Preparation method of white koji rich in Witzia ciliaris and application of white koji in treatment of functional gastrointestinal diseases

Abstract

The invention discloses a preparation method of aspergillus candidus rich in Witzia ciliaris and application of the aspergillus candidus to treatment of functional gastrointestinal diseases. Mixing kaolin, flour and water, fermenting, drying and crushing to obtain a fermented product 1; mixing the white tea leaves with water, decocting, and filtering to obtain tea soup and tea residues; mixing the tea residues with fresh garlic, fresh rhizoma phragmitis, semen raphani and almonds, and grinding into thick liquid to obtain a thick liquid mixture; putting coarse powder of unhulled rice, wheat, rice, malt, rice sprout, emblic leafflower fruit, dried orange peel, liquorice, lucid ganoderma, cape jasmine, black bean, turmeric, elsholtzia, pepper, platycodon grandiflorum and mulberry leaf into a stirrer for stirring, putting the ground mixture into the stirrer for stirring, putting tea soup into the stirrer for stirring to obtain a mixture; performing high-pressure sterilization on the mixture; putting the fermented product 1 and the sterilized mixture into a stirrer, and stirring to obtain a soft material; and cutting the soft material into blocks, uniformly spreading a layer of the fermentation product 1 on the surfaces of the blocks, and fermenting to obtain a fermentation product 2, namely the white koji rich in Witzia ciliaris, which can be used for treating functional gastrointestinal diseases.

Description

Technical Field

[0001] The present application belongs to the field of fermentation technology, and specifically relates to a method for preparing white koji rich in Weizmannella coagulans and its application in treating functional gastrointestinal disorders. Background Art

[0002] Functional dyspepsia (FD) is an important functional gastrointestinal disorder. It is a common digestive system disease characterized by chronic dyspepsia symptoms, including upper abdominal pain, fullness, early satiety, nausea, vomiting and loss of appetite, but these symptoms cannot be explained by organic, systemic or metabolic diseases. The pathogenesis of FD is complex and involves multiple factors, including gastric motility disorder, psychological factors, dietary factors and gastrointestinal infections such as Helicobacter pylori. Among them, gastric motility disorder is an important factor in functional dyspepsia, which is manifested as delayed gastric emptying and decreased gastric fundus receptive relaxation function. In addition, patients with functional dyspepsia are often related to psychological factors, such as anxiety and depression, which disrupt the normal physiological activities of the central nervous system and cause uncoordinated operation of gastrointestinal function. With the accelerated pace of modern life and increased mental and psychological pressure, the prevalence of functional dyspepsia is also increasing year by year. Psychological factors play an important role in the onset of functional dyspepsia. Due to the complexity of the disease, Western medicine treatment of FD still has some limitations: first, there are large differences in the response of different patients to Western medicine treatment, and Western medicine may cause drug resistance and dependence problems; second, FD is a chronic and recurrent disease, and patients often need to rely on Western medicine treatment for a long time; in addition, FD patients are often accompanied by anxiety and depression, and these psychological factors may aggravate symptoms, making the condition more difficult to control with Western medicine; in addition, long-term use of certain Western medicines may bring side effects, increasing the economic and psychological burden on patients.

[0003] Compared with the limitations of Western medicine in treating FD, TCM has the following advantages in treating FD: TCM pays more attention to overall conditioning. TCM adopts the method of syndrome differentiation and treatment, focusing on overall conditioning and etiological treatment, rather than just symptom relief. In addition, TCM has the characteristics of multiple components, multiple targets and multiple functions. It can provide comprehensive treatment for complex diseases such as FD and has comprehensive efficacy. It not only focuses on symptom improvement, but also focuses on improving the overall quality of life of patients, including the adjustment of psychological state. Moreover, the efficacy of TCM in treating FD is relatively stable, with a lower recurrence rate and fewer adverse reactions. Therefore, the application of TCM in treating FD has gradually gained favor and attention.

