A Chinese medicine composition for treating constipation, preparation method and application

Abstract

This invention belongs to the field of traditional Chinese medicine composition technology, and discloses a traditional Chinese medicine composition for treating constipation, its preparation method, and its application. The traditional Chinese medicine composition, by weight, includes 20-120 parts of raw Atractylodes macrocephala, 0-20 parts of Citrus aurantium, and 0-20 parts of Prunus persica. The preparation method includes: S1, pulverizing raw Atractylodes macrocephala and Citrus aurantium, and breaking Prunus persica into pieces; S2, weighing and mixing the powders, adding water to the mixture to extract volatile oil and extract; S3, encapsulating the volatile oil, combining the extracts, concentrating, and drying to obtain a dry extract powder; S4, mixing the volatile oil encapsulation and dry extract powder with excipients to obtain the desired traditional Chinese medicine composition; and the application of the traditional Chinese medicine composition in slow-transit constipation and constipation due to spleen deficiency. The traditional Chinese medicine composition provided by this invention has a simplified formulation and is safe and effective; the optimized preparation method improves quality and efficiency, making it more effective in treating patients with constipation due to spleen deficiency and weak spleen and stomach.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, specifically to a traditional Chinese medicine composition for treating constipation, its preparation method, and its application. Background Technology

[0002] Existing Western medicines for treating constipation mainly include bisacodyl, polyethylene glycol 4000 powder, mosapride, rubiprostone, linaclotide, elecibarbital, and tercapranolol. These drugs treat constipation by stimulating intestinal sensory nerve endings, regulating intestinal moisture, activating 5-HT4 receptors, activating chloride ion channels, activating guanylate cyclase C, regulating bile acids, and inhibiting the NHE3 receptor pathway. They primarily act as "promotes" and "lactates," effectively relieving short-term constipation, but cannot cure constipation. Furthermore, they have numerous adverse reactions, and tolerance gradually develops with increased dosage and duration of use. Traditional Chinese medicine (TCM) treatment of constipation addresses different pathogenesis and syndrome types, such as cold, heat, deficiency, and excess, using a syndrome differentiation and treatment approach. For example, Ma Ren Run Chang Wan, Xiao Jian Zhong He Ji, and Zhi Shi Dao Zhi Wan are mostly used for excess constipation; Yang Yin Run Chang Fang, Ji Chuan Tang, and Hua Yu Tong Bian Tang are used for yin deficiency constipation, yang deficiency constipation, and blood deficiency constipation, respectively. Both Qi Rong Run Chang Oral Liquid and Qi Huang Tong Mi Soft Capsules use Astragalus membranaceus as the principal ingredient to treat constipation due to Qi deficiency. They primarily utilize herbs containing rhubarb and anthraquinone compounds, and long-term use carries the risk of melanosis coli. For individuals with weak spleen and stomach causing constipation, simply using laxatives will worsen the weakness and cause significant side effects; currently, there are no targeted treatments for this condition.

[0003] For individuals with constipation due to spleen and stomach weakness, such as the elderly, young women trying to lose weight, and obese men with weak constitutions, the underlying cause is spleen deficiency, characterized by both superficial excess and fundamental deficiency, with dampness accumulation due to spleen deficiency. Treatment should combine tonification and purgation, with strengthening the spleen as the primary element. Therefore, treating constipation due to spleen deficiency requires not only lubricating the intestines and relieving constipation but also addressing the root cause by strengthening the spleen, resolving dampness, and promoting qi circulation to remove blood stasis. Based on this principle, this invention focuses on the spleen, aiming to "nourish the body's vital energy and eliminate stagnation," providing a drug with significant efficacy, few side effects, and high safety for treating constipation due to spleen and stomach weakness. Summary of the Invention

[0004] This invention aims to provide a traditional Chinese medicine composition for treating constipation, its preparation method, and its application. The composition is simplified and does not contain rhubarb anthraquinone components or related medicinal materials, ensuring its safety and efficacy. Furthermore, the preparation method is optimized to improve its quality and efficiency, making it more effective in treating constipation caused by spleen deficiency.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] A traditional Chinese medicine composition for treating constipation includes the following components by weight: 20-120 parts of raw Atractylodes macrocephala, 0-20 parts of Citrus aurantium, and 0-20 parts of Prunus persica.

[0007] A traditional Chinese medicine composition for treating constipation includes the following components by weight: 60-120 parts of raw Atractylodes macrocephala, 10-20 parts of Citrus aurantium, and 10-20 parts of Prunus persica.

[0008] The preparation method of the above-mentioned traditional Chinese medicine composition for treating constipation includes the following steps:

[0009] S1. Weigh out the raw Atractylodes macrocephala, Citrus aurantium and Prunus persica according to the specified amounts, and crush the raw Atractylodes macrocephala and Citrus aurantium into powder, and break the Prunus persica into pieces;

[0010] S2. Weigh the powder prepared in step S1 according to the weight ratio of the composition and mix them. Add 4 to 12 times the amount of water to the mixture and extract to obtain volatile oil and extract.

[0011] S3. The volatile oil obtained in step S2 is encapsulated with β-cyclodextrin or hydroxypropyl-β-cyclodextrin to obtain a volatile oil inclusion complex; the extracts obtained in step S2 are combined, concentrated, and dried to obtain a dry extract powder.

[0012] S4. Mix the volatile oil inclusion complex and dry powder obtained in step S3 with excipients to obtain the desired traditional Chinese medicine composition.

[0013] Furthermore, in S2, the volatile oil and extract are extracted by steam distillation in oil-water extraction for 20-80 minutes, and the extraction is repeated twice.

[0014] Furthermore, in S3, the method for preparing the volatile oil inclusion complex is as follows: first, the volatile oil is dissolved in 95% ethanol, and then it is added to a saturated solution of β-cyclodextrin or hydroxypropyl-β-cyclodextrin. The inclusion complex is then carried out by ultrasonication or saturated aqueous solution method. After crystallization, filtration, and drying at room temperature, the obtained β-cyclodextrin or hydroxypropyl-β-cyclodextrin inclusion complex is the desired volatile oil inclusion complex.

