A traditional Chinese medicine composition for treating functional constipation in children and a preparation method thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating functional constipation of children, which is prepared from the following raw medicine materials in parts by weight: 10-30 parts of Rubus parvifolius L, 10-30 parts of Paederus fuscipes Motschulsky, 10-30 parts of Atractylodes macrocephala Koidz, 5-20 parts of Rehmannia glutinosa Libosch, 5-20 parts of Citrus reticulata Blanco, 5-20 parts of Magnolia officinalis Rehd et Wils, 5-20 parts of Pogostemonis Herba, and 5-20 parts of Nelumbinis Folium. The medicine composition can fundamentally improve the intestinal function of children with functional constipation, and can avoid drug dependence and side effects caused by long-term use of western medicine purgative, effectively treat functional constipation, and prevent children from suffering from fecal impaction. The clinical application proves that the application can effectively treat functional constipation of children, keep the children's stool unobstructed, has no side effects, has good long-term curative effect, and effectively prevents children from suffering from fecal impaction.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine preparations, and particularly relates to a traditional Chinese medicine composition for treating functional constipation in children and a preparation method thereof. Background Art

[0002] Constipation is a common gastrointestinal motility disorder. According to literature, the prevalence of constipation in the general population ranges from 2% to 28%. According to relevant literature, the prevalence in children in my country is 18.8%, and pediatric constipation accounts for 3% to 5% of all pediatric outpatient visits. In recent years, with changes in lifestyle and a more refined diet, the incidence of pediatric constipation has gradually increased. It is generally believed that over 95% of pediatric constipation is functional, with less than 5% caused by underlying organic diseases. A systematic review of studies conducted internationally showed that the prevalence of functional constipation in children ranges from 0.5% to 35%, with an average prevalence of 9.5%. Functional constipation in children, also known as habitual constipation or simple constipation, refers to primary, persistent constipation not caused by systemic or intestinal diseases. Clinical symptoms include decreased bowel movement frequency, hard stools, and painful defecation, which may be accompanied by abdominal pain, fecal impaction, and fecal incontinence (usually overflow incontinence caused by fecal impaction).

[0003] Fecal impaction, a clinical symptom of constipation, can lead to fecal incontinence, severely impacting children's quality of life. Fear of defecation can lead to reduced eating habits, leading to malnutrition and restricted growth and development. Furthermore, children are unable to integrate into normal life and learning, and parental scolding often leads to psychological problems. Repeated fecal contamination often leads to perianal skin ulcers, infections, and pain. Therefore, prevention is the primary approach to fecal impaction, with effective treatment of constipation being key. However, there are currently few medications specifically for pediatric constipation, and Western medicines can only provide symptomatic laxatives. Traditional Chinese medicines (TCMs) and Chinese patent medicines lack recognition of children's specific constitutions, often using adult prescriptions or even high doses of anthraquinone laxatives, which damage children's intestines and are inconsistent with their physiological needs, resulting in poor efficacy. Summary of the Invention

[0004] The purpose of the present invention is to provide a new Chinese medicine composition with definite efficacy, targeted at the physiological and pathological characteristics of children, capable of effectively treating functional constipation in children and preventing fecal impaction, and a preparation method thereof.

[0005] The present invention provides a traditional Chinese medicine composition for treating functional constipation in children, which is prepared from the following raw materials in parts by weight:

[0006] 10-30 parts of Radix Glycyrrhizae, 10-30 parts of Caulis Atractylodes macrocephalae, 10-30 parts of Rhizoma Atractylodis Macrocephalae, 5-20 parts of Rehmannia glutinosa, 5-20 parts of Pericarpium Citri Reticulatae, 5-20 parts of Magnolia Bark, 5-20 parts of Pogostemon Cablin, and 5-20 parts of Lotus Leaf.

[0007] Furthermore, it is prepared from the following raw materials in parts by weight:

[0008] 10-20 parts of Radix Glycyrrhizae, 10-20 parts of Caulis Achyranthis Bidentatae, 10-20 parts of Rhizoma Atractylodis Macrocephalae, 5-15 parts of Rehmannia Glutinosa, 5-15 parts of Pericarpium Citri Reticulatae, 5-15 parts of Cortex Magnoliae Officinalis, 5-15 parts of Pogostemon Cablins, and 5-15 parts of Lotus Leaf.

[0009] Furthermore, it is prepared from the following raw materials in parts by weight:

[0010] 10-15 parts of Radix Glycyrrhizae, 10-15 parts of Caulis Atractylodes macrocephalae, 10-15 parts of Rhizoma Atractylodis Macrocephalae, 5-9 parts of Rehmannia glutinosa, 5-9 parts of Pericarpium Citri Reticulatae, 5-9 parts of Magnolia officinalis, 5-9 parts of Patchouli, and 5-6 parts of Lotus leaf.