[0004] Daqu is generally made of wheat, barley and other raw materials, which are crushed and pressed into brick-shaped koji. The temperature and humidity are artificially controlled to allow various microorganisms in nature to grow and reproduce on it. Because of its large block shape, it is named Daqu. There are many types of Daqu, and the names are not consistent. According to the different raw materials for making koji, it can be divided into wheat koji, rice koji and bran koji. According to the different methods of making koji, it can be divided into handmade koji and machine-made koji. According to the different sources of the bacteria used for making koji, it can also be divided into natural (natural) culture koji and pure bacteria culture koji. According to the different colors of the koji blocks, it can also be divided into red koji, black koji and white koji. The performance of each type of koji is different.

[0005] The present invention formulates a Baiqu prescription based on the theory of traditional Chinese medicine and the complex pathogenesis of FD, including 6 Chinese medicines for digestion and lipid reduction, such as Fuding old white tea, 3 Chinese medicines for regulating qi and strengthening the spleen, such as tangerine peel, 3 Chinese medicines for clearing away heat, detoxifying and promoting diuresis, such as gardenia, 4 Chinese medicines for dispelling wind and cold and warming the stomach, such as turmeric, and 3 Chinese medicines for promoting lung function and resolving phlegm, such as mulberry leaves, for a total of 25 Chinese medicines. The advantage of this prescription lies in the characteristics of overall conditioning and comprehensive treatment. It not only focuses on the relief of symptoms, but also focuses on adjusting and improving the overall physical and mental condition and physiological functions of patients. It can effectively relieve patients' symptoms, reduce the recurrence rate, and improve patients' quality of life. The most important innovation of the present invention is that the Baiqu is rich in Weizmannella coagulans ( Weizmannia_coagulans ), which brings many benefits to the treatment of FD. Weizmannella coagulans is a spore-forming probiotic with remarkable heat resistance, acid resistance and bile resistance. In the treatment of FD, this bacterium can consume free oxygen in the intestines and stomach, creating an environment conducive to the growth of anaerobic microorganisms such as lactobacilli and bifidobacteria, thereby helping to improve the balance of intestinal microorganisms. In addition, studies have shown that Weizmannella coagulans can promote intestinal peristalsis, increase fecal water content, help relieve constipation, and may relieve symptoms such as abdominal distension and abdominal pain in patients with FD. In particular, due to its high temperature and high pressure resistance, Weizmannella coagulans can remain active during the processing of a variety of foods, including hot drinks and baked goods, which makes it easy to be added to a variety of foods and supplements for consumers to take. Studies have shown that Weizmannella coagulans has the ability to inhibit Helicobacter pylori, improve the barrier function of the gastrointestinal tract, reduce inflammation, and help alleviate the symptoms of FD patients. In addition, Weizmannella coagulans has obtained GRAS certification from the FDA, and its safety and health benefits are supported by clinical studies. The efficacy of the white koji in the present invention in treating FD is further improved after being fermented with coagulant Weizmannella, providing a new perspective and method for the treatment of FD. Summary of the invention

[0006] The purpose of the present invention is to provide a method for preparing white koji rich in coagulant Weizmannella and application thereof in treating functional gastrointestinal disorders.

[0007] To achieve the above object, the present invention adopts the following technical solution: A method for preparing white koji rich in Weizmannella coagulans is carried out according to the following steps: S1: Mix kaolin, flour and water, ferment at 35-40°C for 48 hours, dry, and crush to obtain fermentation product 1; S2: mixing white tea leaves with water, boiling at 100° C. for 1 hour, filtering, and obtaining white tea soup and white tea dregs; S3: mixing white tea residue with fresh garlic, fresh reed root, radish seed and bitter almond, and grinding to obtain a grinding mixture; S4: adding rice meal, wheat meal, rice meal, malt meal, malt meal, emblica meal, tangerine peel meal, liquorice meal, red ganoderma meal, gardenia meal, black bean meal, turmeric meal, elsholtzia meal, Zanthoxylum meal, platycodon meal and mulberry leaf meal into a blender and stirring for 20 minutes, adding the pulping mixture and stirring for 20 minutes, and then adding white tea soup and stirring for 15 minutes to obtain a mixture; S5: sterilizing the mixture by high pressure at 100-120° C. for 60 min to obtain a sterilized mixture; S6: putting the fermented product 1 and the sterilized mixed material into a blender and blending for 20 minutes to obtain a soft material; S7: cutting the soft material into blocks to obtain semi-finished products; S8: Evenly spread a layer of fermentation product 1 on the surface of the semi-finished product, and ferment it in a fermentation room to obtain fermentation product 2, which is white koji rich in coagulant Weizmannella.

