A traditional Chinese medicine composition for lubricating intestines and defecating and a preparation method and application thereof

Abstract

The application relates to the technical field of traditional Chinese medicines, and provides a traditional Chinese medicine composition for moistening intestines and relieving constipation as well as a preparation method and application of the traditional Chinese medicine composition. Raw material components of the traditional Chinese medicine composition contain, in weight parts, 23-42 weight parts of donkey-hide gelatin beads, 23-42 weight parts of siler, 5-8 weight parts of nard, 5-8 weight parts of gentiana, 11-21 weight parts of dried orange peel, 11-21 weight parts of angelica, 11-21 weight parts of bitter orange, 11-21 weight parts of cooked rhubarb, 5-8 weight parts of sloe, 11-21 weight parts of hemp seeds and 5-8 weight parts of schizonepeta. The traditional Chinese medicine composition provided by the application can produce a significant synergistic effect among the components, so that the purposes of moistening intestines, relieving constipation and treating constipation are achieved; and the traditional Chinese medicine composition has the effects of mild drug efficacy, remarkable curative effect, high safety and the like.

Description

[0001] This application claims priority to Chinese Patent Application No. CN202411739397.6, filed on November 29, 2024, entitled "A Traditional Chinese Medicine Composition for Relieving Intestinal Lubrication and Its Preparation Method and Application", the entire contents of which are incorporated herein by reference. Technical Field

[0002] This application relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for relieving constipation and its preparation method and application. Background Technology

[0003] Constipation is a condition characterized by difficulty in defecation, prolonged defecation cycles (less than 3 times per week), or short cycles but with hard, dry stools that are difficult to pass, or soft stools with frequent urges to defecate but incomplete bowel movements. In recent years, with the increasing refinement of diets, faster pace of life, and greater work pressure, the prevalence of constipation in my country has been on the rise. It not only affects appetite and can induce diseases such as anal fissures, hemorrhoids, and colon cancer, but also, in some patients, long-term constipation can lead to insomnia, irritability, depression, anxiety, and other mental and psychological disorders, affecting work, study, and daily life. Especially for patients with cardiovascular diseases, prolonged abdominal pressure during defecation reduces blood return to the heart and increases intracranial pressure, greatly increasing the probability of malignant arrhythmias and cerebrovascular accidents, thus endangering the patient's life.

[0004] Because the causes of constipation are not yet fully understood and the mechanisms are complex, Western medicine lacks specific treatment methods for constipation in clinical practice. Treatment mainly relies on osmotic laxatives, bulk-forming laxatives, stimulant laxatives, lubricant laxatives, and other drugs that enhance gastric motility and promote the production of beneficial microorganisms. Although traditional osmotic or stimulant laxatives (such as polyethylene glycol, bisacodyl, lactulose, and sulfates) are inexpensive and initially effective, long-term use can lead to dependence, reduced efficacy, numerous adverse reactions, and a high relapse rate. They can even damage intestinal nerves, disrupt the body's normal flora, and worsen constipation. Therefore, there is a need to develop new laxative drugs that are mild, effective, and safe. Summary of the Invention

[0005] The purpose of this application is to provide a traditional Chinese medicine composition for relieving constipation, its preparation method, and its application. The components of this composition exhibit significant synergistic effects, thereby achieving the purpose of relieving constipation and treating constipation. Furthermore, the composition is mild, has significant therapeutic effects, and is highly safe. The specific technical solution is as follows:

[0006] The first aspect of this application provides a traditional Chinese medicine composition for relieving constipation, wherein the raw material components of the traditional Chinese medicine composition, by weight, include: 23-42 parts of donkey-hide gelatin beads, 23-42 parts of saposhnikovia root, 5-8 parts of notopterygium root, 5-8 parts of gentian root, 11-21 parts of dried tangerine peel, 11-21 parts of angelica root, 11-21 parts of immature bitter orange peel, 11-21 parts of bitter almond, 11-21 parts of prepared rhubarb, 5-8 parts of apricot kernel, 11-21 parts of hemp seed, and 5-8 parts of schizonepeta.

[0007] The raw material components of the traditional Chinese medicine composition, by weight, consist of 23-42 parts of donkey-hide gelatin beads, 23-42 parts of saposhnikovia root, 5-8 parts of notopterygium root, 5-8 parts of gentian root, 11-21 parts of dried tangerine peel, 11-21 parts of angelica root, 11-21 parts of immature bitter orange peel, 11-21 parts of bitter almond, 11-21 parts of prepared rhubarb, 5-8 parts of apricot kernel, 11-21 parts of hemp seed, and 5-8 parts of schizonepeta.

[0008] In some embodiments of this application, the raw material components of the traditional Chinese medicine composition, by weight, include: 26-39 parts of donkey-hide gelatin beads, 26-39 parts of saposhnikovia root, 5-8 parts of notopterygium root, 5-8 parts of gentian root, 13-20 parts of dried tangerine peel, 13-20 parts of angelica root, 13-20 parts of immature bitter orange peel, 13-20 parts of bitter almond, 13-20 parts of prepared rhubarb, 5-8 parts of apricot kernel, 13-20 parts of hemp seed, and 5-8 parts of schizonepeta.

[0009] In some embodiments of this application, the raw material components of the traditional Chinese medicine composition, by weight, consist of 26-39 parts of donkey-hide gelatin beads, 26-39 parts of saposhnikovia root, 5-8 parts of notopterygium root, 5-8 parts of gentian root, 13-20 parts of dried tangerine peel, 13-20 parts of angelica root, 13-20 parts of immature bitter orange peel, 13-20 parts of bitter almond, 13-20 parts of prepared rhubarb, 5-8 parts of apricot kernel, 13-20 parts of hemp seed, and 5-8 parts of schizonepeta.

[0010] In some embodiments of this application, the traditional Chinese medicine composition further includes a pharmaceutically acceptable carrier or excipient; preferably, the pharmaceutically acceptable carrier or excipient is selected from at least one of solvents, diluents, disintegrants, precipitation inhibitors, surfactants, flow aids, binders, lubricants, dispersants, suspending agents, isotonic agents, thickeners, emulsifiers, preservatives, stabilizers, hydrating agents, emulsification accelerators, buffers, absorbents, colorants, flavorings, sweeteners, ion exchangers, release agents, coating agents, flavoring agents, and antioxidants.

[0011] In some embodiments of this application, the traditional Chinese medicine composition is formulated as a pharmaceutically acceptable preparation; preferably, the traditional Chinese medicine composition is formulated as any one of the dosage forms of granules, decoctions, pills, tablets or capsules.

[0012] The second aspect of this application provides a method for preparing granules of a traditional Chinese medicine composition, comprising the steps of:

[0013] (1) The herbs Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed and Schizonepeta tenuifolia described in the first aspect of this application are decocted and extracted with water, and then the filtrate is collected by filtration; the filtrate is concentrated into a clear paste.

[0014] (2) The prepared rhubarb and donkey-hide gelatin beads described in the first aspect of this application are pulverized and sieved to obtain fine powder of donkey-hide gelatin beads and fine powder of prepared rhubarb;

[0015] (3) Mix the fine powder of donkey-hide gelatin beads, the fine powder of cooked rhubarb and the excipients evenly, and then add the clear paste for granulation to obtain the traditional Chinese medicine composition granules; or, (3') dry the clear paste and pulverize it, mix it evenly with the fine powder of donkey-hide gelatin beads and the fine powder of cooked rhubarb, then add the excipients and wetting agent, mix it evenly and granulate it, and then dry it again to obtain the traditional Chinese medicine composition granules; or, (3'') dry the clear paste and pulverize it, mix it evenly with the fine powder of donkey-hide gelatin beads and the fine powder of cooked rhubarb, and then add the excipients for granulation to obtain the traditional Chinese medicine composition granules.

[0016] In some embodiments of this application, in step (1), the weight of the water is 4-10 times the total weight of the following herbs: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia; the decoction extraction is performed 2-3 times, with each decoction extraction lasting 0.5-3 hours; the concentration is performed under reduced pressure, with the temperature of the reduced pressure concentration being 65-85°C; and the relative density of the extract is 1.05-1.20.

[0017] In some embodiments of this application, in step (3), step (3') or step (3''), the mass ratio of the excipient to the extract is 1:(0.5-2); the excipient includes dextrin, lactose and steviol glycosides in a mass ratio of (1-3):1:(0.006-0.06).

[0018] In some embodiments of this application, the granulation process parameters in step (3) include: air inlet temperature of 80-100℃, atomization pressure of 0.3-0.4 bar, and liquid inlet speed of 7-20 rpm.

[0019] In some embodiments of this application, in step (3'), the drying method is selected from at least one of vacuum drying, belt drying and spray drying; the wetting agent is selected from water or an aqueous solution of ethanol with a volume fraction of 70%-95%; and the temperature of the re-drying is 40℃-60℃.

[0020] In some embodiments of this application, in step (3''), the drying method is selected from at least one of vacuum drying, belt drying and spray drying.

[0021] The third aspect of this application provides a method for preparing a traditional Chinese medicine decoction, comprising the steps of: decocting and extracting the following herbs as described in the first aspect of this application: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia, and then filtering and collecting the filtrate; pulverizing and sieving the following herbs as described in the first aspect of this application: Rheum palmatum and Colla corii as described in the first aspect of this application, and then mixing them evenly with the filtrate to obtain the traditional Chinese medicine decoction.

[0022] In some embodiments of this application, the weight of the water is 4-10 times the total weight of the following herbs: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia. Preferably, the decoction extraction is performed 2-3 times, and each decoction extraction takes 0.5-3 hours.

[0023] The fourth aspect of this application provides a method for preparing a traditional Chinese medicine composition tablet, comprising the following steps: decocting and extracting the following herbs as described in the first aspect of this application: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia, and then filtering and collecting the filtrate; concentrating the filtrate into a clear extract; drying and pulverizing the clear extract to obtain an extract powder; pulverizing and sieving the following herbs as described in the first aspect of this application: Rheum palmatum and Colla corii as described in the first aspect of this application, then mixing them evenly with excipients and the extract powder, then adding water for granulation, then adding magnesium stearate and mixing evenly, and finally compressing into tablets to obtain a traditional Chinese medicine composition tablet.

[0024] In some embodiments of this application, the weight of the water is 4-10 times the total weight of the following herbs: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia; the decoction extraction is performed 2-3 times, with each extraction lasting 0.5-3 hours; the concentration is performed under reduced pressure at a temperature of 65-85°C; the relative density of the extract is 1.05-1.20; the drying is performed under reduced pressure at a temperature of 65-85°C; the mass ratio of the excipients to the extract powder is (0.5-1.5):1; the excipients include dextrin, lactose, and steviol glycosides in a mass ratio of (1-3):1:(0.006-0.06); and the mass of magnesium stearate is 0.4%-0.6% of the mass of the granules obtained from granulation.

[0025] Some embodiments of this application include the following steps:

[0026] (1) Weigh the raw material components according to the following weight parts: 26-39 parts of donkey-hide gelatin beads, 26-39 parts of saposhnikovia root, 5-8 parts of notopterygium root, 5-8 parts of gentian root, 13-20 parts of dried tangerine peel, 13-20 parts of angelica root, 13-20 parts of bitter orange peel, 13-20 parts of bitter almond, 13-20 parts of prepared rhubarb, 5-8 parts of apricot kernel, 13-20 parts of hemp seed, and 5-8 parts of schizonepeta.

[0027] (2) The above-weighed Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed and Schizonepeta tenuifolia are decocted and extracted 2-3 times with water. The weight of water added each time is 4-10 times the total weight of Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed and Schizonepeta tenuifolia. The decoction time is 0.5-3 hours. The extracts from each decoction are filtered through a 150-220 mesh filter cloth. The filtrates are combined and concentrated under reduced pressure at 65-85℃ to a clear extract with a relative density of 1.05.

[0028] (3) The above-weighed cooked rhubarb and donkey-hide gelatin beads were crushed and passed through an 80-mesh sieve to obtain fine powder of cooked rhubarb and fine powder of donkey-hide gelatin beads respectively.

[0029] (4) Mix the excipients (dextrin: lactose: steviol glycosides = 1-3:1:0-0.06, mass ratio), fine powder of cooked rhubarb, and fine powder of donkey-hide gelatin beads evenly and place them in a one-step granulator. Spray the above-mentioned clear paste into the granulator for granulation (the mass ratio of excipients to clear paste is 1:0.5-2). The granulation process parameters include: air inlet temperature 80-100℃, atomization pressure 0.3-0.4 bar, and liquid inlet speed 7-20 rpm to obtain the traditional Chinese medicine composition granules.

[0030] Some embodiments of this application include the following steps:

[0031] (1) Weigh the raw material components according to the following weight parts: 31.2 parts of donkey-hide gelatin beads, 31.2 parts of saposhnikovia root, 6.2 parts of notopterygium root, 6.2 parts of gentian root, 15.6 parts of dried tangerine peel, 15.6 parts of angelica root, 15.6 parts of bitter orange peel, 15.6 parts of bitter almond, 15.6 parts of prepared rhubarb, 6.2 parts of apricot kernel, 15.6 parts of hemp seed, and 6.2 parts of schizonepeta.

[0032] (2) The above-weighed Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia were decocted and extracted twice with water. The weight of water added in the first decoction was 10 times the total weight of Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia, and the extraction time for the first decoction was 2 hours. The weight of water added in the second decoction was 8 times the total weight of Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia, and the extraction time for the second decoction was 1 hour. The extracts from both decoctions were filtered through a 200-mesh filter cloth, and the filtrates were combined and concentrated under reduced pressure at 65°C to a clear extract with a relative density of 1.05.

[0033] (3) The above-weighed cooked rhubarb and donkey-hide gelatin beads were crushed and passed through an 80-mesh sieve to obtain fine powder of cooked rhubarb and fine powder of donkey-hide gelatin beads respectively.

[0034] (4) Mix the excipients (dextrin: lactose: steviol glycosides = 1-2:1:0-0.03, mass ratio), fine powder of cooked rhubarb, and fine powder of donkey-hide gelatin beads evenly and place them in a one-step granulator. Spray the above-mentioned clear paste into the granulator for granulation (the mass ratio of excipients to clear paste is 1:2). The granulation process parameters include: air inlet temperature 90℃, atomization pressure 0.35 bar, and liquid inlet speed 15 rpm to obtain the traditional Chinese medicine composition granules.

[0035] In some embodiments of this application, the bitter almonds in step (2) are preferably steamed or added later.

[0036] The fifth aspect of this application provides the use of the traditional Chinese medicine composition described in the first aspect of this application in the preparation of a medicament for the prevention and / or treatment of constipation; wherein the constipation is slow transit constipation, blood deficiency constipation, fluid deficiency constipation, or heat constipation; preferably heat constipation.

[0037] The beneficial effects of this application are:

[0038] This application provides a traditional Chinese medicine composition, which uses twelve raw materials, namely, donkey-hide gelatin beads, saposhnikovia root, notopterygium root, gentian root, tangerine peel, angelica root, bitter orange peel, bitter almond, prepared rhubarb, apricot kernel, hemp seed, and schizonepeta, as raw materials. The components of the prepared traditional Chinese medicine composition can produce significant synergistic effects, thereby achieving the purpose of moistening the intestines and relieving constipation. It also has the effects of mild efficacy, significant therapeutic effect, and high safety. The preparation method is simple, safe and easy to operate, and has low production cost.

[0039] Of course, implementing any product or method of this application does not necessarily require achieving all of the advantages described above at the same time. Attached Figure Description

[0040] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other embodiments can be obtained based on these drawings.

[0041] Figure 1 Typical fluorescence intestinal tracts of zebrafish after different sample treatments;

[0042] Figure 2 Figure showing the comparison of fluorescence intensity values ​​in the intestines of zebrafish after different sample treatments;

[0043] Figure 3 The effect of laxative granules on 6-hour fecal scores in rats with slow transit constipation was shown.

[0044] Figure 4 The effect of the laxative granules on the 24-hour fecal score in rats with slow transit constipation was shown.

[0045] Figure 5 A visual representation of the small intestinal propulsion rate in rats with slow transit constipation after administration of Run Chang granules;

[0046] Figure 6 The effect of Run Chang Granules on the 6-hour fecal score of rats with blood deficiency-type constipation was shown.

[0047] Figure 7 The effect of Run Chang Granules on 24-hour fecal scores in rats with blood deficiency-type constipation was shown.

[0048] Figure 8 A visual representation of the small intestinal propulsion rate in rats with blood deficiency-type constipation after administration of Runchang granules;

[0049] Figure 9 The effect of Runchang Granules on the 6-hour fecal score of rats with body fluid deficiency-type constipation was shown.

[0050] Figure 10 The effect of Run Chang Granules on 24-hour fecal scores in rats with body fluid deficiency-type constipation was shown.

[0051] Figure 11 A visual representation of the intestinal propulsion rate of Runchang Granules in rats with constipation due to body fluid deficiency. Detailed Implementation

[0052] The technical solutions of this application will be clearly and completely described below with reference to the embodiments and accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. All other embodiments obtained by those skilled in the art based on this application are within the scope of protection of this application.

[0053] Constipation is one of the advantageous diseases treated by traditional Chinese medicine. Treatment can be based on holistic diagnosis and treatment, especially the combination of traditional Chinese and Western medicine, and the combined treatment of various traditional Chinese medicine methods. On this basis, individualized and targeted treatment can be implemented. For elderly and weak people with constipation, it can significantly improve the clinical symptoms of patients, eliminate pathogens without harming the body's vital energy, and address both the symptoms and the root cause. It also has the advantages of few toxic side effects, is easy for patients to accept, and has broad development prospects.

[0054] For constipation medications, top-selling products on the market, such as Shouhui Tongbian Capsules, Biantong Tablets / Capsules, Maren Runchang Pills / Capsules, Maren Pills / Soft Capsules, and Danggui Longhui Tablets / Capsules, mainly focus on syndromes such as Qi and Yin deficiency, Spleen and Kidney Yang deficiency, and Liver Qi stagnation transforming into fire. The traditional Chinese medicine composition discovered by the inventors in this application not only has the effect of clearing heat and relieving constipation, clearing heat from the spleen and stomach, but also has the effects of nourishing Yin and generating fluids, replenishing Qi and nourishing blood. It can be used to treat constipation in the elderly or those with weak constitutions caused by excessive fire, fluid deficiency, and blood deficiency. Compared with the aforementioned products, it belongs to different TCM syndrome types, filling a gap in the market and possessing high clinical value.