[0015] Furthermore, during the inclusion process, the weight ratio of volatile oil to β-cyclodextrin or hydroxypropyl-β-cyclodextrin to water is 1:6 to 10:48 to 120; the inclusion temperature is 30 to 50°C; the inclusion time is 1 to 3 hours; after completion, it is placed at 4°C for 24 hours, and after crystallization and filtration, it is dried at room temperature.

[0016] Furthermore, in S3, the concentrated extract is concentrated under reduced pressure, and the drying method is vacuum drying or spray drying.

[0017] Furthermore, in S4, the excipient is dextrin; the weight ratio of the dry extract powder to the excipient is 1 to 8:1.

[0018] The preparation method of the above-mentioned traditional Chinese medicine composition for treating constipation includes the following steps:

[0019] M1. Crush raw Atractylodes macrocephala and Fructus Aurantii Immaturus; since Semen Persicae has a large amount of oil, grind it into paste powder.

[0020] M2. Weigh the fine powder of raw Atractylodes macrocephala, the fine powder of Fructus Aurantii Immaturus, and the paste powder of Semen Persicae according to the weight ratio of the composition, mix them evenly, add refined honey, and the weight ratio of the mixed medicinal powder to the refined honey is 1:0.8 - 1.5, and the temperature of the mixed honey is 50 - 80 °C, then make into honey pills containing the traditional Chinese medicine composition by combining lumps.

[0021] The application of the above traditional Chinese medicine composition for treating constipation in slow transit constipation, including difficult defecation, reduced defecation quantity, dry feces, intestinal motility disorder, insufficient intestinal fluid secretion, abnormal digestive and absorption functions; and in spleen qi deficiency constipation, including slow intestinal transit, abnormal intestinal fluid secretion, difficult defecation and reduced defecation quantity caused by insufficient spleen qi.

[0022] Principle of the technical solution:

[0023] Raw Atractylodes macrocephala is bitter, sweet, and warm, belonging to the spleen and stomach meridians, and has the effect of promoting defecation. Although it is a bitter and drying product, it is rich in fat, can invigorate the spleen and benefit qi, promote the rising of clear yang and the descending of turbid yin, generate body fluids, and defecation can occur without using laxatives. It is a good medicine for promoting defecation due to spleen deficiency and dampness entrapment. And many medical experts such as the old gentleman Long Xiang in the Later Wei Dynasty and Professor Tong Xiaolin have proposed to use a large dose of raw Atractylodes macrocephala to play the role of promoting defecation. Since constipation is often accompanied by stagnation of qi in the intestinal tract, regulating qi and promoting qi movement should be implemented throughout.

[0024] Fructus Aurantii Immaturus is bitter, pungent, sour, slightly cold, belonging to the spleen and stomach meridians, and has the functions of promoting qi circulation to resolve phlegm and breaking qi to disperse stagnation. The combination of Fructus Aurantii Immaturus and Atractylodes macrocephala has a history of thousands of years in the treatment of gastrointestinal motility dysfunction diseases. It was first seen in Zhizhu Decoction in Synopsis of the Golden Chamber. The existing Zhizhu Pills {Fructus Aurantii Immaturus (fried) 250g, Atractylodes macrocephala (bran-fried) 500g}, Zhizhu Granules {Fructus Aurantii Immaturus (bran-fried) 333g, Atractylodes macrocephala (bran-fried) 666g, Folium Nelumbinis 100g}, their functions and indications are all to invigorate the spleen and promote digestion, promote qi movement and eliminate dampness, and are used for weakness of the spleen and stomach, indigestion, and fullness and discomfort in the epigastric and abdominal regions. In addition, traditional Chinese medicine believes that for diseases of the spleen and stomach, if the disease lasts for a long time and involves collateral channels and stagnation of stasis, then blood-activating and stasis-dispelling drugs need to be added.

[0025] Semen Persicae is bitter, sweet, and neutral, belonging to the heart, liver, and large intestine meridians, and has the effect of promoting the unblocking of stagnation. It is suitable for constipation due to internal binding of stasis-heat or qi stagnation and blood stasis, and its nature is mild, making it a good medicine for habitual constipation.

[0026] Based on the theory of traditional Chinese medicine, the present invention combines raw Atractylodes macrocephala, Fructus Aurantii Immaturus, and Semen Persicae into a formula, and重用 raw Atractylodes macrocephala. For defecation weakness caused by spleen weakness and senile refractory constipation, the above three herbs, one tonifying, one reducing, and one moistening, complement each other and jointly play the effects of strengthening the spleen and resolving dampness, promoting qi movement and removing stasis, and moistening the intestines and promoting defecation. The medicinal ingredients are simple, effective and safe; the present invention focuses on solving intestinal function problems from the root,弥补 the defect that promoters can only improve constipation symptoms but cannot completely cure, and充分体现 the unique advantages of traditional Chinese medicine in treating diseases by seeking the root cause and treating both the symptoms and the root cause.

[0027] In addition, Atractylodes macrocephala and Citrus aurantium contain abundant volatile oils. Studies have shown that Atractylodes macrocephala volatile oil, mainly composed of atractylone, can promote gastrointestinal motility in mice and counteract the inhibitory effect of atropine on intestinal peristalsis in mice; Citrus aurantium volatile oil also has a significant prokinetic effect on gastrointestinal motility and is positively correlated with the content of limonene in it; however, the decoctions currently used in clinical practice cannot extract and retain the volatile oils, resulting in the loss of some key active ingredients. This invention focuses on the extraction of volatile oils from these two herbs. After crushing them into coarse powder, steam distillation is used for extraction to maximize the extraction of the active ingredients. Furthermore, considering that volatile oils are easily oxidized and decomposed during storage and use due to the combined effects of light, oxygen, temperature, and other environmental factors, the obtained volatile oils are further encapsulated with β-cyclodextrin or hydroxypropyl-β-cyclodextrin to stabilize the volatile oils and improve their bioavailability.

