A traditional Chinese medicine cellulose granule for lubricating intestines and defecating, and a preparation method and application thereof

Abstract

The application discloses a traditional Chinese medicine cellulose granule for lubricating intestines and defecating, and a preparation method and application thereof. The traditional Chinese medicine cellulose granule is prepared from the following raw materials in parts by weight: 1-8 parts of wheat cellulose, 1-10 parts of xylo-oligosaccharide, 1-10 parts of angelica, 1-10 parts of cistanche, and 1-5 parts of isomalt. The application combines the syndrome differentiation and treatment of virtual constipation in traditional Chinese medicine, and selects medicine capable of improving constipation for compounding. Meanwhile, the synergistic effect between the insoluble dietary fiber wheat cellulose and the soluble dietary fiber xylo-oligosaccharide is added, which is remarkable for constipation, has a synergistic effect, and can greatly improve the symptoms of virtual constipation. The obtained product is simple, cheap and effective, and can avoid the bitter taste of internal traditional Chinese medicine.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine cellulose granule for moistening the intestines and promoting bowel movements, and a preparation method and application thereof. Background Art

[0002] Functional constipation refers to primary, persistent, organic, or biochemical abnormalities, resulting from dysfunction of the colon, rectum, and anus. It is a common and frequently occurring clinical condition. Changes in lifestyle and dietary structure have led to a gradual increase in the incidence of constipation, particularly among the elderly and women who have undergone childbirth. Constipation is characterized by prolonged retention of feces in the large intestine, caused by food residues remaining in the intestinal cavity for an inordinate amount of time. The three main symptoms of constipation are stool that is too small, too hard, and too difficult to pass.

[0003] The harmful effects of constipation are gradual, and the harm of long-term, stubborn constipation to the human body cannot be ignored. Constipation affects the patient's appetite and intestinal nutrient absorption, and can cause symptoms such as abdominal distension, abdominal pain, nausea, vomiting, and loss of appetite. It can even induce intestinal malignancies (such as colon cancer), hepatic encephalopathy, and cardiovascular and cerebrovascular diseases. Constipation is closely related to some anorectal diseases, such as hemorrhoids and anal fissures. Therefore, early prevention and reasonable treatment of constipation will greatly reduce the serious consequences and social burden brought by constipation.

[0004] Traditional Chinese medicine (TCM) has a history of treating constipation for thousands of years. Using TCM's holistic perspective and dialectical treatment theory to guide medication can achieve definite therapeutic effects, significantly improve constipation, and reduce recurrences. Chronic constipation is common in frail people, such as the elderly and women. According to TCM theory, these people are prone to qi and blood deficiency, which results in a lack of fluid in the intestines, leading to constipation—this is known as deficiency constipation, which is defined as qi and blood deficiency and fluid deficiency leading to dry intestines according to TCM syndrome differentiation. TCM is undoubtedly effective in treating constipation in the elderly, and boasts a wide selection of medicines, flexible formulations, and minimal toxic and side effects, advantages unmatched by chemically synthesized drugs. For example, patent documents CN105641335A and CN106806470A provide Chinese herbal compositions that moisturize the intestines and relieve constipation, while patent document CN107183705A provides functional foods containing various extracts that moisturize the intestines and relieve constipation.

[0005] Modern medicine primarily relies on laxatives, drugs that promote intestinal motility, enemas, and suppositories, which can relieve symptoms but not the root cause, and also have certain side effects. The top treatment principles in the "Chinese Expert Consensus on Chronic Constipation (2019)" are: lifestyle adjustments such as increasing dietary fiber and water, and increasing exercise are the basic treatment for chronic constipation. Dietary fiber includes soluble dietary fiber and insoluble dietary fiber; bulking laxatives (wheat bran, etc.) are highly recommended. The gas produced by the fermentation of soluble dietary fiber by intestinal microorganisms can also promote intestinal peristalsis and speed up the excretion of feces. Insoluble dietary fiber has strong water absorption and swelling capacity, is not easily digested by enzymes, and is not easily fermented by intestinal microorganisms. As a result, it can form more solid food residues, increase the mass and volume of feces, and make the feces softer and easier to excrete.

[0006] There are many products currently available on the market to treat constipation, but the numerous Chinese patent medicines on the market all have their own problems. Many contain irritating ingredients such as anthraquinones (rhubarb, aloe vera, senna leaves, and Polygonum multiflorum). These laxatives are fast-acting and effective in relieving constipation, primarily through the myenteric plexus. Long-term use can damage the myenteric plexus, leading to decreased colonic responsiveness to intestinal stimulation, weakened colonic motility, and even loss of spontaneous defecation, a condition known as "laxative colon." Therefore, long-term use of irritant laxatives is discouraged, and only short-term or intermittent use is recommended.

[0007] The combination of traditional Chinese medicine ingredients and dietary fiber can achieve greater efficacy in treating functional constipation, with fewer side effects, lower drug tolerance, and significant long-term results. Currently, there are very few such products on the market, so they have great market potential.

[0008] In view of this, it is hoped to provide a Chinese medicinal cellulose granule for moistening the intestine and promoting bowel movements of the present invention. Summary of the Invention

[0009] In response to the above technical problems, the purpose of the present invention is to provide a Chinese medicine cellulose granule for moisturizing the intestines and promoting bowel movements, as well as its preparation method and application, to comprehensively treat constipation and improve the efficacy; the resulting product is simple, inexpensive, and effective, while avoiding the bitter taste of large amounts of Chinese medicine taken orally.

