Use of a traditional Chinese medicine composition in the preparation of a medicine for treating or preventing anti-helicobacter pylori

Abstract

This invention provides a novel use of a traditional Chinese medicine composition for preparing drugs or health products for treating or preventing Helicobacter pylori infection, belonging to the field of traditional Chinese medicine technology. The traditional Chinese medicine composition of this invention consists of Polygonum multiflorum, Aloe vera, Cassia tora seed, Ginseng, Lycium barbarum fruit, Donkey-hide gelatin, Citrus aurantium fruit, and Atractylodes macrocephala, and has the effects of nourishing Yin and replenishing Qi, clearing turbidity and promoting bowel movement. The Helicobacter pylori strain of this invention has significant inhibitory and bactericidal effects in vitro, effectively inhibiting Helicobacter pylori in rats, and has positive clinical efficacy in treating Helicobacter pylori infection. It can reduce the use of antibiotics, thereby reducing the drug resistance rate of Helicobacter pylori, with high safety and few toxic side effects, and has broad application prospects and positive clinical significance.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the use of a traditional Chinese medicine composition in the preparation of drugs or health products for treating or preventing Helicobacter pylori infection. Background Technology

[0002] Helicobacter pylori (Hp) is a spiral-shaped, microaerophilic, Gram-negative bacillus with a strong infectious capacity. Currently, Hp is one of the most widespread bacteria in the world, infecting more than half of the global population. Although public health conditions have greatly improved in recent years, Hp infection rates remain high in many countries; in my country, the Hp infection rate is approximately 52.2%. As early as 1994, the International Agency for Research on Cancer (IARC), a branch of the World Health Organization, classified Hp as a Group 1 carcinogen for gastric cancer.

[0003] Currently, the main treatments for *Helicobacter pylori* (Hp) include standard triple therapy and bismuth quadruple therapy. Other treatment options include concomitant therapy, sequential therapy, combination therapy, and probiotic therapy. Both standard triple therapy and bismuth quadruple therapy are eradication therapies primarily based on antibiotics. Standard triple therapy consists of one proton pump inhibitor (PPI) plus two antibiotics, with a treatment course of 7–14 days. Bismuth quadruple therapy consists of one PPI plus one bismuth agent plus two antibiotics, with a treatment course of 10 or 14 days. Commonly used antibiotics include clarithromycin, amoxicillin, metronidazole, tetracycline, furazolidone, and levofloxacin. The other therapies are also variations of antibiotic-based treatments.

[0004] The aforementioned treatments easily lead to drug resistance in the body, causing intestinal flora imbalance. The proportion of drug-resistant *Helicobacter pylori* strains is constantly rising worldwide, and new, less resistant antibiotics are becoming increasingly difficult to detect. Currently, clinically, there are few effective methods besides constantly changing antibiotic combinations, increasing antibiotic dosages, and extending treatment duration. Therefore, researching more effective drugs against *Helicobacter pylori* is an urgent problem to be solved.

[0005] Traditional Chinese medicine (TCM) is a unique health resource with advantages such as broad spectrum of low toxicity, multiple targets, and multiple pathways. TCM has significant advantages in improving symptoms, increasing the eradication rate of Helicobacter pylori (H. pylori), and reducing the recurrence rate, and has gradually become a research hotspot in H. pylori infection data. TCM believes that the pathogenesis of H. pylori infection lies in spleen and stomach weakness, and the main causes are invasion of damp-heat pathogens and poor dietary habits.

[0006] Chinese patent CN100453105C discloses a composition and preparation method for invigorating qi and nourishing yin, purging turbidity and promoting bowel movement, which has now been approved for production. The product is Shouhui Tongbian Capsules. This product is a compound traditional Chinese medicine preparation made from eight herbs: Polygonum multiflorum, Aloe vera, Cassia tora, Lycium barbarum, donkey-hide gelatin, ginseng, Atractylodes macrocephala, and Citrus aurantium. It can be used to specifically treat functional constipation. The prescription for Shouhui Tongbian Capsules is based on the clinical experience of renowned traditional Chinese medicine doctors. This prescription, based on traditional Chinese medicine theory and integrating clinical experience, supplements the laxative and detoxifying herbs with blood-nourishing and dryness-moistening herbs, and also with qi-tonifying and spleen-strengthening herbs. This allows the herbs to eliminate turbidity and achieve a balance of tonification and purgation, using the principle of unblocking as the primary function, with both downward movement and upward movement, purging and tonification, a balance of action and restraint, a balance of urgency and gentleness, ensuring that tonification does not cause stagnation and purging does not harm the body's vital energy. This guides the entire formula to act on the spleen and stomach, restoring the normal function of ascending clear qi and descending turbid qi in the middle jiao.