[0028] Beneficial effects of the technical solution:

[0029] 1. The traditional Chinese medicine composition provided by this invention is a novel combination. Based on the use of raw Atractylodes macrocephala in large doses, it also uses Citrus aurantium and Prunus persica. The formula has a reasonable ratio, simple ingredients, and definite curative effect. Compared with Zhishu pills and Zhishu granules made only by Atractylodes macrocephala and Citrus aurantium, pharmacodynamic experiments have shown that the formula of this invention has a better laxative effect.

[0030] 2. Compared with existing Chinese medicines containing Atractylodes macrocephala and Citrus aurantium (such as Qi Rong Run Chang Oral Liquid, Yi Qi Tong Bian Granules, and Shou Hui Tong Bian Capsules), Qi Rong Run Chang Oral Liquid is composed of Astragalus membranaceus (processed), Cistanche deserticola, Atractylodes macrocephala, Pseudostellaria heterophylla, Rehmannia glutinosa, Scrophularia ningpoensis, Ophiopogon japonicus, Angelica sinensis, Polygonatum sibiricum (processed), Morus alba, black sesame, Cannabis sativa seed, Prunus japonica seed, Citrus aurantium (stir-fried with wheat bran), and honey. This medicine uses Astragalus membranaceus and Cistanche deserticola as the principal herbs and is used for deficiency of both Qi and Yin, and spleen and kidney deficiency. This invention addresses constipation caused by insufficient lubrication of the large intestine, a condition known as deficiency constipation. The Yiqi Tongbian Granules, composed of Polygonum multiflorum, Atractylodes macrocephala, Astragalus membranaceus (processed), Cistanche deserticola, Citrus aurantium, Cimicifuga foetida, and Cannabis sativa, are used for constipation due to deficiency of both Qi and Yin, and disordered ascending and descending functions. The Shouhui Tongbian Capsules use ginseng and aloe vera as the principal herbs, Polygonum multiflorum and donkey-hide gelatin as the assistant herbs, and Lycium barbarum, Cassia tora, Atractylodes macrocephala, and Citrus aurantium as adjuvant herbs. Citrus aurantium is also used as the guiding herb for those with deficiency of both Qi and Yin, accompanied by internal accumulation of toxins. This invention uses raw Atractylodes macrocephala as the principal herb in a large dosage. While other Chinese herbs may also use Atractylodes macrocephala, they are not raw, are not the principal herb, and their usage, dosage, and efficacy differ. This invention's herbal composition primarily targets spleen-deficiency constipation, applicable to various TCM syndromes and populations. Furthermore, this invention does not contain rhubarb anthraquinone components or related medicinal materials, resulting in better safety and long-term use.

[0031] 3. Compared with clinical decoctions, the traditional Chinese medicine composition provided by this invention retains the effective ingredients to the maximum extent, enhances the extraction, utilization and stability of volatile oils, improves efficacy, and solves the problems of difficult storage, use and portability of clinical decoctions; the honey pill dosage form retains more ingredients and expands the application dosage forms of the traditional Chinese medicine composition.

[0032] 4. The preparation method of the traditional Chinese medicine composition provided by the present invention establishes an innovative process of "oil-water dual extraction" + "volatile oil encapsulation" of Shutong granules through "quality improvement and efficiency enhancement", which improves the extraction rate of volatile oil and effective components, solves the problem of volatility stability, and enhances the efficacy. The developed product is derived from clinical practice and its efficacy is higher than that of clinical decoctions.

[0033] 5. This invention provides new treatments and medications for people with constipation due to spleen deficiency and dampness, such as the elderly with weak spleen and stomach, patients after major surgery, young women who are trying to lose weight, obese and weak men, and people who overeat. Attached Figure Description

[0034] Figure 1 This is a process diagram illustrating the preparation of a traditional Chinese medicine composition for treating constipation according to the present invention.

[0035] Figure 2 This is a statistical graph showing the laxative effects (x±SD, n=6) of the aqueous extract, volatile oil, and aqueous extract plus volatile oil on loperamide-induced constipation in mice in Example 6 of the present invention.

[0036] In the figure, A represents the propulsion rate of charcoal powder in the small intestine; B represents the water content of residual feces in the colon.

[0037] Figure 3 The image shows the effect of the traditional Chinese medicine composition granules prepared in Example 10 of this invention on the colonic pathological tissue (HE staining) of mice with spleen deficiency and constipation. Detailed Implementation

[0038] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments:

[0039] Example 1

[0040] Preparation of Traditional Chinese Medicine Composition Y1 Decoction

[0041] First, weigh out 60 parts of raw Atractylodes macrocephala, 10 parts of Citrus aurantium, and 10 parts of Prunus persica according to their weight.

[0042] Then, mix the medicinal materials according to the proportions, add an appropriate amount of water to soak for 30 minutes, boil over high heat for 60 minutes, pour out the liquid, add an appropriate amount of water to the dregs and boil for 60 minutes, combine the two liquids, and concentrate under reduced pressure until dry.

[0043] Example 2

[0044] Preparation of the traditional Chinese medicine composition Y2 decoction

[0045] First, weigh out 60 parts of raw Atractylodes macrocephala and 10 parts of Citrus aurantium according to their weight;

[0046] Then, the medicinal materials are formulated and mixed in proportion, soaked in an appropriate amount of water for 30 min, decocted with strong fire for 60 min, and the medicinal liquid is poured out; the medicinal residues are decocted with an appropriate amount of water for 60 min, and the two decoctions are combined and concentrated under reduced pressure to dryness.

[0047] Example 3

[0048] Preparation of the decoction of traditional Chinese medicine composition Y3

[0049] First, weigh 60 parts of raw Atractylodes macrocephala and 10 parts of peach kernels by weight;

[0050] Then, the medicinal materials are formulated and mixed in proportion, soaked in 8 times the amount of water for 30 min, decocted with strong fire for 60 min, and the medicinal liquid is poured out; the medicinal residues are decocted with an appropriate amount of water for 60 min, and the two decoctions are combined and concentrated under reduced pressure to dryness.