[0011] Furthermore, it is prepared from the following raw materials in parts by weight:

[0012] 15 parts of Radix Glycyrrhizae, 15 parts of Caulis Atractylodes macrocephalae, 15 parts of Radix Atractylodes macrocephalae, 9 parts of Rehmannia root, 9 parts of Pericarpium Citri Reticulatae, 9 parts of Magnolia bark, 9 parts of Patchouli, and 6 parts of Lotus leaf;

[0013] or:

[0014] 10 parts of Radix Glycyrrhizae, 10 parts of Caulis Atractylodes macrocephalae, 10 parts of Rhizoma Atractylodis Macrocephalae, 5 parts of Radix Rehmanniae, 5 parts of Pericarpium Citri Reticulatae, 5 parts of Cortex Magnoliae, 5 parts of Pogostemon Cablins, and 5 parts of Lotus Leaf.

[0015] The Atractylodes macrocephala is raw Atractylodes macrocephala, and the Rehmannia root is raw Rehmannia root.

[0016] Furthermore, it is a preparation prepared from the powder of the raw material drug, or the water or organic solvent extract of the raw material drug as the active ingredient, and pharmaceutically acceptable excipients.

[0017] Furthermore, the preparation is an oral preparation.

[0018] Furthermore, the oral preparations include granules, pastes, powders, pills, solutions, mixtures, granules, and pills.

[0019] The present invention also provides a method for preparing the aforementioned Chinese medicine composition, which comprises the following steps:

[0020] (1) Weigh the raw materials according to the ratio;

[0021] (2) Grind the raw material into powder, or extract it with water or organic solvent, and add pharmaceutically acceptable excipients to the extract to obtain the product.

[0022] Furthermore, the dried tangerine peel, magnolia bark and patchouli in the raw materials of step (2) are extracted by distillation with water, and the volatile oil and aqueous solution are collected respectively; the medicinal residue and the remaining raw materials are decocted with water, filtered, the filtrate is combined with the aqueous solution, concentrated, and finally the volatile oil and pharmaceutically acceptable excipients are added and mixed to obtain the product.

[0023] Further, the amount of water added during distillation is 8-10 times the amount of medicinal material, and the distillation extraction is performed for 6 hours; the decoction is performed twice, the first time with water added in an amount of 10 times the amount of medicinal material, and the decoction extraction is performed for 80 minutes, the second time with water added in an amount of 8 times the amount of medicinal material, and the decoction extraction is performed for 60 minutes, and the decoction liquids are combined.

[0024] Further, the volatile oil is encapsulated by a clathrate.

[0025] The present application finally provides a use of the aforementioned traditional Chinese medicine composition in the preparation of a medicine for treating functional constipation.

[0026] Further, the medicine is a medicine for treating functional constipation of children and preventing fecal impaction of children.

[0027] In the traditional Chinese medicine composition of the present application, the Herba Dispori: is sweet and slightly bitter in taste, slightly warm in nature, and is attributed to the spleen, stomach and kidney channels. It has the functions of nourishing yin and tonifying deficiency, and strengthening the spleen and digesting food. It is used for deficiency and debilitation, dysentery, malnutrition, stomachache and abdominal distension, leukorrhea and tinea. The Materia Medica: "It is mainly used for abdominal distension and accumulation of food". The Classified Herbal Medicine: "It digests food accumulation, promotes lactation and tonifies deficiency". It has a strong effect of digesting food and strengthening the spleen. It is effective when used alone, such as powder for treating food accumulation and abdominal distension (Guizhou Commonly Used Folk Herbal Medicine Manual); water decoction for treating infantile mass (Shaanxi Chinese Herbal Medicine). Modern pharmacological research has found that it can promote gastrointestinal motility, regulate gastrointestinal function, and has immunoregulatory effect, improving the specific and non-specific immune capacity of the body.

[0028] The Paederia scandens: is sweet and slightly bitter in taste, and is attributed to the heart, liver, spleen and kidney channels. It has the functions of expelling wind and dampness, digesting food accumulation, relieving cough and relieving pain. It is used for rheumatic arthralgia, sprains and strains, enteritis, dysentery and indigestion in children. The Chongqing Herbal Medicine: "It strengthens the spleen, removes dampness, and tonifies deficiency. It is commonly used for infantile emaciation, spleen deficiency and deficiency of qi, and food accumulation and malnutrition in children. It is mainly used for anti-inflammatory and analgesic aspects. Modern research has found that the extract of Paederia scandens has a great effect on gastrointestinal motility, which can not only improve diarrhea, but also improve the slow intestinal peristalsis caused by morphine to treat constipation. The Sichuan Chinese Herbal Medicine records that Paederia scandens can be used with Herba Dispori to treat infantile malnutrition and food accumulation. Therefore, the combination of the two can strengthen the spleen and digest food accumulation, tonify and purge, promote gastrointestinal motility, and serve as the monarch herb.