[0007] Chinese patent CN111298005A discloses the use of Shouhui Tongbian Capsules in treating enteritis; Chinese patent CN112336799B discloses the use of a traditional Chinese medicine composition, specifically the use of Shouhui Tongbian Capsules in relieving or treating perinatal diseases in women of childbearing age; Chinese patent CN114450021A discloses the use of a traditional Chinese medicine composition, specifically the use of Shouhui Tongbian Capsules in treating edema; Chinese patent CN111228389A discloses the use of a traditional Chinese medicine composition, specifically the use of Shouhui Tongbian Capsules in preparing drugs for the prevention and treatment of abdominal distension; Chinese patent CN113117006A discloses the use of a traditional Chinese medicine composition, specifically the use of Shouhui Capsules in anti-skin aging drugs or cosmetics; and Chinese patent CN113995801A discloses the use of Shouhui Tongbian Capsules in relieving hangovers.

[0008] Currently, there are no studies or reports on the use of Shouhui Tongbian Capsules in treating or preventing Helicobacter pylori infection. Summary of the Invention

[0009] This invention provides the use of a traditional Chinese medicine composition in the preparation of drugs or health products for treating or preventing Helicobacter pylori infection.

[0010] One of the objectives of this invention is to provide a traditional Chinese medicine composition for use in the preparation of drugs or health products for treating or preventing Helicobacter pylori infection.

[0011] In some embodiments, the traditional Chinese medicine composition mainly consists of Polygonum multiflorum, aloe vera, cassia seed, ginseng, wolfberry, donkey-hide gelatin, immature bitter orange, and Atractylodes macrocephala.

[0012] In a preferred embodiment, the traditional Chinese medicine composition mainly comprises the following components by weight: 25-400 parts of Polygonum multiflorum, 40-400 parts of Aloe vera, 40-250 parts of Cassia tora, 20-100 parts of Ginseng, 30-100 parts of Lycium barbarum, 20-180 parts of Colla corii asini, 40-280 parts of Citrus aurantium, and 10-80 parts of Atractylodes macrocephala.

[0013] In a preferred embodiment, the traditional Chinese medicine composition mainly comprises the following components by weight: 40-200 parts of Polygonum multiflorum, 50-200 parts of Aloe vera, 60-160 parts of Cassia tora, 40-80 parts of Ginseng, 50-80 parts of Lycium barbarum, 30-150 parts of Colla corii asini, 60-160 parts of Citrus aurantium, and 30-60 parts of Atractylodes macrocephala.

[0014] The second objective of this invention is to provide a pharmaceutical preparation of a traditional Chinese medicine composition, wherein the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients constitute a pharmaceutically acceptable dosage form.

[0015] In some embodiments, the dosage form is a capsule, tablet, granule, mixture, pill, drop pill, powder, or granule.

[0016] In a preferred embodiment, the traditional Chinese medicine composition is a capsule.

[0017] A third objective of this invention is to provide the ratio of the traditional Chinese medicine composition to pharmaceutically acceptable excipients in the capsule.

[0018] In some embodiments, the traditional Chinese medicine composition in the capsule is prepared by combining pharmaceutically acceptable excipients in a weight ratio of 1:1.5 to 8.5.

[0019] In a more preferred embodiment, the traditional Chinese medicine composition is prepared by mixing pharmaceutically acceptable excipients in a weight ratio of 1:2.0 to 5.5.

[0020] In a preferred embodiment, the excipients include a filler and a binder, wherein the filler is one or more of mannitol, lactose, sorbitol, sucrose, and cyclodextrin; and the binder is one or more of a 75% ethanol solution of 3% PVP, a 50% ethanol solution of 3% hydroxypropyl methylcellulose, an aqueous solution of 10% povidone K30, and 30% starch paste.

[0021] In a more preferred embodiment, the filler is a mixture of cyclodextrin and sorbitol, with a weight ratio of 1:0.5-1.4; preferably, the cyclodextrin is hydroxypropyl-β-cyclodextrin.

[0022] The fourth objective of this invention is to provide a method for preparing a pharmaceutical preparation of a traditional Chinese medicine composition.