[0051] Example 4

[0052] Pharmacodynamic evaluation of rats with spleen qi deficiency constipation

[0053] Materials and methods

[0054] Experimental animals: 56 male SD rats, weighing 180 - 200 g, purchased from Beijing SPF Biotechnology Co., Ltd., certificate number: SCXK(Beijing)2019 - 0010; the rats were raised in the Animal Experiment Center of Beijing University of Chinese Medicine; feeding conditions: temperature 25°C, humidity 60°, 12 h light and dark cycle. The 56 male SD rats were randomly divided into 8 groups, namely blank group, model group, Qirong Runchang Oral Liquid, Y1, Y2, Y3, and Zhizhu Pills group. Except for the blank group with normal diet and water intake, the modeling process for the remaining groups was as follows: continuously intragastrically administered 6.0 g / kg (raw drug amount / body weight) of senna water extract for 7 days to create a spleen deficiency state in the experimental rats; on the 8th day, the senna water decoction was discontinued, and the spleen deficiency state was maintained by the method of improper diet, that is, low - fiber diet was given every other day, and at the same time, 2 mg / kg of loperamide hydrochloride was intragastrically administered to induce constipation in rats for 8 consecutive days to establish a rat model of spleen qi deficiency constipation. After the modeling was completed, they were randomly divided into 7 groups. While maintaining the above - mentioned modeling method, the rats in each group were given corresponding drug treatments; the blank group was given distilled water. The administration period was 2 weeks. After the administration was completed, 40 min after intragastrically administering 3% D - xylose solution to the rats, blood was taken from the orbital cavity for kit detection. Then, all the rats were separately housed in single cages, and the food intake and fecal count of each rat in 24 h were recorded. At the same time, the water content of fresh feces was detected. Then, the rats were fasted without water restriction for 18 h, intragastrically administered charcoal powder solution every other day, anesthetized 30 min later, and the samples were taken to count various physiological parameter indexes.

[0055] Experimental methods

[0056] Assessment of Small Intestinal Charcoal Propulsion Rate: Thirty minutes after oral administration of charcoal, the patient was euthanized by cervical dislocation. The abdominal cavity was quickly opened, the mesentery was separated, and a complete segment of the small intestine, from the upper end to the pylorus of the stomach and the lower end to the ileocecal junction, was cut and placed on a platform. The small intestine was gently stretched into a straight line and its length was measured to obtain the "total length of the small intestine." The distance from the pylorus of the stomach to the tip of the charcoal-propelled portion was defined as the "charcoal propulsion length." The charcoal propulsion rate was calculated using the following formula:

[0057] Charcoal powder propulsion rate (%) = {charcoal powder propulsion length (cm)} / {total small intestine length (cm)} × 100%.

[0058] Assessment of fecal moisture content in the colon: The entire large intestine was removed, and any remaining feces were taken out and weighed. The feces were then placed in a vacuum drying oven at 60°C and dried to constant weight, weighed again, and the fecal moisture content was calculated using the following formula:

[0059] Fecal moisture content (%) = (fecal wet weight - fecal dry weight) / fecal wet weight × 100%.

[0060] Gastric emptying rate assessment: During rat sampling, the total stomach weight was measured. After rinsing the stomach contents with physiological saline, the saline was wiped clean with filter paper, and the empty stomach weight was measured again. The gastric emptying rate was calculated using the following formula:

[0061] Gastric emptying rate (%) = {1 - (total stomach weight - empty stomach weight) / total stomach weight} * 100%.

[0062] Method for determining D-xylose content: Add 1.5 mL of phloroglucinol reagent to each tube, 0.015 mL of double-distilled water to the test tube, 0.015 mL of 200 mg / L D-xylose standard solution (1.33 mmol / L) to the standard tube, and 0.015 mL of rat serum sample from each group to the test tube. After mixing, simultaneously place each tube in boiling water at 100℃ for 4 min, remove and immediately cool in ice water, mix again, and measure the absorbance (OD) value of each tube at a wavelength of 554 nm. Calculate the D-xylose content in serum using the following formula:

[0063]

[0064] Serum α-amylase activity assay: Add 0.2 mL of substrate buffer to each tube, preheat at 37°C for 5 min, add 0.04 mL of rat serum sample from each group to the test tube, mix well, and incubate at 37°C for 7.5 min. Add 0.2 mL of iodine working solution to each tube. Add 1.2 mL of double-distilled water to the test tube and 1.24 mL to the blank tube. Mix well, zero the absorbance (OD) at 660 nm wavelength with double-distilled water. Calculate serum α-amylase activity using the following formula:

[0065]

[0066] In this experiment, the concentration of the substrate buffer solution was 0.4 mg / mL; the addition amount of the substrate buffer solution was 0.2 mL; the reaction time was 7.5 min, the sampling amount was 0.04 mL; the sample dilution factor was 100 times.

[0067] Example 5

[0068] Pharmacodynamic evaluation of slow transit constipation mice

[0069] 1. Materials and methods

[0070] Experimental animals: 40 KM mice, half male and half female, weighing 18 - 22 g, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., certificate number: SCXK(Beijing)2016 - 0006; the mice were housed in the barrier environment of the animal house of Beijing University of Chinese Medicine; feeding conditions: temperature, 25°C, humidity 60°, 12 h light and dark cycle, fed with normal maintenance feed, and free access to water. The 40 KM mice, half male and half female, were randomly divided into 5 groups, with 8 mice in each group, namely the blank group, the model group, the high-dose Y1 group (10 g / kg), the low-dose Y1 group (5 g / kg), and the Maren Runchang Pills group (3 g / kg). Except for the blank group, the other groups were intragastrically administered loperamide hydrochloride (6.0 mg / kg) at 9 am every day to induce constipation in mice, and the blank group was given 0.5% CMC-Na. Intragastric administration of drugs was carried out 1 hour after modeling for 7 consecutive days. Then, the mice were fasted but not water-restricted for 18 hours. On the 8th day, the blank group was given 0.5% CMC-Na, and the model group and the drug administration groups were given 6.0 mg / kg of loperamide hydrochloride. 1 hour later, each group was given the prepared charcoal powder (the charcoal powder in the blank group and the model group did not contain any drugs, while the charcoal powder in the drug administration groups contained the corresponding doses of drugs).

[0071] The experimental method was the same as that in Example 4.

