Medicine for treating helicobacter pylori infection

Abstract

The invention relates to the technical field of medicines, and discloses a medicine for treating helicobacter pylori infection, which comprises the following raw materials: a substance a and pharmaceutically acceptable auxiliary materials, the structural formula of the substance a is shown as a formula (I). The substance a has a good bactericidal effect on helicobacter pylori and can be used for treating and preventing helicobacter pylori infection; and the substance a has a specific structure, can realize efficient sterilization in vivo and can be rapidly degraded at the same time, the degradation product is rapidly discharged out of the body, the substance a and the common degradation product thereof are actually nontoxic and very high in safety, and the substance a cannot be absorbed by the human body, has no side effect and cannot cause the helicobacter pylori to generate drug resistance.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and particularly to a drug for treating Helicobacter pylori infection. Background Art

[0002] Clinically, the onset of most patients with gastritis and gastric ulcer is caused by Helicobacter pylori infection. In severe cases, it can also cause the occurrence of diseases such as chronic pharyngitis and oral ulcers. It infects people of different races and regions around the world, and the infection rate increases with age. It is about 80% in developing countries and about 40% in developed countries. The infection rate in men is slightly higher than that in women, and the infection rate in pets is higher than that in humans.

[0003] At present, the treatment regimens for positive Helicobacter pylori include two major categories. One is a regimen mainly based on antibiotics supplemented with acid suppressants (bismuth agents), and the second is a regimen based on proton pump inhibitors. In addition, there are two other antibiotics, and the most commonly used ones are amoxicillin, metronidazole, etc. The above drugs have a long treatment cycle, many types of drugs to take, and relatively large side effects on the human body.

[0004] Quaternary ammonium salt disinfectants belong to cationic surfactants and have bactericidal and detergency effects. They are generally used for the cleaning and disinfection of non-critical items in hospitals and can also be used for hand disinfection. Dissolving them in ethanol can enhance their bactericidal effect as skin disinfectants, and they are often used for item or in vitro disinfection. Since these compounds can change the permeability of the bacterial cell membrane, they are often compounded with other disinfectants to improve their bactericidal effect and speed. Although there are also literatures disclosing that quaternary ammonium salts with specific structures can be combined with other substances to inhibit Helicobacter pylori, generally they are used in vitro or for Helicobacter pylori in the oral cavity, and their treatment effect still needs to be improved. Summary of the Invention

[0005] Based on the technical problems existing in the background art, the present invention provides a drug for treating Helicobacter pylori infection. Substance a of the present invention has a good bactericidal effect on Helicobacter pylori and can be used for treating and preventing Helicobacter pylori infection; due to its specific structure, substance a can achieve efficient sterilization in the body while being rapidly degraded, and the degradation products can be rapidly excreted from the body without residue in the body. Substance a and its common degradation products are actually non-toxic and have high safety, and the application to the human body has a low safety risk; substance a can be rapidly degraded in the body, and the degradation products are fatty acid-like / fatty acids and dicationic choline. Substance a will not be absorbed by the human body, has no side effects, and will not cause Helicobacter pylori to develop drug resistance.

[0006] The present invention provides a drug for treating Helicobacter pylori infection, and its raw materials include: substance a and pharmaceutically acceptable excipients; the structural formula of substance a is shown in formula (I): Formula (I); Among them, R1 and R2 are independently selected from one of C6-C12 alkyl groups, and X is one of Cl, Br, I or NO 3 - ; R3 is any one of the following structures: ; R4, R5, R6, and R7 are independently selected from one of C1-C4 saturated alkyl groups.

[0007] Preferably, R1 and R2 are independently selected from one of C6-C12 saturated straight-chain alkyl groups.

[0008] Preferably, R3 is .

[0009] Preferably, R4, R5, R6, and R7 are all methyl.

[0010] Preferably, R1 and R2 are C8 saturated straight-chain alkyl groups.