[0023] Includes the following steps:

[0024] (1) Grind the donkey-hide gelatin and ginseng into a fine powder and sift it for later use;

[0025] (2) Weigh out wolfberry, atractylodes macrocephala and immature bitter orange according to the proportion, soak them in water, boil them, filter them, and concentrate them to obtain concentrated liquid;

[0026] (3) Weigh out Polygonum multiflorum, Cassia tora, and Aloe vera according to the proportion, remove impurities, wash, dry, grind and sieve to obtain fine powder;

[0027] (4) Combine the fine powder obtained in step (1) and the concentrated liquid obtained in step (2), mix them evenly, concentrate them into a thick paste, adjust the pH value to 5.5-6.5, dry under reduced pressure, pulverize and sieve, and mix with the fine powder in step (3) to obtain the traditional Chinese medicine composition.

[0028] (5) Mix the traditional Chinese medicine composition from step (4) with the filler evenly, then mix with the binder to granulate, dry and fill into capsules to obtain the traditional Chinese medicine composition drug preparation.

[0029] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0030] (1) Experiments have shown that it has a significant inhibitory effect on Helicobacter pylori and has a very effective inhibitory and killing effect on standard strains and drug-resistant strains of Helicobacter pylori from different sources in vitro.

[0031] (2) Pharmacodynamic experiments have demonstrated that the herbal composition of this invention can effectively inhibit Helicobacter pylori in rats, achieving an eradication rate of up to 80%. It significantly inhibits the activation of the TLRs / NF-κB pathway during Helicobacter pylori infection and significantly inhibits the secretion of TNF-α, IL-6, and IL-8 during infection. It has a positive clinical effect in treating Helicobacter pylori infection, and its application can reduce the use of antibiotics, thereby lowering the drug resistance rate of Helicobacter pylori. Furthermore, the Shouhui preparation has high safety and few toxic side effects, and also possesses the effects of invigorating qi and nourishing yin, purging turbidity and promoting bowel movements, and reducing weight and lipids, thus improving the coordinated functioning of internal organs. Attached Figure Description

[0032] Figure 1 To compare the expression levels of TNF-α in the mucous membranes of mice in each group;

[0033] Figure 2 The expression levels of IL-6 in the mucous membranes of rats in each group were compared.

[0034] Figure 3 The expression levels of IL-8 in the mucous membranes of rats in each group were compared. Detailed Implementation

[0035] The following are specific embodiments of the present invention, which further illustrate the technical solutions of the present invention in detail. However, they should not be construed as limiting the scope of the present invention to the following implementation examples. Any modifications or substitutions made based on ordinary technical knowledge and common practices in the art without departing from the above-described technical premises of the present invention are all included within the scope of the present invention.

[0036] Example 1: A preparation of capsules for treating or preventing Helicobacter pylori infection

[0037] Polygonum multiflorum 40 parts by weight, Aloe vera 50 parts by weight, Cassia seed 60 parts by weight, Ginseng 40 parts by weight

[0038] 50 parts by weight of wolfberry, 30 parts by weight of donkey-hide gelatin, 60 parts by weight of immature bitter orange, and 30 parts by weight of atractylodes macrocephala.

[0039] The preparation method is as follows:

[0040] (1) Grind the prescribed amount of donkey-hide gelatin and ginseng into a fine powder through an 80-mesh sieve and set aside;

[0041] (2) Weigh out wolfberry, atractylodes macrocephala, and immature bitter orange according to the ratio, add 12 times the amount of water and soak for 1.5 hours, boil over high heat for 15 minutes, filter to obtain filtrate, and set aside the residue. Add 6 times the amount of water to the residue, boil over high heat and then simmer over low heat for 1.5 hours, filter to obtain filtrate, combine the two filtrates, and concentrate the filtrate to a relative density of 1.10 at 70℃ to obtain concentrated solution;

[0042] (3) Weigh out Polygonum multiflorum, Cassia tora, and Aloe vera according to the proportion, remove impurities, wash, dry, grind and sieve through 60-80 mesh to obtain fine powder;

[0043] (4) Combine the concentrated liquid obtained in step (2) and the fine powder obtained in step (1), mix them evenly, concentrate them into a thick paste, adjust the pH value to 5.5, dry under reduced pressure, pulverize and sieve through a 70-mesh sieve, and mix with the fine powder in step (3) to obtain the traditional Chinese medicine composition.

[0044] (5) Weigh the Chinese herbal composition obtained in step (4), add 1 times its weight of sorbitol and hydroxypropyl-β-cyclodextrin and mix evenly (the weight ratio of sorbitol and hydroxypropyl-β-cyclodextrin is 1:1), then mix with an appropriate amount of 3% hydroxypropyl methylcellulose 50% ethanol solution with a pH of 6.0 and granulate. After drying, fill into capsules to obtain capsules.

