Preparation method and application of traditional Chinese medicine composition for improving diarrhea

Abstract

The invention discloses a preparation method and application of a traditional Chinese medicine composition for improving diarrhea, relates to the technical field of traditional Chinese medicine compositions, and solves the problem of poor clinical improvement effect of existing compatibility. The preparation method comprises the following steps: processing rhizoma zingiberis, rhizoma atractylodis macrocephalae, radix glycyrrhizae and fructus gardeniae, adding ginseng, weighing the processed rhizoma zingiberis, rhizoma atractylodis macrocephalae, radix glycyrrhizae and fructus gardeniae, uniformly mixing, crushing, decocting with water for multiple times, filtering with gauze, and merging filtrates to obtain the traditional Chinese medicine composition. The invention can be used for preparing the traditional Chinese medicine preparation for improving diarrhea. The dosage forms of the traditional Chinese medicine preparation comprise granules, oral thick paste, oral liquid, powder, pills, tablets and capsules. The traditional Chinese medicine composition can be applied to prevention and health care of acute and chronic diarrhea and functional dyspepsia, can be intermittently taken by people with long-term spleen deficiency and easy diarrhea at low dosage, and can also be used for combined medication. On the premise of maintaining cell safety, side effects of traditional hormone therapy are avoided through component synergy, and a new direction is provided for developing a novel anti-diarrhea preparation with both safety and high efficiency.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine compositions, and particularly relates to a preparation method and application of a traditional Chinese medicine composition for improving diarrhea. Background Art

[0002] With the high-fat trend of the global diet structure, the rapid increase of environmental stress factors, and the accelerating variation of pathogenic microorganisms, the incidence of diarrhea and related gastrointestinal diseases shows a significant upward trend. The 2021 report of the World Health Organization pointed out that the annual number of cases of viral gastroenteritis has reached 170 million, and infectious diarrhea caused by norovirus, rotavirus, etc. shows a rapid spread characteristic among dense populations. At the same time, the prevalence of chronic functional gastrointestinal diseases such as diarrhea-predominant irritable bowel syndrome (IBS-D) is increasing, and most patients face the dilemma of repeated symptoms, causing continuous damage to the quality of life.

[0003] Modern medicine mainly relies on treatment means such as antibiotics, intestinal motility inhibitors, and probiotic regulation, but clinical practice reveals that it has unavoidable defects: the resistance rate of fluoroquinolone antibiotics has exceeded 50%, and the decline in the α-diversity of the intestinal flora caused by broad-spectrum antibiotics can reach 40% - 60%. Although antidiarrheal drugs such as loperamide can relieve symptoms in the short term, they cannot block the high recurrence rate of IBS-D patients. This treatment dilemma has prompted the academic community to turn its attention to the traditional Chinese medicine system with the advantage of multi-target regulation.

[0004] The core of traditional Chinese medicine in treating diarrhea lies in the overall regulation concept of "invigorating the spleen and warming the middle, removing dampness and regulating the pivot". Among them, the compatibility of ginseng and dried ginger originated from the classic combination of Lizhong Decoction in Treatise on Febrile and Miscellaneous Diseases. Ginsenoside Rg1 contained in ginseng can enhance the activity of intestinal sodium-potassium pump by activating the AMPK signaling pathway and promote water and sodium absorption; 6-gingerol in dried ginger can reduce intestinal hypersensitivity by inhibiting the TRPV1 channel. The two work together to improve the clinical symptoms of most patients with diarrhea due to spleen and stomach deficiency and cold. However, with the evolution of the modern disease spectrum, the limitations of this compatibility are becoming increasingly prominent. On the one hand, ginseng is good at invigorating qi, and dried ginger specializes in dispelling cold, and both lack the key role of transporting and transforming dampness. For diarrhea due to spleen deficiency and excessive dampness, due to the inability to effectively promote gastrointestinal water metabolism, dampness pathogens often remain, resulting in repeated diarrhea. On the other hand, dried ginger is pungent and hot, and long-term use can easily consume yin fluid; ginseng is greasy and may hinder the transportation and transformation of the spleen and stomach. The incidence of dry mouth and constipation increases after use in patients with yin deficiency constitution, restricting its long-term application.