[0029] Raw Atractylodes macrocephala: Bitter and sweet in flavor, warm in nature, enters the spleen and stomach meridians; it strengthens the spleen and replenishes qi, dispels dampness and promotes diuresis, stops sweating, and stabilizes pregnancy. It is used for spleen deficiency, poor appetite, abdominal distension and diarrhea, phlegm and fluid retention, dizziness and palpitations, edema, spontaneous sweating, and fetal movement disorder. Atractylodes macrocephala strengthens the spleen and replenishes qi, and "Compendium of Materia Medica" calls it "the most important herb for replenishing spleen qi." The Ben Jing Feng Yuan states: "Atractylodes macrocephala is sweet, warm, and rich in flavor. It is the yin in the yang meridian, capable of both ascending and descending, and enters the spleen and stomach meridians... Atractylodes macrocephala possesses the Qi of the Zhonggong Chonghe, and is therefore the dominant herb in spleen and stomach tonification. When the spleen and earth are strong, clear Qi ascends and the essence rises, while turbid Qi descends and the dregs are transported." The Yi Xue Zhong Can Xi Lu further states: "(Atractylodes macrocephala) possesses all the virtues of earth, making it an essential herb for postnatal life. Therefore, it can benefit the four organs of metal, wood, water, and fire." These and other statements fully demonstrate that Atractylodes macrocephala has multiple functions of strengthening the spleen and replenishing Qi, as well as regulating and regulating Qi. Atractylodes macrocephala strengthens the spleen to aid intestinal transport and restore the mechanism of the intestines' downward movement. Therefore, it can also treat constipation caused by spleen deficiency, intestinal dysfunction, turbid Qi failure, and poor bowel movements. Furthermore, Atractylodes macrocephala increases intestinal fluid. Raw Atractylodes macrocephala is an irregular, thick mass with a delicate aroma, a sweet and slightly spicy taste, and a slightly sticky texture when chewed, moistening the intestines and preventing dry stool. The Shennong Bencao Jingdu records that "Atractylodes macrocephala's function is to dry the body, and its merit lies in its high fat content." The Shanghan Lun Leifang states, "Atractylodes macrocephala produces body fluids for the stomach and intestines." The Bencao Huibian provides a detailed explanation: The spleen hates dampness; if dampness prevails, Qi cannot be transformed, and how can body fluids be produced? Therefore, it is said that the bladder is the reservoir of body fluids, where Qi can be transformed and released. Using Atractylodes macrocephala to remove dampness allows Qi to circulate and body fluids to be produced. Therefore, using raw Atractylodes macrocephala not only strengthens the spleen and replenishes Qi, but also promotes the spleen's production of body fluids, increasing intestinal body fluids and moistening the intestines, making it a ministerial herb.

[0030] Rehmannia root: Sweet, cold. Entries the Heart, Liver, and Kidney meridians. Clears heat, cools blood, nourishes Yin, and promotes fluid production. Used for fever with red tongue, thirst, internal heat due to Yin deficiency, bone steaming, fatigue fever, internal heat-induced polydipsia, hematemesis, epistaxis, and rashes. "Treatise on Febrile Diseases" records the treatment of fluid deficiency and constipation: "Yangming febrile disease, without upper Jiao symptoms, with a bowel movement for several days, should be treated immediately. If the patient has Yin deficiency, Cheng Qi should not be used: 30 grams of Yuanshen, 24 grams of Ophiopogon japonicus (including the heart), and 24 grams of fine Rehmannia root. Add 8 cups of water, boil 3 cups, and drink until the decoction is complete if the mouth is dry. If incontinence persists, continue taking." It effectively replenishes intestinal fluids and promotes bowel movements. Combined with Atractylodes macrocephala, it replenishes Qi and nourishes Yin, serving as a companion herb.

[0031] Tangerine peel: Bitter, pungent, and warm; enters the spleen and lung meridians. It regulates qi, balances the middle, expels dampness, and resolves phlegm. It is used for chest and abdominal distension, loss of appetite, vomiting, and hiccups. "Sui Xi Ju Diet" states: "It detoxifies fish and crab poisons. It treats belching, bloating, malnutrition, malaria, diarrhea, constipation, and beriberi." "Pu Ji Fang" states: "For constipation: boil tangerine peel (with the white part removed and soaked in wine) until soft, roast and grind into powder, and take 2 qian of it with warm wine." Tangerine peel, when combined with Atractylodes macrocephala, strengthens the spleen and promotes qi circulation, normalizing bowel function and serving as an adjuvant.

[0032] Magnolia officinalis: Bitter, pungent, and warm. It enters the spleen, stomach, lung, and large intestine meridians. It primarily dries dampness, eliminates phlegm, and relieves qi and distension. It is used for dampness stagnation, abdominal distension, vomiting and diarrhea, food accumulation and qi stagnation, abdominal distension and constipation, and cough and wheezing caused by phlegm and fluid retention. Zhu Zhenheng commented: "Magnolia officinalis is a qi-regulating herb. It is warm and dispersing, eliminating stomach fullness." "Magnolia officinalis can treat abdominal distension because its pungent flavor invigorates qi," emphasizing its role in promoting the flow of spleen and stomach qi, making it an adjuvant.

[0033] Patchouli: Pungent and slightly warm in nature. It enters the spleen, stomach, and lung meridians. Its aromatic properties dissipate dampness, soothe the stomach and stop vomiting, dispel summer heat and relieve symptoms of nausea. It treats dampness blocking the middle jiao, causing abdominal distension, loss of appetite, vomiting, and diarrhea. Combined with dried tangerine peel and magnolia bark, its aromatic properties invigorate the spleen, strengthen the middle jiao spleen and stomach, and promote smooth Qi flow, serving as an adjuvant.