[0008] In step S1, the weight ratio of kaolin: flour: water is 1:2:0.4.

[0009] In step S2, the white tea leaves are white tea leaves aged for 5 to 10 years, and the weight ratio of white tea leaves to water is 1:3.

[0010] In step S3, the weight ratio of the white tea residue: fresh garlic: fresh reed root: radish seed: almond is 20.85:1:4.75:1.42:1.60.

[0011] In step S4, the weight ratio of paddy: wheat: rice: malt: malt: emblica: tangerine peel: liquorice: ganoderma: gardenia: black bean: turmeric: elsholtzia: prickly ash: platycodon: mulberry leaf: ground mixture: white tea soup is 25.78:25.78:29.56:4:4:4:5.93:1.98:1.98:3.95:3.95:21.67:8:1:2:2:36.89:77.87.

[0012] In step S6, the weight ratio of the fermentation product 1 to the sterilized mixture is 0.009:1.

[0013] In step S8, the weight ratio of the semi-finished product to the fermented product 1 is 100:1.

[0014] In step S8, the fermentation process lasts for a total of 10 days. On the 1st to 3rd day of fermentation, the temperature is controlled at 35°C and the humidity is controlled at 70%. On the 4th to 6th day of fermentation, the temperature is controlled at 38°C and the humidity is controlled at 80%. On the 7th to 10th day of fermentation, the temperature is controlled at 33°C and the humidity is controlled at 70%.

[0015] A white koji rich in coagulant Weizmannella prepared by the above preparation method.

[0016] The application of the white koji rich in coagulant Weizmannella is one or more of the following: 1) Application in the preparation of products with Bacillus coagulans as active ingredient; 2) Application in the preparation of drugs for treating functional gastrointestinal disorders.

[0017] The significant advantages of the present invention are: (1) It has an overall conditioning effect: Based on the theory of traditional Chinese medicine, the Baiqu formula used in the present invention combines multiple functions such as promoting digestion and reducing blood lipids, regulating qi and strengthening the spleen, clearing away heat and detoxifying, dispelling wind and cold, and promoting lung function and resolving phlegm, thereby achieving an overall conditioning of functional dyspepsia (FD).

[0018] (2) Comprehensive treatment is possible: This prescription not only relieves symptoms, but also aims to improve the patient's overall physical and mental condition and physiological functions, providing a comprehensive treatment plan.

[0019] (3) Innovative application of probiotics can play a therapeutic role in various ways: Baiqu is fermented with Weizmannella coagulans, which is heat-resistant, acid-resistant and bile-resistant. These properties of Weizmannella coagulans enable it to remain active during a variety of food processing processes, making it easy to add to food and supplements. Weizmannella coagulans helps consume intestinal free oxygen and create an environment that is conducive to the growth of anaerobic microorganisms such as Lactobacillus and Bifidobacterium. It has the ability to inhibit Helicobacter pylori, which helps improve gastrointestinal barrier function and reduce inflammation. Weizmannella coagulans may help promote intestinal motility and relieve constipation, and relieve symptoms such as abdominal distension and abdominal pain in patients with FD. Weizmannella coagulans has obtained GRAS certification from the FDA, and its safety and health benefits are supported by clinical studies.

[0020] (4) Good comprehensive treatment effect: Through the overall conditioning and comprehensive treatment of traditional Chinese medicine prescriptions, especially after fermentation rich in Weizmannella coagulans, its efficacy in treating FD is further improved. The present invention can effectively relieve FD symptoms and reduce disease recurrence. The present invention helps to improve the quality of life of FD patients. It provides a new perspective and method for the treatment of FD. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 : The appearance of the white koji prepared by the present invention.