[0005] In view of the above problems, the classical prescription Lizhong Pills are improved by introducing Atractylodes macrocephala and Glycyrrhiza uralensis. Atractylodes macrocephala contains components such as atractylone and atractylenolide I, which can enhance the dampness-dispelling ability through two pathways, improve the water fluid transport efficiency, promote the reabsorption of intestinal cavity water, and inhibit intestinal cavity secretion. After adding Atractylodes macrocephala, the therapeutic effect of diarrhea with spleen deficiency and dampness excess type is improved. Glycyrrhizic acid combines with gingerol in dried ginger, reducing the activation intensity of TRPV1 channels and decreasing intestinal burning sensation; glycyrrhizopolysaccharide increases the secretion of intestinal mucus, relieving mucosal dryness; and inhibits the P-gp efflux effect of ginsenoside Rb1, enhancing its bioavailability and reducing the dosage requirement of single herbs. Although this improvement scheme has alleviated the problems of recurrent diarrhea, dry mouth and constipation, there are still clinical application contradictions that cannot be ignored. On the one hand, when the daily intake of glycyrrhizic acid exceeds 100 mg, it can cause pseudoaldosteronism, and its water and sodium retention effect increases the medication risk for hypertensive patients, and its slow-acting property delays the control of acute diarrhea; although the drying component Atractylenolide III of Atractylodes macrocephala can improve the curative effect of diarrhea with spleen deficiency and dampness entrapment type, it may increase the water content of feces in patients with damp-heat syndrome, directly conflicting with the pathogenesis. In addition, the original prescription has excessive warming and tonifying and insufficient clearing heat, and it is difficult to take into account the diarrhea induced by dietary heat accumulation in modern people, and the overall improvement effect is not good. Summary of the Invention

[0006] In order to solve the above problems existing in the existing traditional Chinese medicine prescriptions, a new anti-diarrhea preparation with both safety and high efficiency is provided, and the present invention proposes a preparation method and application of a traditional Chinese medicine composition for improving diarrhea.

[0007] The technical solution of the present invention is specifically as follows: A preparation method of a traditional Chinese medicine composition for improving diarrhea, comprising the following steps: S1. Processing of dried ginger: Heat river sand in a medicine frying pan to 180 - 200 °C, add dried ginger slices, and stir-fry for 10 - 15 min; S2. Processing of Atractylodes macrocephala: Preheat the frying pan to 180 - 200 °C, put wheat bran and stir-fry for 1 - 2 min, then put raw Atractylodes macrocephala slices, and keep the pan temperature at 160 - 180 °C and continuously stir-fry for 8 - 10 min; S3. Processing of Glycyrrhiza uralensis: Lay Glycyrrhiza uralensis slices flat, spray yellow rice wine, and then moisten for 1 h; Mix refined honey and water and heat to 60 °C, add the moistened Glycyrrhiza uralensis slices and mix well, then moisten until the honey solution is completely absorbed to obtain honey-moistened Glycyrrhiza uralensis; Preheat the frying pan to 90 - 100 °C, put the honey-moistened Glycyrrhiza uralensis, and keep the pan temperature and continuously stir-fry until the Glycyrrhiza uralensis slices have no raw core; S4. Processing of Gardenia jasminoides: Remove the fruit stalks, mildewed parts and impurities from mature gardenia fruits, crush them into particles with a particle size of 5-8 mm, raise the temperature of the pot to 120-150 °C, stir-fry evenly for 8-10 min, then raise the temperature to 180-200 °C and continue stir-frying until uniform charred spots appear on the pericarp, and then raise the temperature to 220-250 °C and stir-fry for 5-8 min; S5. Weigh ginseng and the processed dried ginger, licorice, atractylodes macrocephala and gardenia fruits obtained in steps S1-S4 respectively, mix them evenly and crush them, then carry out multiple water decoction extractions and filter with gauze, and combine the filtrates to obtain a traditional Chinese medicine composition.