[0055] The first aspect of this application provides a traditional Chinese medicine composition for relieving constipation, wherein the raw material components of the traditional Chinese medicine composition, by weight, include: 23-42 parts of donkey-hide gelatin beads, 23-42 parts of saposhnikovia root, 5-8 parts of notopterygium root, 5-8 parts of gentian root, 11-21 parts of dried tangerine peel, 11-21 parts of angelica root, 11-21 parts of immature bitter orange peel, 11-21 parts of bitter almond, 11-21 parts of prepared rhubarb, 5-8 parts of apricot kernel, 11-21 parts of hemp seed, and 5-8 parts of schizonepeta. For example, the weight percentages of donkey-hide gelatin beads can be 23, 25, 26, 29, 31, 33, 35, 37, 39, 41, 42, or any two values ​​within this range; the weight percentages of Saposhnikovia divaricata can be 23, 25, 26, 29, 31, 33, 35, 37, 39, 41, 42, or any two values ​​within this range; the weight percentages of Notopterygium incisum can be 5, 6, 7, 8, or any two values ​​within this range; the weight percentages of Gentiana macrophylla can be 5, 6, 7, 8, or any two values ​​within this range; the weight percentages of Citrus reticulata peel can be 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or any two values ​​within this range; and the weight percentages of Angelica sinensis can be 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or any two values ​​within this range. The weight parts of Citrus aurantium can be 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or any two values ​​in between; the weight parts of Prunus armeniaca can be 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or any two values ​​in between; the weight parts of Rheum palmatum can be 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or any two values ​​in between; the weight parts of Prunus japonica seed can be 5, 6, 7, 8 or any two values ​​in between; the weight parts of Cannabis sativa seed can be 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or any two values ​​in between; and the weight parts of Schizonepeta tenuifolia can be 5, 6, 7, 8 or any two values ​​in between.

[0056] Those skilled in the art will understand that the weight proportions of the aforementioned Chinese medicinal materials are relative, and the amount of one or more of the medicinal materials can be reasonably adjusted based on traditional Chinese medicine theory and actual needs. All obvious variations of such reasonably adjusted formulations are within the scope of this application.

[0057] The inventors of this application discovered in their research that a traditional Chinese medicine composition prepared from twelve ingredients—donkey-hide gelatin beads, saposhnikovia root, notopterygium root, gentian root, tangerine peel, angelica root, bitter orange peel, bitter almond, prepared rhubarb, apricot kernel, hemp seed, and schizonepeta—possesses the effects of nourishing yin and promoting body fluids, replenishing qi and blood, clearing heat and relieving constipation. It is minimally irritating and has a mild effect, making it suitable for preventing and / or treating constipation in the elderly or those with weak constitutions caused by excessive internal heat. The components of this traditional Chinese medicine composition exhibit a significant synergistic effect, thereby achieving the purpose of lubricating the intestines and relieving constipation; furthermore, it has the advantages of mild efficacy, significant therapeutic effect, and high safety.

[0058] All raw materials used in this application are available through purchase. The processing methods for the medicinal slices can be carried out in accordance with relevant regulations, for example:

[0059] Ejiao beads: These are solid gelatinous products made from the dried or fresh skin of the donkey (Equus asinus L.) through decoction and concentration. The processing technology is based on Part I of the 2020 edition of the Chinese Pharmacopoeia and should comply with the relevant regulations under the "Ejiao beads" section. The place of origin is Heze, Shandong.

[0060] Fangfeng: It is the processed product of the dried root (Fangfeng) of Saposhnikovia divaricata (Turcz.) Schishk., a plant of the Apiaceae family; the processing technology is in accordance with Part I of the 2020 edition of the Chinese Pharmacopoeia and complies with the relevant provisions under the "Fangfeng" decoction pieces; the place of origin is Bayannur, Inner Mongolia.

[0061] Notopterygium incisum Ting ex HT Chang (Notopterygium incisum Ting ex HT Chang) is a processed product of dried rhizome and root (Notopterygium incisum Ting ex HT Chang). The processing technology is based on Part I of the 2020 edition of the Chinese Pharmacopoeia and complies with the relevant regulations under the "Notopterygium incisum" decoction pieces. The place of origin is Ganzi, Sichuan.

[0062] Gentiana dahurica Fisch. is a processed product of the dried root (Gentiana dahurica Fisch.) of the Gentianaceae family. The processing technology is in accordance with Part I of the 2020 edition of the Chinese Pharmacopoeia and complies with the relevant provisions under the "Gentiana" decoction pieces section. The place of origin is Qinghai.

[0063] Chenpi (dried tangerine peel): a processed product of dried mature peel (Citrus reticulata Blanco) and its cultivated varieties, belonging to the Rutaceae family; the processing technology is based on Part I of the 2020 edition of the Chinese Pharmacopoeia and complies with the relevant regulations under the "Chenpi" decoction pieces; the place of origin is Jinhua, Zhejiang.

[0064] Angelica sinensis: It is the processed and prepared product of the dried root (Angelica sinensis) of the plant Angelica sinensis (Oliv.) Diels in the Umbelliferae family; the preparation process is based on Part I of the Chinese Pharmacopoeia 2020 Edition and complies with the relevant regulations under the item of "Angelica sinensis" cut pieces; the place of origin is Dingxi, Gansu.

[0065] Fructus Aurantii Immaturus: It is the processed and prepared product of the dried immature fruit (Fructus Aurantii Immaturus) of the plant Citrus aurantium L. in the Rutaceae family and its cultivated varieties; the preparation process is based on Part I of the Chinese Pharmacopoeia 2020 Edition and complies with the relevant regulations under the item of "Fructus Aurantii Immaturus" cut pieces; the place of origin is Jiangxi.

[0066] Semen Armeniacae Amarum: It is the processed and prepared product of the dried mature seed (Semen Armeniacae Amarum) of the plant Prunus mandshurica (Maxim.) Koehne in the Rosaceae family; the preparation process is based on Part I of the Chinese Pharmacopoeia 2020 Edition and complies with the relevant regulations under the item of "Semen Armeniacae Amarum" cut pieces; the place of origin is Hebei.

[0067] Radix et Rhizoma Rhei Praeparata: It is the processed and prepared product of the dried root and rhizome (Radix et Rhizoma Rhei) of the plant Rheum officinale Baill. in the Polygonaceae family; the preparation process is based on Part I of the Chinese Pharmacopoeia 2020 Edition and complies with the relevant regulations under the item of "Radix et Rhizoma Rhei Praeparata" cut pieces; the place of origin is Sichuan.

[0068] Semen Pruni: It is the processed and prepared product of the dried mature seed (Semen Pruni) of the plants Prunus humilis Bge. and Prunus japonica Thunb. in the Rosaceae family; the preparation process is based on Part I of the Chinese Pharmacopoeia 2020 Edition and complies with the relevant regulations under the item of "Semen Pruni" cut pieces; the place of origin is Chifeng, Inner Mongolia.

[0069] Fructus Cannabis: It is the processed and prepared product of the dried mature fruit (Fructus Cannabis) of the plant Cannabis sativa L. in the Moraceae family; the preparation process is based on Part I of the Chinese Pharmacopoeia 2020 Edition and complies with the relevant regulations under the item of "Fructus Cannabis" cut pieces; the place of origin is Jincheng, Shanxi.

[0070] Herba Schizonepetae: It is the processed and prepared product of the dried aerial part (Herba Schizonepetae) of the plant Schizonepeta tenuifolia Briq. in the Lamiaceae family; the preparation process is based on Part I of the Chinese Pharmacopoeia 2020 Edition and complies with the relevant regulations under the item of "Herba Schizonepetae" cut pieces; the place of origin is Baoding, Hebei.

[0071] In some embodiments of this application, the raw material components of the traditional Chinese medicine composition, by weight, include: 26-39 parts by weight of donkey-hide gelatin beads, 26-39 parts by weight of saposhnikovia root, 5-8 parts by weight of notopterygium root, 5-8 parts by weight of gentian root, 13-20 parts by weight of dried tangerine peel, 13-20 parts by weight of angelica root, 13-20 parts by weight of immature bitter orange peel, 13-20 parts by weight of bitter almond, 13-20 parts by weight of prepared rhubarb, 5-8 parts by weight of apricot kernel, 13-20 parts by weight of hemp seed, and 5-8 parts by weight of schizonepeta. Further research by the inventors has revealed that traditional Chinese medicine compositions with controlled raw material components within this range have better effects in lubricating the intestines, relieving constipation, and treating constipation.

[0072] In some embodiments of this application, the raw material components of the traditional Chinese medicine composition, by weight, consist of 23-42 parts of donkey-hide gelatin beads, 23-42 parts of saposhnikovia root, 5-8 parts of notopterygium root, 5-8 parts of gentian root, 11-21 parts of dried tangerine peel, 11-21 parts of angelica root, 11-21 parts of immature bitter orange peel, 11-21 parts of bitter almond, 11-21 parts of prepared rhubarb, 5-8 parts of apricot kernel, and 11-21 parts of hemp seed. The formula is composed of 5-8 parts by weight of Schizonepeta tenuifolia; preferably, it is composed of 26-39 parts by weight of donkey-hide gelatin beads, 26-39 parts by weight of Saposhnikovia divaricata, 5-8 parts by weight of Notopterygium incisum, 5-8 parts by weight of Gentiana macrophylla, 13-20 parts by weight of dried tangerine peel, 13-20 parts by weight of Angelica sinensis, 13-20 parts by weight of Citrus aurantium, 13-20 parts by weight of bitter almond, 13-20 parts by weight of prepared rhubarb, 5-8 parts by weight of Prunus japonica seed, 13-20 parts by weight of hemp seed and 5-8 parts by weight of Schizonepeta tenuifolia.

[0073] In the traditional Chinese medicine composition for relieving constipation provided in this application, donkey-hide gelatin pearls are sweet and neutral in nature, entering the lung, liver, and kidney meridians, nourishing yin and moistening dryness, nourishing blood and moistening the intestines; hemp seed is sweet and neutral in nature, entering the spleen, stomach, and large intestine meridians, moistening the intestines and relieving constipation, while also nourishing and tonifying deficiency; Prunus japonica seed is bitter, pungent, sweet, and neutral, entering the spleen and large intestine meridians, moistening dryness and lubricating the intestines, promoting urination and relieving constipation, while also purging intestinal heat, and together they are the principal herbs. Aurantium is good at regulating qi and relieving chest congestion, promoting circulation and relieving bloating; Citrus reticulata peel regulates qi and strengthens the spleen; the two combined regulate qi and relieve constipation, making qi flow smoothly and bowel movements easy; Saposhnikovia divaricata and Notopterygium incisum disperse wind-evil and assist in the distribution of qi, blood, and body fluids, and together they are the assistant herbs. Prepared rhubarb retains the cold nature of rhubarb, purging fire and relieving constipation, clearing accumulated heat in the stomach and intestines, and preventing dry stool from forming internally; Angelica sinensis nourishes and harmonizes blood, moistens the intestines and relieves constipation; Prunus armeniaca seed clears lung qi and moistens the large intestine, facilitating the large intestine's function of transmission, and together they are the adjuvant herbs. Gentian root clears deficiency heat and eliminates damp heat; its texture is moist and can also moisten dryness. Schizonepeta root ascends and disperses wind-heat, serving as an adjuvant.

[0074] In some embodiments of this application, the traditional Chinese medicine composition further includes a pharmaceutically acceptable carrier or excipient; preferably, the pharmaceutically acceptable carrier or excipient is selected from at least one of solvents, diluents, disintegrants, precipitation inhibitors, surfactants, flow aids, binders, lubricants, dispersants, suspending agents, isotonic agents, thickeners, emulsifiers, preservatives, stabilizers, hydrating agents, emulsification accelerators, buffers, absorbents, colorants, flavorings, sweeteners, ion exchangers, release agents, coating agents, flavoring agents, and antioxidants.

[0075] In some embodiments of this application, the traditional Chinese medicine composition is formulated as a pharmaceutically acceptable preparation; preferably, the traditional Chinese medicine composition is formulated as any one of the dosage forms of granules, decoctions, pills, tablets or capsules.

[0076] The second aspect of this application provides a method for preparing granules of a traditional Chinese medicine composition, comprising the steps of:

[0077] (1) The ingredients of Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata, Angelica sinensis, Citrus aurantium, Prunus armeniaca, Prunus japonica, Cannabis sativa and Schizonepeta tenuifolia (prepared according to the proportion of each ingredient in the first aspect of this application) are added to water and decocted for extraction, and then filtered and the filtrate is collected; the filtrate is concentrated into a clear paste.

[0078] (2) The prepared rhubarb and donkey-hide gelatin beads (prepared according to the proportion of each raw material component described in the first aspect of this application) are pulverized and sieved to obtain fine powder of donkey-hide gelatin beads and fine powder of prepared rhubarb.

[0079] (3) Mix the fine powder of donkey-hide gelatin beads and the fine powder of cooked rhubarb with the excipients evenly, and then add the clear paste for granulation to obtain the traditional Chinese medicine composition granules (boiling granulation); or, (3') dry the clear paste and pulverize it, mix it evenly with the fine powder of donkey-hide gelatin beads and the fine powder of cooked rhubarb, then add the excipients and wetting agent, mix it evenly and granulate it, and then dry it again to obtain the traditional Chinese medicine composition granules (wet granulation); or, (3'') dry the clear paste and pulverize it, mix it evenly with the fine powder of donkey-hide gelatin beads and the fine powder of cooked rhubarb, then add the excipients for granulation to obtain the traditional Chinese medicine composition granules (dry granulation).

[0080] This application does not impose any particular limitation on the mesh size of the sieve used for sieving, as long as the inventive purpose of this application can be achieved. For example, a 70-100 mesh sieve can be used. This application also does not impose any particular limitation on the filtration method, as long as the inventive purpose of this application can be achieved. For example, a 150-220 mesh filter cloth can be used for filtration. The granulation described in this application can be performed using a granulator.

[0081] In some embodiments of this application, in step (1), the weight of the water is 4-10 times the total weight of the following herbs: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia. In some embodiments of this application, the weight of the water can be 4, 5, 6, 7, 8, 9, or 10 times the total weight of the following herbs: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia, or any two values ​​within this range. Controlling the amount of water within the above range in this application is beneficial for better extraction of the effective components from each herbal decoction piece.

[0082] In some embodiments of this application, in step (1), the decoction extraction is performed 2-3 times, with each decoction extraction lasting 0.5-3 hours. When the decoction extraction is performed 2-3 times, the filtrates need to be combined. In some embodiments of this application, the decoction extraction time for each extraction is 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, or any two values ​​within this range. By controlling the number of decoction extractions and the extraction time for each extraction within the above range, this application facilitates better extraction of the effective components from each Chinese herbal medicine.

[0083] In some embodiments of this application, in step (1), the concentration is vacuum concentration, and the vacuum concentration temperature is 65-85°C. In some embodiments of this application, the vacuum concentration temperature can be 65°C, 70°C, 75°C, 80°C, 85°C, or a range of any two values ​​therein. Controlling the vacuum concentration temperature within the above range in this application is beneficial for better concentration of the extract while minimizing the loss of active ingredients.

[0084] In some embodiments of this application, in step (1), the relative density of the extract is 1.05-1.20. The relative density of the extract described in this application is measured at room temperature, such as 25°C. In some embodiments of this application, the relative density of the extract can be 1.05, 1.10, 1.15, 1.20, or a range consisting of any two values ​​in between. Controlling the relative density of the extract within the above range in this application is beneficial for subsequent granulation and minimizes the loss of active ingredients.

[0085] In some embodiments of this application, in step (3), step (3'), or step (3''), the mass ratio of the excipient to the extract is 1:(0.5-2). In some embodiments of this application, the mass ratio of the excipient to the extract can be 1:0.5, 1:0.8, 1:1, 1:1.2, 1:1.5, 1:1.8, 1:2, or a range consisting of any two ratios therein. Controlling the mass ratio of the excipient to the extract within the above ranges in this application is beneficial for better granulation.

[0086] In some embodiments of this application, in step (3), step (3'), or step (3''), the excipients include dextrin, lactose, and steviol glycosides in a mass ratio of (1-3):1:(0.006-0.06). In some embodiments of this application, the mass ratio of dextrin, lactose, and steviol glycosides is 1:1:0.006, 2:1:0.006, 3:1:0.006, 1:1:0.01, 2:1:0.01, 3:1:0.01, 1:1:0.06, 2:1:0.06, 3:1:0.06, or any range of two ratios therein. Controlling the mass ratio of dextrin, lactose, and steviol glycosides within the above ranges in this application is beneficial for better granulation and results in granules with a better taste.

[0087] In some embodiments of this application, the granulation process parameters in step (3) include: an inlet air temperature of 80-100℃, an atomization pressure of 0.3-0.4 bar, and a liquid inlet speed of 7-20 rpm. In some embodiments of this application, the inlet air temperature can be 80℃, 85℃, 90℃, 95℃, 100℃, or any two values ​​within this range; the atomization pressure can be 0.3 bar, 0.32 bar, 0.34 bar, 0.36 bar, 0.38 bar, 0.4 bar, or any two values ​​within this range; and the liquid inlet speed can be 7 rpm, 9 rpm, 11 rpm, 13 rpm, 15 rpm, 17 rpm, 20 rpm, or any two values ​​within this range. Controlling the inlet air temperature, atomization pressure, and liquid inlet speed within the above ranges in this application is beneficial for better granulation.

[0088] In some embodiments of this application, in step (3'), the drying method is selected from at least one of vacuum drying, belt drying and spray drying.

[0089] In some embodiments of this application, in step (3'), the wetting agent is selected from water or an aqueous ethanol solution with a volume fraction of 70%-95%. In some embodiments of this application, the volume fraction of the aqueous ethanol solution can be 70%, 75%, 80%, 85%, 90%, 95%, or any two values ​​within this range. Controlling the volume fraction of the aqueous ethanol solution within the above range in this application is beneficial for better wetting. This application does not impose any particular limitation on the amount of wetting agent used, as long as the inventive purpose of this application is achieved; it can be selected according to actual needs or the type of wetting agent.