[0010] In order to achieve the above object, the present invention adopts the following technical solutions:

[0011] In a first aspect, the present invention provides a Chinese medicinal cellulose granule for moistening the intestine and promoting bowel movements, which is prepared from the following raw materials in parts by weight:

[0012]

[0013] In the above technical solution, wheat cellulose is an insoluble dietary fiber and a bulk laxative. It expands after absorbing water in the intestine, thereby increasing stool volume, expanding intestinal volume, stimulating intestinal peristalsis, causing defecation reflex, and relieving constipation. It contains almost no phytic acid, which better overcomes the defects of traditional cellulose due to the presence of phytic acid and immunogenicity, avoids inducing intestinal inflammation, and is safer.

[0014] Xylooligosaccharides: A soluble dietary fiber, xylooligosaccharides are functional polysaccharides composed of 2-7 xylose molecules linked by β-1,4 glycosidic bonds. Compared to other oligosaccharides, such as soy oligosaccharides, fructooligosaccharides, and isomaltooligosaccharides, they offer unique advantages in selectively promoting the proliferation of intestinal bifidobacteria, with their bifidogenic activity 10-20 times greater than that of other polysaccharides. Xylooligosaccharides selectively promote the proliferation of intestinal bifidobacteria, promote bowel movements, and improve the intestinal environment and protect the intestines.

[0015] Angelica: replenishes blood and promotes blood circulation, moistens the intestines and promotes bowel movements, and relieves constipation caused by blood deficiency.

[0016] Cistanche: nourishes kidney yang, moistens the intestines and promotes bowel movements, and relieves constipation caused by kidney deficiency.

[0017] Isomalt: Compared with sucrose or white sugar, isomalt has the characteristics of relatively low sweetness, low dental caries, low calories, and no effect on blood sugar.

[0018] In the above technical solution, unlike most existing methods of treating constipation with Chinese medicine compositions, the product of the present invention is made into granules for easy oral administration. In terms of ingredients, there are only four active ingredients, which are simple in composition. At the same time, the active ingredients are compounded with insoluble dietary fiber, soluble dietary fiber, and Chinese medicine ingredients, which work synergistically, have good effects in moistening the intestines, promoting bowel movements, and preventing constipation. The raw materials are common and the efficacy is very significant.

[0019] As a further preferred embodiment of the above technical solution, the Chinese medicine cellulose granules are made from the following raw materials in parts by weight:

[0020]

[0021] As a further preferred embodiment of the above technical solution, the Chinese medicine cellulose granules are made from the following raw materials in parts by weight:

[0022]

[0023]

[0024] In a second aspect, the present invention provides a method for preparing the above-mentioned traditional Chinese medicine cellulose granules, comprising the following steps:

[0025] (1) Weigh wheat cellulose, xylo-oligosaccharide, angelica sinensis, Cistanche deserticola, and isomalt according to the amount, grind the isomalt, sieve it, and set aside;

[0026] (2) Add 9-12 times the amount of water to angelica and Cistanche deserticola and boil for 2-3 times, boiling for 1-3 hours each time. After boiling, filter and obtain the filtrate for later use;

[0027] (3) The filtrate obtained in step (2) is concentrated under reduced pressure to obtain a thick paste; the first portion of wheat cellulose is then added, stirred evenly, dried under reduced pressure, and finally crushed and sieved to obtain an extract powder for later use;

[0028] (4) The sieved isomalt, the second portion of wheat cellulose, the xylooligosaccharide and the extract powder obtained in step (3) are uniformly mixed, and then granulated, dried, granulated and packaged to obtain the Chinese medicine cellulose granules.

[0029] In the above technical solution, the active ingredients in angelica and cistanche are first fully extracted by water; a portion of wheat fiber is added to the thick paste and then dried under reduced pressure, so that the prepared product is loose and easy to crush, which reduces the drying time and ensures that the product does not have the burnt smell caused by ordinary drying and spray drying.

[0030] As a further preferred embodiment of the above technical solution, in step (1), the isomalt is crushed and then passed through an 80-mesh sieve.

[0031] As a further preferred embodiment of the above technical solution, in step (2), the decoction is completed and filtered through 200 mesh.

[0032] As a further preferred embodiment of the above technical solution, in step (3), the specific operation of vacuum concentration is: vacuum concentration to a relative density of 1.20 to 1.30 under the conditions of -0.06 to -0.10 MPa and ≤70°C; the process parameters of vacuum drying are: -0.06 to -0.10 MPa, 50 to 70°C.

[0033] As a further preferred embodiment of the above technical solution, in step (3), the amount of the first portion of wheat cellulose is 20-30% of the total amount of wheat cellulose.

[0034] As a further preferred embodiment of the above technical solution, in step (4), 85% ethanol is used as a wetting agent for granulation, and 14-mesh granulation is used; and 12-mesh granulation is used for whole granulation.

[0035] In a third aspect, the present invention also aims to protect the use of the above-mentioned traditional Chinese medicine cellulose granules in the preparation of medicines for treating deficiency constipation.