[0008] Preferably, the mass ratio of the river sand to the dried ginger slices is 5:1, and the thickness of the dried ginger slices is 2-3 mm.

[0009] Preferably, the dosage of the yellow rice wine is 5% of the mass of the licorice slices, and the concentration of the yellow rice wine is 10%.

[0010] Preferably, the mass ratio of the refined honey to water in the mixture is 1:1.

[0011] Preferably, in step S5, the mass ratio of the ginseng, the processed dried ginger, licorice, atractylodes macrocephala and gardenia fruits is 3:3:2:3:4.

[0012] Preferably, the mass of water in the water decoction extraction is 10-12 times the total mass of the medicinal materials.

[0013] Preferably, the number of times of water decoction extraction is 1-3 times, and the decoction time for each time is 1.5 h.

[0014] The present invention also provides a traditional Chinese medicine composition for improving diarrhea, which is prepared by using the above preparation method.

[0015] An application of the above traditional Chinese medicine composition for improving diarrhea, which is used for preparing a traditional Chinese medicine preparation for improving diarrhea; the dosage forms of the traditional Chinese medicine preparation include granule, paste, oral liquid, powder, pill, tablet and capsule.

[0016] The pharmacological effects of the present invention are as follows: Combined with traditional Chinese medicine theory, the present invention has carried out reasonable compatibility of prescriptions and studied the preparation process and pharmacological effects of the prescriptions. The medicinal flavors included in the prescriptions are ginseng, dried ginger, licorice, atractylodes macrocephala, and gardenia jasminoides. Among them, ginseng: sweet and slightly bitter in taste, slightly warm in nature, attributing to the spleen, lung, heart, and kidney meridians. It has the effects of invigorating qi and securing collapse, strengthening the spleen and benefiting the lung, calming the mind and promoting intelligence, and nourishing blood and promoting fluid production. Dried ginger: pungent and hot in taste, attributing to the spleen, stomach, kidney, heart, and lung meridians. It warms the middle-jiao to dispel cold, restores yang and promotes blood circulation, and warms the lungs to resolve fluid-retention. It is used for epigastric and abdominal cold pain, vomiting and diarrhea, cold limbs and weak pulse, and cold fluid-retention cough. Licorice: sweet and flat in taste, attributing to the heart, lung, spleen, and stomach meridians. It invigorates the spleen and replenishes qi, clears heat and detoxifies, reduces phlegm and relieves cough, alleviates spasm and pain, and harmonizes various medicinal herbs. Atractylodes macrocephala: bitter, sweet, and warm in taste, attributing to the spleen and stomach meridians. It strengthens the spleen and replenishes qi, dries dampness and promotes diuresis, consolidates the exterior and stops sweating, and prevents miscarriage. Gardenia jasminoides: cold in nature, bitter in taste, attributing to the heart, lung, and triple energizer meridians, and has the effects of clearing heat and purging fire, cooling blood and detoxifying, and promoting diuresis to remove jaundice.

[0017] Compared with the prior art, the specific beneficial effects of the present invention include: 1. The present invention applies an ancient prescription in modern times and uses modern technology to improve the immunity of patients while achieving the effects of strengthening the spleen and nourishing the stomach, anti-inflammatory and antidiarrheal. Through a special processing technology, prepared ginger (stir-fried) is used to enhance the effect of warming the middle-jiao to dispel cold and reduce the pungent and dry nature, which is applicable to stomachache and diarrhea caused by deficiency-cold of the spleen and stomach. Atractylodes macrocephala is stir-fried with bran to promote the conversion of atractylon and enhance the effect of drying dampness. Licorice is processed with honey, and honey synergistically enhances the mucosal protection effect. Gardenia jasminoides is processed into stir-fried gardenia jasminoides (stir-fried until the surface is charred black), which promotes the conversion of geniposide to genipin, enhances the affinity for μ-opioid receptor, reduces cold nature, and enhances the astringent antidiarrheal effect.