[0034] Lotus leaf: Bitter, neutral. Enters the Liver, Spleen, and Stomach meridians. Clears heat and relieves summer heat, promotes the development of clear yang, cools the blood, and stops bleeding. It is used for thirst caused by summer heat, diarrhea due to dampness, diarrhea caused by spleen deficiency, vomiting and epistaxis due to blood heat, and hematochezia and metrorrhagia. This prescription primarily utilizes its ability to promote the development of clear yang, strengthening the spleen's function of transporting and transforming clear substances while preventing excessive qi-draining effects that can damage vital energy. Tangerine peel and Magnolia bark are the guiding herbs in this prescription.

[0035] The Chinese medicine composition for treating functional constipation of the present invention mainly utilizes Geshanxiao to strengthen the spleen and stomach and eliminate stagnation, and Jishiteng to eliminate food stagnation and replenish deficiency, both of which are monarch drugs, while Atractylodes macrocephala has the function of replenishing qi, strengthening the spleen and raising the clear fluid, and Radix Rehmanniae has the function of nourishing yin and promoting fluid production, both of which are ministerial drugs for replenishing qi and yin, while Pericarpium Citri Reticulatae has the function of regulating qi and strengthening the spleen, while Patchouli has the function of aromatically invigorating the spleen, and Magnolia officinalis has the function of lowering qi and eliminating fullness, thus restoring the normal function of the spleen to ascend and descend the stomach, as adjuvant drugs, and lotus leaf is used to promote the clear yang, on the one hand, to help the spleen transport and transform the clear fluid, and on the other hand, to prevent Pericarpium Citri Reticulatae and Magnolia officinalis from excessively lowering qi and damaging vital energy, as guiding drugs. This prescription contains 8 herbs, and is targeted at the physiological characteristics of children's constipation: children are in the peak period of growth and development, and their spleen is often insufficient, with the fundamental pathogenesis of spleen and stomach weakness. In addition, improper diet can easily lead to stagnation of gastrointestinal contents, resulting in constipation. This prescription adopts the method of strengthening the spleen and eliminating stagnation, replenishing qi and nourishing yin, raising the clear fluid and lowering turbidity, and harmonizing the spleen and stomach. The entire formula combines both attacking and tonifying, using tonification as a purgative, thereby restoring normal spleen and stomach function, allowing the large and small intestines to perform their respective functions and maintaining smooth bowel movements. The pharmaceutical composition of the present invention can fundamentally improve intestinal function in children while avoiding the drug dependence and side effects associated with long-term use of Western laxatives. It effectively treats functional constipation in children and prevents fecal impaction. Clinical application has demonstrated that the Chinese herbal composition of the present invention can effectively treat functional constipation in children, maintain smooth bowel movements, has no side effects, and exhibits excellent long-term efficacy, effectively preventing fecal impaction in children.

[0036] Obviously, based on the above contents of the present invention, according to common technical knowledge and customary means in this field, without departing from the above basic technical ideas of the present invention, other various forms of modifications, replacements or changes can be made.

[0037] The following further describes the above content of the present invention in detail through specific embodiments in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention fall within the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 Comparison of body weight of mice in each group

[0039] Figure 2 Comparison of fecal water content among the groups

[0040] Figure 3 Comparison of intestinal propulsion rate among the groups DETAILED DESCRIPTION

[0041] Example 1. Preparation of the medicine of the present invention

[0042] Recipe: 15g of Geshanxiao, 15g of Cistanche deserticola, 15g of raw Atractylodes macrocephala, 9g of raw Rehmannia glutinosa, 9g of dried tangerine peel, 9g of Magnolia officinalis, 9g of Patchouli, and 6g of lotus leaf.

[0043] Preparation method:

[0044] (1) Weigh the raw material medicine slices according to the proportion;

[0045] (2) Take dried tangerine peel, Magnolia officinalis, and Patchouli and add 8-10 times of water to distill and extract for 6 hours, collect the volatile oil and set aside, and collect the distilled aqueous solution separately; decoct the medicinal residue and the remaining medicinal materials such as Cynanchum wilfordii with water twice, and add water 10 times and 8 times of the amount of medicinal materials respectively, and extract for 80 minutes for the first time and 60 minutes for the second time, combine the decoction, filter, combine the filtrate with the above aqueous solution, concentrate the solution, and add the volatile oil to obtain the compound decoction.

[0046] (3) The compound decoction and edible preservatives are mixed and packaged to form a mixture.

[0047] Example 2: Preparation of the drug of the present invention

[0048] Recipe: 10g of Geshanxiao, 10g of Cistanche deserticola, 10g of raw Atractylodes macrocephala, 5g of raw Rehmannia glutinosa, 5g of dried tangerine peel, 5g of Magnolia officinalis, 5g of Patchouli, and 5g of lotus leaf.

[0049] Preparation method:

[0050] (1) Weigh the raw material medicine slices according to the proportion;

[0051] (2) Take dried tangerine peel, Magnolia officinalis, and Patchouli and add 8-10 times of water to distill and extract for 6 hours, collect the volatile oil and set aside, and collect the distilled aqueous solution separately; decoct the medicinal residue and the remaining medicinal materials such as Cynanchum wilfordii with water twice, and add water 10 times and 8 times of the amount of medicinal materials respectively, and extract for 80 minutes for the first time and 60 minutes for the second time, combine the decoction, filter, combine the filtrate with the above aqueous solution, concentrate the solution, and add the volatile oil to obtain the compound decoction.

