A traditional Chinese medicine composition, pharmaceutical preparation and preparation method for improving functional constipation in children.

Abstract

This disclosure relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition, pharmaceutical preparation, and preparation method for improving functional constipation in children. By weight, the traditional Chinese medicine composition comprises: 5-15 parts of stir-fried radish seeds, 7-17 parts of stir-fried malt, 5-15 parts of hemp seeds, 4-13 parts of Polygonatum odoratum, 2-8 parts of dried tangerine peel, 2-8 parts of citronella, 3-10 parts of stir-fried cassia seeds, and 1-6 parts of raw licorice root. The traditional Chinese medicine composition described in this disclosure is mild in nature, has both medicinal and edible properties, and a pleasant taste. It can treat functional constipation in children with spleen deficiency and qi stagnation, and intestinal dryness and fluid depletion, addressing both the symptoms and the root cause, and has significant clinical value.

Description

Technical Field

[0001] This disclosure relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition, pharmaceutical preparation and preparation method for improving functional constipation in children. Background Technology

[0002] Functional constipation in children is a common digestive system disorder, accounting for over 90% of childhood constipation, especially prevalent in children aged 1-14. Long-term constipation can negatively impact children's growth and development, making early intervention crucial for their healthy development. Clinically, the main symptoms are dry, hard stools, difficulty defecating, and prolonged intervals between bowel movements, often accompanied by abdominal distension, poor appetite, dry mouth, and fatigue. Traditional Chinese medicine believes that children's internal organs are delicate and their physical constitution is not yet fully developed, with a "frequently deficient spleen." Improper feeding or emotional imbalances can easily lead to impaired spleen and stomach function, qi stagnation, and fluid deficiency, resulting in dysfunction of the large intestine and ultimately constipation. The core pathogenesis is often spleen deficiency and qi stagnation, along with intestinal dryness and fluid depletion. Treatment should focus on strengthening the spleen, regulating qi, and moistening the intestines.

[0003] Currently, clinical treatment options for functional constipation in children are mainly divided into two categories: Western medicine and Traditional Chinese Medicine (TCM). Western medicine treatment focuses on symptomatic relief. In the acute phase, enemas, rectal suppositories, and oral medications are often used to relieve defecation difficulties and clear fecal blockages. Commonly used medications include warm saline solution, glycerin suppositories, and osmotic laxatives. Maintenance treatment may be supplemented with prokinetic drugs and probiotics. While Western medicine treatments are relatively quick to take effect, they are mostly symptomatic, with limited long-term efficacy and a high relapse rate after discontinuation. Long-term use of stimulant laxatives such as rhubarb and senna can lead to abdominal pain, diarrhea, electrolyte imbalance, and drug dependence, making them unsuitable for long-term, repeated use in children. Furthermore, Western medicine lacks specific drugs tailored to the physiological characteristics of children's digestive system and standardized dosage guidelines, resulting in poor medication adherence in children.

[0004] Traditional Chinese medicine (TCM) treatment of functional constipation in children has the advantages of syndrome differentiation and holistic regulation. Many TCM formulas and prepared medicines are currently used clinically, but several shortcomings remain: some formulas have simple combinations or focus too much on relieving constipation while neglecting to strengthen the spleen and regulate qi, leading to easy relapse after constipation is relieved; some formulas use strong laxatives such as rhubarb, senna leaves, and aloe vera, which, while providing rapid relief, can easily damage the child's spleen and stomach, causing adverse reactions such as abdominal pain and diarrhea, making them unsuitable for long-term use; some formula ingredients pose potential safety risks, making it difficult to meet the long-term conditioning needs of children; and some formulas have poor taste, resulting in low compliance among children.

[0005] Therefore, developing a traditional Chinese medicine composition that is mild in nature, highly safe, and has a pleasant taste is of great clinical value. Summary of the Invention

[0006] To address the aforementioned technical problems, this disclosure provides a traditional Chinese medicine composition, pharmaceutical preparation, and preparation method for improving functional constipation in children. The traditional Chinese medicine composition is mild in nature, has the same origin as food and medicine, and has a pleasant taste. It can treat functional constipation in children with spleen deficiency and qi stagnation, and dryness of intestines and depletion of body fluids, thus having important clinical value.

