo that had no effect or influence. The weight of the placebo was the same as the weight of the dried tangerine peel in the formulations of Examples 1-3.

[0055] Modeling: Except for the blank control group, the other 5 groups were modeled by gavage with compound diphenoxylate once a day for 3 consecutive days. The criteria for successful modeling were: a ≥30% reduction in the number of defecation times in 24 hours compared to before modeling, and a reduction in the dryness and wetness of the stool.

[0056] After successful modeling, the drug was administered once daily by gavage for 10 consecutive days. The blank control group was administered an equal volume of 0.5% sodium carboxymethyl cellulose solution by gavage. The positive control group was administered polyethylene glycol 4000 powder at 2 g / kg body weight. The low, medium, and high dose groups were all administered Chinese herbal extract powder at 2 g / kg body weight, which was administered by gavage as a decoction. The comparative experimental group was administered Chinese herbal extract powder without tangerine peel formula at 2 g / kg body weight, which was administered by gavage as a decoction.

[0057] The study measured the time of first defecation, the number of defecations in 24 hours, their weight and water content, small intestinal propulsion rate, and the content of MUC2 and SP in colon tissue.

[0058] The data is shown in Table 1 below: Table 1 The conclusions are as follows: As shown in Table 1 above, the medium dose can significantly improve the defecation function and enhance intestinal motility in mice with functional constipation, and has the unique advantage of promoting intestinal mucus secretion, which fully demonstrates its effectiveness.

[0059] Secondly, the effect of the medium dose is comparable to that of polyethylene glycol 4000 powder, showing advantages in the functional treatment of constipation. Then, regarding the comparative experimental group, the comparative experimental group used the medium dose formula. After replacing it with a placebo that had no effect or influence, the effect dropped sharply. This illustrates that tangerine peel (Citri Reticulatae Pericarpium) can harmonize the properties of the principal, assistant, and adjuvant drugs, improve the overall compatibility of the composition, and has irreplaceable properties.

[0060] Experimental Example 2: Mouse Toxicity Experiment The study observed the toxic effects of long-term oral administration of the key components of this formulation on mice to clarify its long-term safety and provide a basis for long-term clinical use. Core verification: After long-term administration, mice showed no obvious toxic symptoms, and there were no abnormal changes in hematology, blood biochemistry, or organ tissues.

[0061] Experimental Preparation: Experimental Animals: 80 SPF-grade Kunming mice, half male and half female, weighing 18-22g, purchased from an experimental animal center, animal license number: SCXK-2024-0001; Housing Environment: Temperature 22-25℃, relative humidity 55%-65%, 12h diurnal rhythm, free access to water and food, acclimatization for 3 days before starting the experiment. Experimental Drugs: This traditional Chinese medicine composition; 0.5% sodium carboxymethyl cellulose solution; Experimental Instruments: Electronic balance, high-speed refrigerated centrifuge, fully automated blood cell analyzer, fully automated biochemical analyzer, optical microscope, pathological sectioner, etc.

[0062] Experimental Protocol: Grouping: 80 mice were randomly divided into 4 groups of 20 mice each (10 males and 10 females): blank control group, low-dose group, medium-dose group, and high-dose group. Dosage: Based on the adult clinical daily dose, the low-dose, medium-dose, and high-dose groups were administered 2 g / kg. Administration: All groups were administered the decoction by gavage once daily for 28 days. The blank control group was administered an equal volume of 0.5% sodium carboxymethyl cellulose solution by gavage.

[0063] Detection method: General toxicity observation: Observe and record the mice's mental state, diet, water intake, defecation, activity and mortality daily; weigh the mice once a week at a fixed time and calculate the weight gain rate.

[0064] Hematological parameters were measured: 28 days after administration, blood was randomly drawn from the orbital cavity of each group, and white blood cell count (WBC), red blood cell count (RBC), hemoglobin (Hb), platelet count (PLT), and lymphocyte percentage (LYM%) were measured using a fully automated blood cell analyzer.

[0065] Blood biochemical index testing: The above blood samples were centrifuged to separate serum, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr), total protein (TP), albumin (ALB), total cholesterol (TC) and triglycerides (TG) were detected using a fully automated biochemical analyzer.

[0066] Organ coefficient and pathological examination: After blood tests, mice were euthanized, and the heart, liver, spleen, lungs and kidneys were dissected. The wet weight of the organs was measured by electronic balance, and the organ coefficient was calculated (organ coefficient = organ wet weight / body weight × 100%). Each organ was fixed in 10% formaldehyde solution, routinely dehydrated, embedded, sectioned, stained with hematoxylin and eosin (HE), and the morphological changes of the tissues were observed under an optical microscope.