[0052] (3) The compound decoction is added with excipients to form pills, which are then dried and packaged into pills.

[0053] Example 3: Preparation of the drug of the present invention

[0054] Recipe: 20g of Geshanxiao, 20g of Cistanche deserticola, 20g of raw Atractylodes macrocephala, 15g of raw Rehmannia glutinosa, 15g of dried tangerine peel, 15g of Magnolia officinalis, 15g of Patchouli, and 15g of lotus leaf.

[0055] Preparation method:

[0056] (1) Weigh the raw material medicine slices according to the proportion;

[0057] (2) Take dried tangerine peel, Magnolia officinalis, and Patchouli and add 8-10 times of water to distill and extract for 6 hours, collect the volatile oil and set aside, and collect the distilled aqueous solution separately; decoct the medicinal residue and the remaining drugs such as Cynanchum wilfordii with water twice, and add water 10 times and 8 times of the amount of medicinal materials respectively, and extract for 80 minutes for the first time and 60 minutes for the second time. Combine the decoctions, filter, combine the filtrate with the above aqueous solution, concentrate the solution to a paste, dry at 40-80℃, granulate, add volatile oil and excipients to make pellets, dry and package to obtain drop pills.

[0058] Example 4. Preparation of the medicine of the present invention

[0059] Recipe: 10g of Geshanxiao, 10g of Cistanche deserticola, 10g of raw Atractylodes macrocephala, 5g of raw Rehmannia glutinosa, 5g of dried tangerine peel, 5g of Magnolia officinalis, 5g of Patchouli, and 5g of lotus leaf.

[0060] Preparation method:

[0061] (1) Weigh the raw material medicine slices according to the proportion;

[0062] (2) Take dried tangerine peel, Magnolia bark, and Patchouli and add 8-10 times of water to distill and extract for 6 hours, collect the volatile oil and set aside, and collect the distilled aqueous solution separately; decoct the medicinal residue and the remaining medicinal materials such as Cynanchum wilfordii with water twice, and add water 10 times and 8 times of the amount of medicinal materials respectively, and extract for 80 minutes for the first time and 60 minutes for the second time. Combine the decoctions, filter, combine the filtrate with the above aqueous solution, concentrate the solution to a paste, dry at 40-80℃, granulate, add volatile oil and excipients, mix and package to obtain granules.

[0063] Example 5: Preparation of the drug of the present invention

[0064] Recipe: 30g of Geshanxiao, 30g of Cistanche deserticola, 30g of raw Atractylodes macrocephala, 20g of raw Rehmannia glutinosa, 20g of dried tangerine peel, 20g of Magnolia officinalis, 20g of Patchouli, and 20g of lotus leaf.

[0065] Preparation method:

[0066] (1) Weigh the raw material medicine slices according to the proportion;

[0067] (2) Take dried tangerine peel, Magnolia bark, and Patchouli and add 8-10 times of water to distill and extract for 6 hours, collect the volatile oil, and encapsulate it with inclusion compound, dry it for later use, and collect the distilled aqueous solution separately; decoct the medicinal residue and the remaining drugs such as Cynanchum wilfordii with water twice, and add water 10 times and 8 times of the amount of medicinal materials respectively, and extract for 80 minutes for the first time and 60 minutes for the second time. Combine the decoctions, filter, combine the filtrate with the above aqueous solution, concentrate the solution to a paste, dry it at 40-80℃, granulate it, add the volatile oil encapsulated by the inclusion compound and excipients, mix and package it to obtain granules.

[0068] The beneficial effects of the present invention are described below through test examples.

[0069] Test Example 1 Study on the efficacy of the Chinese medicine composition of the present invention

[0070] 1 Experimental materials and animals

[0071] 1.1 Experimental Animals

[0072] Sixty-three 6-week-old C57BL / 6 mice weighing 20–30 g were housed under the following conditions: room temperature 20–24°C, 50–60% humidity, and a 12-h artificial day / night cycle. This study was conducted in strict accordance with the National Institutes of Health Guidelines for Laboratory Animal Experiments.

[0073] 1.2 Medication

[0074] All the above herbs, including cyperus rotundus, radix atractylodes macrocephalae, radix rehmanniae, dried tangerine peel, magnolia bark, patchouli, and lotus leaf, are from Henan Bencao Traditional Chinese Medicine Store Chain Co., Ltd. Loperamide hydrochloride: National Medicine Approval No. H10910085, Xi'an Janssen Pharmaceutical Co., Ltd.

[0075] 1.3 Model preparation

[0076] A slow-transit constipation model was established using loperamide hydrochloride via gavage. Based on previous experience and other literature, loperamide hydrochloride (10 mg / kg) was administered daily at 7:00 PM for 14 days. A control group received an equivalent dose of normal saline. During the modeling period, mice were given normal food and water. Except for the control group, all other groups received loperamide hydrochloride to establish a functional constipation mouse model. Model success was assessed primarily by fecal water content and intestinal propulsion rate.