[0018] 2. By introducing the gardenia jasminoides component, the present invention specifically solves the application defects of the existing compatibility in clinical practice at the level of medicinal property compatibility and molecular mechanism. Specifically, iridoid glycosides (such as geniposide) in gardenia jasminoides inhibit the phosphorylation of calmodulin kinase II in the intestinal plexus, block the influx of calcium ions, directly relax the intestinal smooth muscle, and quickly relieve spastic diarrhea. Compared with the slow-acting antidiarrheal effect of glycyrrhizic acid, the onset time is greatly shortened and there is no risk of electrolyte disorder, and the dosage of licorice is further reduced, effectively avoiding the risk of water and sodium retention. The dampness-drying ability of atractylodes macrocephala may exacerbate the loss of intestinal mucus in patients with damp-heat syndrome. Geniposide promotes the excretion of bile acids, reduces the intestinal osmotic pressure, and indirectly reduces the secretion of body fluid. The two form a dynamic balance of "drying dampness - promoting diuresis". Moreover, geniposide can inhibit the TLR4 / MyD88 / NF-κB pathway and offset the potential pro-inflammatory risk of atractylodes macrocephala. Geniposide can also promote bile secretion and regulate the intestinal flora through the NF-κB pathway, combining the effects of clearing heat and promoting diuresis and strengthening the spleen.

[0019] 3. The bitter-cold property of Gardenia jasminoides Ellis is combined with the pungent-heat property of dried ginger to form a compatibility of "eliminating the property and retaining the function" (it is recorded in Compendium of Materia Medica that "ginger-processed Gardenia jasminoides Ellis can reduce its cold property"), which can enhance the qi-tonifying effect of ginseng. In addition, when prepared ginger and stir-fried Gardenia jasminoides Ellis are combined, hydrogen bond formation between 6-gingerol and geniposide may occur to form a stable complex, neutralizing the bitter-cold property and avoiding damage to the spleen yang.

[0020] The traditional Chinese medicine composition provided by the present invention can be used for acute and chronic diarrhea, such as infectious diarrhea caused by bacterial enteritis and viral gastroenteritis; functional dyspepsia; for prevention and health care applications, those with a weak spleen and prone to diarrhea for a long time can intermittently take low-dose preparations to regulate the physique; it can also be used in combination drug regimens, cooperate with Bifidobacterium to treat antibiotic-associated diarrhea, and when suffering from severe infectious diarrhea, montmorillonite powder can also be short-term combined for accelerating symptom control. Description of the Drawings

[0021] Figure 1 Results of cell viability after treatment with ginseng-dried ginger-atractylodes macrocephala-knotweed extract; Figure 2 Results of cell viability after treatment with ginseng-dried ginger extract; Figure 3 Results of cell viability after treatment with ginseng-dried ginger-atractylodes macrocephala-knotweed-Gardenia jasminoides Ellis extract; Figure 4 Results of the inhibitory effect of each intervention component in Example 2 of effects on IL-1β secretion; Figure 5 Results of the inhibitory effect of each intervention component in Example 2 of effects on IL-6 secretion; Figure 6 Results of the inhibitory effect of each intervention component in Example 2 of effects on TNF-α secretion. Detailed Embodiments

[0022] To make the technical solutions of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings of the present invention. It should be noted that the following embodiments are only used to better understand the technical solutions of the present invention and should not be construed as a limitation of the present invention. In addition, the raw materials and equipment used in the present invention are all commercially available conventional products and are obtained through public market procurement.

[0023] Example 1. The processing technology of the raw materials in the diarrhea-improving composition of the present invention is as follows: Dried ginger: Pour river sand into a frying pan and heat it to 200 °C (the sand shows a smooth state), add dried ginger slices that are dry, free of mildew, and 2-3 mm thick, and quickly stir-fry (sand: ginger ≈ 5:1), stir-fry until the surface of the ginger slices is dark yellow and the inside is brownish yellow (about 10-15 minutes).