[0067] The data is shown in Table 2 below: Table 2 The conclusions are as follows: This formula, administered via gavage at 2g / kg for 28 days, showed no significant toxicity in mice. No abnormalities were observed in the general condition, hematological indicators, blood biochemical indicators, organ coefficients, or organ tissue morphology of the mice. This formula is highly safe for long-term use and poses no toxic risk.

[0068] The pathological results are as follows: Under an optical microscope, the morphology of the heart, liver, spleen, lungs, and kidneys of mice in each drug-treated group was normal, consistent with the blank control group: hepatocytes showed no degeneration or necrosis, glomeruli and renal tubules were intact, cardiomyocytes were arranged regularly, spleen follicles were clearly visible, lung tissue showed no inflammatory infiltration, and there were no toxicity-related pathological changes.

[0069] Experimental Example 3: Clinical Patient Experiment: Including adult group, elderly woman group and child group, the formula of Example 2 was used as the optimal formula, and the decoction prepared by the traditional Chinese medicine composition was obtained using this formula.

[0070] Specifically as follows: Volunteers were selected based on the following criteria: constipation duration ≥ 6 months, frequency of spontaneous bowel movements ≤ 2 times per week, accompanied by hard stools and difficulty in defecation; age matching the corresponding group requirements (adult group 18-60 years, elderly women group 60-80 years, children group 4-12 years); no use of other constipation medications in the past month; and signing of informed consent and cooperation in completing the experiment.

[0071] A randomized controlled trial design was adopted, and a total of 200 patients were included, who were divided into 3 experimental groups and 1 positive control group according to the population.

[0072] The study included 50 participants in each of the following groups: an adult group, an elderly women group, a children group, and a positive control group. The adult and elderly women groups received an oral decoction, one dose daily, divided into two doses taken with warm water, for four consecutive weeks. The children group also received an oral decoction, divided into two doses taken with warm water, for four consecutive weeks. The positive control group received oral polyethylene glycol 4000 powder for four consecutive weeks. During the treatment period, participants were prohibited from consuming any medications or foods that might affect bowel movements.

[0073] Determine the efficacy criteria: Marked effect: ≥5 spontaneous bowel movements per week, stool characteristics returned to normal (3-4 points), and the difficulty in defecation score dropped to 0 points; Effective: 3-4 spontaneous bowel movements per week, stool characteristics score improved by 2 points or more, and the difficulty in defecation score dropped to 1 point; Ineffective: The above effective criteria were not met. The total effective rate = (number of markedly effective cases + number of effective cases) / total number of cases × 100%.

[0074] The data is shown in Table 3 below: Table 3 The conclusions are as follows: This traditional Chinese medicine composition has significant therapeutic effects on functional constipation in three population groups: adults, elderly women, and children. It can significantly increase the frequency of bowel movements, improve the condition of dry stools, and alleviate defecation difficulties. The efficacy in the adult and elderly women groups is superior to that of the commonly used polyethylene glycol 4000 powder, while the efficacy in the children group is comparable to the positive control. Furthermore, no serious adverse reactions were observed in any of the three population groups after treatment, indicating high safety. This composition can be used as a clinical treatment option for functional constipation in different population groups.

[0075] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any indirect modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A traditional Chinese medicine composition for invigorating the spleen and moistening the intestines, characterized in that, According to the weight ratio, it comprises fried atractylodes, codonopsis, poria, dried tangerine or orange peel, hemp seeds, and sloe fruit; Among them, fried atractylodes 13-18 parts, codonopsis 10-15 parts, poria 8-13 parts, dried tangerine or orange peel 4-8 parts, hemp seeds 13-18 parts, and sloe fruit 8-12 parts.

2. The traditional Chinese medicine composition for invigorating the spleen and moistening the intestines according to claim 1, characterized in that, According to the weight ratio, fried atractylodes 15 parts, codonopsis 12 parts, poria 10 parts, dried tangerine or orange peel 6 parts, hemp seeds 15 parts, and sloe fruit 10 parts.

3. The traditional Chinese medicine composition for invigorating the spleen and moistening the intestines according to claim 1, characterized in that, According to the weight ratio, fried atractylodes 18 parts, codonopsis 15 parts, poria 13 parts, dried tangerine or orange peel 8 parts, hemp seeds 18 parts, and sloe fruit 12 parts.

4. The traditional Chinese medicine composition for invigorating the spleen and moistening the intestines according to claim 1, characterized in that, According to the weight ratio, fried atractylodes 13 parts, codonopsis 10 parts, poria 8 parts, dried tangerine or orange peel 4 parts, hemp seeds 13 parts, and sloe fruit 8 parts.

5. A clinical preparation comprising a spleen-tonifying and intestine-moistening traditional Chinese medicine composition according to any one of claims 2-4.