[0077] 2 Experimental methods

[0078] 2.1 Grouping and intervention

[0079] One week before the experiment, mice were acclimatized to the environment and had free access to food and water. Mice were randomly divided into 7 groups, with 9 mice in each group, for a total of 7 groups, namely Group A (blank group), Group B (model group), Group C (full formula group), Group D (monarch drug group), Group E (monarch drug plus minister drug group 1), Group F (monarch drug plus minister drug group 2), and Group G (no monarch drug group). Except for the blank group, the model group and other groups were gavaged with loperamide hydrochloride to prepare a functional constipation mouse model for 2 weeks. Starting from the third week, each group was given the corresponding drug gavage at the human-mouse conversion dose for 2 consecutive weeks. The model group was given an equal dose of normal saline by gavage, and the blank group did not receive any treatment. All mice had free access to water and food.

[0080] The prescription of the whole prescription group is: Geshanxiao 15g, Cistanche deserticola 15g, Raw Atractylodes macrocephala 15g, Raw Rehmannia glutinosa 9g, Tangerine peel 9g, Magnolia bark 9g, Patchouli 9g, and Lotus leaf 6g; the prescription of the monarch drug group is: Geshanxiao 15g, Cistanche deserticola 15g; the prescription of the monarch drug plus minister drug group 1 is: Geshanxiao 15g, Cistanche deserticola 15g, Raw Atractylodes macrocephala 15g; the prescription of the monarch drug plus minister drug group 2 is: Geshanxiao 15g, Cistanche deserticola 15g, Raw Rehmannia glutinosa 9g; the group without monarch drugs is: Raw Atractylodes macrocephala 15g, Raw Rehmannia glutinosa 9g, Tangerine peel 9g, Magnolia bark 9g, Patchouli 9g, and Lotus leaf 6g.

[0081] Preparation method:

[0082] For the whole-prescription group, tangerine peel, Magnolia bark, and Patchouli were added with 8-10 times the amount of water and distilled for 6 hours. The volatile oil was collected and set aside, and the distilled aqueous solution was collected separately. The medicinal residues and the remaining drugs such as Cyperus rotundus were decocted twice with water, and the amount of water added was 10 times and 8 times the amount of medicinal materials, respectively. The extraction time was 80 minutes for the first time and 60 minutes for the second time. The decoctions were combined and filtered. The filtrate was combined with the above aqueous solution, the solution was concentrated, and the volatile oil was added to obtain the compound decoction, which was sealed and stored in a refrigerator at 4°C.

[0083] The monarch drug group, monarch drug plus minister drug group 1, monarch drug plus minister drug group 2, and no monarch drug group were prepared by taking each drug in the prescription into a compound decoction containing the same weight of the original drug according to the same method as the full prescription group, and the decoction was sealed and stored in a refrigerator at 4°C.

[0084] 2.2 Observation indicators and methods

[0085] 2.2.1 General Condition of Mice

[0086] From the beginning of modeling and drug administration, the mice's spirit, activity, fur, food and water intake, body weight, and defecation were dynamically observed.

[0087] 2.2.2 Water content of feces

[0088] At the end of the fourth week of treatment, fresh feces from each group of mice (3 feces per mouse) were collected and weighed to obtain the wet feces weight (W1). The feces were then placed in a 60°C oven and weighed again 12 hours later to obtain the dry feces weight (W2). Fecal moisture content was calculated as follows: fecal moisture content = [(W1 - W2) / W1] x 100%.

[0089] 2.2.3 Intestinal propulsion rate

[0090] Three mice were randomly selected from each group and fasted for 18 hours. They were then gavaged with 0.1 ml / 10 g of a prepared 10% activated carbon suspension. Thirty minutes later, the mice were anesthetized intraperitoneally with 2% sodium pentobarbital and then sacrificed. The abdominal cavity was quickly opened to fully expose the entire gastrointestinal tract. The mesentery was gently separated, and the entire intestinal tract from the pylorus to the anus was accurately cut and gently pulled to form a straight line. The intestine was allowed to rest for 30 seconds. The distance from the pylorus to the front edge of the black semisolid paste and the end of the colon was measured, and the intestinal propulsion rate (IPR) was calculated. IPR (%) = distance from the pylorus to the front edge of the black semisolid paste (cm) / distance from the pylorus to the end of the colon (cm) x 100%.

[0091] 3 Experimental results

[0092] 3.1 Comparison of general conditions of mice in each group

[0093] Before the experiment, the mice in each group were in good spirits, agile, with shiny fur, normal food and water intake, normal defecation frequency, and moderate stool dryness and wetness. After the start of the experiment, the mice in the blank group gradually gained weight, were in good spirits, and had continuous strips of feces. The mice in the other groups began to show varying degrees of changes around the 7th day after the start of modeling: their fur gradually turned yellow, the glossiness deteriorated, their spirits were worse than before, their stool volume was small, and the texture was dry and hard, and granular. After the end of the treatment, the general condition and food and water intake of the different drug intervention groups improved to varying degrees, and their weight also increased. The model group gained weight slowly, and the weight gain of the full-prescription group was significantly higher than that of the other treatment groups and the model group, see Table 1, Figure 1 .