[0045] Example 2: A preparation of capsules for treating or preventing Helicobacter pylori infection

[0046] Polygonum multiflorum 200 parts by weight, Aloe vera 200 parts by weight, Cassia tora 160 parts by weight, Ginseng 80 parts by weight

[0047] 80 parts by weight of wolfberry, 150 parts by weight of donkey-hide gelatin, 160 parts by weight of immature bitter orange, and 60 parts by weight of atractylodes macrocephala.

[0048] Step (5) in the preparation method is as follows: Weigh the traditional Chinese medicine composition obtained in step (4), add 0.5 times its weight of sorbitol and hydroxypropyl-β-cyclodextrin and mix evenly (the weight ratio of sorbitol and hydroxypropyl-β-cyclodextrin is 0.8:1), then mix with an appropriate amount of 3% hydroxypropyl methylcellulose 50% ethanol solution with a pH of 6.0 and granulate, dry and fill into capsules to obtain capsules.

[0049] Example 3: A preparation of capsules for treating or preventing Helicobacter pylori infection

[0050] A capsule formulation for the treatment or prevention of Helicobacter pylori infection.

[0051] Polygonum multiflorum 120 parts by weight, Aloe vera 160 parts by weight, Cassia seed 140 parts by weight, Ginseng 50 parts by weight

[0052] 75 parts by weight of wolfberry, 75 parts by weight of donkey-hide gelatin, 50 parts by weight of atractylodes macrocephala, and 120 parts by weight of immature bitter orange.

[0053] The preparation method is the same as in Example 1.

[0054] Comparative Example 1: A capsule preparation for treating or preventing Helicobacter pylori infection

[0055] Polygonum multiflorum 220 parts by weight, Aloe vera 220 parts by weight, Cassia seed 30 parts by weight, Ginseng 30 parts by weight

[0056] 20 parts by weight of wolfberry, 10 parts by weight of donkey-hide gelatin, 30 parts by weight of immature bitter orange, and 20 parts by weight of atractylodes macrocephala.

[0057] Preparation method: (1)-(4) are the same as in Example 1. Step (5) is: mix the Chinese medicine composition obtained in step (4) with hydroxypropyl-β-cyclodextrin evenly, then mix with an appropriate amount of 3% hydroxypropyl methylcellulose 50% ethanol solution with a pH of 6.0 to granulate, dry and fill into capsules to obtain capsules.

[0058] Comparative Example 2: A preparation of capsules for treating or preventing Helicobacter pylori infection

[0059] Polygonum multiflorum 120 parts by weight, Aloe vera 130 parts by weight, Cassia seed 110 parts by weight, Ginseng 65 parts by weight

[0060] 75 parts by weight of wolfberry, 90 parts by weight of donkey-hide gelatin, 110 parts by weight of immature bitter orange, and 45 parts by weight of atractylodes macrocephala.

[0061] Preparation method:

[0062] 1) Take eight kinds of raw medicinal materials: Polygonum multiflorum, Cassia seed, Aloe vera, donkey-hide gelatin, wolfberry, Atractylodes macrocephala, Citrus aurantium and ginseng. Among them, Polygonum multiflorum, ginseng, Atractylodes macrocephala and Citrus aurantium are sliced, donkey-hide gelatin is melted, Aloe vera is crushed, and wolfberry and Cassia seed are cleaned and set aside.

[0063] 2) Mix cassia seeds and aloe vera, reflux with 6 times the amount of 50% ethanol once, for 1 hour each time, filter, combine the filtrates, recover the ethanol under reduced pressure, and concentrate into extract I for later use, and keep the residue for later use.

[0064] 3) Extract the volatile oil from Atractylodes macrocephala and Citrus aurantium with 8 times the amount of water to obtain the volatile oil, medicinal liquid and residue for later use;

[0065] 4) Mix Polygonum multiflorum and ginseng, soak in 8 times the amount of water for 1.5 hours, add the dregs from step 2) and step 3) and decoct for 2 hours. Release the decoction, then decoct in 9 times the amount of water for 2 hours. Release the decoction, combine the decoction with the liquid from step 3), filter, concentrate under reduced pressure to an extract with a relative density of 1.2-1.4, add 95% ethanol to make the alcohol content reach 65%, cold settle for 48 hours, filter, recover the ethanol under reduced pressure, concentrate to extract II, and set aside.

[0066] 5) Combine extract I and extract II, mix evenly, dry to obtain dry extract, pulverize the dry extract and add 0.5 kg of melted donkey-hide gelatin solution, add dextrin and 85% ethanol solution according to the formula, mix evenly, granulate, dry, and granulate. Add the volatile oil mentioned in step 3) to the obtained granules, mix evenly, and fill the granules into capsules to obtain the final product.