[0036] Clinically, constipation in the elderly often results from blood and yang deficiency. Blood deficiency and fluid deficiency, as fluid and blood share the same origin, deprive the intestines of nourishment. Deficiency of fluid and blood prevents them from moistening the intestines, leading to dryness of the intestines. Blood is the carrier of qi, and prolonged blood deficiency inevitably leads to qi deficiency, which in turn leads to fatigue and worsening constipation. Senile constipation is particularly closely linked to the kidneys. Clinically, the theory that "the kidneys are the gateway to the stomach" is fundamental. Sufficient kidney yin moistens the large intestine, promoting smooth bowel movements. A sufficient vital fire transforms body fluids, enhancing large intestine conduction. The large intestine's function in excreting waste is the functional basis and external manifestation of the concept that "the kidneys open up to the two yin organs." Therefore, treating the kidneys is crucial. Yang qi deficiency is treated by warming the kidneys and replenishing essence, while yin deficiency is treated by nourishing yin and tonifying the kidneys. As the saying goes, "The kidneys govern the five fluids; when body fluids are moist, bowel movements are normal." Cistanche deserticola nourishes kidney yang, moistens the intestines, and promotes bowel movements, while angelica nourishes and invigorates blood circulation, making it suitable for constipation caused by blood and essence deficiency. Therefore, compounding Cistanche deserticola and Angelica sinensis on the basis of wheat cellulose and oligoxylose can greatly improve the symptoms of people with deficiency constipation. Therefore, based on the components provided by the present invention, other usage forms such as adding other components or adding auxiliary materials are all possible and fall within the scope of the present invention.

[0037] Compared with the prior art, the present invention has the following beneficial effects:

[0038] 1. The Chinese medicine cellulose granules provided by the present invention are combined with the traditional Chinese medicine differentiation and treatment of deficiency constipation, and the medicinal materials related to improving constipation are selected for compatibility. At the same time, the synergistic effect between the insoluble dietary fiber wheat cellulose and the soluble dietary fiber oligoxylose is added to have a significant effect on constipation and a synergistic effect, which can greatly improve the symptoms of deficiency constipation. The ingredients are simple and clear, and the efficacy is good.

[0039] 2. The Chinese medicine cellulose granules provided by the present invention have a good taste after brewing, completely changing the rough feeling of wheat bran fiber after brewing, with less mechanical stimulation to the gastrointestinal tract, improving consumer experience, and avoiding the bitter taste of a large amount of Chinese medicine taken orally.

[0040] 3. The preparation method of the Chinese medicine cellulose granules provided by the present invention is to add a part of wheat fiber to the concentrated Chinese medicine paste and then dry it under reduced pressure, so that the prepared product is loose and easy to crush, greatly reducing the drying time, and is fast and efficient; at the same time, it ensures product quality and avoids the burnt smell brought about by ordinary drying and spray drying processes.

[0041] 4. The Chinese medicinal cellulose granules provided by the present invention specifically use insoluble dietary fiber wheat fiber, which greatly increases the weight and volume of feces, softens feces, normalizes feces hardness, shortens intestinal transit time, and makes feces excretion smoother; compared with other insoluble dietary fibers, wheat fiber has high water holding capacity, high swelling power, and extremely high dietary fiber content (95%), and almost no phytic acid, which better overcomes the defects of traditional cellulose due to the presence of phytic acid and immunogenicity, avoids inducing intestinal inflammation, and is safer.

[0042] 5. The traditional Chinese medicine cellulose granules provided by the present invention can not only improve the β diversity of intestinal flora, but also solve the intestinal flora disorder caused by constipation, reshape the intestinal flora homeostasis to relieve constipation.

[0043] In summary, the present invention focuses on moistening the intestines and promoting bowel movements to treat constipation. The preferred active substances act synergistically to ensure good therapeutic effects. At the same time, the preparation method is optimized, and the prepared granules are easy to take. Part of the wheat fiber is added during the preparation process to avoid processes such as spray drying, thereby ensuring product quality and facilitating large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 Figure 2 shows the α-diversity analysis of intestinal flora, including (A) Good's coverage index, (B) Chao1 index, (C) Shannon index, and (D) Simpson index. Compared with the control group, ***P < 0.001; compared with the model group, #P < 0.05, ##P < 0.01, and ###P < 0.001.

[0045] Figure 2 Figure 2 shows the β-diversity analysis of intestinal flora, including (A) PCoA plot based on Weighted Unifrac and (B) NMDS analysis based on ASV.

[0046] Figure 3 Figure 2 Analysis of microbial composition at different taxonomic levels, including (A) relative abundance of species at the phylum level, (B) relative abundance of major species at the phylum level, and (C, D, E) relative abundance of species at the genus level. Compared with the control group, *P < 0.05, ***P < 0.001; compared with the model group, #P < 0.05, ##P < 0.01, ###P < 0.001. DETAILED DESCRIPTION

[0047] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0048] Unless otherwise specified, the medicinal materials in the present invention were purchased from the market. Wheat cellulose was purchased from Guangzhou Mandy Biotechnology Co., Ltd. with a specification of WF600-30; and oligoxylose was purchased from Henan Jianjiu Industrial Co., Ltd. with a specification of 95%.

[0049] Example 1

[0050] A Chinese medicinal cellulose granule for moistening the intestine and relieving constipation is prepared from the following raw materials in parts by weight:

[0051]

[0052] In this embodiment, a method for preparing the above-mentioned traditional Chinese medicine cellulose granules is also provided, comprising the following steps:

[0053] (1) Weigh wheat cellulose, xylo-oligosaccharide, angelica sinensis, Cistanche deserticola, and isomalt according to the amount, grind the isomalt, and sieve through 80 mesh for later use;

[0054] (2) Add 10 times the amount of water to angelica and Cistanche deserticola and boil them three times for 2 hours each time. After boiling, filter through 200 mesh to obtain the filtrate for later use.