[0007] In a first aspect, this disclosure provides a traditional Chinese medicine composition for improving functional constipation in children, wherein, by weight, the traditional Chinese medicine composition comprises: 5-15 parts of stir-fried radish seeds, 7-17 parts of stir-fried malt, 5-15 parts of hemp seeds, 4-13 parts of Solomon's seal rhizome, 2-8 parts of dried tangerine peel, 2-8 parts of Buddha's hand citron, 3-10 parts of stir-fried cassia seeds, and 1-6 parts of raw licorice root.

[0008] Specifically, the weight of stir-fried radish seeds can be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 parts, but is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0009] The weight portions of roasted malt can be 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17 parts, but are not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0010] The weight of hemp seeds can be selected as 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 parts, but is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0011] The weight of Solomon's Seal can be selected as 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 parts, but is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0012] The weight of dried tangerine peel can be 2, 3, 4, 5, 6, 7 or 8 parts, but is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0013] The weight of Buddha's Hand can be selected as 2, 3, 4, 5, 6, 7 or 8 parts, but is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0014] The weight of roasted cassia seeds can be 3, 4, 5, 6, 7, 8, 9, or 10 parts, but is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0015] The weight of raw licorice can be 1 part, 2 parts, 3 parts, 4 parts, 5 parts or 6 parts, but is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0016] This invention uses stir-fried radish seeds as the principal ingredient to relieve indigestion and bloating, regulate qi and promote bowel movement, thereby clearing the bowels and removing stagnation. The formula uses roasted malt, hemp seeds, and Solomon's seal as auxiliary ingredients; among them, roasted malt invigorates the spleen and stomach, aids digestion; hemp seeds are sweet and moistening, lubricate the intestines and relieve constipation; Solomon's seal nourishes yin, generates fluids, and moistens the intestines. The formula uses dried tangerine peel, Buddha's hand citron, and stir-fried cassia seed as adjuvants; among them, dried tangerine peel and Buddha's hand citron regulate qi and stomach, relieve bloating and fullness; stir-fried cassia seed moistens the intestines and promotes bowel movement; Raw licorice is used as the guiding herb to invigorate qi, replenish the middle jiao, and harmonize the effects of other herbs.

[0017] The traditional Chinese medicine composition disclosed herein is nourishing without causing stagnation, and moisturizing without being harsh, thus achieving the effects of strengthening the spleen, regulating qi, and moistening the intestines to relieve constipation.

[0018] In this disclosure, adding too much or too little of any medicinal material will affect the efficacy.

[0019] The following are preferred technical solutions of this disclosure, but are not intended to limit the technical solutions provided by this disclosure. The technical objectives and beneficial effects of this disclosure can be better achieved through the following technical solutions.

[0020] As a preferred technical solution of this disclosure, the traditional Chinese medicine composition comprises, by weight: 8-10 parts of stir-fried radish seeds, 10-12 parts of stir-fried malt, 8-12 parts of hemp seeds, 6-10 parts of Solomon's seal rhizome, 3-5 parts of dried tangerine peel, 3-5 parts of Buddha's hand, 4-7 parts of stir-fried cassia seeds, and 2-4 parts of raw licorice root.

[0021] As a preferred technical solution of this disclosure, the traditional Chinese medicine composition comprises, by weight: 10 parts stir-fried radish seeds, 12 parts stir-fried malt, 10 parts hemp seeds, 8 parts Solomon's seal rhizome, 4 parts dried tangerine peel, 4 parts Buddha's hand, 6 parts stir-fried cassia seeds, and 3 parts raw licorice root.

[0022] Secondly, this disclosure provides a pharmaceutical preparation for improving functional constipation in children, the pharmaceutical preparation containing an extract of the traditional Chinese medicine composition as described in the first aspect; The dosage form of the pharmaceutical preparation includes any one of granules, powders, capsules, tablets, mixtures, or oral liquids.

[0023] Specifically, the pharmaceutical preparation uses an extract of a traditional Chinese medicine composition as its active ingredient.

[0024] Thirdly, this disclosure provides a method for preparing a pharmaceutical preparation for improving functional constipation in children as described in the second aspect, the method comprising the following steps: (1) The traditional Chinese medicine composition is mixed with water and decocted to obtain an aqueous extract; (2) The aqueous extract is prepared into the dosage form of the drug preparation.