[0022] Figure 2 :Effects of Baiqu on gastric emptying rate and small intestinal propulsion rate in mice with gastrointestinal motility disorder model (x±s, n=10). A: Effects of Baiqu on gastric emptying rate in mice with gastrointestinal motility disorder model; B: Effects of Baiqu on small intestinal propulsion rate in mice with gastrointestinal motility disorder model. Compared with the blank group##P<0.01; compared with the model group**P<0.01.

[0023] Figure 3 :Effects of Baiqu on gastrointestinal hormone levels in gastrointestinal dysmotility model mice (x±s, n=10). A: Effects of Baiqu on somatostatin (GAS) in gastrointestinal dysmotility model mice; B: Effects of Baiqu on motilin (MTL) in gastrointestinal dysmotility model mice; C: Effects of Baiqu on substance P (SP) in gastrointestinal dysmotility model mice; D: Effects of Baiqu on somatostatin (SS) in gastrointestinal dysmotility model mice. Compared with the blank group##P<0.01; compared with the model group**P<0.01. DETAILED DESCRIPTION

[0024] In order to make the contents of the present invention easier to understand, the technical solution of the present invention is further described below in conjunction with specific implementation methods, but the present invention is not limited thereto.

[0025] The kaolin involved in the following examples has a particle size of 100 mesh.

[0026] The Fuding white tea leaves involved in the following embodiments are 6-year-old Fuding white tea leaves purchased from Fuding Watson Gardenia White Tea Co., Ltd., with a production number of WS20070901.

[0027] The raw medicinal materials involved in the following embodiments, such as paddy rice, wheat, rice, malt, malt, emblica, tangerine peel, liquorice, red ganoderma, gardenia, black bean, turmeric, elsholtzia, prickly ash, platycodon, and mulberry leaf, need to be crushed into coarse powder with a particle size of 30 mesh before use.

[0028] Fresh garlic: It is the bulb of the garlic plant of the genus Allium in the lily family. It is harvested when the leaves wither in May and June every year, and then the soil is removed for fresh use.

[0029] Fresh reed root: It is the rhizome of the grass family reed. It is dug in spring, summer and autumn, cleaned of soil, cut off the residual stems, buds and fibrous roots on the nodes, peeled off the membranous leaves, or buried in wet sand for fresh use. When purchasing, it is best to choose those that are thick, yellow-white, shiny, without fibrous roots, and tender.

[0030] Radish seeds: The dried mature seeds of the cruciferous plant radish. When the fruits are ripe in summer, the plants are harvested, dried in the sun, the seeds are rubbed out, impurities are removed, and then dried in the sun.

[0031] Bitter almonds are the dried mature seeds of the apricot plant of the Rosaceae family. The mature fruits are harvested in summer, the pulp and shell are removed, and the seeds are taken out and dried.

[0032] Paddy: The mature seeds of the rice plant.

[0033] Wheat: The seeds of the genus Triticeae in the Poaceae family.

[0034] Rice: It is the product after the husked rice grains are removed and is the fruit of the mature rice.

[0035] Malt: It is the germinated caryopsis of barley, a plant of the genus Hordeum in the Poaceae family. It is made by germinating and drying mature barley fruits. Soak the barley in water, take it out and put it in a basket, cover it with a cattail bag, and sprinkle water frequently. When the buds are 3 to 5 mm long, take them out and dry them in the sun. The endosperm is large, milky white, and powdery. The best ones are yellow, large, plump, and have complete buds.

[0036] Millet sprouts: It is a processed product made by germinating and drying the mature fruits of millet, a grass plant. Soak the millet in water, maintain a suitable temperature and humidity, and wait until the fibrous roots grow to about 6mm, then dry them in the sun or at a low temperature.

[0037] Phyllanthus emblica: It is the dried mature fruit of Phyllanthus emblica of the Euphorbiaceae family. It is harvested from winter to the next spring when the fruit is ripe, and then the impurities are removed and dried.

[0038] Tangerine peel: It is the peel of various citrus fruits such as Fuju or Zhuju in the Rutaceae family. Pick the ripe fruits after October, peel them, and dry them in the shade or in the sun. The ones with thin peel, large pieces, red color, oily and strong aroma are preferred.