[0024] Atractylodes macrocephala: Select raw Atractylodes macrocephala, remove impurities, and sift out debris. If the Atractylodes macrocephala is too dry, spray 5% yellow rice wine, mix well, and moisten for 30 minutes. Preheat the wok to 180 - 200 °C, add wheat bran. When the wheat bran starts to smoke and turns dark yellow (about 1 - 2 minutes), quickly add the Atractylodes macrocephala slices and stir-fry continuously over medium heat (the wok temperature is maintained at 160 - 180 °C) for 8 - 10 minutes. When the surface of the Atractylodes macrocephala turns dark yellow, with occasional charred spots, emitting a burnt wheat aroma and no raw drug smell, it indicates that the processing is completed.

[0025] Licorice: Spread the licorice slices flat, spray 10% yellow rice wine (5% dosage), and moisten for 1 hour. Mix refined honey and drinking water in a ratio of 1:1, heat to 60 °C to form diluted honey water, mix well with the licorice slices, and moisten for 2 hours (until the honey liquid is completely absorbed). Preheat the wok to 90 - 100 °C, and add the honey-moistened licorice. Keep stir-frying while maintaining the wok temperature until the surface of the medicinal materials is shiny, loose when held, not sticky, with a yellowish-white cross-section and no raw center, indicating that the processing is completed.

[0026] Gardenia jasminoides: Select mature Gardenia jasminoides fruits (preferably those with red-yellow color), remove the fruit stalks, mildew, and impurities, crush them into particles with a particle size of 5 - 8 mm. Raise the wok temperature to 120 - 150 °C, stir-fry evenly for 10 minutes, then raise the temperature to 180 - 200 °C and continue stir-frying for 15 - 20 minutes until uniform charred spots appear on the pericarp, and then quickly raise the temperature to 220 - 250 °C and stir-fry rapidly for 5 - 8 minutes. When the surface is charred black and the inside is dark brown, it indicates that the processing is completed.

[0027] Example 2. (1) Weighing: Weigh 3 parts of processed ginseng, 3 parts of dried ginger, 2 parts of licorice, 3 parts of Atractylodes macrocephala, and 4 parts of Gardenia jasminoides by weight; (2) Crush the medicinal materials weighed in step (1) into coarse powder, then extract the ginseng by water decoction. The mass of water is 11 times the total mass of the ginseng medicinal materials, decoct for 3 times, 1.5 hours each time, filter with gauze, and combine the filtrates after each decoction to obtain a traditional Chinese medicine composition (ginseng - dried ginger - licorice - Atractylodes macrocephala - Gardenia jasminoides extract).

[0028] Example 3. Dry the traditional Chinese medicine composition in Example 2 at 60 °C, crush it with a pulverizer, pass through a 90-mesh sieve, add an appropriate amount of maltodextrin to the powder, mix well, and make into granules.

[0029] Example 4. (1) Weighing: Weigh 3 parts of ginseng, 3 parts of dried ginger, 2 parts of licorice, 3 parts of Atractylodes macrocephala, 4 parts of Gardenia jasminoides, 6 parts of honey, and 1 part of rock sugar by weight; (2) Crush the five processed medicinal materials weighed in step (1) into coarse powder, then extract by water decoction. The mass of water is 14 times the total mass of the 5 medicinal materials, decoct for 3 times, 1.5 hours each time, filter with gauze, and combine the filtrates after each decoction; (3) After combining the filtrates, concentrate them to one-sixth of the volume, then add 6 parts of honey and 1 part of rock sugar, and boil them into a paste to obtain the paste extract.