[0025] As a preferred technical solution of this disclosure, the steps for preparing the aqueous extract include: decocting the traditional Chinese medicine composition with water at least twice, each time for 1 to 3 hours, filtering after each decoction, and combining the filtrates to obtain the aqueous extract.

[0026] As a preferred technical solution of this disclosure, in the step of preparing the aqueous extract, the total mass of water is 14 to 20 times the mass of the traditional Chinese medicine composition, such as 14 times, 15 times, 16 times, 17 times, 18 times, 19 times or 20 times, but is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0027] As a preferred technical solution of this disclosure, in step (1) of preparing the aqueous extract, the decoction is performed twice. In the first decoction, the mass of water is 8 to 10 times the mass of the traditional Chinese medicine composition, for example, 8, 9, or 10 times; the decoction time is 1 to 3 hours, for example, 1 hour, 1.2 hours, 1.4 hours, 2 hours, 2.5 hours, or 3 hours. In the second decoction, the mass of water is 6 to 8 times the mass of the traditional Chinese medicine composition, for example, 6, 6.5, 7, 7.5, or 8 times; the decoction time is 1 to 3 hours, for example, 1 hour, 1.5 hours, 2 hours, or 3 hours, but it is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0028] As a preferred technical solution of this disclosure, before decocting in step (1), the water is soaked for 20 to 40 minutes, such as 20 minutes, 30 minutes or 40 minutes, but not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0029] Soaking allows the raw materials of traditional Chinese medicine to be fully moistened, which is conducive to the dissolution of active ingredients.

[0030] As a preferred technical solution of this disclosure, step (1) involves stirring during the frying process; preferably, stirring is performed once every 10 to 20 minutes.

[0031] For example, this disclosure provides a method for preparing granules to improve functional constipation in children, comprising: S1. The aqueous extract obtained in step (1) is concentrated under reduced pressure to obtain a clear extract; S2. Dry the obtained extract to obtain a powder of traditional Chinese medicine extract; S3. Mix the obtained Chinese herbal extract powder, excipients and humectants to prepare wet granules; the obtained wet granules are dried to obtain granules.

[0032] As a preferred technical solution of this disclosure, in the step of preparing the extract, the vacuum degree of the reduced pressure concentration is 0.06~0.08MPa, for example 0.06MPa, 0.07MPa or 0.08MPa; the temperature is 55~65℃, for example 55℃, 58℃, 60℃ or 65℃, but is not limited to the listed values, and other unlisted values ​​within the above range are also applicable.

[0033] As a preferred technical solution of this disclosure, the relative density of the ointment is 1.10~1.15 (measured at 60℃), such as 1.10, 1.11, 1.12, 1.13, 1.14 or 1.15, but is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0034] As a preferred technical solution of this disclosure, in step S2, the drying includes spray drying, with an inlet air temperature of 155~165℃, such as 155℃, 160℃ or 165℃; an outlet air temperature of 75~85℃, such as 75℃, 80℃ or 85℃; an atomization pressure of 0.2~0.3MPa, such as 0.2MPa, 0.25MPa or 0.3MPa; and a feed rate of 20~30ml / min, such as 20ml / min, 25ml / min or 30ml / min, but not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0035] As a preferred technical solution of this disclosure, the moisture content of the traditional Chinese medicine extract powder is ≤6wt%.

[0036] As a preferred technical solution of this disclosure, the excipient includes xylitol.

[0037] As a preferred technical solution of this disclosure, the mass ratio of the Chinese herbal extract powder to the excipient is 1:(1.5~2), such as 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9 or 1:2, but is not limited to the listed values. Other unlisted values ​​within the above range are also applicable.

[0038] As a preferred technical solution of this disclosure, the wetting agent includes purified water.

[0039] As a preferred technical solution of this disclosure, the steps for preparing wet granules include: mixing the traditional Chinese medicine extract powder with an excipient to obtain a uniform powder; spraying a wetting agent onto the uniform powder in a "small amount, multiple times" manner, while spraying and stirring rapidly, with the stirring speed controlled at 200~300 r / min to avoid local powder over-wetting and sticking; stirring to form a soft material, with the standard being that it "can be formed into a ball when squeezed in the hand, and can be easily dispersed when released," and there is no obvious stickiness when lightly rubbed between the fingertips, and no dry powder falling off; if sticking and clumping occur, a small amount of excipient can be added to adjust the viscosity; if the soft material is too dry and difficult to form, a small amount of purified water can be added until the forming requirements are met, and wet granules are obtained.