6. The clinical preparation according to claim 5, characterized in that, The clinical preparation is a tablet, granules, capsules, decoction, pills, oral liquid, and syrup.

7. A method for preparing a traditional Chinese medicine composition for invigorating the spleen and moistening the intestines based on the composition of claim 5, characterized in that, The method comprises the following steps: Step S01: raw material pretreatment: take the above-mentioned medicinal materials, and clean and process according to the standard of the pharmacopoeia, remove impurities and non-medicinal parts of fried atractylodes, codonopsis, poria, and dried tangerine or orange peel, and screen and remove shriveled grains and silt from hemp seeds and sloe fruit, and rinse with clean water several times, drain the water, and grind fried atractylodes, codonopsis, poria, and dried tangerine or orange peel after cleaning into coarse powder; grind hemp seeds and sloe fruit separately into medium powder; Step S02: adopt water decoction extraction method, put the above-mentioned four kinds of coarse powder into an extraction tank, add 10 times the amount of purified water, soak for 20-30 min; heat to 95-100 ℃, keep decocting for 50-60 min, collect the first decoction; add 7-8 times the amount of purified water to the residue, heat to 95-100 ℃, decoct for 40-45 min, collect the second decoction; combine the two decoctions, filter with a 200-mesh screen to remove drug residue impurities, and obtain spleen-tonifying water extract; Step S03: adopt low-temperature pressing and solvent-assisted extraction combined method, put the ground hemp seeds and sloe fruit into a low-temperature press, press at 40-45 ℃, collect the first pressed oil; add 5-6 times the amount of anhydrous ethanol to the pressed cake, reflux extract at 45-50 ℃ water bath for 5-30 min, filter to collect the alcohol extract; distill the alcohol extract under reduced pressure to recover ethanol, and obtain oil concentrate; combine the first pressed oil and the oil concentrate, and obtain intestine-moistening ingredient extract, which is stored in the dark; Step S04: mix the spleen-tonifying water extract and the intestine-moistening ingredient extract, add 0.1% chitosan solution, stir uniformly, and stand for 2 h; then adopt plate and frame filter pressing, and the pressure is 0.35-0.5 MPa, to obtain clear mixed extract; Step S05: put the clear mixed extract into a vacuum concentration tank, concentrate under reduced pressure at a vacuum degree of 0.07-0.09 MPa and a temperature of 60-65 ℃, to obtain clear paste with a relative density of 1.15-1.

20. Step S06: dry the paste, set the inlet temperature to 160-170℃, set the outlet temperature to 80-85℃ and the feeding speed to 10-15mL / min to obtain the dried traditional Chinese medicine extract powder, the moisture content of the traditional Chinese medicine extract powder is controlled below 5.0%, and the traditional Chinese medicine extract powder is the spleen and intestine moistening traditional Chinese medicine composition.

8. The method for preparing a spleen-strengthening and bowel-moistening traditional Chinese medicine composition according to claim 7, characterized in that, In step S01, all medicinal materials meet the processing requirements, wherein the fried atractylodes rhizome needs to use any one of the soil-fried or bran-fried products, and the hemp seeds need to be dried at a low temperature of less than or equal to 60℃, the fried atractylodes rhizome, codonopsis pilosula, poria cocos and dried tangerine or orange peel are crushed into coarse powder and passed through a 20-mesh sieve, and the hemp seeds and sloe seeds are separately crushed into medium powder and passed through a 40-mesh sieve.

9. The method for preparing a spleen-strengthening and bowel-moistening traditional Chinese medicine composition according to claim 8, characterized in that, For the decoction: take the traditional Chinese medicine extract powder, add an appropriate amount of purified water to dissolve, adjust the volume to the corresponding medicinal liquid volume of the daily dose, the medicinal liquid volume is 150-300mL, and sterilize after dispensing; wherein, the adult is 250mL-300mL, and the child is 150mL-250mL; For the granules: take the traditional Chinese medicine extract powder, add dextrin and sucrose powder to the traditional Chinese medicine extract powder, the amount of dextrin is 30% of the mass of the traditional Chinese medicine extract powder, and the amount of sucrose powder is 20% of the mass of the traditional Chinese medicine extract powder, use ethanol to prepare soft material, pass through a 16-mesh sieve to granulate, dry at 60℃, and pack after sizing; For the capsules: take the traditional Chinese medicine extract powder, directly fill the traditional Chinese medicine extract powder into enteric-coated capsules, the adult daily dosage is 0.5g per capsule, and the child daily dosage is 0.35g per capsule.

10. The spleen and intestine moistening traditional Chinese medicine composition obtained by the preparation method of claim 9 is applied to functional constipation.

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