[0090] In some embodiments of this application, the re-drying temperature in step (3') is 40°C-60°C. In some embodiments of this application, the re-drying temperature can be 40°C, 45°C, 50°C, 55°C, 60°C, or a range of any two values ​​in between. Controlling the re-drying temperature within the above range in this application is beneficial for quickly removing moisture from the particles while minimizing the loss of active ingredients.

[0091] In some embodiments of this application, in step (3''), the drying method is selected from at least one of vacuum drying, belt drying and spray drying.

[0092] The third aspect of this application provides a method for preparing a traditional Chinese medicine decoction. The method involves decocting and extracting the following ingredients (as described in the first aspect of this application): Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia) with water, followed by filtration and collection of the filtrate. Then, the following ingredients (as described in the first aspect of this application): Rheum palmatum (processed) and Colla corii asini (prepared according to the proportions of the ingredients described in the first aspect of this application) are pulverized, sieved, and then mixed evenly with the filtrate to obtain the traditional Chinese medicine decoction.

[0093] This application does not impose any particular limitation on the mesh size of the sieve used for sieving, as long as the purpose of this invention can be achieved. For example, a 70-100 mesh sieve can be used. This application also does not impose any particular limitation on the filtration method, as long as the purpose of this invention can be achieved. For example, a 150-220 mesh filter cloth can be used for filtration.

[0094] In some embodiments of this application, the weight of the water is 4-10 times the total weight of the following herbs: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia. In some embodiments of this application, the weight of the water can be 4, 5, 6, 7, 8, 9, or 10 times the total weight of the following herbs: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia, or any two values ​​within this range. Controlling the amount of water within the above range in this application is beneficial for better extraction of the effective components from each herbal decoction piece.

[0095] In some embodiments of this application, the decoction extraction is performed 2-3 times, with each extraction lasting 0.5-3 hours. When the decoction extraction is performed 2-3 times, the filtrates need to be combined. In some embodiments of this application, the extraction time for each decoction is 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, or any combination of two values ​​in between. By controlling the number of decoction extractions and the extraction time within the above ranges, this application facilitates better extraction of the effective components from each Chinese herbal medicine.

[0096] The fourth aspect of this application provides a method for preparing a tablet of a traditional Chinese medicine composition, comprising the steps of:

[0097] The ingredients described in the first aspect of this application, namely Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia (prepared according to the proportions of the raw material components described in the first aspect of this application), are decocted and extracted with water, and then the filtrate is collected by filtration. The filtrate is concentrated into a clear extract. The clear extract is dried and pulverized to obtain an extract powder. The ingredients described in the first aspect of this application, namely Rheum palmatum and Colla corii asini (prepared according to the proportions of the raw material components described in the first aspect of this application), are pulverized and sieved. Then, they are mixed evenly with excipients and the extract powder, and then water is added for granulation. After that, magnesium stearate is added and mixed evenly, and then tablets are compressed to obtain a traditional Chinese medicine composition tablet.

[0098] This application does not impose any particular limitation on the mesh size of the sieve used for sieving, as long as the inventive objective is achieved. For example, a 70-100 mesh sieve can be used. This application also does not impose any particular limitation on the filtration method, as long as the inventive objective is achieved. For example, a 150-220 mesh filter cloth can be used for filtration. This application does not impose any particular limitation on the amount of water used during the granulation process, as long as the inventive objective is achieved.

[0099] In some embodiments of this application, the weight of the water is 4-10 times the total weight of the following herbs: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia. In some embodiments of this application, the weight of the water can be 4, 5, 6, 7, 8, 9, or 10 times the total weight of the following herbs: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia, or any two values ​​within this range. Controlling the amount of water within the above range in this application is beneficial for better extraction of the effective components from each herbal decoction piece.

[0100] In some embodiments of this application, the decoction extraction is performed 2-3 times, with each extraction lasting 0.5-3 hours. When the decoction extraction is performed 2-3 times, the filtrates need to be combined. In some embodiments of this application, the extraction time for each decoction is 0.5 hours, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, or any combination of two values ​​in between. By controlling the number of decoction extractions and the extraction time within the above ranges, this application facilitates better extraction of the effective components from each Chinese herbal medicine.

[0101] In some embodiments of this application, the concentration is vacuum concentration, and the vacuum concentration temperature is 65-85°C. In some embodiments of this application, the vacuum concentration temperature can be 65°C, 70°C, 75°C, 80°C, 85°C, or a range of any two values ​​therein. Controlling the vacuum concentration temperature within the above range in this application is beneficial for better concentration of the extract while minimizing the loss of active ingredients.

[0102] In some embodiments of this application, the relative density of the extract is 1.05-1.20. The relative density of the extract described in this application is measured at room temperature, such as 25°C. In some embodiments of this application, the relative density of the extract can be 1.05, 1.10, 1.15, 1.20, or a range of any two values ​​within this range. Controlling the relative density of the extract within the above range in this application facilitates better subsequent granulation while minimizing the loss of active ingredients.

[0103] In some embodiments of this application, the drying is vacuum drying, and the vacuum drying temperature is 65-85°C. In some embodiments of this application, the vacuum drying temperature can be 65°C, 70°C, 75°C, 80°C, 85°C, or a range of any two values ​​therein. Controlling the vacuum drying temperature within the above range in this application is beneficial for quickly removing moisture from the extract while minimizing the loss of active ingredients.

[0104] In some embodiments of this application, the mass ratio of the excipient to the extract powder is (0.5-1.5):1. In some embodiments of this application, the mass ratio of the excipient to the extract powder can be 0.5:1, 0.6:1, 0.8:1, 1:1, 1.2:1, 1.5:1, or a range consisting of any two ratios therein. Controlling the mass ratio of the excipient to the extract powder within the above range is beneficial for better granulation.

[0105] In some embodiments of this application, the excipients include dextrin, lactose, and steviol glycosides in a mass ratio of (1-3):1:(0.006-0.06). In some embodiments of this application, the mass ratio of dextrin, lactose, and steviol glycosides is 1:1:0.006, 2:1:0.006, 3:1:0.006, 1:1:0.01, 2:1:0.01, 3:1:0.01, 1:1:0.06, 2:1:0.06, 3:1:0.06, or any range of two ratios within this range. Controlling the mass ratio of dextrin, lactose, and steviol glycosides within the above ranges in this application facilitates better granulation and results in tablets with a better taste.

[0106] In some embodiments of this application, the mass of magnesium stearate is 0.4%-0.6% of the mass of the granulated particles. In some embodiments of this application, the mass of magnesium stearate can be 0.4%, 0.45%, 0.5%, 0.55%, 0.6% of the mass of the granulated particles, or a range consisting of any two values ​​therein. Controlling the amount of magnesium stearate within the above range in this application is beneficial for better and more complete release of the active ingredients in the tablets.

[0107] The CAS number for steviol glycoside used in this application is 57817-89-7, and its chemical structural formula is C. 38 H 60 O 18 .

[0108] The methods for preparing granules, decoctions, and tablets of the traditional Chinese medicine composition provided in this application are simple, safe, highly operable, and have low production costs. The pills or capsules described in this application can be prepared using the same methods as those for granules, decoctions, or tablets.

[0109] The fifth aspect of this application provides the use of the traditional Chinese medicine composition described in the first aspect of this application in the preparation of a medicament for the prevention and / or treatment of constipation.

[0110] In some embodiments of this application, the constipation is constipation in the elderly.

[0111] In some embodiments of this application, the constipation is slow transit constipation, blood deficiency constipation, fluid deficiency constipation, or heat constipation; preferably heat constipation.

[0112] Unless otherwise specified or defined, the terms used in this application shall have their general meanings known to those skilled in the art.

[0113] Those skilled in the art will understand that, based on the description herein, the applicable active extracts and preparations of traditional Chinese medicines used in this application can be prepared using appropriate traditional Chinese medicinal materials, alone or in mixtures thereof, through conventional methods of pulverization, extraction, and separation in the art, such as soaking, percolation, liquid-liquid extraction, water extraction with alcohol precipitation, alcohol extraction with water precipitation, and dialysis. Alternatively, one or more active extracts of the traditional Chinese medicines used in this application can be purchased commercially and then combined with extracts of other traditional Chinese medicines to obtain the active extracts of traditional Chinese medicines used in this application. These variations of traditional Chinese medicine compositions and preparations are all within the scope of this application.

[0114] The pharmaceutical compositions and pharmaceutical formulations of this application can be formulated in unit dose form. The term "unit dose form" means a physically dispersed unit suitable for use as a unit dose in human subjects and other mammals, each unit containing a predetermined amount of the pharmaceutical composition or pharmaceutical formulation of this application and suitable pharmaceutically acceptable excipients calculated to produce the desired therapeutic effect.

[0115] As used in this application, the term "treatment" has its general meaning, and in this application specifically refers to the treatment of an individual animal that may suffer from constipation with the drug of this application in order to produce a therapeutic, curative, alleviating, or reducing effect on the disease.

[0116] The actual dosage level and administration time of the traditional Chinese medicine composition or the active ingredient in the traditional Chinese medicine composition of this application can be adaptively changed so that the amount of the active ingredient can effectively achieve the desired therapeutic response for a specific test individual, composition and administration method, without toxicity to the test individual.

[0117] As used in this application, the term "individual" or "animal individual" has its general meaning and, in this application, may refer to an animal individual suffering from or potentially suffering from constipation, or an animal individual used for a specific purpose, such as scientific research. Specifically, the individual refers to an animal individual, particularly a mammalian individual, such as a human, pig, dog, cat, cow, sheep, horse, rat, mouse, rabbit, guinea pig, monkey, etc.

[0118] The embodiments and comparative examples provided below illustrate the implementation of this application in more detail. Various tests and evaluations were conducted according to the methods described below. Furthermore, unless otherwise specified, "parts" and "%" are quality standards.

[0119] Example 1

[0120] (1) Weigh the following raw material components by weight: 156g of donkey-hide gelatin beads, 156g of saposhnikovia root, 31g of notopterygium root, 31g of gentian root, 78g of dried tangerine peel, 78g of angelica root, 78g of immature bitter orange peel, 78g of bitter almond (steamed), 78g of prepared rhubarb, 31g of apricot kernel, 78g of hemp seed and 31g of schizonepeta.

[0121] (2) The above-weighed Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia were decocted and extracted twice with water. The weight of water added in the first decoction was 10 times the total weight of Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia, and the extraction time for the first decoction was 2 hours. The weight of water added in the second decoction was 8 times the total weight of Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia, and the extraction time for the second decoction was 1 hour. The extracts from both decoctions were filtered through a 200-mesh filter cloth, and the filtrates were combined and concentrated under reduced pressure at 65°C to a clear extract with a relative density of 1.05.

[0122] (3) The above-weighed cooked rhubarb and donkey-hide gelatin beads were crushed and passed through an 80-mesh sieve to obtain fine powder of cooked rhubarb and fine powder of donkey-hide gelatin beads respectively.

[0123] (4) Mix the excipients (dextrin: lactose: steviol glycosides = 2:1:0.03, mass ratio), fine powder of cooked rhubarb, and fine powder of donkey-hide gelatin beads evenly and place them in a one-step granulator. Spray the above-mentioned clear paste into the granulator for granulation (the mass ratio of excipients to clear paste is 1:2). The granulation process parameters include: air inlet temperature 90℃, atomization pressure 0.35 bar, and liquid inlet speed 15 rpm to obtain the traditional Chinese medicine composition granules.

[0124] Example 2

[0125] (1) Weigh the following raw material components by weight: 31g of donkey-hide gelatin beads, 31g of saposhnikovia root, 6g of notopterygium root, 6g of gentian root, 16g of dried tangerine peel, 16g of angelica root, 16g of bitter orange peel, 16g of bitter almond, 16g of prepared rhubarb, 6g of apricot kernel, 16g of hemp seed and 6g of schizonepeta.

[0126] (2) Steam the above-weighed bitter almonds at 80-100℃ for 30 minutes; add water to the bitter almonds and the above-weighed saposhnikovia, notopterygium, gentian, tangerine peel, angelica, immature bitter orange, apricot kernel, hemp seed, and schizonepeta for extraction twice. The weight of water added in the first extraction is 6 times the total weight of saposhnikovia, notopterygium, gentian, tangerine peel, angelica, immature bitter orange, bitter almond, apricot kernel, hemp seed, and schizonepeta. The first extraction is carried out by boiling over high heat and then simmering over low heat for 0.5 hours. The weight of water added in the second extraction is 5 times the total weight of saposhnikovia, notopterygium, gentian, tangerine peel, angelica, immature bitter orange, bitter almond, apricot kernel, hemp seed, and schizonepeta. The second extraction is carried out by boiling over high heat and then simmering over low heat for 0.5 hours. Both extracts are filtered through a 200-mesh filter cloth, and the filtrates are combined.

[0127] (3) The above-weighed cooked rhubarb and donkey-hide gelatin beads were crushed and passed through an 80-mesh sieve to obtain fine powder of cooked rhubarb and fine powder of donkey-hide gelatin beads respectively.

[0128] (4) The above-mentioned combined filtrate, cooked rhubarb powder and donkey-hide gelatin powder are thoroughly mixed to obtain a decoction of traditional Chinese medicine composition.

[0129] Example 3

[0130] (1) Weigh the following raw material components by weight: 188g of donkey-hide gelatin beads, 188g of saposhnikovia root, 38g of notopterygium root, 38g of gentian root, 94g of dried tangerine peel, 94g of angelica root, 94g of bitter orange peel, 94g of bitter almond, 94g of prepared rhubarb, 38g of apricot kernel, 94g of hemp seed and 38g of schizonepeta.

[0131] (2) The above-weighed Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed and Schizonepeta tenuifolia were decocted and extracted three times with water. The weight of water added in the first decoction was 6 times the total weight of Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed and Schizonepeta tenuifolia, and the decoction time was 3 hours. The weight of water added in the second decoction was 4 times the total weight of Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed and Schizonepeta tenuifolia, and the decoction time was 1 hour. The weight of water added in the third decoction was 4 times the total weight of Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed and Schizonepeta tenuifolia, and the decoction time was 1 hour. The extracts from all three extractions were filtered through a 200-mesh filter cloth. The filtrates were combined and concentrated under reduced pressure at 85°C to a clear extract with a relative density of 1.20. The extract was then dried under reduced pressure at 65°C and pulverized to obtain the extract powder.

[0132] (3) The above-weighed cooked rhubarb and donkey-hide gelatin beads were crushed and passed through an 80-mesh sieve to obtain fine powder of cooked rhubarb and fine powder of donkey-hide gelatin beads respectively.

[0133] (4) Mix the excipients (dextrin: lactose: steviol glycosides = 2:1:0.03, mass ratio), fine powder of cooked rhubarb, fine powder of donkey-hide gelatin beads and the above extract powder (mass ratio of excipients to extract powder is 1:1) evenly and place them in a one-step granulator, spray water in and granulate; add magnesium stearate (mass of magnesium stearate is 0.5% of the mass of the granules obtained by granulation) to the granules and mix well, compress into tablets to obtain the traditional Chinese medicine composition tablets.

[0134] Examples 4-7

[0135] Except for adjusting the amount of each raw material component as shown in Table 1, the rest is the same as in Example 1.

[0136] Example 8

[0137] Except for replacing the excipients (dextrin:lactose:stevioside = 2:1:0.03, mass ratio) with (lactose:stevioside = 1:0.03, mass ratio), everything else is the same as in Example 1.

[0138] Example 9

[0139] Except for replacing the excipients (dextrin: lactose: steviol glycosides = 2:1:0.03, by mass) with (dextrin: steviol glycosides = 1:0.03, by mass), everything else is the same as in Example 1.

[0140] Example 10

[0141] Except for replacing the excipients (dextrin:lactose:stevioside = 2:1:0.03, mass ratio) with (dextrin:lactose:stevioside = 1:1:0.03, mass ratio), everything else is the same as in Example 1.

[0142] Example 11

[0143] Except for replacing the excipients (dextrin:lactose:steviosides = 2:1:0.03, mass ratio) with (dextrin:lactose:steviosides = 1:2:0.03, mass ratio), everything else is the same as in Example 1.

[0144] Example 12

[0145] Except for replacing the excipients (dextrin:lactose:steviosides = 2:1:0.03, by mass) with (soluble starch:lactose:steviosides = 1:2:0.03, by mass), everything else is the same as in Example 1.

[0146] Example 13

[0147] Except for replacing the excipients (dextrin: lactose: steviol glycosides = 2:1:0.03, mass ratio) with (dextrin: mannitol: steviol glycosides = 1:2:0.03, mass ratio), everything else is the same as in Example 1.

[0148] Example 14

[0149] (1) Weigh the following raw materials by weight: 156g of donkey-hide gelatin beads, 156g of saposhnikovia root, 31g of notopterygium root, 31g of gentian root, 78g of dried tangerine peel, 78g of angelica root, 78g of bitter orange peel, 78g of bitter almond, 78g of prepared rhubarb, 31g of apricot kernel, 78g of hemp seed and 31g of schizonepeta.

[0150] (2) The 12 medicinal materials weighed above were decocted and extracted twice with water. The weight of water added in the first decoction was 10 times the total weight of the medicinal materials, and the extraction time was 2 hours. The weight of water added in the second decoction was 8 times the total weight of the medicinal materials, and the extraction time was 1 hour. The extracts from both decoctions were filtered through a 200-mesh filter cloth. The filtrates were combined and concentrated under reduced pressure at 65°C to a clear extract with a relative density of 1.05.

[0151] (3) After the excipients (dextrin: lactose: steviol glycosides = 2:1:0.03, mass ratio) are mixed evenly, they are placed in a one-step granulator and the above-mentioned clear extract is sprayed in for granulation (the mass ratio of excipients to clear extract is 1:2). The granulation process parameters include: air inlet temperature 90℃, atomization pressure 0.35 bar, liquid inlet speed 15 rpm, to obtain the traditional Chinese medicine composition granules.

[0152] Example 15

[0153] (1) Weigh the following raw materials by weight: 156g of donkey-hide gelatin beads, 156g of saposhnikovia root, 31g of notopterygium root, 31g of gentian root, 78g of dried tangerine peel, 78g of angelica root, 78g of bitter orange peel, 78g of bitter almond, 78g of prepared rhubarb, 31g of apricot kernel, 78g of hemp seed and 31g of schizonepeta.

[0154] (2) Grind the above 12 ingredients into fine powder, pass through a 120-mesh sieve, and mix well. Add 110g of refined honey to every 100g of powder to make honey pills, thus obtaining the Chinese medicine composition pills.