[0011] Preferably, the structural formula of substance a is shown as one of formulas (II)-(III): Formula (II), named compound 10; Formula (III), named compound 11.

[0012] Preferably, the dosage form of the drug is an oral preparation, a respiratory administration dosage form, a topical dosage form, a mucosal dosage form or a cavity administration dosage form.

[0013] The above oral preparations can be: powders, tablets, granules, capsules, solutions, emulsions, suspensions, etc.

[0014] The above respiratory administration dosage forms can be sprays, aerosols, powder aerosols, etc.

[0015] The topical dosage form can be topical solutions, lotions, liniments, ointments, plasters, pastes, patches, etc.

[0016] The mucosal dosage form can be eye drops, nasal drops, ophthalmic ointments, gargles, sublingual tablets, adhesive tablets, film dressings, etc.

[0017] The cavity administration dosage form can be suppositories, aerosols, effervescent tablets, drops and dripping pills, etc.

[0018] Preferably, pharmaceutically acceptable excipients include at least one of solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, antiadhesives, chelating agents, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoaming agents, thickening agents, clathrates, humectants, absorbents, diluents, flocculants, deflocculants, filter aids, and release retardants.

[0019] The preparation method of the above-mentioned substance a can refer to the preparation method described in the patent with the application number 202210890033.2 and the invention title "A Degradable Gemini Quaternary Ammonium Salt and Its Preparation Method, Fungicide".

[0020] Preferably, its raw materials by weight include: 0.04 - 0.06 parts of active ingredient, 0 - 1 part of gum resin, 0 - 0.5 part of wax liquid, 1 - 0.5 parts of sweetening agent, 0.01 - 0.03 parts of essence; wherein, the active ingredient is one or more of the compounds in compound a; more preferably, the active ingredient is one or more of compound 10 and compound 11.

[0021] Preferably, its raw materials by weight include: 0.05 part of active ingredient, 0 - 1 part of gum resin, 0 - 0.5 part of wax liquid, 1 - 0.5 parts of sweetening agent, 0.02 part of essence.

[0022] Compared with the currently commonly used triple or quadruple antibiotic drugs, which not only damage the stomach but also have a long administration time, the inventor found that compound a still has a good effect of killing Helicobacter pylori when used in a very small amount, and compound a can be degraded within a short time, and the degradation products are fatty acid-like / fatty acids and dicationic choline. Compound a will not be absorbed by the human body, has no side effects, and will not cause Helicobacter pylori to develop drug resistance; the drug treatment cycle of the present invention is very short, only need to be taken for two days, once a day.

[0023] In addition, the acute oral toxicity tests (mice) of compound a and its degradation products are both greater than 5000 mg / kg, both are actually non-toxic, and have high safety.

[0024] Preferably, the gum resin is natural gum or glycerol resin.

[0025] Preferably, when the gum resin is 0, the wax liquid is 0.

[0026] Preferably, when the gum resin is 0, the sweetening agent is one or more of sucrose and fructose.

[0027] Preferably, when the weight part of the gum resin is greater than 0, the sweetening agent is one or more of sorbitol, mannitol, maltitol, and xylitol.

[0028] Preferably, the essence is one or more of mint essence, peach essence, and lemon essence.

[0029] Preferably, the wax liquid is beeswax.

[0030] Preferably, when the gum resin is 0, the method of using the composition for treating Helicobacter pylori infection is: hold in the mouth until the composition dissolves, and then swallow.

[0031] Preferably, when the weight part of the gum resin is greater than 0, the method of using the composition for treating Helicobacter pylori infection is: chew until tasteless and then spit out.

[0032] Compound a is bitter in taste, and a sweetener is added to improve the taste.

[0033] When used by chewing, when it is tasteless after chewing, it can be considered that compound a has been completely chewed out, and then spit out.