[0055] (3) The filtrate obtained in step (2) is concentrated under reduced pressure (-0.06 to -0.10 MPa, ≤70°C) to a relative density of 1.20 to 1.30 (60±5°C) to obtain a thick paste; the first portion of wheat cellulose (25% of the total amount) is then added, stirred evenly, and dried under reduced pressure (-0.06 to -0.10 MPa, 60°C), and finally crushed and sieved through 80 mesh to obtain an extract powder for later use;

[0056] (4) The sieved isomalt, the second portion of wheat cellulose, the xylo-oligosaccharide and the extract powder obtained in step (3) are uniformly mixed, and then 85% ethanol (approximately 20% of the total amount) is used as a wetting agent to prepare a soft material, granulated with 14 mesh, dried at 60±5° C. until the moisture content of the granules is controlled to be below 5%, and granulated with 12 mesh to obtain dry granules; finally, the obtained dry granules are packaged in a composite film at 6 g / bag to obtain a Chinese medicine cellulose granule product.

[0057] Example 2

[0058] A Chinese medicinal cellulose granule for moistening the intestine and relieving constipation is prepared from the following raw materials in parts by weight:

[0059]

[0060] In this embodiment, a method for preparing the above-mentioned traditional Chinese medicine cellulose granules is also provided, comprising the following steps:

[0061] (1) Weigh wheat cellulose, xylo-oligosaccharide, angelica sinensis, Cistanche deserticola, and isomalt according to the amount, grind the isomalt, and sieve through 80 mesh for later use;

[0062] (2) Add 11 times the amount of water to angelica and Cistanche deserticola and boil them three times, boiling for 2.5 hours each time. After boiling, filter through 200 mesh to obtain the filtrate, which is set aside.

[0063] (3) The filtrate obtained in step (2) is concentrated under reduced pressure (-0.06 to -0.10 MPa, ≤70°C) to a relative density of 1.20 to 1.30 (60±5°C) to obtain a thick paste; the first portion of wheat cellulose (25% of the total amount) is then added, stirred evenly, and dried under reduced pressure (-0.06 to -0.10 MPa, 60°C), and finally crushed and sieved through 80 mesh to obtain an extract powder for later use;

[0064] (4) The sieved isomalt, the second portion of wheat cellulose, the xylo-oligosaccharide and the extract powder obtained in step (3) are uniformly mixed, and then 85% ethanol (approximately 20% of the total amount) is used as a wetting agent to prepare a soft material, granulated with 14 mesh, dried at 60±5° C. until the moisture content of the granules is controlled to be below 5%, and granulated with 12 mesh to obtain dry granules; finally, the obtained dry granules are packaged in a composite film at 6 g / bag to obtain a Chinese medicine cellulose granule product.

[0065] Example 3

[0066] A Chinese medicinal cellulose granule for moistening the intestine and relieving constipation is prepared from the following raw materials in parts by weight:

[0067]

[0068] In this embodiment, a method for preparing the above-mentioned traditional Chinese medicine cellulose granules is also provided, comprising the following steps:

[0069] (1) Weigh wheat cellulose, xylo-oligosaccharide, angelica sinensis, Cistanche deserticola, and isomalt according to the amount, grind the isomalt, and sieve through 80 mesh for later use;

[0070] (2) Add 9 times the amount of water to angelica and Cistanche deserticola and boil them three times, boiling for 1.5 hours each time. After boiling, filter through 200 mesh to obtain the filtrate for later use.

[0071] (3) The filtrate obtained in step (2) is concentrated under reduced pressure (-0.06 to -0.10 MPa, ≤70°C) to a relative density of 1.20 to 1.30 (60±5°C) to obtain a thick paste; the first portion of wheat cellulose (25% of the total amount) is then added, stirred evenly, and dried under reduced pressure (-0.06 to -0.10 MPa, 60°C), and finally crushed and sieved through 80 mesh to obtain an extract powder for later use;

[0072] (4) The sieved isomalt, the second portion of wheat cellulose, the xylo-oligosaccharide and the extract powder obtained in step (3) are uniformly mixed, and then 85% ethanol (approximately 20% of the total amount) is used as a wetting agent to prepare a soft material, granulated with 14 mesh, dried at 60±5° C. until the moisture content of the granules is controlled to be below 5%, and granulated with 12 mesh to obtain dry granules; finally, the obtained dry granules are packaged in a composite film at 6 g / bag to obtain a Chinese medicine cellulose granule product.

[0073] Comparative Example 1

[0074] The formula and preparation method are basically the same as those in Example 1, except that the wheat cellulose is replaced by oat cellulose.

[0075] Comparative Example 2

[0076] The formula and preparation method are basically the same as those in Example 1, except that xylooligosaccharide is replaced by fructooligosaccharide.

[0077] Comparative Example 3

[0078] The formula and preparation method are basically the same as those in Example 1, except that Cistanche deserticola is replaced by Cassia seed.

[0079] Comparative Example 4

[0080] A Chinese medicinal cellulose granule for moistening the intestine and relieving constipation is prepared from the following raw materials in parts by weight:

[0081]

[0082] In this comparative example, a method for preparing the above-mentioned traditional Chinese medicine cellulose granules is also provided, comprising the following steps:

[0083] (1) Weigh wheat cellulose, xylo-oligosaccharide, angelica sinensis, Cistanche deserticola, and isomalt according to the amount, grind the isomalt, and sieve through 80 mesh for later use;

[0084] (2) Add 10 times the amount of water to angelica and Cistanche deserticola and boil them three times for 2 hours each time. After boiling, filter through 200 mesh to obtain the filtrate for later use.