[0067] I. Verification Implementation Example:

[0068] The physicochemical properties of Examples 1-3 and Comparative Examples 1-2 of the present invention were determined by stability tests.

[0069] The capsules prepared in Examples 1-3 and Comparative Examples 1-2 of this invention were tested for dispersion uniformity, disintegration time, water content and long-term stability. The test results are shown in Table 1.

[0070] Method for determining moisture content: The moisture content of the capsules was calculated using the drying method.

[0071] Method for detecting dispersion uniformity: Take 2 capsules each from the capsules prepared in Examples 1-3 and Comparative Examples 1-2, place the inner capsule in 100mL of water at 20℃±1℃, shake for 3min, and pass through a No. 2 sieve.

[0072] Disintegration time test method: Take 6 capsules each from the capsules prepared in Examples 1-3 and Comparative Examples 1-2, and test them in water at a temperature of 37℃±1℃ using a lift-type disintegration apparatus.

[0073] Long-term testing: The product was placed at a temperature of 25℃±2℃ and a relative humidity of 60%±10% for 36 months, and then the disintegration time and moisture content were tested.

[0074] Table 1. Stability test results for each example group

[0075]

[0076] As can be seen from Table 1, the capsules of Examples 1-3 of the present invention have good disintegration effects and can disintegrate completely within the specified time (the pharmacopoeia stipulates that disintegration is complete within 30 minutes). In particular, the various indicators of Example 3 are better than those of the other examples. In contrast, the weight parts of some traditional Chinese medicines in the traditional Chinese medicine composition of Example 1 are not entirely within the scope of the present invention. In the long-term stability test, the disintegration time was significantly prolonged and the water content was significantly increased. In contrast, the weight parts of the traditional Chinese medicine composition of Example 2 are within the scope of the present invention, but the preparation method is different from the present invention, and therefore it cannot achieve the technical effects of the present invention.

[0077] II. In vitro antibacterial test of Shouhui preparation

[0078] 1. Determination of MIC value

[0079] Test drug: Shouhui Tongbian Capsules (0.35g / capsule) were produced by Lunan Houpu Pharmaceutical Co., Ltd., with the national drug approval number Z20150041. The positive control drug was clarithromycin (MCE Company, batch number: 16542).

[0080] Strains: Helicobacter pylori standard strains ATCC43505, ATCC700393, SS1, NCTC26695; drug-resistant strains: QYZ-001, QYZ-002.

[0081] 1.1 Experimental Methods

[0082] After removing the capsule shell, Shouhui Tongbian Capsules were dissolved in water and filtered through a 0.22μm filter membrane. Multiple concentration gradients of the drug were prepared using a two-fold dilution method, including 500.00mg / ml, 250.00mg / ml, 125.00mg / ml, 62.50mg / ml, 31.25mg / ml, and 15.62mg / ml. Clarithromycin was used as a positive control and dissolved in DMSO to prepare a stock solution. Before use, the solution was diluted to the corresponding concentration gradients (DMSO content ≤1%). 50μl of the prepared drug solution was added to a 96-well plate, with at least three replicates for each drug concentration. Negative control wells (containing only the drug, without bacterial inoculation), growth control wells (containing no drug, only bacterial inoculation), and clarithromycin positive control wells (containing clarithromycin and bacterial inoculation) were included. Remove the bacterial strain from the incubator, scrape the bacterial growth onto PBS with a moistened sterile cotton swab, adjust the turbidity of the bacterial suspension to 1 McF using BHI containing 20% ​​FBS, dilute 10-fold, and inoculate into the aforementioned drug-containing 96-well plates (the final turbidity of the bacterial suspension in the 96-well plate is approximately 1 × 10⁶ CFU / ml). Immediately place the 96-well plate in an incubator and incubate at 37°C under microaerophilic conditions with shaking at 150 rpm for 72 hours. Observe the results after incubation. Results are only usable when the growth control shows a button-like appearance or obvious turbidity. Visually observe from bottom to top; the drug concentration at which the bacterial turbidity significantly decreases is the MIC. The MIC value is determined within 3 generations after resuscitation, and the MIC value is measured three times. The inhibitory results of the first-harvest compound on Helicobacter pylori are shown in Table 2.

[0083] Table 2. Inhibition results of Shouhui Tongbian Capsules on Helicobacter pylori

[0084]

[0085] Note: "-" indicates no bacterial growth, and "+~++++" indicates bacterial growth.