[0072] 2. Experimental results

[0073] 2.1 Effect on the intestinal charcoal powder propulsion of spleen qi deficiency constipation rats

[0074] As shown in Table 1, compared with the model group, the intestinal charcoal powder propulsion rate of Y1 was significantly enhanced (P < 0.01), comparable to that of Qirong Runchang Oral Liquid group, Y2 and Y3 also had certain improvement effects (P < 0.05), while although the Zhizhu Pills group had certain improvement, there was no statistical difference.

[0075] Table 1 Effect of the traditional Chinese medicine composition on the intestinal charcoal powder propulsion of spleen qi deficiency constipation rats

[0076]

[0077]

[0078] Note: Compared with the blank group,## P < 0.01; compared with the model group, * P<0.05, ** P < 0.01.

[0079] 2.2 Effects on fecal quantity and water content in rats with spleen deficiency and constipation

[0080] Compared with the model group, the daily fecal output of rats in the Y1, Y2, Y3 and Qirong Runchang Oral Liquid groups was significantly increased (P < 0.05). Although the Zhishu Pill group also showed an increase, there was no statistically significant difference. Among them, Y1 and Y3 showed better effects than Y2, possibly because the peach kernels in Y1 and Y3 are rich in cellulose, which can compensate for the lack of fiber in the low-fiber diet, promote intestinal peristalsis, lubricate the intestines, and stimulate fecal excretion.

[0081] Spleen deficiency constipation refers to a condition where feces remain in the intestines for too long, resulting in hardened stools, prolonged defecation cycles, and loose stools. While there is an urge to defecate, defecation is difficult and inefficient. Only cases of actual constipation will present with dry stools. The results of fecal water content analysis in rat models showed that the rats did not exhibit dry stools, consistent with the symptoms of spleen deficiency constipation. Although there was no statistically significant difference in fecal water content across all groups, a certain trend was observed. For example, in the spleen deficiency constipation model rats, the reduced ability to transport and transform fluids due to spleen deficiency may have led to a slight increase in fecal water content. After drug treatment, Atractylodes macrocephala, with its spleen-strengthening and dampness-drying effects, reduced fecal water content in groups Y1 and Y2, bringing it closer to the normal group. Astragalus and Cistanche deserticola oral liquid, with its dual function of tonifying both qi and yin, also improved fecal water content to some extent, as shown in Table 2.

[0082] Table 2. Effects of traditional Chinese medicine composition on fecal quantity and water content in rats with spleen deficiency and constipation.

[0083]

[0084]

[0085] Note: Compared with the blank group, ### P < 0.001; compared with the model group, * P<0.05, ** P < 0.01.

[0086] 2.3 Effects on food intake in rats with spleen deficiency and constipation

[0087] Compared with the model group, the food intake of rats in the Y1, Qirong Runchang Oral Liquid, and Zhishu Pill groups was significantly increased (P<0.05). The food intake of rats in the Y2 group also showed some improvement, but there was no statistical difference. The effect of Y2 was slightly stronger than that of Y3, possibly due to the combination of Atractylodes macrocephala and Citrus aurantium in Y2, which have the effect of strengthening the spleen and promoting digestion. Zhishu Pill is mainly used to treat spleen and stomach weakness, poor appetite and abdominal distension, so it has a more significant effect on improving food intake, as shown in Table 3.

[0088] Table 3. Effects of traditional Chinese medicine composition on 24-hour food intake in rats with spleen deficiency and constipation.

[0089]

[0090] Note: Compared with the blank group, ## P < 0.01; compared with the model group, * P < 0.05.

[0091] 2.4 Effects on gastric emptying rate in rats with spleen deficiency and constipation

[0092] Compared with the model group, the gastric emptying rate of Y1, Y2, Y3 and Qirong Runchang Oral Liquid groups was significantly enhanced (P<0.05), with Y1 showing better results than Y2 and Y3. Atractylodes macrocephala has a tonifying effect, while Citrus aurantium has a purging effect, thus achieving the effect of tonifying without causing stagnation. Therefore, in terms of gastric emptying rate, Y1 (Atractylodes macrocephala, Citrus aurantium, and Peach Kernel group) and Y2 (Atractylodes macrocephala and Citrus aurantium group) were better than Y3 (Atractylodes macrocephala and Peach Kernel group), as shown in Table 4.

[0093] Table 4. Effects of traditional Chinese medicine composition on gastric emptying in rats with spleen deficiency and constipation.

[0094]

[0095] Note: Compared with the blank group, #### P < 0.0001; compared with the model group, * P<0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001.

[0096] 2.5 Effects on spleen and stomach function in rats with spleen deficiency and constipation

[0097] Compared with the model group, the D-xylose content in the serum of Y1 rats was significantly increased (P<0.01), while that in Y2 rats was somewhat improved (P<0.05). Compared with the model group, the α-amylase activity in the serum of Y1 and Y2 rats was significantly increased (P<0.01); the α-amylase activity in Y3 rats was also increased (P<0.05), as shown in Table 5.

[0098] Table 5. Effects of traditional Chinese medicine composition on serum D-xylose content and α-amylase activity in rats with spleen deficiency and constipation.

[0099]

[0100]

[0101] Note: Compared with the blank group, ## P < 0.01; compared with the model group, * P<0.05, ** P < 0.01.

[0102] 2.6 Effects of loperamide-induced slow-transit constipation in mice

[0103] Compared with the model group, the intestinal charcoal propulsion rate of mice in both the high- and low-dose Y1 groups was significantly increased (P<0.01), and the fecal water content in the colon of mice in the high-dose Y1 group was significantly increased (P<0.05). Specific data are shown in Table 6. This indicates that the herbal composition Y1 of this invention can significantly improve slow-transit constipation in mice, as shown in Table 6.

[0104] Table 6. Effects of traditional Chinese medicine composition on loperamide-induced slow transit constipation in mice. n=8)

[0105]

[0106] Note: Compared with the blank group, # P<0.05, ## P < 0.01; compared with the model group, * P<0.05, ** P < 0.01.