[0155] Example 16

[0156] Except for adjusting the dosage of each raw material component as shown in Table 1, the rest is the same as in Example 2, and a traditional Chinese medicine decoction (intestinal lubricating decoction) is obtained.

[0157] Comparative Examples 1-12

[0158] Except for adjusting the amount of each raw material component as shown in Table 1, the rest is the same as in Example 1.

[0159] Table 1. Raw material components of each embodiment and comparative example

[0160] The following efficacy tests illustrate the effects of the traditional Chinese medicine compositions of the various embodiments and comparative examples of this application on the treatment of constipation. Unless otherwise specified, the laxative granules in the following tests are all granules of the traditional Chinese medicine composition prepared in Example 1.

[0161] I. Zebrafish efficacy test

[0162] 1. Sample preparation

[0163] The traditional Chinese medicine composition granules prepared in Example 1 of this application, the traditional Chinese medicine composition tablets prepared in Example 3 of this application, and the traditional Chinese medicine composition granules prepared in Comparative Examples 1-12 of this application, all used standard dilution water as the solvent.

[0164] The traditional Chinese medicine decoction prepared in Example 2 of this application does not require dilution.

[0165] Positive control: Domperidone Domperidone tablets (hereinafter referred to as domperidone), batch number NBJ6613, were purchased from Xi'an Janssen Pharmaceutical Co., Ltd., and the solvent was DMSO (dimethyl sulfoxide).

[0166] 2. Laboratory animals

[0167] Zebrafish were raised in aquarium water at 28℃ (water quality: 200mg of instant sea salt added per 1L of reverse osmosis water, conductivity 450-550μS / cm; pH 6.5-8.5; hardness 50-100mg / L CaCO3), provided by the applicant's aquarium breeding center. The laboratory animal use license number is: SYXK (Zhejiang) 2022-0004. The breeding and management met the requirements of international AAALAC certification (certification number: 001458), and the IACUC ethics review number is: IACUC-2024-9499-01.

[0168] 3. Instruments, consumables and reagents

[0169] Dissecting microscope (SZX7, OLYMPUS, Japan); CCD camera (VertA1, Shanghai Tusen Vision Technology Co., Ltd., China); Precision electronic balance (CP214, OHAUS, USA); Motorized focusing continuous zoom fluorescence microscope (AZ100, Nikon, Japan); 6-well plate (Zhejiang Belamber Biotechnology Co., Ltd., China); 150mm×25mm petri dish (OrangeScientific, Belgium).

[0170] Aluminum sulfate (lot number RH424739, Shanghai E. En Chemical Technology Co., Ltd., China); Methylcellulose (lot number C2004046, Shanghai Aladdin Biochemical Technology Co., Ltd., China); Nile red (lot number SLBP9326V, Sigma, India); Dimethyl sulfoxide (DMSO, lot number BCCD8942, Sigma, Switzerland).

[0171] 4. Testing methods and results

[0172] (1) Maximum Detection Concentration (MTC)

[0173] Wild-type AB strain zebrafish, 5 days post-fertilization (5 dpf), were randomly selected and placed in culture dishes. A constipation model was established by administering aluminum sulfate in water, while Nile red was administered in water as a fluorescent indicator of intestinal contents. After feeding at 28°C for 3 hours, the zebrafish were randomly assigned to 6-well plates, with 30 zebrafish treated in each well (experimental group). Water-soluble samples were administered (sample concentrations are shown in Table 2), and a normal control group and a model control group were also included, with a volume of 3 mL per well. After treatment at 28°C for 4.5 hours, the MTC of the samples in the model zebrafish was measured.

[0174] The experimental results are shown in Table 2.

[0175] Table 2. Experimental results of treating constipation with samples of different concentrations (n=30)

[0176] Note: "-" indicates that it does not exist; 2000 μg / mL is the maximum concentration for administration. If the concentration is higher than this, the sample will not dissolve completely and cannot be administered. Therefore, administration tests at concentrations higher than this have not been conducted.

[0177] Under the above experimental conditions, the MTC of the traditional Chinese medicine composition granules prepared in Example 1 of this application for treating constipated zebrafish was 2000 μg / mL.

[0178] (2) Evaluation of efficacy in treating constipation

[0179] Wild-type AB strain zebrafish (5 dpf) were randomly selected and placed in petri dishes. A constipation model was established by administering aluminum sulfate in water, while Nile red was administered in water as a fluorescent indicator of intestinal contents. After feeding at 28℃ for 3 h, the zebrafish were randomly assigned to 6-well plates, with 30 zebrafish treated in each well (experimental group). Water-soluble samples were administered (sample concentrations are shown in Table 3). The positive control, domperidone, had a concentration of 75.0 µg / mL. Normal and model control groups were also included, with a volume of 3 mL per well. After treatment at 28℃ for 4.5 h, 10 zebrafish from each group were randomly selected, photographed under a fluorescence microscope, and the images were saved. Data were analyzed and collected using NIS-Elements D 3.20 advanced image processing software. The fluorescence intensity of the zebrafish intestines was analyzed, and the efficacy of the samples in treating constipation was evaluated using statistical analysis. Statistical results are expressed as mean ± SE. Statistical analysis showed that p < 0.05 was statistically significant.

[0180] The experimental results are shown in Table 3. Figure 1 and Figure 2 As shown. Among them, Figure 1 Typical fluorescence intensity images of zebrafish intestines after different sample treatments (yellow dashed boxes indicate the analysis sites in zebrafish). Figure 2 The image shows a comparison of the fluorescence intensity values ​​in the intestines of zebrafish after different sample treatments.

[0181] Table 3. Results of the experiment evaluating the efficacy of different samples in treating constipation (n=10)

[0182] Note: Compared with the model control group, ;

[0183] "-" indicates that it does not exist.

[0184] As can be seen from Table 3, the traditional Chinese medicine compositions prepared in Examples 1-3 of this application all have good efficacy in treating constipation. By comparing the results of Example 1 and Comparative Examples 1-12, it can be seen that when some raw material components of the traditional Chinese medicine composition are not within the scope of this application, the intestinal fluorescence intensity significantly increases, indicating that the efficacy in treating constipation significantly decreases. The above results show that significant synergistic effects can be produced among the components of the traditional Chinese medicine composition provided in this application, so as to achieve the purpose of moistening the intestines and relieving constipation and treating constipation.

[0185] II. Pharmacodynamic experiment for treating slow transit constipation

[0186] Slow Transit Constipation (STC) is a functional intestinal disease with the core feature of colonic motility disorder. It belongs to an important subtype of chronic constipation. Its clinical manifestations mainly include a significant decrease in defecation frequency (less than 3 times a week), dry and hard feces, difficult defecation, and a sense of incomplete evacuation. The course of the disease usually lasts for more than 6 months. According to epidemiological studies, the global prevalence of chronic constipation is about 10%-15%. Among them, about 15%-30% of patients meet the STC diagnostic criteria, and the incidence rate in women is about 2-3 times that in men, which may be related to factors such as hormone levels and differences in pelvic floor structures. It seriously affects the quality of life of patients and may also cause other health problems, such as anal fissure and hemorrhoids, increasing the pain and medical burden of patients. Therefore, it needs to be focused on and addressed in the prevention and treatment of constipation. In this experiment, a slow transit constipation model (western medicine diagnostic criteria) was established to study the pharmacodynamic effects of the traditional Chinese medicine composition granule (i.e., Runchang Granule) prepared in the examples of this application in treating slow transit constipation.

[0187] Experiment 1:

[0188] 1. Experimental materials

[0189] (1) Animals

[0190] Experimental animals: 48 SPF-grade male SD rats, weighing 180-210 g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., with the certificate number: SYXK (Jin) 2020-0005. After the rats were purchased, they were raised in the Experimental Animal Center of Tianjin University of Traditional Chinese Medicine. They were housed in separate cages, with 2 rats in each cage (separated by a partition in the middle), fed with ordinary diet and given free access to water. The environmental temperature was 23±2°C, and the environmental humidity was 35±5%. The day-night cycle was 24 hours. After one week of adaptive feeding, the experiment was carried out. The approval number of the Experimental Animal Welfare and Ethics Committee: TCM-LAEC2025037Z1517.

[0191] (2) Reagents and drugs

[0192] Mosapride citrate tablets: batch number: 240104, Yabao Pharmaceutical Group Co., Ltd.; Compound diphenoxylate (Henan Dingchang Pharmaceutical Co., Ltd., batch number: 23082204); Sodium carboxymethyl cellulose (Beijing Solarbio Technology Co., Ltd., batch number: 24240605006); Activated charcoal powder (Dalian Meilun Biotechnology Co., Ltd., batch number: N1126D); Carmine (Shanghai Maclean Biochemical Co., Ltd., batch number: C14984921). The laxative granules are the traditional Chinese medicine composition granules prepared in Example 1.

[0193] 2. Test methods

[0194] (1) Animal grouping, modeling and drug administration

[0195] Forty-eight male SD rats (weighing 180–210 g) were randomly divided into six groups: normal group, slow-transmission model group, low-dose Runchang granules group (clinically equivalent dose, calculated based on crude drug amount, 2.43 g crude drug / kg), medium-dose Runchang granules group (4.86 g crude drug / kg), high-dose Runchang granules group (9.72 g crude drug / kg), and positive control drug mosapride (3 mg / kg) group, with eight rats in each group.

[0196] A slow-transit constipation model was established using compound diphenoxylate for a total of 14 days. From day 1 to day 14, rats in the slow-transit model group and each drug administration group were administered 20 mg / kg compound diphenoxylate suspension by gavage daily; rats in the normal group were administered an equal volume of CMC-Na solution (solvent) by gavage daily.

[0197] From day 15 to day 21, the model group was continuously administered 20 mg / kg of compound diphenoxylate suspension by gavage daily. Based on the model establishment, each drug administration group was given different interventions: low-dose group (2.43 g / kg, clinically equivalent dose based on crude drug amount), medium-dose group (4.86 g / kg, based on crude drug amount), high-dose group (9.72 g / kg, based on crude drug amount), and positive control drug mosapride group (3 mg / kg). All were administered by gavage at a volume of 1 mL / 100 g for 7 consecutive days. The normal group and slow-transport model group were administered an equal volume of physiological saline by gavage.

[0198] (2) Sampling and testing indicators

[0199] a) General condition observation

[0200] Observe and record the rats' condition (mental state, activity, fur, water intake, etc.) daily.

[0201] b) Stool collection and scoring

[0202] The Bristol fecal scoring scale was used to score the characteristics of rat feces based on fecal shape and consistency.

[0203] Table 4 Bristol Stool Scoring Table

[0204] c) Observation of stool volume and fecal moisture content

[0205] Collect feces within 6 h and 24 h after gavage, and record the total number of particles and wet weight. Place the collected feces in a constant temperature drying oven at 90℃ for 3 h, weigh the dry weight of the feces, and calculate the fecal moisture content (%): Fecal moisture content (%) = (wet weight - dry weight) / (wet weight) × 100%.

[0206] d) Measurement of small intestinal propulsion rate

[0207] After recording the time of the first red stool excretion, the rats were fasted but allowed free access to water for 12 hours. They were then administered 2 mL of 10% (w / v) activated charcoal suspension by gavage. Thirty minutes later, the rats were anesthetized, blood was collected from the abdominal aorta, and the rats were euthanized. The intact intestinal segment from the pylorus to the cecum was then dissected. The intestinal segment was gently straightened and accurately measured using a ruler.

[0208] 1) Total length of the small intestine (from pylorus to cecum);

[0209] 2) The distance the charcoal powder travels from the tip to the pylorus. The small intestinal propulsion rate (%) is calculated using the formula: Small intestinal propulsion rate (%) = (charcoal powder propulsion distance / total small intestinal length) × 100%, which is used to assess intestinal peristalsis.

[0210] (3) Statistical analysis

[0211] Experimental data were statistically processed. Results are expressed as mean ± standard deviation (x̄ ± s). One-way ANOVA was used for comparisons between groups, with P < 0.05 considered statistically significant.

[0212] 3. Test Results

[0213] (1) Observation of the general condition of rats

[0214] During the establishment of the slow transit constipation model, the normal group rats showed good mental state, quick response, soft and shiny fur, normal appetite, and robust body shape. Compared with the normal group, the slow transit model group rats showed mental fatigue, slow response, sparse and yellow fur, decreased appetite, and loose skin. After administration of Runchang granules, the general condition of rats in each dose group of Runchang granules improved.

[0215] (2) The Bristol fecal scoring scale was used to score the feces of rats with slow transit constipation.

[0216] a) Rat fecal score at 6 h

[0217] Compared with the normal group, the 6-hour fecal score of rats in the slow-transport model group was significantly lower (P<0.01); compared with the slow-transport model group, the 6-hour fecal score of each dose group of the laxative granules was significantly increased (P<0.05 or P<0.01), with the low-dose group showing a significant increase on days 4 and 5 of administration (P<0.05 or P<0.01), the medium-dose group showing a significant increase on days 3 and 5 of administration (P<0.05 or P<0.01), and the high-dose group showing a significant increase on days 5 and 6 of administration (P<0.01); the 6-hour fecal score of mosapride was significantly lower on day 2 of administration (P<0.01). Specific results are shown in Tables 5-1 and 5-2. Figure 3 As shown.

[0218] Table 5-1 Effects of Runchang Granules on 6-hour fecal scores in rats with slow transit constipation

[0219] Note: Compared with the normal group, Compared with the slow transmission model group, #P<0.05, ##P<0.01.

[0220] Table 5-2 Effects of Runchang Granules on 6-hour fecal scores in rats with slow transit constipation

[0221] Note: Compared with the normal group, Compared with the slow transmission model group, #P<0.05, ##P<0.01.

[0222] b) Rat fecal score at 24 h

[0223] Compared with the normal group, the 24-hour fecal score of rats in the slow-transport model group was significantly lower (P<0.01); compared with the slow-transport model group, the 24-hour fecal score of each dose group of the laxative granules was significantly increased (P<0.05 or P<0.01). Among them, the low-dose group showed a significant increase on days 2, 3, and 7 of administration (P<0.01), the medium-dose group showed a significant increase on days 1-5 and 7 of administration (P<0.01), and the high-dose group showed a significant increase on days 1-5 of administration (P<0.05 or P<0.01); the mosapride group showed a significant increase in 24-hour fecal score on days 1 and 4 of administration (P<0.01). Specific results are shown in Tables 6-1, 6-2, and 6-3. Figure 4 As shown.

[0224] Table 6-1 Effects of Runchang Granules on 24-hour fecal scores in rats with slow transit constipation

[0225] Note: Compared with the normal group, Compared with the slow transmission model group,## P<0.01.

[0226] Table 6-2 Effects of Runchang Granules on 24-hour fecal scores in rats with slow transit constipation

[0227] Note: Compared with the normal group, Compared with the slow transmission model group, # P<0.05, ## P<0.01.

[0228] (3) Effects of Run Chang Granules on the total number of fecal particles and total wet weight of feces in rats with slow transit constipation within 6 hours

[0229] a) Total number of fecal particles in rats within 6 hours

[0230] Compared with the normal group, the total number of fecal particles in the slow-transmission model group was significantly reduced within 6 hours (P<0.05 or P<0.01); compared with the slow-transmission model group, the total number of fecal particles in the medium-dose laxative granule group was significantly increased within 6 hours on days 1, 4, and 7 after administration (P<0.05 or P<0.01); and the total number of fecal particles in the mosapride group was significantly increased within 6 hours on day 7 after administration (P<0.05). Specific results are shown in Tables 7-1 and 7-2.

[0231] Table 7-1 Effect of Run Chang Granules on the Total Number of Fecal Particles (particles) in Rats with Slow Transit Constipation within 6 Hours

[0232] Note: Compared with the normal group, , Compared with the slow transmission model group, # P<0.05, ## P<0.01.

[0233] Table 7-2 Effect of Run Chang Granules on the Total Number of Fecal Particles (particles) in Rats with Slow Transit Constipation within 6 Hours

[0234] Note: Compared with the normal group, Compared with the slow transmission model group, # P<0.05, ## P<0.01.

[0235] b) Total wet weight of rat feces within 6 hours

[0236] Compared with the normal group, the total wet weight of feces in rats in the slow-transport model group was significantly reduced within 6 hours (P<0.05 or P<0.01). Compared with the slow-transport model group, the total wet weight of feces in the low- and medium-dose groups of the laxative granules was significantly increased within 6 hours. Specifically, the low-dose group showed a significant increase on day 4 of administration (P<0.05), and the medium-dose group showed a significant increase on days 1, 4, 5, and 7 of administration (P<0.05 or P<0.01). Mosapride had no significant effect on the total wet weight of feces in rats within 6 hours (P>0.05). Specific results are shown in Tables 8-1 and 8-2.

[0237] Table 8-1 Effect of Runchang Granules on Total Wet Fecal Weight (g) in Rats with Slow Transit Constipation within 6 Hours

[0238] Note: Compared with the normal group, , Compared with the slow transmission model group, #P<0.05, ##P<0.01.

[0239] Table 8-2 Effect of Runchang Granules on Total Wet Fecal Weight (g) in Rats with Slow Transit Constipation within 6 Hours

[0240] Note: Compared with the normal group, Compared with the slow transmission model group, #P<0.05.

[0241] c) Weight of a single rat feces at 6 hours

[0242] The weight of a single fecal pellet at 6 hours was not significantly different between the slow-transport model group and the normal group (P>0.05). Compared with the slow-transport model group, the medium and high dose groups of the laxative granules significantly increased the weight of a single fecal pellet at 6 hours on day 5 (P<0.05 or P<0.01). Mosapride had no significant effect on the weight of a single fecal pellet at 6 hours (P>0.05). Specific results are shown in Tables 9-1 and 9-2.

[0243] Table 9-1 Effect of Run Chang Granules on the weight of a single feces (g) of a rat with slow transit constipation at 6 h

[0244] Table 9-2 Effect of Run Chang Granules on the Weight of a Single Granule (g) in Rats with Slow Transit Constipation at 6 H

[0245] Note: Compared with the slow transmission model group, #P<0.05, ##P<0.01.