[0086] Based on the above experimental results, the inhibitory effects of Shouhui preparation on Helicobacter pylori from different sources are shown in Table 3.

[0087] Table 3. Inhibition results of Shouhui Tongbian Capsules on Helicobacter pylori from different sources.

[0088] strains ATCC43505 ATCC700393 SS1 NCTC26695 QYZ-001 QYZ-002 MIC (mg / ml) 31.25 62.50 31.25 31.25 62.50 31.25

[0089] 2. Determination of MBC value

[0090] Take 100 μl of the liquid from each of the 96 wells cultured for 72 h in the micro-broth assay, and evenly spread it onto fresh blood agar plates from wells containing drug concentrations of 1, 2, and 4 times the MIC. After culturing for 72 h, observe the results. The drug concentration that kills 99.9% of the bacteria is defined as the MBC. The inhibitory results of the Shouhui preparation on various Helicobacter pylori strains are shown in Table 4.

[0091] Table 4. Inhibition results of Shouhui Tongbian Capsules on various Helicobacter pylori strains.

[0092] strains ATCC43505 ATCC700393 SS1 NCTC26695 QYZ-001 QYZ-002 MBC (mg / ml) 31.25 62.50 31.25 31.25 62.50 62.50

[0093] As shown in Table 2-4, Shouhui laxative capsules exhibited good inhibitory activity against multiple susceptible and drug-resistant Helicobacter pylori strains, with MIC values ​​ranging from 31.25 to 62.5 μl / mL and MBC values ​​also ranging from 31.25 to 62.5 μl / mL. This indicates that Shouhui preparations have highly effective inhibitory and bactericidal effects against both standard and drug-resistant Helicobacter pylori strains in vitro.

[0094] III. Effects of Shouhui preparations on the efficacy of Helicobacter pylori seroconversion

[0095] 1. Experimental Methods

[0096] 1.1 Preparation of bacterial culture

[0097] Helicobacter pylori ATCC43504 strain was inoculated into Buchner agar medium and cultured at 37°C for 3 days in a microaerophilic environment. After Gram staining and microscopic examination, urokinase, peroxide and catalase tests were performed to confirm Helicobacter pylori. The bacterial culture was then cultured in Buchner broth for 3 days to obtain the bacterial solution for later use.

[0098] 1.2 Modeling and Testing

[0099] Wistar rats, half male and half female, were first administered 5% sodium bicarbonate solution by gavage (2 mL / rat), followed by bacterial suspension by gavage 1.5 mL / rat 15 minutes later. This was repeated once a week for a total of 5 weeks. After model establishment, tail blood was collected to test for anti-Helicobacter pylori related antibodies; a positive result indicated successful model establishment. 150 rats were randomly selected and divided into 5 groups of 30 each: a model control group, a positive control group, an experimental group, and control groups (Examples 1-2). The experimental group received Shouhui Tongbian capsules (0.24 g / kg) once daily for 10 days. Control groups (Examples 1-2) received the same amount of the preparation by gavage. The positive control group received clarithromycin tablets (Shanghai Abbott Pharmaceutical Co., Ltd., 160 mg / kg / day), and the model control group received the same amount of physiological saline by gavage. After administration, the rats were fasted for one day, sacrificed, and their stomachs were cut open. Three pieces of stomach tissue were taken for gastric mucosal smears, bacterial cultures, and rapid urokinase tests. The number of positive results was counted. The eradication rate was calculated when all three indicators were negative. The results are recorded in Table 5.

[0100] Table 5. Effect of Shouhui Tongbian Capsules on the Negative Conversion Efficacy of Helicobacter pylori

[0101] Experimental Project Number of positive microscopic examination samples (animals) Number of HP culture positive (animals) Number of urokinase positive (animals) Eradication rate (%) Model control group 30 30 30 0 Positive control group 5 4 4 83.3 First Gathering Group 5 4 6 80.0 Comparative Example 1 12 9 10 60.0 Comparative Example 2 13 10 11 56.7

[0102] As can be seen from Table 5 above, the composition in the present invention can effectively inhibit Helicobacter pylori. On the premise of a lower dose, the final eradication rate of Helicobacter pylori can reach 80%.

[0103] IV. Effect of Shouhui Laxative Capsule on Mice Infected with Helicobacter pylori

[0104] 1. Experimental Materials and Methods

[0105] 1.1 Experimental Materials

[0106] C57 mice were selected as experimental animals, all male, 6 - 8 weeks old, with a body weight of 18 - 22 g, from Lunan Pharmaceutical Group Co., Ltd., and the experimental animal license number is SYXK(Lu)20230023.