[0107] As can be seen from the above description, the traditional Chinese medicine composition Y1 provided by the present invention can significantly promote small intestinal propulsion, defecation and increase water content, indicating that it has a significant therapeutic effect on slow transit constipation mice; the traditional Chinese medicine compositions Y1, Y2 and Y3 all have significant therapeutic effects on spleen-deficiency constipation rats, promoting small intestinal propulsion and defecation, improving spleen and stomach function, gastric emptying and food intake. Y1 has a better therapeutic effect than Y2 and Y3, and compared with the already marketed drug Zhishu Pill, the formula of the present invention (Atractylodes macrocephala, Citrus aurantium and Prunus persica) has a better laxative effect.

[0108] Example 6

[0109] The original decoction of the traditional Chinese medicine composition Y1 of this invention has shown definite clinical efficacy. Given that Atractylodes macrocephala and Citrus aurantium contain abundant volatile oils, and literature review has found that they have significant prokinetic effects on the gastrointestinal tract, this was further confirmed through pharmacological experiments. Therefore, using only the decoction would waste the volatile oil components and affect the efficacy; if it were modified to extract both oil and water, the effect of improving constipation could be significantly enhanced.

[0110] This embodiment illustrates the advantages of using steam distillation to achieve both oil and water extraction in the traditional Chinese medicine composition Y1.

[0111] 1. Preparation of samples of traditional Chinese medicine composition Y1 using different extraction methods

[0112] Raw Atractylodes macrocephala and Citrus aurantium were crushed into coarse powder. Peach kernels were broken into appropriate pieces. The ingredients were weighed and mixed according to the ratio. The mixture was soaked in 8 times the amount of water for 30 minutes. The mixture was then extracted by steam distillation for 60 minutes, once, and the volatile oil and extract were collected. The volatile oil from the two extractions was combined to obtain the total volatile oil (HFY). The extracts from the two extractions were combined and concentrated under reduced pressure to a thick paste to obtain the water extract (ST). The volatile oil and the water extract were mixed to obtain the oil-water dual extract (ST+HFY).

[0113] 2. Effects of samples prepared by different extraction methods of traditional Chinese medicine composition Y1 on slow-transit constipation mice.

[0114] like Figure 2 As shown, the aqueous extract (ST), volatile oil (HFY), and aqueous extract plus volatile oil (ST+HFY) of the herbal composition Y1 of this invention can all improve loperamide-induced constipation symptoms in mice. The charcoal propulsion rate increased significantly by 13.82%, 18.64%, and 24.62%, respectively, and the water content of residual feces in the colon increased significantly by 12.02%, 14.53%, and 16.45%, respectively. This indicates that the volatile oil of the herbal composition Y1 of this invention has a clear efficacy, and its effect is better when used in combination with the aqueous extract. Therefore, the oil-water dual extraction process of the herbal composition Y1 of this invention is superior.

[0115] Example 7

[0116] like Figure 1 As shown, this embodiment illustrates the method for preparing granules of traditional Chinese medicine composition provided by the present invention.

[0117] Prescription: 900g of raw Atractylodes macrocephala, 150g of Citrus aurantium, and 150g of Prunus persica.

[0118] Preparation: Raw Atractylodes macrocephala and Citrus aurantium are coarsely powdered and combined with Prunus persica kernel. Add 6.4 L of water and extract twice, 1 hour each time. Filter and collect the volatile oil and extract. Concentrate and dry the extract under reduced pressure at 60℃ to obtain a dry extract powder. Weigh 90 g of β-cyclodextrin and add it to 720 mL of water. Heat until completely dissolved. Prepare a 50% anhydrous ethanol solution from the extracted volatile oil and add it dropwise to the β-cyclodextrin solution. Stir at 50℃ for 3 hours, then let stand at 4℃ for 24 hours to crystallize. Filter and dry at 40℃ to obtain the volatile oil β-cyclodextrin inclusion complex. Mix the dry extract powder and inclusion complex evenly, add an appropriate amount of maltodextrin, and granulate by dry granulation to obtain 1000 g of the final product.

[0119] Specifications: 10g per bag.

[0120] Dosage and administration: Dissolve in boiling water and drink. Take 1-2 sachets 3 times a day.

[0121] Example 8

[0122] This embodiment illustrates the method for preparing granules of the traditional Chinese medicine composition provided by the present invention. Unlike Example 7, each component (1200g of raw Atractylodes macrocephala, 200g of Citrus aurantium, and 200g of Prunus persica) is weighed according to the raw material ratio described in Example 7, and wet granulation is performed.

[0123] Prescription: 1200g of raw Atractylodes macrocephala, 200g of Citrus aurantium, and 200g of Prunus persica.

[0124] Preparation: Raw Atractylodes macrocephala, Citrus aurantium, and Prunus persica kernel are extracted twice with 16L of water, each time for 4 hours. The extracts are filtered, and the volatile oil and extract are collected. The extract is concentrated under reduced pressure at 60℃ to 0.4g crude drug / mL, and spray-dried (feed rate 500ml / h, atomization pressure 8×10KPa, inlet temperature 120℃) to obtain a dry extract powder. 40g of β-cyclodextrin is weighed and added to 320mL of water and heated until completely dissolved. The extracted volatile oil is prepared into a 50% anhydrous ethanol solution and added dropwise to the β-cyclodextrin solution. The mixture is stirred at 50℃ for 3 hours, then placed at 4℃ for 24 hours to allow crystallization. The crystals are filtered and dried at room temperature to obtain the volatile oil β-cyclodextrin inclusion complex. The dry extract powder and inclusion complex are mixed evenly, an appropriate amount of dextrin is added, and 95% ethanol is sprayed in to form a soft mass. The mass is then wet-granulated to obtain 1400g of the final product.

[0125] Specifications: 12g per bag.

[0126] Dosage and administration: Dissolve in boiling water and drink. Take 1-2 sachets 3 times a day.

[0127] Example 9

[0128] This embodiment illustrates the method for preparing honey pills from traditional Chinese medicine compositions provided by the present invention.

[0129] Prescription: 300g of raw Atractylodes macrocephala, 50g of Citrus aurantium, and 50g of Prunus persica.