[0246] (4) Effects of Runchang Granules on the total number of fecal particles and total wet weight of feces in rats with slow transit constipation within 24 hours

[0247] a) Total number of fecal particles in rats over 24 hours

[0248] Compared with the normal group, the total number of fecal particles in the slow-transmission model group was significantly reduced within 24 hours (P<0.05 or P<0.01). Compared with the slow-transmission model group, the total number of fecal particles in each dose group of the laxative granules was significantly increased within 24 hours (P<0.05 or P<0.01). Specifically, the low-dose group showed a significant increase on days 1 and 7 of administration (P<0.05 or P<0.01), the medium-dose group showed a significant increase on days 1, 2, 5, and 7 of administration (P<0.05 or P<0.01), and the high-dose group showed a significant increase on days 1, 4, 5, and 7 of administration (P<0.05). The mosapride group showed a significant increase in the total number of fecal particles within 24 hours on days 5 and 7 of administration (P<0.05). Specific results are shown in Tables 10-1 and 10-2.

[0249] Table 10-1 Effect of Run Chang Granules on the Total Number of Fecal Particles (particles) in Rats with Slow Transit Constipation within 24 h

[0250] Note: Compared with the normal group, , Compared with the slow transit model group, #P<0.05, ##P<0.01. Table 10-2 Effect of Run Chang Granules on the total number of fecal particles (particles) in slow transit constipation rats within 24 h.

[0251] Note: Compared with the normal group, Compared with the slow transmission model group, #P<0.05, ##P<0.01.

[0252] b) Total wet weight of rat feces within 24 hours

[0253] Compared with the normal group, the total wet weight of feces in the slow-transport model group was significantly reduced within 24 hours (P<0.05 or P<0.01). Compared with the slow-transport model group, the total wet weight of feces in all dose groups of the laxative granules was significantly increased within 24 hours (P<0.05 or P<0.01). Among them, the low-dose group showed a significant increase on days 1 and 6 of administration (P<0.01), while the medium-dose and high-dose groups showed significant increases on days 1, 2, and 4-7 of administration (P<0.05 or P<0.01). The mosapride group showed a significant increase in total wet weight of feces within 24 hours on days 1, 5, 6, and 7 of administration (P<0.05 or P<0.01). Specific results are shown in Tables 11-1 and 11-2.

[0254] Table 11-1 Effect of Runchang Granules on 24-hour fecal wet weight (g) in rats with slow transit constipation

[0255] Note: Compared with the normal group, , Compared with the slow transmission model group, #P<0.05, ##P<0.01.

[0256] Table 11-2 Effect of Runchang Granules on 24-hour fecal wet weight (g) in rats with slow transit constipation

[0257] Note: Compared with the normal group, , Compared with the slow transmission model group, #P<0.05, ##P<0.01.

[0258] c) Weight of a single rat feces over 24 hours

[0259] The 24-hour fecal weight of the slow-transport model group was not significantly different from that of the normal group (P>0.05). Compared with the slow-transport model group, the 24-hour fecal weight of the medium- and high-dose laxative granules increased to varying degrees (P<0.05 or P<0.01). Among them, the medium-dose group showed a significant increase on day 4 of administration (P<0.05), and the high-dose group showed a significant increase on days 4 and 5 of administration (P<0.05 or P<0.01). Mosapride had no significant effect on the 24-hour fecal weight of rats (P>0.05). Specific results are shown in Tables 12-1 and 12-2.

[0260] Table 12-1 Effect of Run Chang Granules on the Weight of a Single Granule (g) in Rats with Slow Transit Constipation at 24 h

[0261] Note: Compared with the slow transmission model group, #P<0.05, ##P<0.01.

[0262] Table 12-2 Effect of Run Chang Granules on the Weight of a Single Granule (g) in Rats with Slow Transit Constipation at 24 h

[0263] Note: Compared with the slow transmission model group, #P<0.05.

[0264] (5) Effects of Runchang Granules on Colonic Water Metabolism in Rats with Slow Transit Constipation

[0265] Fecal water content can indirectly reflect the colon's water metabolism function.

[0266] a) Water content of rat feces at 6 h

[0267] Compared with the normal group, the fecal water content at 6 h was significantly lower in the slow-transmission model group (P<0.05 or P<0.01). Compared with the slow-transmission model group, the fecal water content at 6 h was significantly increased in both the low- and high-dose groups of the laxative granules (P<0.05). Specifically, the fecal water content at 6 h was significantly increased in the low-dose group on day 5 of administration (P<0.05), and significantly increased in the high-dose group on days 5 and 6 of administration (P<0.05). Mosapride had no significant effect on the fecal water content at 6 h in rats (P>0.05). Specific results are shown in Tables 13-1 and 13-2.

[0268] Table 13-1 Effect of Run Chang Granules on Fecal Moisture Content (%) in Rats with Slow Transit Constipation at 6 H

[0269] Note: Compared with the normal group, , .

[0270] Table 13-2 Effect of Run Chang Granules on Fecal Moisture Content (%) in Rats with Slow Transit Constipation at 6 H

[0271] Note: Compared with the normal group, , Compared with the slow transmission model group, #P<0.05.

[0272] b) Water content of rat feces at 24 h

[0273] Compared with the normal group, the fecal water content of rats in the slow-transport model group was reduced to some extent at 24 h, with a significant decrease on day 2 of administration (P<0.05). Compared with the slow-transport model group, the fecal water content of rats in the medium- and high-dose groups of the laxative granules was significantly increased at 24 h (P<0.05 or P<0.01). Specifically, the medium-dose group showed a significant increase on days 2 and 5 of administration (P<0.05), and the high-dose group showed a significant increase on days 2, 4, 5, 6, and 7 of administration (P<0.05 or P<0.01). The mosapride group showed a significant increase in fecal water content at 24 h on day 3 of administration (P<0.05). Specific results are shown in Tables 14-1 and 14-2.

[0274] Table 14-1 Effect of Run Chang Granules on 24-hour fecal water content (%) in rats with slow transit constipation

[0275] Note: Compared with the normal group, Compared with the slow transmission model group, #P<0.05, ##P<0.01.

[0276] Table 14-2 Effects of Runchang Granules on the water content of feces in rats with slow transit constipation for 24 h (%)

[0277] Note: Compared with the slow transit model group, #P < 0.05, ##P < 0.01.

[0278] (6)Effects of Runchang Granules on the small intestine propulsion rate in rats with slow transit constipation

[0279] Compared with the normal group, the small intestine propulsion rate of the slow transit model group was significantly decreased (P < 0.05); compared with the slow transit model group, the small intestine propulsion rates of each dose group of Runchang Granules increased in varying degrees. Among them, the low-dose group and the medium-dose group increased significantly (P < 0.05 or P < 0.01); the positive drug mosapride could also significantly increase the small intestine propulsion rate of rats with slow transit constipation (P < 0.05). The above results indicate that Runchang Granules can significantly improve the small intestine motor function of rats with slow transit constipation. The specific results are shown in Table 15 and Figure 5 as follows.

[0280] Table 15 Effects of Runchang Granules on the small intestine propulsion rate in rats with slow transit constipation (%)

[0281] Note: Compared with the normal group, ; compared with the slow transit model group, #P < 0.05, ##P < 0.01.

[0282] Experiment 2:

[0283] 1. Experimental materials

[0284] (1)Animals

[0285] Experimental animals: 80 SPF-grade SD male rats, weighing 180 - 210 g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., with the certificate number: SYXK (Jin) 2020 - 0005. After the rats were purchased, they were raised in the Experimental Animal Center of Tianjin University of Traditional Chinese Medicine. They were housed separately in cages, with 2 rats in each cage (separated by a partition in the middle), fed a normal diet and given free access to water. The environmental temperature was 23 ± 2°C, and the environmental humidity was 35 ± 5%. The day-night cycle was 24 h. After one week of adaptive feeding, the experiment was conducted. The approval number of the Experimental Animal Welfare and Ethics Committee: TCM - LAEC2025037Z1517.

[0286] (2)Reagents and drugs

[0287] Mosapride citrate tablets: batch number: 240104, Yabao Pharmaceutical Group Co., Ltd.; Compound diphenoxylate (Henan Dingchang Pharmaceutical Co., Ltd., batch number: 23082204); Sodium carboxymethyl cellulose (Beijing Solarbio Technology Co., Ltd., batch number: 24240605006).

[0288] 2. Test methods

[0289] (1) Animal grouping, modeling and drug administration

[0290] Eighty male SD rats (weighing 180-210 g) were randomly divided into 10 groups: normal group, slow transport model group, Example 1 and Examples 4-7, Examples 14-15 (clinically equivalent dose, calculated based on crude drug amount, 2.43 g crude drug / kg), and positive control drug mosapride (3 mg / kg) group, with 8 rats in each group.

[0291] A slow-transit constipation model was established using compound diphenoxylate for a total of 14 days. From day 1 to day 14, rats in the slow-transit model group and each drug administration group were administered 20 mg / kg compound diphenoxylate suspension by gavage daily; rats in the normal group were administered an equal volume of CMC-Na solution (solvent) by gavage daily.

[0292] From day 15 to day 21, the model group was continuously administered 20 mg / kg of compound diphenoxylate suspension by gavage daily. Based on the modeling, each treatment group was given different interventions: Examples 1 and 4-7, Examples 14-15 (clinically equivalent dose, calculated based on crude drug amount, 2.43 g crude drug / kg) and the positive control drug mosapride group (3 mg / kg), all were administered by gavage at a volume of 1 mL / 100 g for 7 consecutive days. The normal group and the slow transport model group were administered an equal volume of physiological saline by gavage.

[0293] (2) Observation of stool volume and fecal moisture content

[0294] Collect feces within 24 hours after gavage and record the total number of particles and wet weight. Place the collected feces in a constant temperature drying oven at 90℃ for 3 hours, weigh the dry weight of the feces, and calculate the fecal moisture content (%): Fecal moisture content (%) = (wet weight - dry weight) / (wet weight) × 100%.

[0295] 3. Test Results

[0296] (1) Effects of laxatives on the total number of fecal particles and total wet weight of feces in rats with slow transit constipation within 24 hours

[0297] a) Total wet weight of rat feces within 24 hours

[0298] Compared with the normal group, the total wet weight of feces in the slow-transport model group was significantly reduced within 24 hours (P<0.001). Compared with the slow-transport model group, the total wet weight of feces in each prescription group of the Run Chang Granules was increased within 24 hours. Among them, the total wet weight of feces in Examples 1, 4, and 5 was significantly increased within 24 hours on the 7th day of administration (P<0.05 or P<0.01), while Examples 6 and 7 showed an increasing trend on the 7th day of administration. The increase in total wet weight of feces in Examples 1 and Examples 4-5 was greater than that in Examples 6-7, and the total wet weight of feces in Example 1 was significantly higher than that in Example 7 within 24 hours on the 7th day of administration (P<0.05). The granules of Example 14, in which all medicinal materials were extracted with water, were also included. The total wet weight of feces showed an increasing trend within 24 hours; the total wet weight of feces in the laxative pill formulation group of Example 15 increased significantly within 24 hours; the increase in total wet weight of feces in Example 1 was higher than that in Example 15, and even higher than that in Example 14. The total wet weight of feces in Example 1 within 24 hours on the 7th day of administration was significantly higher than that in Examples 14 and 15 (P<0.05). The total wet weight of feces in the mosapride group increased significantly within 24 hours on the 7th day of administration (P<0.01). Specific results are shown in Table 16.

[0299] Table 16 Effects of laxatives on fecal wet weight (g) in rats with slow transit constipation within 24 h

[0300] Note: Compared with the normal group, Compared with the slow transmission model group, #P<0.05, ##P<0.01; compared with Example 1, ^ P<0.05.

[0301] b) Total number of fecal particles in rats over 24 hours

[0302] Compared with the normal group, the total number of fecal particles in the slow-transport model group was significantly reduced within 24 hours (P<0.001). Compared with the slow-transport model group, the total number of fecal particles in each prescription group of the intestinal lubricating granules was significantly increased within 24 hours on the 7th day of administration (P<0.05 or P<0.01). Among them, the increase in Examples 1 and 4-5 was greater than that in Examples 6-7. The total number of fecal particles in Example 1 was significantly higher than that in Example 6 within 24 hours on the 7th day of administration (P<0.05). The total number of fecal particles in Example 14 granules, in which all medicinal materials were extracted with water, was significantly increased within 24 hours. The total number of fecal particles in Example 15 prescription group of the intestinal lubricating pills was significantly increased within 24 hours. The increase in Example 1 was greater than that in Example 15, and even greater than that in Example 14. The total number of fecal particles in Example 1 was significantly higher than that in Example 15 within 24 hours on the 7th day of administration (P<0.05). The total number of fecal particles in the mosapride group was significantly increased within 24 hours on the 7th day of administration (P<0.01). The specific results are shown in Table 17.

[0303] Table 17 Effect of laxatives on the total number of fecal particles (particles) in rats with slow transit constipation within 24 hours

[0304] Note: Compared with the normal group, Compared with the slow transmission model group, #P<0.05, ##P<0.01; compared with Example 1, ^ P<0.05.

[0305] (2) Effects of laxatives on colonic water metabolism in rats with slow transit constipation

[0306] Fecal water content can indirectly reflect the colon's water metabolism function.

[0307] Water content of rat feces in 24 hours:

[0308] Compared with the normal group, the fecal water content of rats in the slow-transmission model group was significantly reduced 24 h on day 7 after administration (P<0.001). Compared with the slow-transmission model group, the fecal water content of each prescription group of the Run Chang Granules was increased 24 h on day 7 after administration. Among them, the increase was significant in Examples 1 and Examples 4-5 (P<0.05 or P<0.01). The increase in Examples 1 and Examples 4-5 was greater than that in Examples 6-7. The fecal water content of Example 1 was significantly higher than that in Examples 6 and 7 within 24 h on day 7 after administration (P<0.05). The fecal water content of Example 14 granules, in which all medicinal materials were extracted with water, showed an increasing trend. The fecal water content of the Run Chang Pills prescription group was significantly increased 24 h. The increase in Example 1 was greater than that in Example 15, and even greater than that in Example 14. The fecal water content of Example 1 was significantly higher than that in Example 14 within 24 h on day 7 after administration (P<0.05). The mosapride group showed a significant increase in fecal water content 24 h on day 7 of administration (P<0.05). Specific results are shown in Table 18.

[0309] Table 18 Effect of laxatives on fecal water content (%) in rats with slow transit constipation at 24 h

[0310] Note: Compared with the normal group, Compared with the slow transmission model group, #P<0.05, ##P<0.01; compared with Example 1, ^ P<0.05.

[0311] In summary, in this application, a slow transit constipation model was constructed by intragastric administration of 20 mg / kg compound diphenoxylate solution for 14 consecutive days, and the model was comprehensively evaluated by detecting defecation parameters, whole intestinal transit time, etc. The results showed that the intestinal moistening preparation could increase the total number of fecal pellets, total wet weight of feces, and water content of feces in rats with slow transit constipation within 24 hours. The intestinal moistening granules could further increase the total number of fecal pellets, total wet weight of feces, weight of single fecal pellet, water content of feces, and Bristol fecal score in rats with slow transit constipation at 6 hours and 24 hours, improve the carbon powder propulsion rate, and enhance the small intestine motility function. The above results indicate that the intestinal moistening granules have a significant laxative effect on slow transit constipation.

[0312] III. Pharmacodynamic experiment of intestinal moistening granules in the treatment of constipation due to blood deficiency

[0313] Constipation due to blood deficiency is a common traditional Chinese medicine syndrome type in constipation. The clinical manifestations mainly include difficult defecation, dry feces, pale complexion, pale lip color, dizziness, fatigue, insomnia, dreaminess, dry skin, pale tongue, thready and weak pulse, etc. This type of constipation is common in patients with prolonged illness and weakness, during the postpartum recovery period, after blood loss, or with chronic consumptive diseases. In this experiment, an animal model of constipation due to blood deficiency was constructed (according to the traditional Chinese medicine diagnostic criteria) to study the pharmacodynamics of the traditional Chinese medicine composition granule (i.e., intestinal moistening granules) prepared in Example 1 of this application in the treatment of constipation due to blood deficiency, so as to provide a theoretical basis for clinical application.

[0314] 1. Experimental materials

[0315] (1) Animals

[0316] 48 SPF-grade healthy male SD rats, weighing 200 - 220 g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., with the certificate number: SYXK (Jin) 2020 - 0005. After the rats were purchased, they were raised in the Experimental Animal Center of Tianjin University of Traditional Chinese Medicine, and were housed in separate cages, with 2 rats in each cage (separated by a partition in the middle), fed with ordinary diet and given free access to water. The environmental temperature was 23 ± 2°C, the environmental humidity was 35 ± 5%, and there was a 24-hour day-night cycle. After one week of adaptive feeding, the experiment was carried out. The approval number of the Experimental Animal Welfare Ethics Committee: TCM-LAEC2025037Z1517.

[0317] (2) Reagents and drugs

[0318] Lactulose: Batch No.: N241006, Hunan Kelun Pharmaceutical Co., Ltd.; Compound Diphenoxylate (Henan Dingchang Pharmaceutical Co., Ltd., Batch No.: 23082204); Sodium Carboxymethyl Cellulose (Beijing Solarbio Technology Co., Ltd., Batch No.: 24240605006); Cyclophosphamide (Shanxi Pude Pharmaceutical Co., Ltd., Batch No.: Z20235631); Activated Carbon Powder (Dalian Meilun Biotechnology Co., Ltd., Batch No.: N1126D); Carmine (Shanghai Maclean Biochemical Co., Ltd., Batch No.: C14984921).

[0319] 2. Test methods

[0320] (1) Animal grouping, modeling and drug administration

[0321] Forty-eight male SD rats (weighing 200–220 g) were randomly divided into six groups: normal group, blood deficiency model group, low-dose Runchang granules group (clinically equivalent dose, calculated based on crude drug amount, 2.43 g crude drug / kg), medium-dose Runchang granules group (4.86 g crude drug / kg), high-dose Runchang granules group (9.72 g crude drug / kg), and positive control drug lactulose (3.00 g / kg) group, with eight rats in each group.

[0322] A blood deficiency-type constipation model was established using a combination of diphenoxylate and cyclophosphamide for 14 days. From day 1 to day 7, rats in the blood deficiency model group and all treatment groups were administered 10 mg / kg of diphenoxylate suspension by gavage daily (for 7 consecutive days), and cyclophosphamide (20 mg / kg / day, total dose 60 mg / kg) was injected intraperitoneally on days 2, 3, and 4. Rats in the normal group were administered an equal volume of CMC-Na by gavage daily and injected intraperitoneally with an equal volume of physiological saline (solvent).