[0040] As a preferred technical solution of this disclosure, the drying temperature in step S3 is 55~65℃, such as 55℃, 60℃ or 65℃, but is not limited to the listed values. Other unlisted values ​​within the above range are also applicable, and the drying is carried out until the moisture content is ≤6wt%.

[0041] The technical solution provided in this disclosure has the following advantages compared with the prior art: (1) The Chinese medicine composition disclosed herein combines the three methods of strengthening the spleen, regulating qi, and moistening the intestines. It is prepared by mixing fried radish seeds, fried malt, hemp seeds, Solomon's seal, tangerine peel, Buddha's hand, fried cassia seeds and raw licorice in a specific ratio. It targets the core pathogenesis of spleen deficiency and qi stagnation and dryness of intestines and fluid deficiency in children, and takes into account both the root cause and the symptoms. It has important clinical value. (2) The traditional Chinese medicine composition described in this disclosure does not use strong purgative ingredients such as rhubarb, senna leaves, and aloe vera, and has no side effects such as abdominal pain, diarrhea, or dependence. It is mild and safe and suitable for long-term conditioning in children. (3) The raw materials of the traditional Chinese medicine composition described in this disclosure are all national food and medicine homologous items. They are mild in nature, safe and non-toxic, and have a pleasant taste. They are especially suitable for children aged 1 to 14 years. (4) The traditional Chinese medicine composition described in this disclosure can improve intestinal function while improving overall symptoms such as abdominal distension, poor appetite, irritability, and dry mouth. Detailed Implementation

[0042] To better understand the above-mentioned objectives, features, and advantages of this disclosure, the solutions disclosed herein will be further described below. It should be noted that, unless otherwise specified, the embodiments and features described herein can be combined with each other.

[0043] Numerous specific details are set forth in the following description in order to provide a full understanding of this disclosure, but this disclosure may also be implemented in other ways different from those described herein; obviously, the embodiments in the specification are only some, and not all, of the embodiments of this disclosure.

[0044] Example 1 This embodiment provides a traditional Chinese medicine composition for improving functional constipation in children and a method for preparing its granules. The traditional Chinese medicine composition, by weight, comprises: 10 parts stir-fried radish seeds, 12 parts stir-fried malt, 10 parts hemp seeds, 8 parts Solomon's seal rhizome, 4 parts dried tangerine peel, 4 parts Buddha's hand, 6 parts stir-fried cassia seeds, and 3 parts raw licorice root.

[0045] The preparation method of its granules includes the following steps: (1) Soak the stir-fried radish seeds, stir-fried malt, hemp seeds, Solomon's seal, dried tangerine peel, Buddha's hand, stir-fried cassia seeds and raw licorice in water for 30 minutes, then heat to boiling and keep for 1.5 hours, stirring once every 15 minutes; then separate the solid and liquid to obtain the first aqueous extract and the mixed solid. The weight of water added is 9 times the total weight of the traditional Chinese medicine composition; (2) The resulting mixed solid was added to water again, heated to boiling, kept for 1 hour, and stirred every 15 minutes; then the solid and liquid were separated to obtain the second water extract; The weight of water added is 7 times the total weight of the traditional Chinese medicine composition; (3) The first aqueous extract and the second aqueous extract were mixed and then concentrated under vacuum to a clear extract with a relative density of 1.12 (measured at 60℃); The vacuum concentration process involves a vacuum level of 0.07 MPa and a temperature of 60°C.

[0046] (4) The obtained extract was spray-dried and sieved (100 mesh) in sequence to obtain a Chinese herbal extract powder with a moisture content of ≤6wt%; The spray drying process includes an inlet air temperature of 160℃, an outlet air temperature of 80℃, an atomization pressure of 0.25MPa, and a feed rate of 25 mL / min. (5) Mix the obtained Chinese herbal extract powder with xylitol (sieved through 100 mesh) at a mass ratio of 1:1.5, then add purified water in multiple batches while stirring, to make a soft material that can be formed into a ball by hand and easily dispersed by touch, and then make wet granules using a 16-mesh sieve. (6) Dry the obtained wet granules at 60°C until the moisture content is ≤6wt%; (7) The granules dried in step (6) are sieved through a sieve (14 mesh) to obtain granules.