[0030] Example 5. (1) Weighing: Weigh 3 g of ginseng, 3 g of dried ginger, 2 g of licorice, 3 g of atractylodes macrocephala, 4 g of gardenia, 0.5 g of erythritol, and 0.2 g of sodium citrate by weight parts. (2) Crush the ginseng and the processed medicinal materials weighed in step (1) into coarse powder, then carry out water decoction extraction. The mass of water is 14 times the total mass of the 5 kinds of medicinal materials. Decoct for 3 times, 1.5 h each time. Filter with gauze, combine the filtrates after each decoction, cool to room temperature and let stand overnight, then centrifuge at 3600 rmp / min to obtain the supernatant, and concentrate to 200 mL to obtain the extract. (3) Flavoring: Add 0.5 g of erythritol and 0.2 g of sodium citrate to the 200 mL of the extract after centrifugation to obtain the oral liquid.

[0031] Comparative Example 1. The difference from Example 2 is that licorice, atractylodes macrocephala and gardenia are removed from the raw materials to prepare the ginseng-dried ginger extract.

[0032] Comparative Example 2. The difference from Example 2 is that gardenia is removed from the raw materials to prepare the ginseng-dried ginger-atractylodes macrocephala-licorice extract.

[0033] Effect Example 1. Perform cell proliferation-toxicity detection on the traditional Chinese medicine compositions in Example 2, Comparative Example 1 and 2.

[0034] Experimental method: Group and treat RAW264.7 cells. The control group is only treated with the culture medium; the three traditional Chinese medicine intervention groups are treated with different concentrations of traditional Chinese medicine extracts (2.5 / 5 / 10 / 15 / 25 / 50 / 100 / 200 μg / mL) respectively. After treating each group for 24 h, use CCK8 to detect the cell viability of each group and count the cell survival rate.

[0035] Experimental results: The cell survival rate after treatment with the ginseng-dried ginger-atractylodes macrocephala-licorice extract is as Figure 1 shown, the cell survival rate after treatment with the ginseng-dried ginger extract is as Figure 2 shown, and the cell survival rate after treatment with the ginseng-dried ginger-atractylodes macrocephala-licorice-gardenia extract is as Figure 3As shown, it can be seen that compared with the comparative example, the traditional Chinese medicine composition of the present invention has no obvious effect on the activity of RAW264.7 cells at 2.5 - 25 μg / mL (P > 0.05), and the three traditional Chinese medicine compositions at 50 - 200 μg / mL significantly reduce the activity of RAW264.7 cells (P < 0.05). Therefore, the optimal non-cytotoxic concentration range of the three traditional Chinese medicine compositions is 2.5 - 25 μg / mL.

[0036] Effect Example 2. Within the optimal non-cytotoxic concentration range of Effect Example 1, the inhibitory effects of the traditional Chinese medicine compositions in Example 2 and Comparative Examples 1 and 2 on inflammatory responses were verified.

[0037] Experimental method: An inflammatory model of RAW264.7 macrophages was induced by lipopolysaccharide (LPS), and the regulatory effects of the three traditional Chinese medicine compositions on the secretion of inflammatory factors (TNF-α, IL-6, IL-1β) were evaluated respectively. Each traditional Chinese medicine composition intervention component was treated in four groups.

[0038] The one treated only with the culture medium was used as the blank control group; the LPS model group was stimulated with LPS (1 μg / mL) for 24 h; the three traditional Chinese medicine intervention groups were treated with LPS + different concentrations of traditional Chinese medicine extracts (2.5 / 5 / 15 / 25 μg / mL); the positive control group was treated with LPS + dexamethasone (10 μM).

[0039] The cell supernatant was collected, and the concentrations of TNF-α, IL-6, and IL-1β were detected according to the instructions of the ELISA kit, and the differences between groups were compared.