[0034] Since Helicobacter pylori mainly exists in the stomach, and also exists in the oral cavity and esophagus, comprehensive killing from the oral cavity to the stomach should be considered when killing Helicobacter pylori. The existing treatment methods are generally direct perfusion or swallowing, with a very short residence time in the oral cavity, and it is impossible to achieve comprehensive sterilization from the oral cavity to the stomach.

[0035] Through the cooperation of each raw material, the drug can be used in a solid form by holding in the mouth or chewing, so that the active ingredient can stay in the oral cavity for a long time, thereby achieving comprehensive sterilization from the oral cavity to the stomach; the above drug only needs to be used on an empty stomach 2 hours before breakfast, and Helicobacter pylori in the body can be completely cleared after continuous use for two days. The use cycle is very short, with little side effect on the human body and significant treatment effect.

[0036] The gum resin, wax liquid, sweetener, and essence described in the present invention are all of pharmaceutical grade.

[0037] Preferably, its preparation method includes method A or method B; When the gum resin is 0, method A is adopted, which includes the following steps: take each raw material and mix them evenly, heat and melt them evenly to obtain the drug for treating Helicobacter pylori infection; When the weight part of the gum resin is greater than 0, method B is adopted, which includes the following steps: take the active ingredient, gum resin, sweetener, and essence and mix them evenly, heat and expand, and then add the wax liquid and mix evenly to obtain the drug for treating Helicobacter pylori infection.

[0038] Preferably, in both method A and method B, it is heated to 140 - 160 °C.

[0039] The substance a of the present invention has a good bactericidal effect on Helicobacter pylori and can be used to treat Helicobacter pylori infection; when using a very small amount of substance a, it still has a good effect of killing Helicobacter pylori, and its bactericidal effect is much better than that of existing quaternary ammonium salts.

[0040] It has been found through research that the cationic group in the molecule of substance a adsorbs negatively charged Helicobacter pylori bodies through electrostatic force, hydrogen bond force, and hydrophobic binding, etc., aggregates on the cell wall, and produces a chamber resistance effect, resulting in the inhibition of the growth of Helicobacter pylori and its death; at the same time, there is an obvious interaction between the non-bonding orbital n of the sulfur atom in the structure and the P=O of the phospholipid molecule orbital, resulting in a large deformation of the substance a molecule in the cell membrane of Helicobacter pylori, changing the cell membrane permeability, destroying the cell structure, and causing the dissolution and death of Helicobacter pylori cells.

[0041] Moreover, due to its specific structure, substance a can achieve efficient sterilization in the body while being able to degrade rapidly, and the degradation products can be rapidly excreted from the body without residue in the body; and the acute oral toxicity tests (mice) of substance a and its common degradation products are both > 5000 mg / kg, both are actually non-toxic, with high safety, and the application to humans has a low safety risk; the degradation products of substance a are fatty acid-like / fatty acids and dicationic choline, substance a will not be absorbed by the human body, has no side effects, and will not cause Helicobacter pylori to develop drug resistance, and the treatment cycle of substance a for Helicobacter pylori infection is very short and the curative effect is fast. Brief Description of the Drawings

[0042] Figure 1 It is a diagram of the interaction between benzalkonium chloride and the phospholipid molecular layer.

[0043] Figure 2 It is a diagram of the interaction between compound 11 and the phospholipid molecular layer.

[0044] Figure 3 It is the degradation rate results of compound 10, compound 13, and evofimora. Detailed Description of the Invention

[0045] Next, the technical solutions of the present invention will be described in detail through specific examples.

[0046] Example 1

[0047] Compounds 1-9 were prepared according to Examples 1-9 in the invention patent with the application number 202210890033.2.

[0048] Example 2

[0049] Prepare compounds 10 and 11 Add 0.02 mol of dimethylaminoethyl acrylate, 0.02 mol of 1-octanethiol, 0.01 mol of 1,3-dibromopropane, and 10 mL of ethanol to a single-necked flask. Stir at 60 °C under atmospheric pressure for 12 h, then remove the solvent by vacuum distillation. Wash with acetone 2-3 times and then lyophilize to obtain Compound 10.