[0047] Example 2 This embodiment provides a traditional Chinese medicine composition for improving functional constipation in children and a method for preparing its granules. The traditional Chinese medicine composition, by weight, comprises: Five parts of stir-fried radish seeds, seven parts of stir-fried malt, five parts of hemp seeds, four parts of Solomon's seal rhizome, two parts of dried tangerine peel, two parts of Buddha's hand citron, three parts of stir-fried cassia seeds, and one part of raw licorice root.

[0048] The preparation method of its granules includes the following steps: (1) Soak the stir-fried radish seeds, stir-fried malt, hemp seeds, Solomon's seal, dried tangerine peel, Buddha's hand, stir-fried cassia seeds and raw licorice in water for 30 minutes, then heat to boiling and keep for 2 hours, stirring once every 10 minutes; then separate the solid and liquid to obtain the first aqueous extract and the mixed solid. The weight of water added is 10 times the total weight of the traditional Chinese medicine composition; (2) The resulting mixed solid was added to water again, heated to boiling, and kept for 1.5 hours with stirring every 15 minutes; then the solid and liquid were separated to obtain the second water extract. The weight of water added is 6 times the total weight of the traditional Chinese medicine composition; (3) The first aqueous extract and the second aqueous extract were mixed and then concentrated under vacuum to a clear extract with a relative density of 1.15 (measured at 60℃); The vacuum concentration process involves a vacuum level of 0.06 MPa and a temperature of 60°C.

[0049] (4) The obtained extract was spray-dried and sieved (100 mesh) in sequence to obtain a Chinese herbal extract powder with a moisture content of ≤6wt%; The spray drying process includes an inlet air temperature of 155℃, an outlet air temperature of 85℃, an atomization pressure of 0.3MPa, and a feed rate of 20 mL / min. (5) Mix the obtained Chinese herbal extract powder with xylitol (sieved through 100 mesh) at a mass ratio of 1:2, then add purified water in multiple batches while stirring, to make a soft material that can be formed into a ball by hand and easily dispersed by touch, and then make wet granules using a 16-mesh sieve. (6) Dry the obtained wet granules at 60°C until the moisture content is ≤6wt%; (7) The granules dried in step (6) are sieved through a sieve (14 mesh) to obtain granules.

[0050] Example 3 This embodiment provides a traditional Chinese medicine composition for improving functional constipation in children and a method for preparing its granules. The traditional Chinese medicine composition, by weight, comprises: 15 parts of stir-fried radish seeds, 17 parts of stir-fried malt, 15 parts of hemp seeds, 13 parts of Solomon's seal rhizome, 8 parts of dried tangerine peel, 8 parts of Buddha's hand, 10 parts of stir-fried cassia seeds, and 6 parts of raw licorice root.

[0051] The preparation method of its granules includes the following steps: (1) Soak the stir-fried radish seeds, stir-fried malt, hemp seeds, Solomon's seal, dried tangerine peel, Buddha's hand, stir-fried cassia seeds and raw licorice in water for 30 minutes, then heat to boiling and keep for 1.5 hours, stirring once every 10 minutes; then separate the solid and liquid to obtain the first aqueous extract and the mixed solid. Among them, the weight of the added water is 10 times the total weight of the traditional Chinese medicine composition; (2) The obtained mixed solid is added with water again, heated to boiling, maintained for 1.5 h, and stirred every 15 min; then solid-liquid separation is carried out to obtain the second water extract; Among them, the weight of the added water is 8 times the total weight of the traditional Chinese medicine composition; (3) The first water extract and the second water extract are mixed, and then concentrated under reduced pressure in vacuo to a clear paste with a relative density of 1.13 (measured at 60 °C); Among them, the vacuum degree of the vacuum concentration under reduced pressure is 0.06 MPa, and the temperature is 60 °C.

[0052] (4) The obtained clear paste is successively subjected to spray drying and sieving (100 mesh) to prepare a traditional Chinese medicine extract powder with a water content ≤ 6 wt%; Among them, the inlet air temperature of the spray drying is 160 °C, the outlet air temperature is 75 °C, the atomization pressure is 0.2 MPa, and the feeding speed is 30 mL / min; (5) The obtained traditional Chinese medicine extract powder and xylitol (sieved 100 mesh) are mixed according to a mass ratio of ①: 1.8, and then purified water is added in several times while stirring to make a soft material that forms a ball when held in the hand and disperses when lightly touched, and wet granules are prepared by using a 16-mesh sieve; (6) The obtained wet granules are dried at 60 °C until the water content ≤ 6 wt%; (7) The granules dried in step (6) are sieved (14 mesh) to obtain the granule agent.