[0323] From day 8 to day 14, the anemia model group was continuously administered 10 mg / kg of compound diphenoxylate suspension by gavage daily. In addition to the modeling, each treatment group was given different interventions: low-dose group of laxative granules (2.43 g / kg, clinically equivalent dose based on crude drug amount), medium-dose group (4.86 g / kg, based on crude drug amount), high-dose group (9.72 g / kg, based on crude drug amount), and positive control drug lactulose group (3.00 g / kg). All were administered by gavage at a volume of 1 mL / 100 g for 7 consecutive days. The normal group and the anemia model group were administered an equal volume of physiological saline by gavage.

[0324] (2) Sampling and testing indicators

[0325] a) General condition observation

[0326] Observe and record the rats' condition (mental state, activity, fur, water intake, etc.) daily.

[0327] b) Stool collection and scoring

[0328] The Bristol fecal scoring scale was used to score the characteristics of rat feces based on fecal shape and consistency.

[0329] Table 19 Bristol Stool Scoring Table

[0330] c) Observation of stool volume and fecal moisture content

[0331] Collect feces within 6 h and 24 h after gavage, and record the total number of particles and wet weight. Place the collected feces in a constant temperature drying oven at 90℃ for 3 h, weigh the dry weight of the feces, and calculate the fecal moisture content (%): Fecal moisture content (%) = (wet weight - dry weight) / (wet weight) × 100%.

[0332] d) First red stool excretion experiment

[0333] After the final 24-hour fecal collection, the rats were fasted but allowed free access to water for 12 hours. Each group of rats was given the corresponding dose of medication based on the established model, while the normal group and the anemia model group were administered an equal volume of physiological saline via gavage. Subsequently, each rat was administered 1 mL of 6% carmine solution via gavage and placed in cages lined with blank filter paper, allowing free access to food and water. The time of gavage administration and the first bloody stool excretion within 12 hours were recorded.

[0334] e) Measurement of small intestinal propulsion rate

[0335] After recording the time of the first red stool excretion, the rats were fasted but allowed free access to water for 12 hours. They were then administered 2 mL of 10% (w / v) activated charcoal suspension by gavage. Thirty minutes later, the rats were anesthetized, blood was collected from the abdominal aorta, and the rats were euthanized. The intact intestinal segment from the pylorus to the cecum was then dissected. The intestinal segment was gently straightened and accurately measured using a ruler.

[0336] 1) Total length of the small intestine (from pylorus to cecum);

[0337] 2) The distance the charcoal powder travels from the tip to the pylorus. The small intestinal propulsion rate (%) is calculated using the formula: Small intestinal propulsion rate (%) = (charcoal powder propulsion distance / total small intestinal length) × 100%, which is used to assess intestinal peristalsis.

[0338] (3) Statistical analysis

[0339] Experimental data were statistically processed. Results are expressed as mean ± standard deviation (x̄ ± s). One-way ANOVA was used for comparisons between groups, with P < 0.05 considered statistically significant.

[0340] 3. Test Results

[0341] (1) Observation of the general condition of rats

[0342] The normal group rats were in good spirits, responsive, with soft and glossy fur, and had a normal appetite. The blood deficiency model group rats were lethargic and listless, curled up and preferred to lie down, with fluffy fur that was easy to fall out, poor appetite, and slightly pale and bloodless mouth, nose, ears, eyes, and paws. After intervention with Runchang Granules, the mental state, activity level, fur softness, and appetite of rats in all dose groups of Runchang Granules were improved.

[0343] (2) The Bristol fecal scoring scale was used to score the feces of rats with slow transit constipation.

[0344] a) Rat fecal score at 6 h

[0345] Compared with the normal group, the 6-hour stool score of the blood deficiency model group was significantly lower (P<0.01); compared with the blood deficiency model group, the 6-hour stool scores of all dosage groups of Run Chang Granules were significantly increased (P<0.05 or P<0.01), with the low-dose group showing a significant increase on days 2, 3, 5, and 7 (P<0.05 or P<0.01), the medium-dose group showing a significant increase on days 2, 5, and 7 (P<0.01), and the high-dose group showing a significant increase on days 2, 3, 5-7 (P<0.05 or P<0.01); the lactulose group showed a significant increase in 6-hour stool scores on days 2, 3, 5, and 7 after administration (P<0.05 or P<0.01). Specific results are shown in Tables 20-1, 20-2, and... Figure 6 As shown.

[0346] Table 20-1 Effect of Runchang Granules on 6-hour fecal score in rats with blood deficiency-type constipation

[0347] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0348] Table 20-2 Effects of Runchang Granules on 6-hour fecal scores in rats with blood deficiency-type constipation

[0349] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0350] b) Rat fecal score at 24 h

[0351] Compared with the normal group, the 24-hour stool score of the blood deficiency model group was significantly lower (P<0.01); compared with the blood deficiency model group, the 24-hour stool score of each dose group of Run Chang Granules was significantly increased (P<0.05 or P<0.01), with significant increases in the low and medium dose groups from day 3 to day 7 (P<0.05 or P<0.01), and significant increases in the high dose group from day 1 to day 7 (P<0.05 or P<0.01); the lactulose group showed significant increases in 24-hour stool scores on days 2, 3, 6, and 7 after administration (P<0.05 or P<0.01). Specific results are shown in Tables 21-1, 21-2, and... Figure 7 As shown.

[0352] Table 21-1 Effects of Runchang Granules on 24-hour fecal scores in rats with blood deficiency-type constipation

[0353] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0354] Table 21-2 Effects of Runchang Granules on 24-hour fecal scores in rats with blood deficiency-type constipation

[0355] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0356] (3) Effects of Runchang Granules on the total number of fecal particles and total wet weight of feces in rats with blood deficiency constipation within 6 hours

[0357] a) Total number of fecal particles in rats within 6 hours

[0358] Compared with the normal group, the total number of fecal particles in the blood deficiency model group was significantly reduced within 6 hours (P<0.05 or P<0.01); compared with the blood deficiency model group, the total number of fecal particles in the medium and high dose groups of Run Chang Granules was significantly increased within 6 hours on the 4th day of administration (P<0.05); the total number of fecal particles in the lactulose group was significantly increased within 6 hours on the 4th day of administration (P<0.01). Specific results are shown in Tables 22-1 and 22-2.

[0359] Table 22-1 Effect of Runchang Granules on the Total Number of Fecal Particles (particles) in Rats with Blood Deficiency-Type Constipation within 6 Hours

[0360] Note: Compared with the normal group, , Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0361] Table 22-2 Effect of Runchang Granules on the Total Number of Fecal Particles (particles) in Rats with Blood Deficiency-Type Constipation within 6 Hours

[0362] Note: Compared with the normal group, , .

[0363] b) Total wet weight of rat feces within 6 hours

[0364] Compared with the normal group, the total wet weight of feces in rats in the blood deficiency model group was significantly reduced within 6 hours (P<0.05 or P<0.01); compared with the blood deficiency model group, the total wet weight of feces in rats in the high-dose laxative granule group was significantly increased within 6 hours on days 4, 5, and 7 after administration (P<0.05 or P<0.01); and the total wet weight of feces in the lactulose group was significantly increased within 6 hours on day 4 after administration (P<0.05). Specific results are shown in Tables 23-1 and 23-2.

[0365] Table 23-1 Effect of Runchang Granules on Total Wet Fecal Weight (g) in Rats with Blood Deficiency-Type Constipation within 6 Hours

[0366] Note: Compared with the normal group, , Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0367] Table 23-2 Effect of Runchang Granules on Total Wet Fecal Weight (g) in Rats with Blood Deficiency-Type Constipation within 6 Hours

[0368] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05.

[0369] c) Weight of a single rat feces at 6 hours

[0370] Dividing the total wet weight (g) of feces within 6 hours by the total number of fecal particles (particles) within 6 hours will give the weight (g) of a single fecal particle within 6 hours.

[0371] The weight of a single stool pellet at 6 hours was significantly lower in the blood deficiency model group than in the normal group (P<0.05 or P<0.01). Compared with the blood deficiency model group, the weight of a single stool pellet at 6 hours was significantly increased in the low- and medium-dose groups of the laxative granules (P<0.05 or P<0.01). Specifically, the low-dose group showed a significant increase on day 6 of administration (P<0.05), while the medium-dose group showed a significant increase at 6 hours on days 3, 6, and 7 of administration (P<0.05 or P<0.01). The lactulose group showed a significant increase in the weight of a single stool pellet at 6 hours on days 3 and 7 (P<0.05 or P<0.01), which is related to the ability of lactulose to retain water and soften stool. Specific results are shown in Tables 24-1 and 24-2.

[0372] Table 24-1 Effect of Runchang Granules on the weight of a single granule (g) in rats with blood deficiency-type constipation at 6 h

[0373] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0374] Table 24-2 Effect of Runchang Granules on the weight of a single granule (g) in rats with blood deficiency-type constipation at 6 h

[0375] Note: Compared with the normal group, , Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0376] (4) Effects of Runchang Granules on the total number of fecal particles and total wet weight of feces in rats with blood deficiency constipation within 24 hours

[0377] a) Total number of fecal particles in rats over 24 hours

[0378] Compared with the normal group, the total number of fecal particles in the blood deficiency model group was significantly reduced within 24 hours (P<0.05 or P<0.01). Compared with the blood deficiency model group, the total number of fecal particles in the medium- and high-dose groups of Run Chang Granules was significantly increased within 24 hours (P<0.05 or P<0.01). Specifically, the medium-dose group showed a significant increase on days 4, 5, and 6 (P<0.05 or P<0.01), while the high-dose group showed a significant increase on day 4 (P<0.05). The lactulose group had no significant effect on the total number of fecal particles in rats within 24 hours (P>0.05). Specific results are shown in Tables 25-1 and 25-2.

[0379] Table 25-1 Effect of Runchang Granules on the Total Number of Fecal Particles (particles) in Rats with Blood Deficiency-Type Constipation within 24 Hours

[0380] Note: Compared with the normal group, , Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0381] Table 25-2 Effect of Runchang Granules on the Total Number of Fecal Particles (particles) in Rats with Blood Deficiency-Type Constipation within 24 Hours

[0382] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0383] b) Total wet weight of rat feces within 24 hours

[0384] Compared with the normal group, the total wet weight of feces in rats in the blood deficiency model group was significantly reduced within 24 hours (P<0.01). Compared with the blood deficiency model group, the total wet weight of feces in the medium- and high-dose groups of Runchang Granules was significantly increased within 24 hours (P<0.05 or P<0.01). Specifically, the total wet weight of feces in the medium-dose group of Runchang Granules was significantly increased within 24 hours on days 1, 4, 5, and 6 of administration (P<0.05 or P<0.01), while the total wet weight in the high-dose group was significantly increased on days 4, 6, and 7 of administration (P<0.05). Lactulose had no significant effect on the total wet weight of feces in rats within 24 hours (P>0.05). Specific results are shown in Tables 26-1 and 26-2.

[0385] Table 26-1 Effect of Runchang Granules on Total Wet Fecal Weight (g) in Rats with Blood Deficiency-Type Constipation within 24 Hours

[0386] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0387] Table 26-2 Effect of Runchang Granules on Total Wet Fecal Weight (g) in Rats with Blood Deficiency-Type Constipation within 24 Hours

[0388] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0389] c) Weight of a single rat feces over 24 hours

[0390] Dividing the total wet weight of feces (g) over 24 hours by the total number of fecal particles (particles) over 24 hours gives the weight of a single fecal particle (g) over 24 hours.

[0391] The 24-hour fecal weight of the blood deficiency model group was significantly lower than that of the normal group (P<0.05). Compared with the blood deficiency model group, the 24-hour fecal weight of the medium-dose and high-dose groups of the laxative granules was significantly increased on day 7 (P<0.05). The lactulose group had no significant effect on the 24-hour fecal weight of the rats (P>0.05). The specific results are shown in Tables 27-1 and 27-2.

[0392] Table 27-1 Effect of Runchang Granules on the 24-hour fecal weight (g) of a single granule in rats with blood deficiency-type constipation

[0393] Note: Compared with the normal group, .

[0394] Table 27-2 Effect of Runchang Granules on the 24-hour fecal weight (g) of a single granule in rats with blood deficiency-type constipation

[0395] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05.

[0396] (5) Effects of Runchang Granules on Colonic Water Metabolism in Rats with Blood Deficiency-Type Constipation

[0397] Fecal water content can indirectly reflect the colon's water metabolism function.

[0398] a) Water content of rat feces at 6 h

[0399] Compared with the normal group, the fecal water content at 6 h was significantly lower in the blood deficiency model group on days 1, 2, 4-7 after modeling (P<0.05 or P<0.01). Compared with the blood deficiency model group, the fecal water content at 6 h was significantly increased in all dosage groups of Run Chang Granules (P<0.05 or P<0.01). Among them, the low-dose group showed a significant increase on days 3 and 4 after administration (P<0.05 or P<0.01), the medium-dose group showed a significant increase on days 2, 5, and 7 after administration (P<0.01), and the high-dose group showed a significant increase on days 3-7 after administration (P<0.05). The lactulose group showed a significant increase in fecal water content at 6 h on days 1, 2, 5-7 after administration (P<0.05). Specific results are shown in Tables 28-1 and 28-2.

[0400] Table 28-1 Effect of Runchang Granules on Fecal Moisture Content (%) in Rats with Blood Deficiency-Type Constipation at 6 H

[0401] Note: Compared with the normal group, , Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0402] Table 28-2 Effect of Runchang Granules on Fecal Moisture Content (%) in Rats with Blood Deficiency-Type Constipation at 6 Hours

[0403] Note: Compared with the normal group, , Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0404] b) Water content of rat feces at 24 h

[0405] Compared with the normal group, the 24-hour fecal water content in the blood deficiency model group was significantly lower (P<0.05 or P<0.01). Compared with the blood deficiency model group, the 24-hour fecal water content in all dosage groups of the laxative granules group was significantly higher (P<0.05 or P<0.01). Among them, the low-dose group showed a significant increase on days 3 and 4 (P<0.01), the medium-dose group showed a significant increase on days 2-7 (P<0.05 or P<0.01), and the high-dose group showed a significant increase on days 2, 4, 5, 6, and 7 (P<0.05 or P<0.01). The lactulose group showed a significant increase in 24-hour fecal water content on days 1-5 and 7 after administration (P<0.05 or P<0.01). Specific results are shown in Tables 29-1 and 29-2.

[0406] Table 29-1 Effect of Runchang Granules on 24-hour fecal water content (%) in rats with blood deficiency-type constipation

[0407] Note: Compared with the normal group, , Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0408] Table 29-2 Effect of Runchang Granules on 24-hour fecal water content (%) in rats with blood deficiency-type constipation

[0409] Note: Compared with the normal group, , Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0410] (6) Effect of Runchang Granules on the time of first red stool excretion in rats with blood deficiency constipation

[0411] In the experiment on the first excretion of red stool in rats, four rats were observed in each group. During the 12-hour observation period, two rats in the low-dose group and three rats in the medium-dose group excreted red stool. The data of rats that successfully excreted red stool were included in the statistics, and the time of first excretion of red stool in rats was calculated.

[0412] Compared with the normal group, the time to excretion of the first red stool was significantly prolonged in the blood deficiency model group (P<0.05); compared with the blood deficiency model group, the time to excretion of the first red stool was significantly shortened in the high-dose group of Runchang granules (P<0.05); the lactulose group had no significant effect on the time to excretion of the first red stool in rats (P>0.05). These results indicate that Runchang granules can significantly improve the whole intestinal transit function of rats with blood deficiency-type constipation. Specific results are shown in Table 30.

[0413] Table 30 Effect of Runchang Granules on the Time (min) of First Powder Excretion of Red Stool in Rats with Blood Deficiency-Type Constipation

[0414] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05.

[0415] (7) Effect of Runchang Granules on Small Intestinal Propulsion Rate in Rats with Blood Deficiency-Type Constipation

[0416] Compared with the normal group, the small intestinal propulsion rate of the blood deficiency model group was significantly decreased (P<0.01); compared with the blood deficiency model group, the small intestinal propulsion rate of all doses of Runchang Granules was significantly increased (P<0.01). These results indicate that different doses of Runchang Granules can significantly increase the small intestinal propulsion rate and improve small intestinal motility. Specific results are shown in Table 31 and... Figure 8 As shown.

[0417] Table 31 Effect of Runchang Granules on Small Intestinal Propulsion Rate (%) in Rats with Blood Deficiency-Type Constipation

[0418] Note: Compared with the normal group, Compared with the blood deficiency model group, ##P<0.01.

[0419] (8) Effects of Runchang Granules on Relevant Indicators of Blood Routine in Rats with Blood Deficiency-Type Constipation

[0420] After the rats were induced to develop anemia by combining compound diphenoxylate with cyclophosphamide, the health status of the rats could be assessed by analyzing the various components in the blood.

[0421] Compared with the normal group, the white blood cell count, red blood cell count, hemoglobin, and hematocrit were significantly decreased in the blood deficiency model group (P<0.01). Compared with the blood deficiency model group, all doses of Run Chang Granules significantly increased white blood cells, red blood cells, hemoglobin, and hematocrit (P<0.05 or P<0.01). The significant increase in hematocrit remained within the normal physiological range, showing no significant difference compared with the normal group (P>0.05). This indicates that the drug can effectively improve the decreased hematocrit in blood deficiency while avoiding adverse reactions such as increased blood viscosity that may be caused by excessively high hematocrit. Specific results are shown in Tables 32-1 and 32-2.

[0422] Table 32-1 Effects of Runchang Granules on Blood Routine of Rats with Blood Deficiency-Type Constipation

[0423] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0424] Table 32-2 Effects of Runchang Granules on Blood Routine Results in Rats with Blood Deficiency-Induced Constipation

[0425] Note: Compared with the normal group, Compared with the blood deficiency model group, #P<0.05, ##P<0.01.

[0426] This experiment used a combination of 10 mg / kg compound diphenoxylate solution and 60 mg / kg cyclophosphamide to establish a blood deficiency-type constipation model in rats. The model was maintained for 7 consecutive days, and defecation parameters and intestinal transit time were comprehensively evaluated. Results showed that Runchang granules increased the number of fecal particles at 6 h and 24 h, fecal wet weight, weight of a single fecal particle, fecal water content, and Bristol fecal score in rats with blood deficiency-type constipation. It also shortened the time to first red stool passage, enhanced intestinal transit function, increased charcoal propulsion rate, and enhanced small intestinal motility, while also having a blood-nourishing effect. These results indicate that Runchang granules have a significant blood-nourishing and laxative effect on blood deficiency-type constipation.