[0085] (3) The filtrate obtained in step (2) was concentrated under reduced pressure (-0.06 to -0.10 MPa, ≤70°C) to a concentrate with a relative density of 1.05 to 1.10 (measured at 60±2°C), 100% of the amount of the medicinal material isomalt was added, stirred and dissolved uniformly, and spray dried (inlet air temperature 170 to 180°C, outlet air temperature 90 to 95°C, liquid inlet speed 16 to 24 rpm, atomization frequency 45 Hz), and the spray-dried powder was passed through an 80-mesh sieve for later use;

[0086] (4) The wheat cellulose, oligoxylose, and the spray-dried powder sieved in step (3) are placed together in a wet granulator and mixed evenly. Subsequently, 85% ethanol (approximately 20% of the total amount) is used as a wetting agent to prepare a soft material, granulated with 14 mesh, dried at 60±5° C. until the moisture content of the granules is controlled to be below 5%, and granulated with 12 mesh to obtain dry granules. Finally, the obtained dry granules are packaged in a composite film at 6 g / bag to obtain a Chinese medicine cellulose granule product.

[0087] The traditional Chinese medicine cellulose granule product prepared in Comparative Example 4 partially has a certain burnt smell.

[0088] Comparative Example 5

[0089] A Chinese medicinal cellulose granule for moistening the intestine and relieving constipation is prepared from the following raw materials in parts by weight:

[0090]

[0091] In this comparative example, a method for preparing the above-mentioned traditional Chinese medicine cellulose granules is also provided, comprising the following steps:

[0092] (1) Weigh wheat cellulose, xylo-oligosaccharide, angelica sinensis, Cistanche deserticola, and isomalt according to the amount, grind the isomalt, and sieve through 80 mesh for later use;

[0093] (2) Add 10 times the amount of water to angelica and Cistanche deserticola and boil them three times for 2 hours each time. After boiling, filter through 200 mesh to obtain the filtrate for later use.

[0094] (3) The filtrate obtained in step (2) is concentrated under reduced pressure (-0.06 to -0.10 MPa, ≤70°C) to a relative density of 1.20 to 1.30 (60±5°C) to obtain a thick paste; after stirring evenly, the mixture is dried under reduced pressure (-0.06 to -0.10 MPa, 60°C) and finally crushed and sieved through 80 mesh to obtain an extract powder for later use;

[0095] (4) The sieved isomalt, wheat cellulose, and xylo-oligosaccharide of step (1) and the extract powder obtained in step (3) are uniformly mixed, and then 85% ethanol (about 20% of the total amount) is used as a wetting agent to prepare a soft material, granulated with 14 mesh, dried at 60±5° C. until the moisture content of the granules is controlled to be less than 5%, and granulated with 12 mesh to obtain dry granules; finally, the obtained dry granules are packaged in a composite film at 6 g / bag to obtain a Chinese medicine cellulose granule product.

[0096] In step (3) of comparative example 5, wheat cellulose was not added during the reduced pressure drying process. The thick paste was difficult to dry and required more than 48 hours to dry. The dried product was hard and difficult to crush, resulting in a hard texture of the final product. However, in step (3) of example 1, some wheat cellulose was added during the reduced pressure drying process. The reduced pressure drying only took 5 to 6 hours, which greatly reduced the drying time. The preparation was faster and more efficient, making it suitable for industrial production.

[0097] Test Example 1: Animal Testing

[0098] In this test example, a mouse constipation model was established by loperamide hydrochloride to evaluate the efficacy of the product of the present invention in moistening the intestines and relieving constipation in mice.

[0099] 1.1 Experimental materials and methods

[0100] Preparation of loperamide hydrochloride suspension: The concentration is 0.03% loperamide hydrochloride capsules, each capsule contains 2 mg of loperamide hydrochloride, take according to the actual dosage, and prepare and use immediately.

[0101] Preparation of ink: Accurately weigh 100g of gum arabic, add 800mL of water, and boil until the solution becomes transparent. Weigh 50g of activated carbon (powdered) and add it to the above solution and boil it three times. After the solution cools, add water to make up to 1000mL. Store in a refrigerator at 4℃ and shake well before use.

[0102] Sample Grouping: In the small intestinal motility and defecation function animal experiments, the product of Example 1 was used as Formulation Group 1, the product of Comparative Example 1 was used as Formulation Group 2, the product of Comparative Example 2 was used as Formulation Group 3, and the product of Comparative Example 3 was used as Formulation Group 4. In the intestinal flora 16S rRNA sequencing experiment, the product of Example 1 was used as the test group, and the samples were divided into a high-dose group and a low-dose group according to different dosages.

[0103] 1.2 Test methods

[0104] 1.2.1 Animal experiments on small intestinal motility

[0105] Thirty-six healthy male SPF Kunming mice, 5-6 weeks old, weighing 30-35g, were randomly divided into 6 groups of 6 mice each after 5 days of adaptive feeding: negative control group, model group, formulation 1 group, formulation 2 group, formulation 3 group, and formulation 4 group.