[0039] Licorice: It is the dried root and rhizome of Glycyrrhiza uralensis, Glycyrrhiza uralensis or Glycyrrhiza glabra. It is harvested in autumn and air-dried in a dry place.

[0040] Red Ganoderma: It is the dried fruiting body of the Polyporaceae fungus Ganoderma. It is harvested throughout the year, and impurities are removed. The lower end of the stem with rotten wood, sand or culture medium attached is cut off, and it is dried in the shade or dried at 40-50℃.

[0041] Gardenia: The dried mature fruit of the Rubiaceae plant Gardenia. The fruit is harvested from September to November when it is ripe and reddish yellow. The fruit stalks and impurities are removed, steamed until steaming or slightly blanched in boiling water, taken out, and dried.

[0042] Black beans: The dried, mature black seeds of soybeans, a plant of the legume family. The mature fruits are harvested in autumn, dried, the seeds are removed, and impurities are removed.

[0043] Turmeric: It is the dried rhizome of the ginger plant turmeric. It is dug up in winter when the stems and leaves wither, washed, boiled or steamed until thoroughly cooked, dried in the sun, and the fibrous roots are removed.

[0044] Elsholtzia: It is the dried aerial part of the plant Elsholtzia of the Lamiaceae family. It is harvested in summer and autumn when the stems and leaves are lush and the fruits are ripe, and then the impurities are removed and the fruit is dried in the sun.

[0045] Zanthoxylum bungeanum: It is the dried mature peel of the green pepper or Zanthoxylum bungeanum plant of the Rutaceae family. The mature fruits are harvested in autumn, dried in the sun, and the seeds and impurities are removed.

[0046] Platycodon grandiflorum: It is the root of Platycodon grandiflorum, a plant of the Campanulaceae family. It is dug up in spring and autumn, cleaned, the fibrous roots are removed, the skin is peeled off while fresh or left on, and dried.

[0047] Mulberry leaves: The dried leaves of the mulberry plant of the Moraceae family. They are harvested after the first frost, and then removed of impurities and sun-dried. Large leaves with yellow-green color are preferred.

[0048] Embodiment 1: A method for preparing white koji rich in Weizmannella coagulans is carried out according to the following steps: S1: 1 part by weight of kaolin, 1 part by weight of flour and 0.4 part by weight of water were mixed, fermented at 36° C. for 48 hours, dried at 40° C. for 48 hours, and crushed to 100 mesh to obtain fermentation product 1.

[0049] S2: Mix 1 part by weight of Fuding white tea leaves with 3 parts by weight of water, boil at 100° C. for 1 hour, and filter to obtain white tea soup and white tea residue.

[0050] S3: 20.85 parts by weight of the white tea residue obtained in step S2 are mixed with 1 part by weight of fresh garlic, 4.75 parts by weight of fresh reed root, 1.42 parts by weight of radish seeds and 1.6 parts by weight of bitter almonds, and the mixture is refined to obtain a refined mixture.

[0051] S4: 25.78 parts by weight of rice meal, 25.78 parts by weight of wheat meal, 29.56 parts by weight of rice meal, 4 parts by weight of malt meal, 4 parts by weight of barley sprout meal, 4 parts by weight of emblica fructus meal, 5.93 parts by weight of dried orange peel meal, 1.98 parts by weight of liquorice meal, 1.98 parts by weight of red ganoderma lucidum meal, 3.95 parts by weight of gardenia jasminoides meal, 3.95 parts by weight of black bean meal, 21.67 parts by weight of turmeric meal, 8 parts by weight of elsholtzia meal, 1 part by weight of Zanthoxylum bungeanum meal, 2 parts by weight of platycodon meal and 2 parts by weight of mulberry leaf meal are put into a U-type mixer and stirred for 20 minutes, 36.89 parts by weight of the grinding mixture obtained in step S3 are added and stirred for 20 minutes, and 77.87 parts by weight of the white tea soup obtained in step S2 are added and stirred for 15 minutes to obtain a mixture.

[0052] S5: sterilize the mixture obtained in step S4 in an autoclave at 100° C. for 60 min and then cool it to obtain a sterilized mixture.