[0107] Helicobacter pylori SS1 (ATCC); RIPA protein lysate and BCA kit (Shanghai Beyotime Biotechnology Co., Ltd.); enzyme - linked immunosorbent assay kit (Shanghai Xitang Biotechnology Co., Ltd.).

[0108] Drugs: Shouhui Laxative Capsule (Lunan Houpu Pharmaceutical Co., Ltd.), Clarithromycin Tablets (Shanghai Abbott Laboratories).

[0109] 1.2 Experimental Methods

[0110] 1.2.1 Hp Culture, Bacterial Solution Preparation Method and Modeling

[0111] Resuscitate SS1 Helicobacter pylori in Columbia blood agar medium containing 8% defibrinated sheep serum, culture it in a micro - aerobic environment of 15% CO2, 5% O2, and 80% NO2 for 48 - 72 h. After amplification culture of positive colonies, collect SS1 Helicobacter pylori with Brucella broth after rapid urease identification and adjust the density to 10 9 CFU / ml for standby.

[0112] After fasting for 24 h, intragastrically administer 5% sodium bicarbonate solution. 30 minutes later, intragastrically administer 0.2 ml of bacterial solution containing 10 9 CFU / ml SS1 Helicobacter pylori, and intragastrically administer continuously 4 times, with an interval of 48 h each time.

[0113] 1.2.2 Grouping and Drug Administration

[0114] Divide the above - mentioned mice into 9 groups, with 10 mice in each group.

[0115] Blank group (Sham): Not infected + normal saline

[0116] Model group (Model): Infected + normal saline

[0117] Positive control group (KLMS): Infection + Clarithromycin tablets (160 mg / kg / day)

[0118] Low-dose group of Shouhui laxative capsules: Infection + Shouhui laxative capsules (0.12g / kg)

[0119] Medium dose of Shouhui Tongbian Capsules: Infection + Shouhui Tongbian Capsules (0.24g / kg)

[0120] High-dose group of Shouhui laxative capsules: Infection + Shouhui laxative capsules (0.48g / kg)

[0121] Comparative Example 1 (D1): Infection + Comparative Example 1 Traditional Chinese Medicine (0.24g / kg)

[0122] Comparative Example 2 (D2): Infection + Comparative Example 2 Traditional Chinese Medicine (0.24g / kg)

[0123] 1.2.3 Measurement Indicators

[0124] The degree of gastric mucosal inflammation in mice was determined. The total protein content was measured using a BCA kit, and the contents of TLR2, TLR4, NF-κB, TNF-α, IL-6, and IL-8 were measured using an enzyme-linked immunosorbent assay (ELISA) kit. The expression levels of TLR2, TLR4, NF-κB, TNF-α, IL-6, and IL-8 per milligram of total protein were calculated.

[0125] 1.2.4 Data Statistics

[0126] Data were processed using SPSS 22.0 software and expressed as (X±S). One-way ANOVA was used for comparisons between groups, with multiple comparisons performed. Sigma Plot 14 was used for plotting. P < 0.05 was considered statistically significant.

[0127] 2 Results

[0128] 2.1 Comparison of expression levels of TLR2, TLR4, and NF-κB pathways

[0129] Table 6. Expression levels of TLRs / NF-κB pathways in the mucosa of mice in each group (X±S)

[0130] Grouping TLR2 (ng / mg) TLR4 (ng / mg) NF-κB (pg / mg) Sham 3.69±0.65 4.36±0.43 57.30±9.01 Model 9.46±0.87 11.52±1.45 213.11±35.28 KLMS 6.40±0.46* 7.72±0.66* 109.47±19.69** Low 6.56±0.40* 8.23±0.76* 130.73±20.09* Medium 6.08±0.38** 7.90±0.91* 116.21±13.73** High 5.69±0.50** 6.87±0.88** 95.95±10.38** D1 7.78±0.64 9.50±1.01 163.85±12.42 D2 7.63±0.36 9.35±1.87 174.55±20.79

[0131] Compared with the model group, *P<0.05, **P<0.01.

[0132] The expression levels of TLR2, TLR4, and NF-κB pathways are shown in Table 6. The experimental results indicate that the expression levels of TLR2, TLR4, and NF-κB in the mucous membranes of mice treated with the herbal composition of this invention were significantly lower than those in the model group, comparable to the positive control group, and even superior in the high-dose group compared to the positive control group. The differences between the high-dose and comparative groups were significant. Therefore, the herbal composition of this invention can significantly inhibit the activation of the TLRs / NF-κB pathway during Helicobacter pylori infection.