[0130] Preparation: Grind raw Atractylodes macrocephala and Citrus aurantium into fine powder, and grind peach kernel into a paste powder. Weigh out the raw Atractylodes macrocephala powder, Citrus aurantium powder, and peach kernel paste powder according to the proportions, mix them evenly, add 400g of medium honey (the temperature of the honey and medicine should be 70℃), and make small or large honey pills.

[0131] Specifications: (1) Small honey pills weigh 20g per 100 pills; (2) Large honey pills weigh 9g per pill.

[0132] Dosage and Administration: Oral administration. For small honeyed pills, take 9 - 18 g (45 - 90 pills) each time, for big honeyed pills, take 1 - 2 pills each time, three times a day.

[0133] Example 10

[0134] This example is used to illustrate the therapeutic effect of traditional Chinese medicine composition Y1 granules on mice with spleen - qi deficiency constipation.

[0135] 1. Materials and Methods

[0136] 1.1 Preparation of intragastric administration liquid of traditional Chinese medicine composition Y1 granules

[0137] Prepared according to Example 7. Before use, weigh Y1 granules and prepare aqueous solutions with concentrations of 0.860 g / mL (80 g of crude drug content), 0.430 g / mL (40 g of crude drug content), and 0.215 g / mL (20 g of crude drug content) respectively.

[0138] 1.2 Establishment and administration of spleen - qi deficiency constipation mouse model

[0139] Experimental animals: 96 KM mice, half male and half female, weighing 18 - 22 g, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., certificate number: SCXK(Beijing)2019 - 0010; the mice were raised in the barrier environment of the animal house of Beijing University of Chinese Medicine; feeding conditions: temperature 25°C, humidity 60°, 12 - hour light and dark cycle, fed with normal maintenance feed, and had free access to water. 84 KM mice, half male and half female, were randomly divided into 7 groups, with 12 mice in each group, namely blank group, model group, mosapride group, Qihuang Tongmi Soft Capsule group, high - dose, medium - dose, and low - dose groups of traditional Chinese medicine composition granules. Continuously intragastric administration of 8.0 g / kg (crude drug content / body weight) aqueous extract of senna for 7 days to cause the spleen - deficiency state of experimental mice, and the blank group was given pure water. From the 8th day, the senna aqueous decoction was stopped, and the spleen - deficiency state was continued by the method of irregular feeding and over - fatigue, that is, feeding every other day and forcing swimming until exhaustion once a day. At the same time, intragastric administration of 6 mg / kg loperamide hydrochloride was used to induce constipation in mice for 8 consecutive days to establish a mouse model of spleen - qi deficiency constipation. From the 16th to 30th day, the above - mentioned modeling method was maintained. After random grouping, each group of mice was given the corresponding drug or distilled water for treatment. After the 30th day, the treatment groups stopped taking drugs, fasted and water - deprived for 18 h, intragastric administration of D - xylose solution, and then intragastric administration of prepared charcoal powder 30 min later (the charcoal powder in the blank group and the model group did not contain any drugs, while the charcoal powder in the drug - administration groups contained the corresponding doses of drugs). After 30 min, blood was collected by eye - ball enucleation, and then the mice were sacrificed by cervical dislocation, and samples were taken for detection of various indexes.

[0140] 1.3 Experimental methods

[0141] Defecation effect assessment: On day 29, mice that had been fasted for 18 hours were gavaged with charcoal powder and then housed in individual cages with free access to food and water. The time of the first black stool and the number of stools excreted within 6 hours were recorded for each animal starting from the time of administration of charcoal powder. The characteristics of the excreted feces were observed and the fecal Bristol trait score was calculated.

[0142] For details on the determination methods of serum D-xylose content, α-amylase activity, small intestinal charcoal propulsion rate, colonic residual fecal quantity and water content, please refer to Example 4.

[0143] 2. Experimental Results

[0144] 2.2 Effects on defecation in mice with spleen deficiency and constipation

[0145] Compared with the model group, the time to first black stool after taking the first capsule of the Y1 granule of the present invention was significantly shortened in the high and medium dose groups, the number of stools within 6 hours was significantly increased, and the Birstol stool characteristics score was significantly increased. Moreover, compared with the mosapride group and the Astragalus and Astragalus Soft Capsule group, the high and medium dose groups of the Y1 granule of the present invention have better therapeutic effects, as shown in Table 7.

[0146] Table 7. Effects of the traditional Chinese medicine composition Y1 granules on defecation in mice with spleen deficiency and constipation.

[0147]

[0148] Note: Compared with the normal group #### P < 0.0001; compared with the model group ** P<0.01, **** P<0.0001.

[0149] 2.3 Effects on spleen and stomach function in mice with spleen deficiency and constipation

[0150] Compared with the model group, the D-xylose content and α-amylase level of mice treated with the high, medium, and low doses of the traditional Chinese medicine composition Y1 granules of this invention were significantly increased. The medium dose of the granules was able to restore the D-xylose content and α-amylase level to the normal levels of the control group, while the high dose group further increased both indicators. These results indicate that the traditional Chinese medicine composition Y1 granules of this invention can significantly improve the spleen deficiency state in mice, and is superior to Qihuang Tongmi soft capsules, while the Western medicine positive control drug mosapride had no significant effect on spleen deficiency, as shown in Table 8.

[0151] Table 8. Effects of the traditional Chinese medicine composition Y1 granules on the spleen and stomach function of mice with spleen deficiency and constipation.

[0152]

[0153]

[0154] Note: Compared with the normal group ### P<0.001, #### P < 0.0001; compared with the model group * P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001.

[0155] 2.4 Effects of charcoal powder on small intestine propulsion in constipation due to spleen deficiency

[0156] Compared with the blank group, the charcoal propulsion rate of mice in the model group was significantly reduced; compared with the model group, the charcoal propulsion rate of mice in the high- and medium-dose groups of the traditional Chinese medicine composition Y1 granules of this invention, as well as the mosapride and Astragalus membranaceus soft capsule groups, was significantly increased (P<0.0001). Compared with the mosapride group and the Astragalus membranaceus soft capsule group, the high-dose group of the traditional Chinese medicine composition Y1 granules of this invention showed better propulsion effect, as shown in Table 9.