[0053] Test example Animal experiment: Take the granule agent obtained in Example 1 as an example 1. Materials 1.1 Test animals: SPF-grade juvenile SD rats, 21 - 28 days old, 60 in number, half male and half female, with a body weight of 40 - 60 g, provided by Beijing Vital River Laboratory Animal Technology Co., Ltd., and the animal production license number: SCXK(Beijing)2021 - 0006.

[0054] Feeding environmental conditions: Adaptively fed for 3 days before the experiment, environmental temperature (23 ± 2) °C, humidity 50% - 60%, circadian rhythm 12 h / 12 h, free access to food and water.

[0055] 1.2 Test drugs and reagents: Test drug: The granule agent obtained in Example 1, and every 3 g of the granule agent is equivalent to 5.7 g of the crude drug.

[0056] Lactulose oral solution, production unit: Sichuan Defeng Pharmaceutical Co., Ltd.; specification: 15 ml / bag; approval number:国药准字H20223553.

[0057] Loperamide Hydrochloride Capsules, manufactured by Sinopharm Rong Sheng Pharmaceutical Co., Ltd.; National Drug Approval Number H19983095; Specification: 2mg.

[0058] Ink suspension: Boil 100g of gum arabic in 800mL of water until transparent, then add 50g of activated carbon and boil three times. After cooling, add water to make up to 1000mL and store at 4℃.

[0059] 1.3 Test Instruments Fully automated microplate reader: Manufacturer: BioTek, Model: Epoch.

[0060] High-speed refrigerated centrifuge: Manufacturer: Thermo Fisher Scientific, Model: MultifugeX1R.

[0061] Electric heating constant temperature drying oven: Manufacturer: Shanghai Yiheng Scientific Instruments Co., Ltd., Model: DHG-9240A.

[0062] 2. Methods 2.1 Establishment of a functional constipation model Model group: Loperamide hydrochloride suspension was administered by gavage for 7 consecutive days at a dose of 10 mg / kg based on loperamide hydrochloride. -1 ·d -1 A functional constipation model of spleen deficiency and qi stagnation, and intestinal dryness and fluid deficiency in juvenile rats was established, and the procedure was performed at a fixed time every day.

[0063] Normal control group: Rats were administered an equal volume of physiological saline and loperamide hydrochloride suspension by gavage at a fixed time each day for 7 consecutive days. The feeding environment, diet, and water conditions were the same as those of the model group. Various indicators were observed simultaneously as a blank reference.

[0064] During the modeling period, the rats' defecation status was observed, and quantitative evaluation criteria were set: the number of defecations was reduced by ≥50% compared with the normal control group, the feces were dry and ball-shaped, defecation was difficult, the food intake was reduced by ≥20% compared with the normal control group, the activity level was significantly reduced, and the fecal water content was reduced by ≥30% compared with the normal control group. The modeling was considered successful if the above conditions were met.

[0065] 2.2 Grouping and administration of experimental animals Rats were randomly divided into a normal control group, a model control group, a low-dose compound group, a medium-dose compound group, a high-dose compound group, and a positive control group (i.e., lactulose group), with 10 rats in each group, 5 males and 5 females.

[0066] Among them, the model control group, compound low-dose group, compound medium-dose group, compound high-dose group and positive control group were modeled according to the method described in 2.1. 30 minutes after successful modeling, each group was administered the drug according to the scheme in Table 1 for 7 consecutive days.

[0067] After the modeling was completed, the normal control group and each group were administered drugs synchronously according to the schedule in Table 1, and the drugs were administered continuously for 7 days.

[0068] Thirty minutes after the last administration, each rat in all the above groups was given 10 mL / kg of ink suspension orally; then each rat was housed in a single cage, with food restricted but water allowed.