[0106] The daily gavage dosage of formula 1, 2, 3, and 4 groups was 1.2 g / kg BW, and the control group and model group were gavaged with an equal volume of distilled water every day. After 7 days of continuous gavage, the mice in each group were fasted for 16 hours, and then the model group and formula 1, 2, 3, and 4 groups were gavaged with 3 mg / kg BW of loperamide hydrochloride suspension. The control group was gavaged with an equal volume of distilled water. 0.5 hours later, formula 1, 2, 3, and 4 groups were given ink containing the corresponding dose of the test drug, and the control group and model group were gavaged with an equal volume of ink. After 25 minutes, the intestinal tube from the pylorus to the ileocecal region was cut, and the length of the intestinal tube was measured as the "total length of the small intestine (cm)", and the length from the pylorus to the ink front was the "small intestine advancement length (cm)". The small intestine advancement rate was calculated according to the following formula: Small intestine advancement rate (%) = (small intestine advancement length / total length of the small intestine) * 100%

[0107] 1.2.2 Animal experiments on defecation function

[0108] Thirty-six healthy male SPF Kunming mice, 5-6 weeks old, weighing 30-35g, were randomly divided into 6 groups of 6 mice each after 5 days of adaptive feeding: negative control group, model group, formulation 1 group, formulation 2 group, formulation 3 group, and formulation 4 group.

[0109] Groups 1, 2, 3, and 4 were gavaged daily with a dose of 1.2 g / kg BW. The control and model groups received an equal volume of distilled water. After 7 days of gavage, mice in each group were fasted for 16 hours. The model and group 1, 2, 3, and 4 were then gavaged with a 6 mg / kg BW loperamide hydrochloride suspension. The control group received an equal volume of distilled water. 0.5 hours later, groups 1, 2, 3, and 4 were given ink containing the corresponding dose of the test drug, while the control and model groups received an equal volume of ink. Mice were housed individually and fed with normal water and food. A timer was started at the end of ink gavage, and the time when the mice passed their first black stool was recorded. Feces were collected from each group over a 5-hour period, and the total number and weight of black stools were recorded.

[0110] 1.3.3 16S rRNA sequencing of intestinal flora

[0111] Twenty-four healthy male SPF Kunming mice, 5-6 weeks old, weighing 30-35g, were randomly divided into four groups of six mice each after five days of adaptive feeding. These groups included a control group, a model group, a high-dose formula group (dosage: 3.6g / kg BW), and a low-dose formula group (dosage: 0.6g / kg BW). Except for the control group, all other groups were gavaged with 10mg / kg BW of loperamide hydrochloride for 14 days to establish a constipation model in mice. Starting on day 8, the high- and low-dose formula groups were gavaged daily with the test drug at each dose, while the control and model groups were given an equal volume of distilled water. After seven consecutive days of gavage, each group fasted for 16 hours, but not water, and their cecal contents were collected and sent for sequencing.

[0112] 1.3 Test results

[0113] Data were processed using SPSS 27.0 software and expressed as (x ± s). One-way analysis of variance was used for comparisons between multiple groups. P < 0.05 indicated statistical significance. The results are as follows:

[0114] 1.3.1 Effects on small intestinal motility in constipated mice

[0115] After administering the corresponding drugs to each experimental group, the small intestinal propulsion function of the experimental group was recorded, and the results are shown in Table 1. Compared with the control group, the small intestinal propulsion rate of the model group was significantly reduced, indicating that the mouse model was successfully established. Compared with the model group, the small intestinal propulsion function of the formulation group and the drug group was enhanced after intervention, and the ink propulsion distance and ink propulsion rate of the small intestine were increased. Compared with the different formulation groups, the effect of formulation group 1 was significantly better than that of formulation groups 2-4. Compared with the comparative example, the product of the embodiment of the present invention can better promote small intestinal motility in constipated mice.

[0116] Table 1: Effects on small intestinal motility in constipated mice ( n=6)

[0117] Group Ink advancement rate (%) control group 84±16 Model Group 49±15*** Formula 1 <![CDATA[70±13 ## ]]> Formula 2 <![CDATA[61±11 # <!-- 9 -->]]> Formula 3 <![CDATA[63±15 # ]]> Formula 4 <![CDATA[66±12 ## ]]>

[0118] Note: Compared with the control group, ***P<0.001; compared with the model group, #P<0.05, ##P<0.01.

[0119] 1.3.2 Effects on defecation function in constipated mice

[0120] After each experimental group was administered the corresponding drug, its effect on the defecation function of constipated mice was recorded. The results are shown in Table 2. Compared with the control group, the model group had a significantly longer time to excrete the first black stool, and the number and weight of black stools excreted within 5 hours were significantly reduced, indicating that the mouse model was successfully established. After treatment with each formula drug group, the time to excrete the first black stool in Formula 1 was significantly shortened, and the number and weight of black stools excreted within 5 hours were significantly increased. The other formulas were able to promote intestinal motility and defecation function in constipated mice to varying degrees. Compared with the different formula groups, the effect of Formula 1 was significantly better than that of Formulas 2-4. Compared with the comparative example, the product of the embodiment of the present invention can better promote intestinal motility and defecation function in constipated mice.