[0427] IV. Efficacy test of laxative granules in treating constipation due to fluid deficiency

[0428] Deficiency of body fluid-induced constipation (hereinafter referred to as constipation due to body fluid deficiency) is relatively common in clinical practice. It is mostly caused by improper diet, excessive consumption of spicy, fragrant, dry, fried and rich-flavored foods, which consume body fluids; or emotional disorders, liver depression transforming into fire, burning and injuring yin fluids; or after febrile diseases, the residual heat lingers, consuming yin fluids; being old and weak, with deficiency of body fluids and qi, etc. These factors cause the intestines to lack moistening, and the feces are dry and difficult to pass. In this experiment, a constipation model of deficiency of body fluid type (traditional Chinese medicine diagnostic criteria) was established to study the pharmacodynamic effects of the traditional Chinese medicine composition granule (i.e., Runchang Granule) prepared in Example 1 of this application in the treatment of constipation due to body fluid deficiency.

[0429] 1. Test materials

[0430] (1) Animals

[0431] 48 SPF-grade healthy male SD rats, weighing 280 - 300 g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., with the certificate number: SYXK (Jin) 2020 - 0005. After the rats were purchased, they were raised in the Experimental Animal Center of Tianjin University of Traditional Chinese Medicine. They were raised in separate cages, with 2 rats in each cage (separated by a partition in the middle), fed with ordinary diet and given free access to water. The environmental temperature was 23 ± 2°C, the environmental humidity was 35 ± 5%, and the day-night cycle was 24 h. The experiment was carried out after one week of adaptive feeding. Approval number of the Experimental Animal Welfare Ethics Committee: TCM-LAEC2025037Z1517.

[0432] (2) Reagents and drugs

[0433] Lactulose: Batch number: N241006, Hunan Kelun Pharmaceutical Co., Ltd.; Compound Diphenoxylate (Henan Dingchang Pharmaceutical Co., Ltd., batch number: 23082204); Sodium Carboxymethylcellulose (Beijing Solarbio Science & Technology Co., Ltd., batch number: 24240605006); Activated carbon powder (Dalian Meilun Biotechnology Co., Ltd., batch number: N1126D); Carmine (Shanghai Macklin Biochemical Co., Ltd., batch number: C14984921).

[0434] 2. Test methods

[0435] (1) Animal grouping and model establishment with drug administration

[0436] 48 male SD rats (weighing 280 - 300 g) were randomly divided into 6 groups: normal group, body fluid deficiency model group, low-dose Runchang Granule group (clinical equivalent dose, calculated based on the crude drug amount, 2.43 g crude drug / kg), medium-dose Runchang Granule group (4.86 g crude drug / kg), high-dose Runchang Granule group (9.72 g crude drug / kg), and positive control drug lactulose group (3.00 g / kg), with 8 rats in each group.

[0437] A constipation model due to fluid deficiency was established using a combination of compound diphenoxylate 15 mg / kg and water restriction for 7 days. From day 1 to day 7, rats in the fluid deficiency model group and each treatment group were administered 15 mg / kg of compound diphenoxylate suspension by gavage daily (for 7 consecutive days), and their daily water intake was restricted to 10 mL / rat / day. Rats in the normal group were administered an equal volume of CMC-Na solution (solvent) by gavage daily, while maintaining free access to food and water.

[0438] From day 8 to day 14, the body fluid deficiency model group maintained the model, and each drug administration group received different interventions on the basis of the model. The low-dose group of Runchang Granules (2.43 g / kg, clinical equivalent dose based on crude drug amount), medium-dose group (4.86 g / kg, based on crude drug amount), high-dose group (9.72 g / kg, based on crude drug amount) and the positive control drug lactulose (3.00 g / kg) group were all administered by gavage at a volume of 1 mL / 100 g for 7 consecutive days. The normal group and the body fluid deficiency model group were administered the same volume of physiological saline by gavage.

[0439] (2) Sampling and testing indicators

[0440] a) General condition observation

[0441] Observe and record the rats' condition (mental state, activity, fur, water intake, etc.) daily.

[0442] b) Stool collection and scoring

[0443] The Bristol fecal scoring scale was used to score the characteristics of rat feces based on fecal shape and consistency.

[0444] Table 33 Bristol Stool Scoring Table

[0445] c) Observation of stool volume and fecal moisture content

[0446] Collect feces within 6 h and 24 h after gavage, and record the total number of particles and wet weight. Place the collected feces in a constant temperature drying oven at 90℃ for 3 h, weigh the dry weight of the feces, and calculate the fecal moisture content (%): Fecal moisture content (%) = (wet weight - dry weight) / (wet weight) × 100%.

[0447] d) First red stool excretion experiment

[0448] After the final 24-hour fecal collection, the rats were fasted but allowed free access to water for 12 hours. Each group of rats was given the corresponding dose of medication in addition to the established model, while the normal group and the fluid deficiency model group were administered an equal volume of physiological saline by gavage. Subsequently, each rat was administered 1 mL of 6% carmine solution by gavage and placed in cages lined with blank filter paper, allowing free access to food and water. The time of gavage administration and the first bloody stool excretion within 12 hours were recorded.

[0449] e) Measurement of small intestinal propulsion rate

[0450] After recording the time of the first red stool excretion, the rats were fasted but allowed free access to water for 12 hours. They were then administered 2 mL of 10% (w / v) activated charcoal suspension by gavage. Thirty minutes later, the rats were anesthetized, blood was collected from the abdominal aorta, and the rats were euthanized. The intact intestinal segment from the pylorus to the cecum was then dissected. The intestinal segment was gently straightened and accurately measured using a ruler.

[0451] 1) Total length of the small intestine (from pylorus to cecum);

[0452] 2) The distance the charcoal powder travels from the tip to the pylorus. The small intestinal propulsion rate (%) is calculated using the formula: Small intestinal propulsion rate (%) = (charcoal powder propulsion distance / total small intestinal length) × 100%, which is used to assess intestinal peristalsis.

[0453] (3) Statistical analysis

[0454] Experimental data were statistically processed. Results are expressed as mean ± standard deviation (x̄ ± s). One-way ANOVA was used for comparisons between groups, with P < 0.05 considered statistically significant.

[0455] 3. Test Results

[0456] (1) Observation of the general condition of rats

[0457] The normal group rats were in good mental condition, responsive, with smooth and shiny fur, normal diet, and healthy physique; the yin deficiency model group rats were lethargic, sluggish, with sparse and yellow fur and loose skin; after administration of Runchang granules, the mental condition, activity level, and fur smoothness of rats in all dose groups of Runchang granules were improved.

[0458] (2) The Bristol fecal scoring scale was used to score the feces of rats with fluid deficiency constipation.

[0459] a) Rat fecal score at 6 h

[0460] Compared with the normal group, the 6-hour stool score of the fluid deficiency model group was significantly lower (P<0.01); compared with the fluid deficiency model group, the 6-hour stool scores of all dosage groups of Run Chang Granules were significantly increased (P<0.05 or P<0.01), with the low-dose group showing a significant increase from day 3 to day 7 (P<0.05 or P<0.01), and the medium and high-dose groups showing a significant increase from day 2 to day 7 (P<0.05 or P<0.01); the lactulose group showed a significant increase in 6-hour stool scores on days 3, 5, 6, and 7 after administration (P<0.05 or P<0.01). Specific results are shown in Tables 34-1, 34-2, and... Figure 9 As shown.

[0461] Table 34-1 Effects of Runchang Granules on 6-hour fecal scores in rats with fluid deficiency-type constipation

[0462] Note: Compared with the normal group, Compared with the Jin-Kui model group, #P<0.05, ##P<0.01.

[0463] Table 34-2 Effects of Runchang Granules on 6-hour fecal scores in rats with fluid deficiency-type constipation

[0464] Note: Compared with the normal group, Compared with the Jin-Kui model group, #P<0.05, ##P<0.01.

[0465] b) Rat fecal score at 24 h

[0466] Compared with the normal group, the 24-hour stool score of the fluid deficiency model group was significantly lower (P<0.01); compared with the fluid deficiency model group, the 24-hour stool score of all dosage groups of the laxative granules was significantly increased (P<0.05 or P<0.01), with the low-dose group showing a significant increase from day 2 to day 7 (P<0.05 or P<0.01), the medium-dose group showing a significant increase from day 1 to day 7 (P<0.05 or P<0.01), and the high-dose group showing a significant increase from day 2 to day 7 (P<0.01); the lactulose group showed a significant increase in 24-hour stool score from day 2 to day 7 after administration (P<0.05 or P<0.01). Specific results are shown in Tables 35-1, 35-2, and... Figure 10 As shown.

[0467] Table 35-1 Effects of Runchang Granules on 24-hour fecal scores in rats with fluid deficiency-type constipation

[0468] Note: Compared with the normal group, Compared with the Jin-Kui model group, #P<0.05, ##P<0.01.

[0469] Table 35-2 Effects of Runchang Granules on 24-hour fecal scores in rats with fluid deficiency-type constipation

[0470] Note: Compared with the normal group, Compared with the Jin-Kui model group, ##P<0.01.

[0471] (3) Effects of Runchang Granules on fecal weight and total wet weight within 6 hours in rats with fluid deficiency-type constipation

[0472] a) Total wet weight of rat feces within 6 hours

[0473] Compared with the normal group, the total wet weight of feces in the fluid deficiency model group was significantly reduced within 6 hours (P<0.05); compared with the fluid deficiency model group, the total wet weight of feces in each dose group of Runchang Granules was significantly increased within 6 hours (P<0.05 or P<0.01). Among them, the low-dose Runchang Granules group showed a significant increase on days 1, 2, 3, 4, and 6 of administration (P<0.05), the medium-dose group showed a significant increase on days 2 and 3 of administration (P<0.05 or P<0.01), and the high-dose group showed a significant increase on days 2 and 3 of administration (P<0.05); the lactulose group had no significant effect on the total wet weight of feces in rats within 6 hours (P>0.05). Specific results are shown in Tables 36-1 and 36-2.

[0474] Table 36-1 Effect of Runchang Granules on Fecal Wet Weight (g) in Rats with Fluid Deficiency-Type Constipation within 6 Hours

[0475] Note: Compared with the normal group, Compared with the Jin-Kui model group, #P<0.05, ##P<0.01.

[0476] Table 36-2 Effect of Runchang Granules on Fecal Wet Weight (g) in Rats with Fluid Deficiency-Type Constipation within 6 Hours

[0477] Note: Compared with the normal group, Compared with the Jin-Kui model group, #P<0.05.

[0478] b) Weight of a single rat feces at 6 hours

[0479] The weight of a single stool pellet in the fluid deficiency model group was significantly lower than that in the normal group (P<0.05 or P<0.01). Compared with the fluid deficiency model group, the weight of a single stool pellet at 6 hours was significantly increased in the low- and medium-dose groups of the laxative granules (P<0.05), with the low-dose group showing a significant increase on day 6 (P<0.05) and the medium-dose group showing a significant increase on day 5 (P<0.05). The weight of a single stool pellet was significantly increased at 6 hours on days 5 and 6 of administration in the lactulose group (P<0.05). This is related to the ability of lactulose to retain water and soften stool. Specific results are shown in Tables 37-1 and 37-2.

[0480] Table 37-1 Effect of Runchang Granules on the Weight of a Single Granule (g) in Rats with Fluid Deficiency-Type Constipation at 6 Hours

[0481] Table 37-2 Effect of Runchang Granules on the Weight of a Single Granule (g) in Rats with Fluid Deficiency-Type Constipation at 6 Hours

[0482] Note: Compared with the normal group, , Compared with the Jin-Kui model group, #P<0.05.

[0483] (4) Effects of Runchang Granules on fecal weight and total wet weight in rats with fluid deficiency-type constipation within 24 hours

[0484] a) Total number of fecal particles in rats over 24 hours

[0485] Compared with the normal group, the total number of fecal particles in the fluid deficiency model group was significantly reduced within 24 hours (P<0.01). Compared with the fluid deficiency model group, the total number of fecal particles in each dose group of the laxative granules increased to some extent within 24 hours, with the low-dose group showing a significant increase on the 4th day of administration (P<0.01). The lactulose group had no significant effect on the total number of fecal particles in rats within 24 hours (P>0.05). Specific results are shown in Tables 38-1 and 38-2.

[0486] Table 38-1 Effect of Run Chang Granules on the Total Number of Fecal Particles (particles) in Rats with Fluid Deficiency-Type Constipation within 24 h

[0487] Note: Compared with the normal group, Compared with the Jin-Kui model group, ##P<0.01.

[0488] Table 38-2 Effect of Run Chang Granules on the Total Number of Fecal Particles (particles) in Rats with Fluid Deficiency-Type Constipation within 24 h

[0489] Note: Compared with the normal group, .

[0490] b) Total wet weight of rat feces within 24 hours

[0491] Compared with the normal group, the total wet weight of feces in the fluid deficiency model group was significantly reduced within 24 hours (P<0.01); compared with the fluid deficiency model group, the total wet weight of feces in each dose group of Run Chang Granules was significantly increased within 24 hours (P<0.05 or P<0.01), with the low-dose group showing a significant increase on days 3 and 4 of administration (P<0.05 or P<0.01), the medium-dose group showing a significant increase on day 4 of administration (P<0.05), and the high-dose group showing a significant increase on day 4 of administration (P<0.05); the lactulose group showed a significant increase in total wet weight of feces within 24 hours on day 6 of administration (P<0.01). Specific results are shown in Tables 39-1 and 39-2.

[0492] Table 39-1 Effects of Runchang Granules on Total Wet Fecal Weight (g) in Rats with Fluid Deficiency-Type Constipation within 24 h

[0493] Note: Compared with the normal group, Compared with the Jin-Kui model group, #P<0.05, ##P<0.01.

[0494] Table 39-2 Effects of Runchang Granules on Total Wet Fecal Weight (g) in Rats with Fluid Deficiency-Type Constipation within 24 Hours

[0495] Note: Compared with the normal group, Compared with the Jin-Kui model group, ##P<0.01.

[0496] c) Weight of a single rat feces over 24 hours

[0497] The weight of a single fecal pellet in the fluid deficiency model group was significantly lower than that in the normal group (P<0.05 or P<0.01). Compared with the fluid deficiency model group, the weight of a single fecal pellet was significantly increased 24 h on day 5 in the medium and high dose groups of Run Chang Granules (P<0.05 or P<0.01). Lactulose had no significant effect on the weight of a single fecal pellet in rats within 24 h (P>0.05). Specific results are shown in Tables 40-1 and 40-2.

[0498] Table 40-1 Effect of Runchang Granules on the 24-hour fecal weight (g) of a single granule in rats with fluid deficiency-type constipation

[0499] Note: Compared with the normal group, , .

[0500] Table 40-2 Effect of Runchang Granules on the 24-hour fecal weight (g) of a single granule in rats with fluid deficiency-type constipation

[0501] Note: Compared with the normal group, Compared with the Jin-Kui model group, #P<0.05, ##P<0.01.

[0502] (5) Effects of Runchang Granules on Colonic Water Metabolism in Rats with Fluid Deficiency-Type Constipation

[0503] Fecal water content can indirectly reflect the colon's water metabolism function.

[0504] a) Water content of rat feces at 6 h

[0505] Compared with the normal group, the fecal water content at 6 h was significantly lower in the fluid deficiency model group from day 1 to day 7 after modeling (P<0.01). Compared with the fluid deficiency model group, the fecal water content at 6 h was significantly increased in all dosage groups of the laxative granules (P<0.05 or P<0.01). Specifically, the low-dose group showed a significant increase from day 1 to day 7 after administration (P<0.05 or P<0.01), the medium-dose group showed a significant increase from day 1 to day 7 after administration (P<0.01), and the high-dose group showed a significant increase from day 2, 3, 4, 6, and 7 after administration (P<0.05 or P<0.01). The fecal water content at 6 h was significantly increased in the lactulose group from day 1 to day 7 after administration (P<0.05 or P<0.01). Specific results are shown in Tables 41-1 and 41-2.

[0506] Table 41-1 Effect of Runchang Granules on Fecal Moisture Content (%) in Rats with Fluid Deficiency-Type Constipation at 6 H

[0507] Note: Compared with the normal group, Compared with the Jin-Kui model group, #P<0.05, ##P<0.01.

[0508] Table 41-2 Effect of Runchang Granules on Fecal Moisture Content (%) in Rats with Fluid Deficiency-Type Constipation at 6 H

[0509] Note: Compared with the normal group, Compared with the Jin-Kui model group, #P<0.05, ##P<0.01.

[0510] b) Water content of rat feces at 24 h

[0511] Compared with the normal group, the 24-hour fecal water content in the fluid deficiency model group was significantly lower (P<0.01); compared with the fluid deficiency model group, the 24-hour fecal water content in all dosage groups of the laxative granules was significantly higher (P<0.05 or P<0.01), with the low, medium, and high dosage groups showing a significant increase from day 2 to day 7 (P<0.05 or P<0.01); the lactulose group showed a significant increase in 24-hour fecal water content from day 1 to day 3 to day 6 (P<0.05 or P<0.01). Specific results are shown in Tables 42-1 and 42-2.

[0512] Table 42-1 Effect of Runchang Granules on 24-hour fecal water content (%) in rats with fluid deficiency-type constipation

[0513] Note: Compared with the normal group, Compared with the Jin-Kui model group, #P<0.05, ##P<0.01.

[0514] Table 42-2 Effect of Runchang Granules on 24-hour fecal water content (%) in rats with fluid deficiency-type constipation

[0515] Note: Compared with the normal group, Compared with the Jin-Kui model group, #P<0.05, ##P<0.01.

[0516] (6) Effects of Runchang Granules on Intestinal Motility in Rats with Fluid Deficiency-Type Constipation

[0517] The time to first stool passage and small intestinal propulsion rate can both reflect intestinal motility to some extent. The time to first stool passage reflects the transit speed of gastrointestinal contents (from the stomach to the rectum); a short time indicates fast transit speed throughout the gastrointestinal tract, while a long time indicates slow transit speed, potentially indicating insufficient motility or obstruction. A high small intestinal propulsion rate indicates rapid movement of small intestinal contents and strong small intestinal motility; a low small intestinal propulsion rate suggests slowed or obstructed small intestinal motility.