[0069] Table 1

[0070] 2.3 Observation Indicators (1) Time of first black stool excretion; (2) Number of bowel movements within 6 hours after gavage with ink suspension; (3) Fecal moisture content: The number of fecal particles excreted within 6 hours after gavage with ink suspension was recorded and weighed (i.e., wet weight); then dried in an electric constant temperature drying oven at 60°C to constant weight, and the fecal weight at this time was recorded (i.e., dry weight). Fecal moisture content (%) = [(wet weight)] dry weight) / wet weight] ×100%; (4) Small intestinal propulsion rate: Immediately after 25 minutes of ink suspension injection, the patient was euthanized by cervical dislocation. The small intestine was dissected and completely dissected. The total length of the small intestine from the pylorus to the ileocecal junction and the distance of injection from the pylorus to the leading edge of the ink suspension were measured. Small intestine propulsion rate (%) = (Ink propulsion distance / Total length of small intestine) × 100%; (5) Acetylcholinesterase (AChE) activity and nitric oxide (NO) content in colon tissue: After recording the rats' defecation indicators on the last day, they were fasted for 12 hours but allowed free access to water. Rats in each group were euthanized by cervical dislocation, and colonic tissue was separated. Surrounding adipose tissue was removed, and a 10% (w / w) tissue homogenate was prepared by adding 9 mL of physiological saline per gram of tissue. The homogenate was then centrifuged at 3000 rpm at low temperature (4℃) for 10 min, and the supernatant was separated and stored at -70℃. The obtained supernatant was used to determine the activity of acetylcholinesterase (AChE) and the content of nitric oxide (NO) in the colonic tissue.

[0071] Acetylcholinesterase (AChE) activity was measured using an AChE detection kit (manufacturer: Yisheng Biotechnology (Shanghai) Co., Ltd., catalog number: 60422ES50), and the specific operation was strictly performed in accordance with the kit instructions.

[0072] Nitric oxide (NO) content was determined using a nitric oxide detection kit (manufacturer: Beijing Pulilai Gene Technology Co., Ltd., catalog number: E1030). The specific operation was strictly performed in accordance with the kit instructions.

[0073] 2.4 Results Analysis and Processing All data comparisons between groups were performed using one-way ANOVA, and pairwise comparisons between groups were performed using the Dunnett method. P <0.05 is statistically significant. P <0.01 is statistically significant.

[0074] 3. Experimental Results (a) Observation of defecation indicators The improvement rate of each defecation index in each group of rats was calculated based on the time of first black stool excretion, the number of defecations within 6 hours, and the fecal water content.

[0075] ×100%.

[0076] The results are shown in Table 2.

[0077] Table 2

[0078] Continued from Table 2

[0079] Note: Compared with the normal control group aa P <0.01; compared with the model group <0.05, <0.01; compared with the lactulose group # P <0.05.

[0080] Table 2 shows that different doses of the traditional Chinese medicine composition described in this disclosure all improved defecation indicators in constipated rats. The low-dose compound group improved defecation-related indicators in rats, and the difference was statistically significant (compared to the model control group). P <0.05); The medium and high doses of the compound preparation significantly shortened the time to first black stool excretion, increased the number of defecations within 6 hours, and increased fecal water content (compared to the model control group). P <0.01), and the improvement effect was better than that of the lactulose group (compared to the lactulose group, P<0.05). The mean improvement rates of each defecation indicator in the low-dose, medium-dose, and high-dose compound groups were 36.90%, 85.02%, and 88.46%, respectively.

[0081] The average improvement rate is calculated as follows: (improvement rate of time to first black stool + improvement rate of number of bowel movements within 6 hours + improvement rate of fecal moisture content) / 3.

[0082] (II) Small intestinal propulsion rate and biochemical indicators The results of the determination of small intestinal propulsion rate, acetylcholinesterase (AChE) activity and nitric oxide (NO) content are shown in Table 3.

[0083] Among them, AChE activity (U·mg) -1 ): Number of acetylcholinesterase activity units per milligram of colon tissue protein; NO content (μmol·g) -1 ): The content of nitric oxide per gram of colon tissue (in micromoles).

[0084] Table 3

[0085] Note: Compared with the normal control group aa P <0.01; compared with the model group <0.05, <0.01; compared with the lactulose group # P <0.05 Compared with the model control group, different doses of the traditional Chinese medicine composition described in this disclosure all improved intestinal motility and biochemical indicators in constipated rats: the low-dose compound group showed a significant increase in all indicators ( P <0.05); The high-dose and medium-dose compound groups significantly increased small intestinal propulsion rate, AChE activity and NO content in colonic tissue (compared with the model group, P <0.01), and the improvement effect was better than that of the lactulose group (compared with the lactulose group, P <0.05).