[0121] Table 2: Effects on defecation parameters in constipated mice ( n=6)

[0122] Group Time to discharge the first black stool (min) Number of black stools within 5 hours (grains) Weight of black stool within 5 hours (g) control group 95.21±35.88 19.55±4.35 0.60±0.15 Model Group 188.75±48.87*** 8.01±5.21* 0.25±0.10* Formula 1 <![CDATA[120.60±25.35 ## ]]> <![CDATA[19.95±4.98 # ]]> <![CDATA[0.65±0.25 # ]]> Formula 2 <![CDATA[141.50±21.05 # ]]> <![CDATA[16.31±7.05 # ]]> 0.45±0.43 Formula 3 <![CDATA[133.47±27.56 # ]]> <![CDATA[17.18±6.67 # ]]> <![CDATA[0.54±0.16 # ]]> Formula 4 <![CDATA[128.52±31.57 # ]]> <![CDATA[18.22±6.25 # ]]> <![CDATA[0.58±0.13 # ]]>

[0123] Note: Compared with the control group, ***P<0.001; compared with the model group, #P<0.05, ##P<0.01.

[0124] 1.3.3 Effects on intestinal flora in constipated mice

[0125] The Good's Coverage index is used to evaluate the sequencing depth of 16S rRNA test samples. The control group, model group, and high- and low-dose formula groups were all above 0.99, indicating that the sequencing depth basically covers all species, the data volume is reasonable, and it can truly reflect the composition of the intestinal microbiome ( Figure 1 A). Chao1 index was used to evaluate the richness of the bacterial community, and Shannon and Simpson indices were used to evaluate the diversity and uniformity of the bacterial community. The results of α diversity showed that there was no significant difference in Chao1 index among the groups ( Figure 1 B); Compared with the control group, the Shannon and Simpson indices in the model group were significantly decreased (P < 0.001, P < 0.001). Compared with the model group, the Shannon and Simpson indices in the high-dose formula group were significantly increased (P < 0.05, P < 0.01), and the Shannon and Simpson indices in the low-dose formula group were more significantly increased (P < 0.001, P < 0.001) ( Figure 1 C, D). The above results show that there is no significant difference in species richness among the groups, but the diversity and uniformity of the intestinal flora of constipated mice are reduced. Both the high- and low-dose groups showed a significant reduction after intervention, and the effect of the low-dose group was more obvious.

[0126] Principal coordinate analysis and non-metric multidimensional scaling analysis were used to assess the similarity between microbial communities, namely the beta diversity of the intestinal flora. The PCoA cluster diagram results showed that ( Figure 2 A), the microbial diversity of the model group and the control group showed obvious differences, while the microbial diversity of mice after administration of the formula drug was closer to that of the control group, and the low-dose formula group and the control group had a large overlap. Figure 2 B), stress = 0.13, and there was no overlap between the sample points of the model group and the control group and the high- and low-dose treatment groups, indicating that there were significant differences in the species composition of the intestinal flora between the groups. In summary, the product of Example 1 of the present invention can improve the β diversity of the intestinal flora, and the low-dose group has a better effect.

[0127] 1.3.4 Regulatory effect on the relative abundance of intestinal flora

[0128] At door level ( Figure 3A, B), there were differences in the composition of intestinal flora in each group. Compared with the control group, the abundance of Bacteroidota (Bacteroidetes) and Firmicutes (Firmicutes) in the model group samples was significantly reduced, and the abundance of Verrucomicrobiota (Verrucomicrobia) was significantly increased; the low-dose group intervention could significantly reduce the abundance of Verrucomicrobiota and increase the abundance of Bacteroidota and Firmicutes, but the differences were not statistically significant. At the genus level ( Figure 3 C, D, E), compared with the control group, Akkermansia (muciniphila) in the model group was significantly upregulated, while Bacteroides (Bacteroides) and Alistipes (Another branch of bacteria) showed a downward trend. Compared with the model group, the levels of Akkermansia in the high and low dose groups of the formula were significantly reduced, while the relative abundance of Bacteroides and Alistipes increased significantly. In summary, constipation causes the disorder of the intestinal flora of mice, and the intervention of the product in Example 1 of the present invention can reshape the homeostasis of the intestinal flora of mice to relieve constipation.

[0129] Test Example 2: Human Trial

[0130] This test example refers to the "Chinese Expert Consensus on Chronic Constipation" and "Traditional Chinese Medicine Internal Medicine" (9th edition) compiled in 2019, proposes the TCM diagnostic principles for deficiency constipation, and evaluates the efficacy of the product of the present invention in moisturizing the intestines and promoting bowel movements in people with deficiency constipation.

[0131] 2.1 Inclusion criteria

[0132] Main symptoms: 1. Difficulty in defecation; 2. Stool that is hard and hard to pass or resembles sheep dung; 3. Strained defecation; 4. No more than three independent and complete bowel movements per week; 5. The interval between each bowel movement is greater than 3 days.

[0133] Secondary symptoms: 1. Hard stool at first but soft at the end, difficulty in defecation despite urge to defecate, sweating and shortness of breath when exerting force, fatigue, pale face and tiredness after defecation; 2. Dry and hard stool, dull complexion, pale lips, palpitations and shortness of breath; 3. Dry and hard stool like sheep dung, emaciation, dizziness, tinnitus, sore waist and knees, hot flashes and night sweats; 4. Dry or soft stool, but difficult to defecate, clear and long urine, pale face and cold limbs.

[0134] Tongue: red tongue, little or cracked coating, yellow coating, and thready pulse.

[0135] Subjects who meet at least two main symptoms and at least one secondary symptom will be included in the population of subjects with deficiency constipation.

[0136] 2.2 Clinical efficacy evaluation criteria

[0137] According to the "Standards for Diagnosis and Efficacy of Clinical Diseases in Traditional Chinese Medicine", the treatment is divided into four levels: clinical cure, marked effect, effective, and ineffective. The evaluation indicators mainly include:

[0138] Clinical recovery: Bowel movements have been normal for one month, with soft stools, once a day, and no discomfort.