[0053] S6: 0.009 parts by weight of the fermented product 1 obtained in step S1 and 1 part by weight of the sterilized mixture obtained in step S5 are put into a U-type blender and stirred for 20 minutes to obtain a soft material.

[0054] S7: Cut the soft material obtained in step S6 into blocks of 4.2 cm×2.7 cm×1 cm to obtain a semi-finished product.

[0055] S8: Evenly sprinkle a layer of fermentation product 1 obtained in step S1 on the surface of the semi-finished product obtained in step S7, the weight ratio of the semi-finished product to the fermentation product 1 is 100:1, and ferment in a fermentation room to obtain fermentation product 2, namely Baiqu; wherein the fermentation process lasts for 10 days in total, the temperature is controlled at 35°C and the humidity is controlled at 70% on the 1st to 3rd day of fermentation, the temperature is controlled at 38°C and the humidity is controlled at 80% on the 4th to 6th day of fermentation, and the temperature is controlled at 33°C and the humidity is controlled at 70% on the 7th to 10th day of fermentation.

[0056] The semi-finished product and white koji were sampled respectively to observe their properties, and their moisture content, ash content, total flavonoids content, and total polyphenol content were measured. The microbial community structure was analyzed using metagenomic sequencing.

[0057] like Figure 1 As shown, the prepared white koji has an off-white or off-yellow appearance.

[0058] As shown in Table 1, the moisture content, ash content, total flavonoids content and total polyphenols content of the semi-finished product were 10.56%, 8.31%, 1.375% and 0.51%, respectively; the moisture content, ash content, total flavonoids content and total polyphenols content of Baiqu were 4.83%, 14.41%, 1.3% and 0.45%, respectively.

[0059] Table 1 Water content, ash content, total flavonoids content and total polyphenols content of semi-finished products and white koji As shown in Table 2-1, the top 10 dominant bacterial species in terms of relative abundance in semi-finished products are Bacillus subtilis ( Bacillus subtilis , 13.97%), Rhizopus microsporus ( Rhizopus microsporus , 8.08%), Monascus purpurogenus ( Monascus purpureus , 3.66%), Lactobacillus plantarum ( Lactiplantibacillus plantarum , 3.39%), Saccharomyces cerevisiae ( Saccharomyces cerevisiae , 2.00%), Aspergillus Ryukyu ( Aspergillus luchuensis , 1.98%), Pediococcus acidilactici ( Pediococcus acidilactici , 1.96%), Lactobacillus-unclassified (Lactiplantibacillus_unclassified , 1.82%), Aspergillus oryzae ( Aspergillus oryzae , 1.78%), Lindnerella fabiennesii ( Cyberlindnera fabianii , 1.63%). As shown in Table 2-2, the top 9 dominant bacterial species in terms of relative abundance in Baiqu are Weizmannella coagulans ( Weizmannia coagulans , 40.39%), unknown species ( unclassified , 13.34%), Weizmannella-unclassified ( Weizmannia unclassified , 13.28%), Pediococcus acidilactici ( Pediococcus acidilactici , 9.60%), Burkholderia multiphaga ( Burkholderia multivorans , 3.27%), fermented Lactobacillus mucilaginosus ( Limosilactobacillus fermentum , 2.46%), Burkholderia spp.-unclassified ( Burkholderia unclassified , 2.30%), Pediococcus-unclassified ( Pediococcus unclassified , 2.29%), Bacillus spp. ( Bacillus toyonensis , 1.32%).

[0060] Table 2-1 Analysis of dominant bacterial flora in semi-finished products (species level) Table 2-2 Analysis of dominant bacterial flora in white koji (species level) Embodiment 2: Preparation of Baiqu decoction: weigh 60g of Baiqu prepared in Example 1, add 600g of water to soak for 30min, extract under reflux in a 100℃ water bath for 3 times, each time for 0.5h, filter with 200-mesh gauze after each extraction, then combine the 3 filtrates, concentrate at 60℃ by rotary evaporation to 100ml, equivalent to 0.6g / mL of the original medicinal material, and store in a 4℃ refrigerator for subsequent animal experiments.