[0040] Experimental results: The results of the inhibitory effects of each intervention component on the secretion of IL-1β are as Figure 4 shown, the results of the inhibitory effects on the secretion of IL-6 are as Figure 5 shown, and the results of the inhibitory effects on the secretion of TNF-α are as Figure 6 shown. Comparing the inhibitory effects of the three traditional Chinese medicine composition administration groups on the inflammatory response, the overall inhibitory effect is Ginseng-Zingiber officinale-Rhizoma Atractylodis Macrocephalae-Glycyrrhiza uralensis extract < Ginseng-Zingiber officinale extract < Ginseng-Zingiber officinale-Rhizoma Atractylodis Macrocephalae-Glycyrrhiza uralensis-Gardenia jasminoides Ellis extract.

[0041] Among them, both the Ginseng-Zingiber officinale extract group (100 μg / mL) and the Ginseng-Zingiber officinale-Rhizoma Atractylodis Macrocephalae-Glycyrrhiza uralensis-Gardenia jasminoides Ellis extract group can reduce the secretion of TNF-α, IL-6, and IL-1β (inhibition rate > 50%), and the effect is better than that of dexamethasone (reducing the side effects of hormones); and the level of IL-1β in the Ginseng-Zingiber officinale-Rhizoma Atractylodis Macrocephalae-Glycyrrhiza uralensis-Gardenia jasminoides Ellis extract is significantly decreased compared with that in the Ginseng-Zingiber officinale-Rhizoma Atractylodis Macrocephalae-Glycyrrhiza uralensis extract, and the reduction effect of the secretion levels of TNF-α and IL-6 is also better.

[0042] The above experimental results indicate that through scientific compatibility and dosage optimization, the traditional Chinese medicine composition of the present invention exhibits biological characteristics and therapeutic advantages significantly superior to those of traditional formulations. Within the safe concentration range (2.5 - 25 μg / mL), the newly introduced Gardenia jasminoides Ellis component can significantly enhance anti-inflammatory activity and break through the bottleneck of the original compatibility. Within the range of non-cytotoxic concentrations, the traditional Chinese medicine composition provided by the present invention (Ginseng - Dry Ginger - Atractylodes macrocephala Koidz. - Licorice Root - Gardenia jasminoides Ellis) has no inhibitory effect on macrophage activity, providing a safety guarantee for subsequent anti-inflammatory functions. The composition of the present invention can achieve an anti-inflammatory effect equivalent to that of traditional compatibility at a dosage above approximately 100 μg / mL at a concentration of 25 μg / mL, with a 4-fold increase in the utilization rate of active ingredients.

[0043] Specifically, IL-1β is the core product of NLRP3 inflammasome activation, and its secretion is regulated by caspase-1 cleavage. Geniposide in Gardenia jasminoides Ellis breaks through the regulatory bottleneck of IL-1β in traditional compatibility by directly inhibiting NLRP3 assembly, regulating potassium ion efflux, and synergistically enhancing the effect of Atractylodes macrocephala Koidz., and can take effect at a low dose.

[0044] The secretion of IL-6 depends on the activation of the TLR4 / MyD88 pathway and STAT3 phosphorylation. Ginsenoside Rg3 in the components of the present invention inhibits the nuclear translocation of STAT3, and 6-gingerol in Dry Ginger and geniposide form a "receptor-kinase" dual-target inhibition. Therefore, the three components of Gardenia jasminoides Ellis - Ginseng - Dry Ginger form a "three-dimensional blockade" of the TLR4 / STAT3 pathway, ultimately achieving a breakthrough in the inhibitory effect on IL-6. The secretion of TNF-α depends on the TRIF (TLR4 adaptor protein) pathway and NF-κB nuclear translocation. Gardenia jasminoides Ellis activates autophagy through geniposide, accelerating the degradation of TRIF; 6-gingerol in prepared Dry Ginger inhibits the IKKβ kinase, and atractylon in the Atractylodes macrocephala Koidz. component upregulates the stability of IκBα, blocking the nuclear translocation of NF-κB. Therefore, Gardenia jasminoides Ellis breaks through the inhibitory limit of traditional compatibility on TNF-α through a triple mechanism of "enhanced autophagy - kinase inhibition - protein stabilization".