[0157] Table 9. Effects of Traditional Chinese Medicine Composition Y1 Granules on Intestinal Charcoal Propulsion in Mice with Spleen Deficiency and Constipation

[0158]

[0159] Note: Compared with the normal group ### P<0.001; compared with the model group **** P<0.001.

[0160] 2.5 Effects on the amount and water content of residual feces in the colon in cases of constipation due to spleen deficiency

[0161] Compared with the control group, the model group mice showed an increase in the amount of residual feces in the colon and a decrease in fecal water content. After a period of administration, the high and medium dose groups of the Y1 granules of the traditional Chinese medicine composition of this invention, as well as the mosapride group and the Astragalus and Astragalus Soft Capsule group, all significantly reduced the amount of residual feces in the colon of mice and significantly increased the fecal water content. Moreover, the high dose group showed better improvement than the mosapride group and the Astragalus and Astragalus Soft Capsule group, as shown in Table 10.

[0162] Table 10 Effects on the amount and moisture content of residual feces in the colon

[0163]

[0164] Note: Compared with the normal group # P<0.05, ### P<0.001; compared with the model group ** P<0.01, *** P<0.001, **** P<0.001.

[0165] 2.6 Effects on the pathological morphology of colon tissue

[0166] like Figure 3 As shown, the thickness of the colonic mucosa and muscularis propria in the model group mice was significantly reduced, and the intestinal lumen was enlarged. The colonic structure of the high-dose group of the herbal composition granules and the mosapride group of this invention were improved to some extent. The submucosa and muscularis propria structure of the control group mice were clearly visible, and no obvious pathological changes were observed. The goblet cells of the intestinal glands of the model group mice were reduced, the crypts were arranged in a disordered manner, and the mucosal edge was damaged. The colonic tissue lesions of the high- and medium-dose Y1 granule groups were improved, the goblet cells increased, the crypts were arranged neatly, and the mucosal edge was intact, similar to the normal group.

[0167] Based on the comprehensive evaluation results of the above indicators, it can be seen that the traditional Chinese medicine composition Y1 granules of the present invention can improve defecation, spleen and stomach function, small intestinal transit and propulsion, and the amount and water content of residual feces in the colon, thereby achieving the effect of treating constipation due to spleen deficiency. Moreover, it has a better therapeutic effect than the marketed drugs mosapride and Astragalus and Astragalus Soft Capsules.

[0168] The above descriptions are merely embodiments of the present invention, and common knowledge regarding specific technical solutions or characteristics is not elaborated upon here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solutions of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A traditional Chinese medicine composition for treating constipation, characterized in that, By weight, it is made from 60-120 parts of raw Atractylodes macrocephala, 10-20 parts of Citrus aurantium and 10-20 parts of peach kernel.

2. The method for preparing a traditional Chinese medicine composition for treating constipation according to claim 1, characterized in that, Includes the following steps: S1. Weigh out the raw Atractylodes macrocephala, Citrus aurantium and peach kernel according to the specified amounts. Crush the raw Atractylodes macrocephala and Citrus aurantium into powder, and break the peach kernel into pieces. S2. Weigh the pulverized material prepared in step S1 according to the weight ratio of the composition and mix them. Add 4 to 12 times the amount of water to the mixture and heat and extract by steam distillation to obtain volatile oil and extract. S3. The volatile oil obtained in step S2 is encapsulated with β-cyclodextrin or hydroxypropyl-β-cyclodextrin to obtain a volatile oil inclusion complex; the extracts obtained in step S2 are combined, concentrated, and dried to obtain a dry extract powder. S4. The volatile oil inclusion complex, dry extract powder and excipients prepared in step S3 are mixed to obtain the traditional Chinese medicine composition.

3. The method for preparing a traditional Chinese medicine composition for treating constipation according to claim 2, characterized in that, In S2, extract for 20-80 minutes, and repeat the extraction twice.

4. The method for preparing a traditional Chinese medicine composition for treating constipation according to claim 2, characterized in that, In S3, the method for preparing the volatile oil inclusion complex is as follows: first, the volatile oil is dissolved in 95% ethanol, and then it is added to a saturated solution of β-cyclodextrin or hydroxypropyl-β-cyclodextrin. The inclusion complex is then prepared by ultrasonication or saturated aqueous solution method. After crystallization, filtration, and drying at room temperature, the β-cyclodextrin or hydroxypropyl-β-cyclodextrin inclusion complex is obtained, thus preparing the volatile oil inclusion complex.

5. The method for preparing a traditional Chinese medicine composition for treating constipation according to claim 4, characterized in that, During the inclusion process, the weight ratio of volatile oil: β-cyclodextrin or hydroxypropyl-β-cyclodextrin: water is 1:6~10:48~120; the inclusion temperature is 30~50 ℃; the inclusion time is 1~3 h; after completion, it is placed at 4 ℃ for 24 hours, and after crystallization and filtration, it is dried at room temperature.

6. The method for preparing a traditional Chinese medicine composition for treating constipation according to claim 2, characterized in that, In S3, the concentration method is vacuum concentration, and the drying method is vacuum drying or spray drying.

7. The method for preparing a traditional Chinese medicine composition for treating constipation according to claim 2, characterized in that, In S4, the excipient is dextrin; the weight ratio of dry extract powder to excipient is 1~8:

1.

8. The method for preparing a traditional Chinese medicine composition for treating constipation according to claim 1, characterized in that, Includes the following steps: M1. Crush raw Atractylodes macrocephala and Citrus aurantium into powder; grind peach kernel into a paste due to its high oil content; M2. Weigh out the raw Atractylodes macrocephala powder, Citrus aurantium powder, and Prunus persica powder according to the weight ratio of the composition, mix them evenly, add refined honey, the weight ratio of the mixed powder to refined honey is 1:0.8~1.5, the mixing temperature is 50~80 ℃, and form into honey pills containing the Chinese medicine composition.

9. The application of the traditional Chinese medicine composition for treating constipation according to claim 1 in the preparation of a drug for treating slow-transit constipation.

10. The use of the traditional Chinese medicine composition for treating constipation according to claim 1 in the preparation of a medicine for treating constipation caused by spleen deficiency.

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