[0139] Significant effect: The symptoms of difficult defecation have improved in the past month. Defecation is smoother and softer than before, and bowel movements are possible at least every other day.

[0140] Effective: The symptoms of difficult defecation have improved in the past month, and the bowel movements are basically smooth, but the bowel movements occasionally take a little longer. Generally, there will be at least one spontaneous bowel movement within 3 days, and the hardness and dryness of the stool have improved.

[0141] Ineffective: Spontaneous defecation is still difficult, the interval between defecation is longer than three days, and the symptoms are not significantly improved compared with before treatment.

[0142] 2.3 Research Methods

[0143] Case grouping: 30 subjects with asthenic constipation were screened according to the above inclusion criteria.

[0144] Treatment plan: Use the granules prepared in Example 1 of the present invention, 1 bag at a time, 2 bags per day.

[0145] 2.4 Research Results

[0146] After one month of treatment, the constipation status of the 30 subjects in the treatment group was recorded, and the number of subjects who were classified as clinically cured, markedly effective, effective, or ineffective according to the above clinical efficacy evaluation grading was counted. The results are shown in Table 3 below.

[0147] Table 3 Human efficacy test results

[0148] Group Number of people get well Significantly effective efficient invalid Treatment group 30 6 14 9 1

[0149] As can be seen from Table 3, after the treatment, 6 patients were evaluated as clinically cured, 14 patients were significantly effective, 9 patients were effective, and 1 patient was ineffective according to the clinical efficacy evaluation criteria. The total number of effective treatments was 29, and the total effective rate was 96.7%.

[0150] The applicant declares that the present invention is illustrated by the above-described embodiments, but the present invention is not limited to these embodiments. This does not mean that the present invention must rely on these embodiments in order to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent replacements for individual raw materials in the present invention's products, additions of auxiliary ingredients, and selection of specific methods, etc., fall within the scope of protection and disclosure of the present invention.

Claims

1. A Chinese medicine cellulose granule for moistening the intestine and relieving constipation, characterized in that: Made from the following raw materials in parts by weight: The preparation of Chinese medicine cellulose granules includes the following steps: (1) Weigh wheat cellulose, xylo-oligosaccharide, angelica sinensis, Cistanche deserticola, and isomalt according to the amount, grind the isomalt, sieve it, and set aside; (2) Add 9-12 times the amount of water to angelica and Cistanche deserticola and boil for 2-3 times, boiling for 1-3 hours each time. After boiling, filter and obtain the filtrate for later use; (3) The filtrate obtained in step (2) is concentrated under reduced pressure to obtain a thick paste; the first portion of wheat cellulose is then added, stirred evenly, dried under reduced pressure, and finally crushed and sieved to obtain an extract powder for later use; (4) uniformly mixing the sieved isomalt, the second portion of wheat cellulose, the xylo-oligosaccharide, and the extract powder obtained in step (3), followed by granulation, drying, granulation, and packaging to obtain a Chinese medicine cellulose granule; Wherein, in step (3), the amount of the first part of wheat cellulose is 20-30% of the total amount of wheat cellulose.

2. A laxative Chinese medicine cellulose granules according to claim 1, characterized in that: Made from the following raw materials in parts by weight:

3. The laxative Chinese medicine cellulose granules according to claim 1, characterized in that: Made from the following raw materials in parts by weight:

4. A method for preparing the traditional Chinese medicine cellulose granules according to any one of claims 1 to 3, characterized in that: The steps include: (1) Weigh wheat cellulose, xylo-oligosaccharide, angelica sinensis, Cistanche deserticola, and isomalt according to the amount, grind the isomalt, sieve it, and set aside; (2) Add 9-12 times the amount of water to angelica and Cistanche deserticola and boil for 2-3 times, boiling for 1-3 hours each time. After boiling, filter and obtain the filtrate for later use; (3) The filtrate obtained in step (2) is concentrated under reduced pressure to obtain a thick paste; the first portion of wheat cellulose is then added, stirred evenly, dried under reduced pressure, and finally crushed and sieved to obtain an extract powder for later use; (4) uniformly mixing the sieved isomalt, the second portion of wheat cellulose, the xylo-oligosaccharide, and the extract powder obtained in step (3), followed by granulation, drying, granulation, and packaging to obtain a Chinese medicine cellulose granule; Wherein, in step (3), the amount of the first part of wheat cellulose is 20-30% of the total amount of wheat cellulose.

5. The preparation method according to claim 4, characterized in that In step (1), the isomalt is crushed and then passed through an 80-mesh sieve.

6. The preparation method according to claim 4, characterized in that In step (2), after decoction is completed, filter through 200 mesh.

7. The preparation method according to claim 4, characterized in that In step (3), the specific operation of reduced pressure concentration is: reduced pressure concentration to a relative density of 1.20 to 1.30 under the conditions of -0.06 to -0.10 MPa and ≤70°C; the process parameters of reduced pressure drying are: -0.06 to -0.10 MPa, 50 to 70°C.

8. The preparation method according to claim 4, characterized in that In step (4), 85% ethanol is used as a wetting agent for granulation, and 14-mesh granulation is used; and 12-mesh granulation is used for whole granulation.

9. Use of the traditional Chinese medicine cellulose granules according to any one of claims 1 to 3 in the preparation of a medicine for treating asthenic constipation.

Images