[0094] Table 1 Changes in body weight of mice in each group

[0095] Group 0 weeks 4 weeks Group A 20.63±1.82 27.01±2.58 Group B 20.57±1.802 23.04±0.838 Group C 20.56±1.53 <![CDATA[27.16±0.74 ### ]]> Group D 20.53±0.71 <![CDATA[23.49±1.30 *** ]]> Group E 21.04±1.58 <![CDATA[23.94±1.73 *** ]]> Group F 20.64±1.24 <![CDATA[23.9±1.31 *** ]]> Group G 20.49±1.50 <![CDATA[23.57±1.34 *** ]]>

[0096] Note: * P<0.05, ** P<0.01, *** P<0.001 (compared with the full prescription group); # P<0.05, ## p<0.01, ### p<0.001 (compared with the model group), ns means p>0.05, the same as in the following tables and figures.

[0097] 3.2 Comparison of fecal water content in each group of mice

[0098] At the end of the treatment at the end of the fourth week, the fecal water content of each group was compared and it was found that the fecal water content of the whole prescription group was significantly higher than that of the model group and other treatment groups (p < 0.05), as shown in Table 2. Figure 2 .

[0099] Table 2 Comparison of fecal water content in each group of mice

[0100]

[0101] 3.3 Comparison of intestinal propulsion rate among mice groups

[0102] At the end of the treatment at the end of the fourth week, the intestinal propulsion rate of each group was compared, and the intestinal propulsion rate of the whole prescription group was significantly higher than that of the model group, the monarch drug group, and the minister drug group (P < 0.05, Table 3, Figure 3 ), although there were certain differences between the whole prescription group and the monarch drug plus minister drug group 1 and the monarch drug plus minister drug group 2, the differences were not significant and had no statistical significance (p>0.05).

[0103] Table 3 Comparison of intestinal propulsion rate of mice in each group (%)

[0104]

[0105] Conclusion: The full formula effectively alleviated functional constipation in mice, increased fecal water content and intestinal propulsion rate, and improved the mice's overall condition. Furthermore, the full formula group demonstrated significant advantages over other monarch herb groups, monarch herb plus assistant herb group 1, monarch herb plus assistant herb group 2, and the no monarch herb group, significantly increasing mouse body weight and fecal water content. The full formula group also outperformed the monarch herb and no monarch herb groups in intestinal propulsion rate, demonstrating the scientific validity of this formula. The full complement of monarch, assistant, and assistant herbs is essential for the formula to achieve its maximum efficacy.

[0106] Test Example 2 Typical Case of Clinical Application

[0107] Patient Liu, male, 9 years old, visited the hospital on August 3, 2023

[0108] Chief complaint: constipation for more than 1 year

[0109] Current medical history: Constipation developed over a year ago after an irregular diet. The stools were dry and hard, and the intervals between bowel movements were prolonged, with bowel movements occurring approximately every 2-3 days. The patient visited a local hospital and was given Chinese medicines such as rhubarb and senna leaves. The medications alleviated the symptoms, but the symptoms recurred after discontinuation of the medications. The patient experienced a gradual worsening of symptoms, including a lack of urge to defecate, bowel movements occurring only once every 3-4 days, dry and hard stools, and difficulty defecating. The patient was also thin, weak in the limbs, had a poor appetite, but was able to sleep well and had regular urination. The patient had a pale tongue with a thin, slightly greasy white coating and a weak, thready pulse.

[0110] TCM diagnosis: constipation - qi deficiency

[0111] Western medicine diagnosis: functional constipation - slow transit constipation

[0112] Treatment: invigorating spleen, eliminating accumulation, tonifying qi and nourishing yin.

[0113] Prescription: Children Constipation Formula

[0114] Geshanxiao 10g, Jixiuteng 10g, Shengbaishu 10g, Shengdihuang 5g, Chenpi 5g, Houpu 5g, Guanghuoxiang 5g, Hol 5g, 6 doses, decoction granules prepared according to Example 4. Advised to defecate regularly, avoid holding stool, and diversify diet.

[0115] August 10, 2013

[0116] After taking the prescription, constipation was significantly relieved, 1-2 days of defecation, soft stool, self-relief, no abdominal pain, abdominal distension, improved diet, spirit, sleep, mouth and tongue, pale, thin white, weak pulse.

[0117] Efficiency does not change the prescription, traditional Chinese medicine, 10 doses, traditional Chinese medicine decoction granules, advised 2 doses for 3 days. Half a month later, the child's mother complained of relief, smooth stool, soft, 1-2 days of defecation, sleep, no special complaints. Stopped medication, followed up for 3 months without recurrence.

[0118] Summary:

[0119] Constipation has many causes, which can be divided into excess constipation and deficiency constipation. Excess constipation can be further divided into heat constipation, cold constipation, damp constipation, and qi constipation according to the different cold and heat. Deficiency constipation can be divided into qi deficiency, blood deficiency, yang deficiency, and yin deficiency according to the different yin and yang of qi and blood. In clinical practice, it is often necessary to carefully identify the cause and treat both the symptoms and the root cause. It is absolutely not advisable to focus on attacking the problem and just purge the patient. This will damage the vital energy and lead to prolonged illness. In this case, the patient was 9 years old and had a body of immature yin and yang. Occasionally, he had an irregular diet that caused intestinal qi obstruction and dry stools. He was advised to eliminate stagnation and remove stagnation while strengthening the spleen and stomach. However, the local doctor prescribed rhubarb and senna leaves, which are bitter and cold laxatives. Although the stool was temporarily unblocked, the vital energy was damaged, the qi and yin were insufficient, and the bowels were unable to move. The intestines were not moistened, so the symptoms were relieved with medication, but recurred after stopping the medication. Upon arrival at the clinic, the child was thin, weak, had a poor appetite, a pale tongue, and a weak pulse, all signs of Qi deficiency and Yin deficiency. A children's constipation prescription was used, with Geshanxiao invigorating the spleen and stomach to eliminate stagnation, Jishiteng digesting food, eliminating stagnation, and replenishing deficiency, Baizhu replenishing Qi and strengthening the spleen, Shengdihuang nourishing Yin and promoting fluid production, Tangerine peel regulating Qi and strengthening the spleen, Patchouli aromatically invigorating the spleen, and Magnolia officinalis dispelling Qi and dispelling fullness, restoring the normal function of the spleen to ascend and descend the stomach, and combined with lotus leaf to promote the clearing of Yang. This prescription strengthens the spleen and eliminates stagnation, replenishes Qi and nourishes Yin, raises the clear and lowers the turbid, and harmonizes the spleen and stomach. It targets the physiological characteristics of children's constipation, especially during the peak period of growth and development, when the spleen is often insufficient and the fundamental pathogenesis of spleen and stomach weakness is weak. In addition, an irregular diet can easily lead to stagnation of gastrointestinal contents and constipation. The entire prescription combines both attacking and replenishing, focusing on replenishing, thereby restoring normal spleen and stomach function, ensuring that the large and small intestines perform their respective functions and maintaining smooth bowel movements, with significant results.

[0120] In summary, clinical application has proved that the Chinese medicine composition of the present invention can effectively treat functional constipation in children, maintain smooth bowel movements, has no side effects, has good long-term efficacy, and effectively prevents fecal impaction in children.

Claims

1. A Chinese medicine composition for treating functional constipation in children, characterized by: The preparation is prepared from the following raw materials in parts by weight: 10-30 parts of Radix Glycyrrhizae, 10-30 parts of Caulis Achyranthis Bidentatae, 10-30 parts of Atractylodes macrocephalae, 5-20 parts of Rehmannia glutinosa, 5-20 parts of Citrus reticulatae, 5-20 parts of Magnolia officinalis, 5-20 parts of Patchouli, and 5-20 parts of Lotus leaf; The preparation method of the Chinese medicine composition comprises the following steps: (1) Weigh the API by weight; (2) Take dried tangerine peel, Magnolia officinalis, and Patchouli, add water for distillation extraction, and collect the volatile oil and aqueous solution respectively; decoct the medicinal residue and the remaining raw materials with water, filter, combine the filtrate with the aqueous solution, concentrate, and then add the volatile oil and pharmaceutically acceptable excipients and mix well to obtain the product.

2. The Chinese medicine composition according to claim 1, characterized in that: It is prepared from the following raw materials in parts by weight: 10-20 parts of Radix Glycyrrhizae, 10-20 parts of Caulis Achyranthis Bidentatae, 10-20 parts of Rhizoma Atractylodis Macrocephalae, 5-15 parts of Rehmannia Glutinosa, 5-15 parts of Pericarpium Citri Reticulatae, 5-15 parts of Cortex Magnoliae Officinalis, 5-15 parts of Pogostemon Cablins, and 5-15 parts of Lotus Leaf.

3. The Chinese medicine composition according to claim 2, characterized in that: It is prepared from the following raw materials in parts by weight: 10-15 parts of Radix Glycyrrhizae, 10-15 parts of Caulis Atractylodes macrocephalae, 10-15 parts of Rhizoma Atractylodis Macrocephalae, 5-9 parts of Rehmannia glutinosa, 5-9 parts of Pericarpium Citri Reticulatae, 5-9 parts of Magnolia officinalis, 5-9 parts of Patchouli, and 5-6 parts of Lotus leaf.

4. The Chinese medicine composition according to claim 3, characterized in that: It is prepared from the following raw materials in parts by weight: 15 parts of Radix Glycyrrhizae, 15 parts of Caulis Atractylodes macrocephalae, 15 parts of Radix Atractylodes macrocephalae, 9 parts of Rehmannia root, 9 parts of Pericarpium Citri Reticulatae, 9 parts of Magnolia bark, 9 parts of Patchouli, and 6 parts of Lotus leaf; or: 10 parts of Radix Glycyrrhizae, 10 parts of Caulis Atractylodes macrocephalae, 10 parts of Rhizoma Atractylodis Macrocephalae, 5 parts of Radix Rehmanniae, 5 parts of Pericarpium Citri Reticulatae, 5 parts of Cortex Magnoliae, 5 parts of Pogostemon Cablins, and 5 parts of Lotus Leaf.

5. The Chinese medicine composition according to any one of claims 1 to 4, characterized in that: The Atractylodes macrocephala is raw Atractylodes macrocephala, and the Rehmannia root is raw Rehmannia root.

6. The Chinese medicine composition according to claim 1, characterized in that: The preparation is an oral preparation; the oral preparation is an ointment, powder, pill, solution, granule, or pill.

7. Use of the traditional Chinese medicine composition according to any one of claims 1 to 6 in the preparation of a medicament for treating functional constipation.

8. The use according to claim 7, characterized in that: The medicine is used to treat functional constipation in children and prevent fecal impaction in children.

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