[0061] Animal experiment: 50 C57 mice, half male and half female, were randomly divided into 5 groups (10 mice in each group) after 6 days of adaptive feeding: blank group, atropine model group (0.001g / kg), positive drug mosapride citrate group (0.003g / kg), Baiqu low-dose group (3g / kg), Baiqu high-dose group (6g / kg). Atropine (0.001g / kg) was injected intraperitoneally twice a day for 4 consecutive days in the atropine model group, positive drug mosapride citrate group, Baiqu low-dose group, and Baiqu high-dose group to complete the model; the blank group was injected intraperitoneally with the same volume of normal saline twice a day for 4 consecutive days. After the model was completed, each drug-treated group was continuously gavaged for 4 days, once a day, with a gavage volume of 10ml / kg; the blank group mice were gavaged with the same volume of normal saline. Before the last administration, the mice were fasted but not watered for 12 hours. Two hours after the last administration, each mouse was gavaged with 0.8 ml of nutrient semisolid paste containing carbon powder. After 20 minutes, blood was collected and the mice were quickly dissected. The gastric cardia and pylorus of the mice were ligated, and the complete stomach was cut. The gastric surface mucosa was removed. The whole stomach was weighed after being wiped dry with filter paper. Then the stomach body was cut open along the greater curvature of the stomach. The stomach contents were washed with saline and wiped dry. The net weight of the stomach was weighed. The difference between the total weight of the stomach and the net weight of the stomach was the weight of the residual content in the stomach. The gastric emptying rate was calculated according to the formula. Gastric emptying rate = [1-(total weight of the stomach-net weight of the stomach) / gavage mass] × 100%. At the same time, the small intestine from the pylorus to the ileocecal region was quickly cut, and the mesentery was gently peeled off and laid directly on white paper. The total length from the pylorus to the ileocecal region and the distance from the pylorus to the front of the black semisolid paste were measured. The percentage of the distance from the pylorus to the front of the black semisolid paste to the total length from the pylorus to the ileocecal region was the small intestine propulsion rate. Mouse eyeball blood was collected in a 1.5 ml centrifuge tube and allowed to stand at room temperature for 1 hour. The tube was then centrifuged at 4°C and 3000 r / min for 15 minutes, and the supernatant was collected and stored at -80°C. The levels of gastrointestinal hormones such as somatostatin (GAS), motilin (MTL), substance P (SP) and somatostatin (SS) in mouse serum were determined according to the instructions of the ELISA detection kit.

[0062] The results show that ( Figure 2 ), compared with the blank control group, the gastric emptying rate and small intestinal propulsion rate of the model group mice were reduced, indicating that the gastrointestinal motility disorder disease model was successfully established by intraperitoneal injection of atropine; after treatment, compared with the model group, the gastric emptying rate and small intestinal propulsion rate of the low-dose Baiqu administration group, the high-dose Baiqu administration group, and the positive drug mosapride citrate administration group were significantly increased. This shows that Baiqu administration can significantly improve the gastrointestinal motility of mice and effectively alleviate gastrointestinal motility disorders.

[0063] Gastrin (GAS) is a hormone that regulates gastrointestinal motility. It can promote gastric motility, enhance the contraction of the lower esophageal sphincter, and reduce gastroesophageal reflux. Motilin (MTL) is a brain-gut peptide distributed in the central nervous system and gastrointestinal tract. It is an important hormone that initiates the interdigestive gastrointestinal migrating motor complex (MMC). Somatostatin (SS) is a polypeptide hormone widely distributed in the digestive system that is secreted by D cells in the pancreatic islets and gastrointestinal mucosa. It can inhibit a variety of physiological functions. SS can act directly through neuroendocrine, and can also indirectly inhibit gastrointestinal motility by acting on other gastrointestinal hormones. Substance P (SP) is mostly distributed in the myenteric plexus and the central nervous system. It can act on smooth muscle, causing it to contract rapidly, thereby promoting gastrointestinal motility. This study further detected the changes in mouse gastrointestinal hormones through ELISA, and the results showed that ( Figure 3 ), compared with the blank group, the levels of GAS, motilin MTL, and SP in the serum of the model group mice were lower than those of the blank group (P<0.01), and the SS level was higher than that of the blank group, indicating that atropine modeling significantly changed the gastrointestinal hormone levels of mice, leading to gastrointestinal motility disorders; while the low-dose Baiqu administration group, the high-dose Baiqu administration group, and the positive drug mosapride citrate administration group could significantly reverse these changes in gastrointestinal hormone levels. This shows that Baiqu administration can improve gastrointestinal motility disorders by regulating the levels of serum gastrointestinal hormones such as GAS, MTL, SP, and SS.