[0045] In summary, this "low-dose - high-efficiency" characteristic of the present invention provides an experimental basis for reducing the clinical dosage of drugs and reducing the toxicity of long-term medication. On the premise of maintaining cell safety, the present invention avoids the side effect risks of traditional hormone therapies through component synergy, providing a core direction for the development of new anti-diarrhea preparations with both safety and high efficiency.

[0046] Obviously, the above embodiments are merely examples given for clear illustration and are not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to enumerate all implementation manners here. And the obvious changes or modifications derived therefrom still fall within the protection scope of the present invention.

Claims

1. A preparation method of a traditional Chinese medicine composition for improving diarrhea, characterized in that, It includes the following steps: S1. Processing of dried ginger: Heat river sand in a medicine frying pan to 180 - 200 °C, add dried ginger slices, and stir-fry for 10 - 15 min; S2. Processing of atractylodes macrocephala: Preheat the frying pan to 180 - 200 °C, put wheat bran and stir-fry for 1 - 2 min, then put raw atractylodes macrocephala slices, and keep the pan temperature at 160 - 180 °C and continuously stir-fry for 8 - 10 min; S3. Processing of licorice: Lay out licorice slices, spray yellow rice wine, and then moisten for 1 h; Mix refined honey and water and heat to 60 °C, add the moistened licorice slices and mix well, then moisten until the honey liquid is completely absorbed to obtain honey-moistened licorice; Preheat the frying pan to 90 - 100 °C, put in the honey-moistened licorice, and keep the pan temperature and continuously stir-fry until there is no raw core in the licorice slices; S4. Processing of gardenia: Remove the fruit stalks, mildewed parts and impurities from mature gardenia fruits, crush them into particles with a particle size of 5 - 8 mm, raise the pan temperature to 120 - 150 °C, stir-fry evenly for 8 - 10 min, then raise the temperature to 180 - 200 °C and continuously stir-fry until uniform charred spots appear on the pericarp, and then raise the temperature to 220 - 250 °C and stir-fry for 5 - 8 min; S5. Weigh ginseng and the processed dried ginger, licorice, atractylodes macrocephala and gardenia in steps S1 - S4 respectively, mix them evenly and crush, then carry out multiple water decoction extractions and filter with gauze, and combine the filtrates to obtain a traditional Chinese medicine composition.

2. The preparation method of the traditional Chinese medicine composition for improving diarrhea according to claim 1, wherein, The mass ratio of the river sand to the dried ginger slices is 5:1, and the thickness of the dried ginger slices is 2 - 3 mm.

3. The preparation method of the traditional Chinese medicine composition for improving diarrhea according to claim 1, wherein, The dosage of the yellow rice wine is 5% of the mass of the licorice slices, and the concentration of the yellow rice wine is 10%.

4. The preparation method of the traditional Chinese medicine composition for improving diarrhea according to claim 1, characterized in that The mass ratio of the mixed refined honey and water is 1:

1.

5. The preparation method of the traditional Chinese medicine composition for improving diarrhea according to claim 1, characterized in that, In step S5, the mass ratio of ginseng to the processed dried ginger, licorice, atractylodes macrocephala and gardenia is 3:3:2:3:

4.

6. The preparation method of the traditional Chinese medicine composition for improving diarrhea according to claim 1, characterized in that, In the water decoction extraction, the mass of water is 10 - 12 times the total mass of the medicinal materials.

7. The preparation method of the traditional Chinese medicine composition for improving diarrhea according to claim 1, characterized in that, The number of times of water decoction extraction is 1 - 3 times, and the decoction time for each time is 1.5 h.

8. A traditional Chinese medicine composition for improving diarrhea, characterized in that, It is prepared by using the preparation method described in any one of claims 1 - 7.

9. Use of a traditional Chinese medicine composition for improving diarrhea as described in claim 8, characterized in that, It is applied to the preparation of a traditional Chinese medicine preparation for improving diarrhea; the dosage forms of the traditional Chinese medicine preparation include granules, paste, oral liquid, powder, pills, tablets and capsules.

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