[0133] 2.2 Expression levels of inflammatory factors

[0134] The expression levels of TNF-α, IL-6, and IL-8 in the gastric mucosa of mice in the model group were significantly higher than those in the control group. The expression levels of TNF-α, IL-6, and IL-8 in the gastric mucosa of mice in each dose group of this invention were significantly lower than those in the model group. Compared with the positive control group, the high-dose group showed significantly better efficacy than the positive control group. The therapeutic effects of each dose group were significantly better than those of comparative groups 1 and 2. See details below. Figure 1-3 The expression levels of TNF-α, IL-6, and IL-8 in the gastric mucosa of the model group mice were significantly higher than those in the control group. This indicates that activation of the TLRs / NF-κB pathway during Helicobacter pylori infection can significantly increase the expression of inflammatory mediators TNF-α, IL-6, and IL-8. Further analysis of the effects of the embodiments of the present invention on the expression of downstream inflammatory mediators of the TLRs / NF-κB pathway during Helicobacter pylori infection showed that after gavage administration of each dose group of the embodiments of the present invention, the expression levels of TNF-α, IL-6, and IL-8 in the gastric mucosa of mice were significantly lower than those in the model group, and the expression levels of TNF-α, IL-6, and IL-8 in the gastric mucosa of mice in each dose group were significantly lower than those in comparative embodiment 1-2. This indicates that Shouhui Tongbian Capsules can significantly inhibit the secretion of TNF-α, IL-6, and IL-8 during Helicobacter pylori infection, and the inhibitory effect of the high-dose group on the secretion and expression of TNF-α, IL-6, and IL-8 is better than that of the positive control group.

[0135] The above results indicate that the Shouhui preparation of this invention can treat or prevent Helicobacter pylori infection, thereby achieving a therapeutic effect.

[0136] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0137] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. The use of a traditional Chinese medicine composition in the preparation of a drug or health product for treating or preventing Helicobacter pylori infection, characterized in that, The traditional Chinese medicine composition consists of Polygonum multiflorum, aloe vera, cassia seed, ginseng, wolfberry, donkey-hide gelatin, immature bitter orange, and Atractylodes macrocephala.

2. The use according to claim 1, characterized in that, The traditional Chinese medicine composition, by weight, mainly comprises the following components: 25-400 parts of Polygonum multiflorum, 40-400 parts of Aloe vera, 40-250 parts of Cassia tora, 20-100 parts of Ginseng, 30-100 parts of Lycium barbarum, 20-180 parts of Colla corii asini, 40-280 parts of Citrus aurantium, and 10-80 parts of Atractylodes macrocephala.

3. The use according to claim 2, characterized in that, The traditional Chinese medicine composition, by weight, mainly includes the following components: 40-200 parts of Polygonum multiflorum, 50-200 parts of Aloe vera, 60-160 parts of Cassia tora, 40-80 parts of Ginseng, 50-80 parts of Lycium barbarum, 30-150 parts of Colla corii asini, 60-160 parts of Citrus aurantium, and 30-60 parts of Atractylodes macrocephala.

4. The use as described in any one of claims 1 to 3, characterized in that, The aforementioned traditional Chinese medicine composition, together with pharmaceutically acceptable excipients, is formulated into a pharmaceutically acceptable dosage form.

5. The use according to claim 4, characterized in that, The dosage form of the traditional Chinese medicine composition is capsule, tablet, granule, mixture, pill, drop pill, powder or granule.

6. The use according to claim 5, characterized in that, The traditional Chinese medicine composition preparation is in capsule form.

7. The use according to claim 6, characterized in that, The capsule is prepared by mixing the traditional Chinese medicine composition with pharmaceutically acceptable excipients in a weight ratio of 1:1.5 to 8.5; further, the traditional Chinese medicine composition is prepared by mixing the pharmaceutically acceptable excipients in a weight ratio of 1:2.0 to 5.

5.

8. The use according to claim 7, characterized in that, The pharmaceutically acceptable excipients include fillers and binders, wherein the fillers are selected from mannitol, lactose, sorbitol, sucrose, and cyclodextrin; and the binders are selected from a 75% ethanol solution of 3% PVP, a 50% ethanol solution of 3% hydroxypropyl methylcellulose, an aqueous solution of 10% povidone K30, and 30% starch paste.

9. The use according to claim 8, characterized in that, The filler is a mixture of cyclodextrin and sorbitol, with a weight ratio of 1:0.5-1.

4.

10. The use according to claim 9, characterized in that, The cyclodextrin is hydroxypropyl-β-cyclodextrin.

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