[0064] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing white koji rich in coagulant Weizmannella, characterized in that: Follow these steps: S1: Mix kaolin, flour and water, ferment at 35-40°C for 48 hours, dry, and crush to obtain fermentation product 1; S2: mixing white tea leaves with water, boiling at 100° C. for 1 hour, filtering, and obtaining white tea soup and white tea dregs; S3: mixing white tea residue with fresh garlic, fresh reed root, radish seed and bitter almond, and grinding to obtain a grinding mixture; S4: adding rice meal, wheat meal, rice meal, malt meal, malt meal, emblica meal, tangerine peel meal, liquorice meal, red ganoderma meal, gardenia meal, black bean meal, turmeric meal, elsholtzia meal, Zanthoxylum meal, platycodon meal and mulberry leaf meal into a blender and stirring for 20 minutes, adding the pulping mixture and stirring for 20 minutes, and then adding white tea soup and stirring for 15 minutes to obtain a mixture; S5: sterilizing the mixture by high pressure at 100-120° C. for 60 minutes to obtain a sterilized mixture; S6: putting the fermented product 1 and the sterilized mixed material into a blender and blending for 20 minutes to obtain a soft material; S7: cutting the soft material into blocks to obtain semi-finished products; S8: Evenly spread a layer of fermentation product 1 on the surface of the semi-finished product, and ferment it in a fermentation room to obtain fermentation product 2, which is white koji rich in coagulant Weizmannella.

2. The preparation method according to claim 1, characterized in that: In step S1, the weight ratio of kaolin: flour: water is 1:2:0.

4.

3. The preparation method according to claim 1, characterized in that: In step S2, the white tea leaves are white tea leaves aged for 5 to 10 years, and the weight ratio of white tea leaves to water is 1:

3.

4. The preparation method according to claim 1, characterized in that: In step S3, the weight ratio of the white tea residue: fresh garlic: fresh reed root: radish seed: almond is 20.85:1:4.75:1.42:1.

60.

5. The preparation method according to claim 1, characterized in that: In step S4, the weight ratio of paddy: wheat: rice: malt: malt: emblica: dried orange peel: liquorice: ganoderma: gardenia: black bean: turmeric: elsholtzia: prickly ash: platycodon: mulberry leaf: pulp mixture: white tea soup is 25.78: 25.78: 29.56: 4: 4: 4: 5.93: 1.98: 1.98: 3.95: 3.95: 21.67: 8：1：2：2：36.89：77.87。 6. The preparation method according to claim 1, characterized in that: In step S6, the weight ratio of the fermentation product 1 to the sterilized mixture is 0.009:

1.

7. The preparation method according to claim 1, characterized in that: In step S8, the weight ratio of the semi-finished product to the fermented product 1 is 100:

1.

8. The preparation method according to claim 1, characterized in that: In step S8, the fermentation process lasts for a total of 10 days. On the 1st to 3rd day of fermentation, the temperature is controlled at 35°C and the humidity is controlled at 70%. On the 4th to 6th day of fermentation, the temperature is controlled at 38°C and the humidity is controlled at 80%. On the 7th to 10th day of fermentation, the temperature is controlled at 33°C and the humidity is controlled at 70%.

9. A white koji rich in coagulant Weizmannella prepared by the preparation method according to any one of claims 1 to 8.

10. The use of white koji as claimed in claim 9, characterized in that: One or more of the following: 1) Application in the preparation of products with Bacillus coagulans as active ingredient; 2) Application in the preparation of drugs for treating functional gastrointestinal disorders.

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