[0086] It should be noted that increased acetylcholinesterase activity helps improve gastrointestinal motility and promotes intestinal peristalsis; nitric oxide can relax intestinal smooth muscle and relieve intestinal spasms, indirectly reducing excessive reabsorption of water in feces, thereby softening the stool. This addresses the root cause of constipation in children caused by spleen deficiency and qi stagnation, and intestinal dryness and fluid depletion, achieving the dual effects of relieving constipation and strengthening the spleen and regulating qi.

[0087] In summary, the traditional Chinese medicine composition disclosed herein can significantly improve defecation disorders in rats with functional constipation, shorten defecation time, increase defecation frequency, soften stool, and enhance gastrointestinal motility. It can also regulate intestinal biochemical indicators, enhance gastrointestinal peristalsis, and improve abnormal intestinal water absorption. It has significant therapeutic and ameliorative effects on functional constipation in children, with a clear dose-response relationship. The high-dose and medium-dose compound groups show particularly outstanding effects, and are superior to the positive control drug lactulose group. The traditional Chinese medicine composition disclosed herein is mild in nature, contains no drastic purgative components, and causes no intestinal irritation. Its safety is superior to conventional laxatives, and it is suitable for the physiological characteristics of children aged 1-14 years, providing a new pharmaceutical prospect for the preparation of drugs to treat functional constipation in children.

[0088] The above description is merely a specific embodiment of this disclosure, enabling those skilled in the art to understand or implement it. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of this disclosure. Therefore, this disclosure is not to be limited to the embodiments described herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A traditional Chinese medicine composition for improving functional constipation in children, characterized in that, The traditional Chinese medicine composition comprises, by weight: 5-15 parts of stir-fried radish seeds, 7-17 parts of stir-fried malt, 5-15 parts of hemp seeds, 4-13 parts of Solomon's seal rhizome, 2-8 parts of dried tangerine peel, 2-8 parts of Buddha's hand citron, 3-10 parts of stir-fried cassia seeds, and 1-6 parts of raw licorice root.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition comprises, by weight: 8-10 parts of stir-fried radish seeds, 10-12 parts of stir-fried malt, 8-12 parts of hemp seeds, 6-10 parts of Solomon's seal rhizome, 3-5 parts of dried tangerine peel, 3-5 parts of Buddha's hand, 4-7 parts of stir-fried cassia seeds, and 2-4 parts of raw licorice root.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The traditional Chinese medicine composition comprises, by weight: 10 parts stir-fried radish seeds, 12 parts stir-fried malt, 10 parts hemp seeds, 8 parts Solomon's seal rhizome, 4 parts dried tangerine peel, 4 parts Buddha's hand, 6 parts stir-fried cassia seeds, and 3 parts raw licorice root.

4. A pharmaceutical preparation for improving functional constipation in children, characterized in that, The pharmaceutical preparation contains an extract of the traditional Chinese medicine composition as described in any one of claims 1-3; The dosage form of the pharmaceutical preparation includes any one of granules, powders, capsules, tablets, mixtures, or oral liquids.

5. A method for preparing a pharmaceutical formulation for improving functional constipation in children as described in claim 4, characterized in that, The preparation method includes the following steps: (1) The traditional Chinese medicine composition is mixed with water and decocted to obtain an aqueous extract; (2) The aqueous extract is prepared into the dosage form of the drug preparation.

6. The preparation method according to claim 5, characterized in that, The steps for preparing the aqueous extract include: decocting the traditional Chinese medicine composition with water at least twice, each time for 1 to 3 hours, filtering after each decoction, and combining the filtrates to obtain the aqueous extract.

7. The preparation method according to claim 5 or 6, characterized in that, In the step of preparing the aqueous extract, the total mass of water is 14 to 20 times the mass of the traditional Chinese medicine composition.

8. The preparation method according to claim 6, characterized in that, In the step of preparing the aqueous extract, the decoction is performed twice. In the first decoction, the mass of water is 8 to 10 times the mass of the traditional Chinese medicine composition, and the decoction time is 1 to 3 hours. In the second decoction, the mass of water is 6 to 8 times the mass of the traditional Chinese medicine composition, and the decoction time is 1 to 3 hours.

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