[0518] a) Effect of Runchang Granules on the time of first red stool excretion in rats with fluid deficiency-type constipation

[0519] In the experiment on the first excretion of red stool in rats, 8 rats were observed in each group. During the 12-hour observation period, 5 rats in the yin deficiency model group, 7 rats in the low-dose laxative granule group, and 5 rats in the high-dose group excreted red stool. The data of rats that successfully excreted red stool were included in the statistics, and the time of excretion of the first red stool in rats was calculated.

[0520] Compared with the normal group, the time to excretion of the first red stool was significantly prolonged in the yin deficiency model group (P<0.01); compared with the yin deficiency model group, the time to excretion of the first red stool was significantly shortened in the medium-dose group of Runchang granules (P<0.01); the lactulose group had no significant effect on the time to excretion of the first red stool (P>0.05). These results indicate that Runchang granules can significantly improve the whole intestinal transit function of rats with yin deficiency constipation. Specific results are shown in Table 43.

[0521] Table 43 Effect of Runchang Granules on the Time (min) of First Powder Red Stool Excretion in Rats with Fluid Deficiency-Type Constipation

[0522] Note: Compared with the normal group, Compared with the Jin-Kui model group, ##P<0.01.

[0523] b) Effect of Runchang Granules on Small Intestinal Propulsion Rate in Rats with Fluid Deficiency-Induced Constipation

[0524] Compared with the normal group, the small intestinal propulsion rate of the fluid deficiency model group was significantly decreased (P<0.01); compared with the fluid deficiency model group, the small intestinal propulsion rate of the medium and high dose groups of Runchang granules was significantly increased (P<0.05 or P<0.01); the lactulose group showed a certain degree of increase in small intestinal propulsion rate, but the difference was not significant (P>0.05). These results indicate that Runchang granules can significantly increase the small intestinal propulsion rate and improve small intestinal motility. Specific results are shown in Table 44 and... Figure 11 As shown.

[0525] Table 44 Effects of Runchang Granules on Small Intestinal Propulsion Rate in Rats with Fluid Deficiency-Induced Constipation

[0526] Note: Compared with the normal group, Compared with the Jin-Kui model group, #P<0.05, ##P<0.01.

[0527] This experiment established a constipation model due to fluid deficiency in rats by gavage administration of 10 mg / kg compound diphenoxylate solution combined with 10 mL of water restriction method. The model was maintained for 7 consecutive days, and defecation parameters and whole intestinal transit time were comprehensively evaluated. Results showed that Runchang granules increased the number of fecal particles at 24 h, fecal wet weight at 6 h and 24 h, weight of a single fecal particle, fecal water content, and Bristol fecal score in rats with constipation due to fluid deficiency. It also shortened the time to first red stool passage, enhanced whole intestinal transit function, increased charcoal propulsion rate, and enhanced small intestinal motility. These results indicate that Runchang granules have a significant laxative effect on constipation due to fluid deficiency.

[0528] V. Clinical efficacy trial of laxative decoction for treating constipation caused by internal heat

[0529] One hundred constipation patients meeting the inclusion criteria were selected as the study subjects and given an oral laxative decoction. A self-controlled before-and-after study method was used to observe the improvement of different TCM syndrome scores and the safety of the medication before and after treatment. Among them, constipation was caused by internal heat (i.e., heat constipation).

[0530] 1. Materials and Methods

[0531] 1.1 General Information

[0532] One hundred patients with constipation symptoms were selected, including 43 males and 57 females, aged >18 years, with a mean age of (56.91±14.95) years.

[0533] 1.2 Diagnostic Criteria

[0534] 1.2.1 Western Medicine Diagnostic Criteria

[0535] The relevant diagnostic criteria were formulated with reference to the Rome IV diagnostic criteria for functional constipation. Patients must have two or more of the following related symptoms: (1) >25% of defecation is difficult (at least once every 4 times, the same below); (2) >25% of defecation is dry or hard stool (meeting the Bristol Stool Characteristics Scale Type 1-2); (3) >25% of defecation is incomplete; (4) >25% of defecation is an anorectal obstruction (or blockage); (5) >25% of defecation requires manual assistance, and spontaneous defecation is <3 times per week.

[0536] 1.2.2 Traditional Chinese Medicine Diagnostic Criteria

[0537] This standard was developed with reference to the relevant criteria of the Colorectal Surgery Group of the Chinese Medical Association's Surgical Branch in assessing constipation symptoms and treatment efficacy. It includes difficulty in defecation, defecation time, presence of a feeling of heaviness, incomplete evacuation, or bloating, as well as the frequency of defecation and the presence of abdominal distension.

[0538] 1.3 Inclusion Criteria

[0539] (1) Meets the diagnostic criteria for constipation; (2) Meets the criteria for constipation in traditional Chinese medicine, and the syndrome is characterized by internal heat excess; (3) Age > 18 years old; (4) Has not used any traditional Chinese medicine (Chinese patent medicine and decoction) or Western medicine for constipation in the past week, or has taken the above medicines in a short period of time (3-5 days) and has stopped taking them for more than 7 days; (5) Has signed the patient's informed consent form.

[0540] 1.4 Exclusion Criteria

[0541] (1) Malignant arrhythmia; (2) Patients with intestinal tumors; (3) Patients with intractable constipation caused by organic lesions; (4) Patients with dysfunction of important organs and systems; (5) Patients with abnormal liver and kidney function; (6) Patients with drug allergies; (7) Patients or their authorized persons who are unwilling to sign a written informed consent form or are unwilling to comply with the research protocol; (8) Patients with mental illness; (9) Patients who have recently undergone surgery; (10) Pregnant women; (11) Other reasons that the researchers believe should not be included.

[0542] 1.5 Treatment Methods

[0543] All enrolled patients were treated with the laxative decoction of Example 16, one dose per day, orally, for 28 days.

[0544] 1.6 Observation Indicators

[0545] Using a self-controlled before-and-after research method, changes in patients' clinical symptoms (average defecation time, weekly defecation frequency, defecation difficulty, anal tenesmus, constipation, abdominal distension), tongue appearance, and pulse were observed before and after treatment. Based on the scoring criteria for different symptoms (see Table 45), patients with a disease assessment score of 3-9 were defined as mild patients; patients with a disease assessment score of 10-12 were defined as moderate patients; and patients with a disease assessment score of 12 or above were defined as severe patients.

[0546] Table 45 Scoring criteria for different symptoms

[0547] 1.7 Efficacy Criteria

[0548] Based on the change in the patient's condition assessment score before and after medication, three outcomes were established: "significantly effective," "effective," and "ineffective." Patients with a change of 5 points or more in their assessment score were defined as "significantly effective"; those with a change of 3-4 points were defined as "effective"; and those with a change of less than 3 points were defined as "ineffective." The overall effective rate was calculated as (significantly effective + effective) / n × 100%.

[0549] 1.8 Statistical Analysis

[0550] Data analysis showed that the measurement data were expressed as “x̄±s”, and the t-test was used. P<0.05 was considered statistically significant.

[0551] 2. Results

[0552] 2.1 Clinical efficacy results

[0553] Through observation and data analysis, the clinical efficacy results after treatment are shown in Table 46. As can be seen from Table 46, after taking the laxative decoction, 17 cases showed significant effects within 14 days, 69 cases showed effectiveness, and the total effective rate reached 86%; within 28 days, 68 cases showed significant effects, 31 cases showed effectiveness, and the total effective rate reached 99%.

[0554] Table 46 Clinical efficacy results after treatment (n, %)

[0555] 2.2 Improvement of clinical symptoms before and after treatment

[0556] The 100 patients included all had varying degrees of symptoms such as prolonged average defecation time, decreased weekly defecation frequency, difficulty in defecation, anal tenesmus, constipation, and abdominal distension. The efficacy results showed that after taking the laxative decoction for 14 or 28 days, the patients experienced significant improvement in symptoms such as prolonged average defecation time, decreased weekly defecation frequency, difficulty in defecation, anal tenesmus, constipation, and abdominal distension (P < 0.05).

[0557] 2.3 Safety Observation

[0558] No adverse drug reactions were observed in any patient during or after treatment.

[0559] The above results indicate that the traditional Chinese medicine composition for relieving constipation in this application can effectively alleviate the clinical symptoms of patients with constipation. It can be used to treat constipation caused by excessive internal heat and deficiency of yin and blood, achieving the effects of clearing heat and moistening the intestines. Moreover, its clinical application is safe and reliable.

[0560] VI. Comparison Test of Process Parameters

[0561] 1. Dissolution rate (naringin, wt%) test at 30 minutes

[0562] Using the small cup method, 150 ml of water was added as the dissolution medium, the rotation speed was 75 rpm, the reagent to be tested was put into the cup, 10 ml of the dissolution solution was aspirated after 30 minutes, filtered, and ready for testing.

[0563] Detection method: Chromatographic conditions: Agela Venusil MP C18 (5µm, 4.6×250mm) column, acetonitrile-0.1% phosphoric acid water = 17:83 mobile phase, detection temperature 30℃, flow rate 1.0ml / min, detection wavelength 283nm.

[0564] Preparation of reference solution: Weigh an appropriate amount of naringin reference standard and add methanol to prepare an 80 μg / ml reference solution.

[0565] Test solution: Accurately pipette 10 μL of the dissolution solution and inject it into the high performance liquid chromatograph. Calculate the component content using the external standard method.

[0566] Dissolution % = Total dissolved components / Total formulation components 100%.

[0567] 2. Particle moisture absorption rate (%) test

[0568] Take a dry, flat weighing bottle and place it in a constant temperature and humidity chamber (set to 75% relative humidity) one day before the test, and accurately weigh it (m1). Take an appropriate amount of granules, spread them evenly in the weighing bottle, and accurately weigh it (m2). Open the weighing bottle and place it under the same constant temperature and humidity conditions as the cap for 24 hours. Then close the cap and accurately weigh it (m3). Moisture absorption rate (%) = (m3-m2) / (m2-m1) × 100%.

[0569] 3. Granulation process, particle state observation, and calculation of particle yield, molding rate, and proportion of particles larger than No. 4 sieve.

[0570] Granules were prepared according to the preparation methods of Examples 1, 8-13. The granulation conditions and granule state of the finished products in each example were observed, and the granule yield, molding rate and the proportion of granules above No. 4 sieve were calculated.

[0571] Granulation yield % = Weight of formulation after granulation / Weight of input materials 100%;

[0572] Formulation rate % = Particle weight between No. 1 and No. 5 pharmacopoeia sieves / Total amount of formulation 100%;

[0573] Percentage of particles larger than No. 4 sieve = Weight of particles that did not pass through the No. 4 pharmacopoeia sieve / Total number of particles from No. 1 to No. 5 sieves 100%.

[0574] 4. Accelerated 3-month moisture change rate (%) and properties

[0575] The granules prepared by the methods in Examples 1, 8-13 were sealed in aluminum-plastic bags and subjected to accelerated testing at 40°C and 75% RH to determine the moisture change rate and observe the properties.

[0576] Moisture change rate % = (March grain moisture / October grain moisture - 1) 100%. 0-month particle moisture content refers to the moisture content measured on day 0.

[0577] The test results of Examples 1, 8-13 are shown in Table 47.

[0578] Table 47 Effect of preparation process on laxative preparation

[0579] In summary, compared with Examples 8-13, the granulation process and the properties and physicochemical properties of the resulting particles in Example 1 are superior.

[0580] The above description is only a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the scope of protection of this application.

Claims

1. A traditional Chinese medicine composition for relieving constipation, wherein, The raw material components of the traditional Chinese medicine composition, by weight, include: 23-42 parts of donkey-hide gelatin beads, 23-42 parts of saposhnikovia root, 5-8 parts of notopterygium root, 5-8 parts of gentian root, 11-21 parts of dried tangerine peel, 11-21 parts of angelica root, 11-21 parts of immature bitter orange peel, 11-21 parts of bitter almond, 11-21 parts of prepared rhubarb, 5-8 parts of apricot kernel, 11-21 parts of hemp seed, and 5-8 parts of schizonepeta.

2. The traditional Chinese medicine composition according to claim 1, wherein, The raw material components of the traditional Chinese medicine composition, by weight, include: 26-39 parts of donkey-hide gelatin beads, 26-39 parts of saposhnikovia root, 5-8 parts of notopterygium root, 5-8 parts of gentian root, 13-20 parts of dried tangerine peel, 13-20 parts of angelica root, 13-20 parts of immature bitter orange peel, 13-20 parts of bitter almond, 13-20 parts of prepared rhubarb, 5-8 parts of apricot kernel, 13-20 parts of hemp seed, and 5-8 parts of schizonepeta.

3. The traditional Chinese medicine composition according to claim 1, wherein, The traditional Chinese medicine composition also includes pharmaceutically acceptable carriers or excipients; Preferably, the pharmaceutically acceptable carrier or excipient is selected from at least one of solvents, diluents, disintegrants, precipitation inhibitors, surfactants, flow aids, binders, lubricants, dispersants, suspending agents, isotonic agents, thickeners, emulsifiers, preservatives, stabilizers, hydrating agents, emulsification accelerators, buffers, absorbents, colorants, flavorings, sweeteners, ion exchangers, release agents, coating agents, flavoring agents, and antioxidants.

4. The traditional Chinese medicine composition according to any one of claims 1-3, wherein, The traditional Chinese medicine composition is formulated into a pharmaceutically acceptable preparation; preferably, the traditional Chinese medicine composition is formulated into any one of the following dosage forms: granules, decoction, pills, tablets or capsules.

5. A method for preparing a traditional Chinese medicine composition granule, wherein, Including the following steps: (1) The ingredients of any one of claims 1-4, namely Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata, Angelica sinensis, Citrus aurantium, Prunus armeniaca, Prunus japonica, Cannabis sativa, and Schizonepeta tenuifolia, are boiled in water and extracted, and then the filtrate is collected by filtration; the filtrate is concentrated into a clear extract. (2) The cooked rhubarb and donkey-hide gelatin beads as described in any one of claims 1-4 are pulverized and sieved to obtain fine powder of donkey-hide gelatin beads and fine powder of cooked rhubarb; (3) Mix the fine powder of donkey-hide gelatin beads, the fine powder of cooked rhubarb and the excipients evenly, and then add the clear paste for granulation to obtain the traditional Chinese medicine composition granules; or, (3') dry the clear paste and pulverize it, mix it evenly with the fine powder of donkey-hide gelatin beads and the fine powder of cooked rhubarb, then add the excipients and wetting agent, mix it evenly and granulate it, and then dry it again to obtain the traditional Chinese medicine composition granules; or, (3'') dry the clear paste and pulverize it, mix it evenly with the fine powder of donkey-hide gelatin beads and the fine powder of cooked rhubarb, and then add the excipients for granulation to obtain the traditional Chinese medicine composition granules.

6. The preparation method according to claim 5, wherein: In step (1), the weight of the water is 4-10 times the total weight of the following herbs: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia; the decoction extraction is performed 2-3 times, with each extraction lasting 0.5-3 hours; the concentration is performed under reduced pressure, and the temperature for this concentration is 65-85℃; the relative density of the extract is 1.05-1.

20. In step (3), step (3') or step (3''), the mass ratio of the excipients to the extract is 1:(0.5-2); the excipients include dextrin, lactose and steviol glycosides in a mass ratio of (1-3):1:(0.006-0.06); in step (3), the granulation process parameters include: air inlet temperature of 80-100℃, atomization pressure of 0.3-0.4 bar, and liquid inlet speed of 7-20 rpm; In step (3'), the drying method is selected from at least one of vacuum drying, belt drying and spray drying; the wetting agent is selected from water or an aqueous solution of ethanol with a volume fraction of 70%-95%; the temperature of the re-drying is 40℃-60℃; In step (3''), the drying method is selected from at least one of vacuum drying, belt drying and spray drying.

7. A method for preparing a decoction of traditional Chinese medicine composition, wherein, Including the following steps: The ingredients of any one of claims 1-4, namely Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia, are decocted in water and extracted, and then the filtrate is collected by filtration. The prepared rhubarb and donkey-hide gelatin beads as described in any one of claims 1-4 are pulverized and sieved, and then mixed evenly with the filtrate to obtain a decoction of traditional Chinese medicine composition. Preferably, the weight of the water is 4-10 times the total weight of the following herbs: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia. Preferably, the decoction extraction is performed 2-3 times, and the decoction extraction time is 0.5-3 hours each time.

8. A method for preparing a tablet of a traditional Chinese medicine composition, wherein, Including the following steps: The ingredients of any one of claims 1-4, namely Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia, are decocted in water and extracted. The filtrate is then collected by filtration. The filtrate is concentrated into a clear extract. The clear extract is dried and pulverized to obtain an extract powder. After pulverizing the prepared rhubarb and donkey-hide gelatin beads as described in any one of claims 1-4 and sieving them, the mixture is then mixed evenly with the excipients and the extract powder. Water is then added for granulation, followed by the addition of magnesium stearate and mixing. The mixture is then compressed into tablets to obtain a traditional Chinese medicine composition tablet.

9. The preparation method according to claim 8, wherein: The weight of the water is 4-10 times the total weight of the following herbs: Saposhnikovia divaricata, Notopterygium incisum, Gentiana macrophylla, Citrus reticulata peel, Angelica sinensis, Citrus aurantium, Prunus armeniaca seed, Prunus japonica seed, Cannabis sativa seed, and Schizonepeta tenuifolia. The decoction and extraction process is performed 2-3 times, with each decoction and extraction lasting 0.5-3 hours. The concentration is a vacuum concentration, and the vacuum concentration temperature is 65-85℃; The relative density of the ointment is 1.05-1.20; The drying process is vacuum drying, and the vacuum drying temperature is 65-85℃. The mass ratio of the excipients to the extract powder is (0.5-1.5):1; The excipients include dextrin, lactose, and steviol glycosides in a mass ratio of (1-3):1:(0.006-0.06); The mass of the magnesium stearate is 0.4%-0.6% of the mass of the granulated particles.

10. Use of the traditional Chinese medicine composition according to any one of claims 1-4 in the preparation of a medicament for the prevention and / or treatment of constipation; wherein the constipation is slow transit constipation, blood deficiency constipation, fluid deficiency constipation, or heat-related constipation; preferably heat-related constipation.

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