[0050] Replace 1,3-dibromopropane with 1,3-dichloropropane and prepare Compound 11 according to the method of Compound 10.

[0051] Example 3

[0052] Prepare Compound 12 Take an aqueous solution of Compound 10 with a mass fraction of 1 wt%, add silver nitrate and mix well (the molar ratio of Compound 10 to silver nitrate is 1:2). Stir at room temperature in the dark for 2 h, centrifuge to take the supernatant, and freeze-dry to obtain Compound 12.

[0053] Comparative Example 1 Prepare Compound 13 Replace "dimethylaminoethyl acrylate" with "dimethylaminoethyl methacrylate", and prepare Compound 13 according to the method of Compound 10 for the rest.

[0054] Comparative Example 2 Prepare Compound 14 Add 0.1 mol of lauric acid to a four-necked flask equipped with a magnetic stirrer. Insert a thermometer, set up a fractional distillation device, set the oil bath to 70 °C, heat and stir until the lauric acid is completely melted, then add a certain amount of p-toluenesulfonic acid and hypophosphorous acid as catalysts, introduce nitrogen for protection, and use a constant pressure funnel to dropwise add 0.18 mol of N,N-dimethylethanolamine. Then raise the temperature to 160 °C and stir for the esterification reaction. Measure the acid value every hour during the reaction. Stop the reaction when the change in acid value is not significant after 7 h of reaction; cool to room temperature, add a 50 wt% aqueous potassium hydroxide solution, stir at 75 °C for 30 min to remove impurities, then transfer to a pear-shaped separatory funnel, add CCl 4 Perform extraction, let stand for 12 h, take the lower layer liquid, and rotary evaporate to remove CCl 4 , to obtain an intermediate; Add the intermediate, 1,3-dichloropropane, and isopropanol to a three-necked flask equipped with a thermometer and a reflux device in sequence. Stir at room temperature for 15 min, then measure the initial amine value; raise the temperature of the system to 100 °C and reflux and stir for 6 h, measure the amine value once every hour during the reaction; after the reaction is completed, distill off isopropanol under reduced pressure to obtain a crude product; recrystallize with a mixed solvent of isopropanol and ethyl acetate to obtain Compound 14.

[0055] Comparative Example 3 Prepare Compounds 15 and 16 Replace "1-octanethiol" with "tetradecanethiol", and prepare compound 15 according to the method of compound 10.

[0056] Replace "1,3-dibromopropane" with "1,7-dibromoheptane", and prepare compound 16 according to the method of compound 10.

[0057] The structural formulas of the above compounds 1-16 are shown in Table 1.

[0058] Comparative Example 4 Dodecyl dimethyl benzyl ammonium chloride and dioctyl dimethyl ammonium chloride are mixed in a weight ratio of 1:1 to obtain a bactericide.

[0059] Comparative Examples 5-9 are commercially available quaternary ammonium salts of chitosan, benzalkonium chloride, didodecyl dimethyl ammonium chloride, benzethonium chloride, and Evomor, respectively.

[0060] Experiment 1 Perform a test on the killing of Helicobacter pylori in simulated gastric acid for compounds 1-12, and the results are shown in Table 2.

[0061] The method for the test on the killing of Helicobacter pylori in simulated gastric acid is as follows: Take each group of substances and place them in simulated gastric acid at 37°C for 2 h, and examine their killing effects on Helicobacter pylori. The concentrations of each group of substances are the same, all being 0.1% w / w.

[0062]

[0063] It can be seen from Table 2 that compounds 1-12 have a good effect on killing Helicobacter pylori, and the bactericidal rate reaches 99.9999% after 2 h at a concentration of 0.1% w / w.

[0064] Experiment 2 Perform a test on the killing of Helicobacter pylori in simulated gastric acid for compounds 1-12, and compare them with the substances in compounds 13-16 and Comparative Examples 4-9. The results are shown in Table 3.

[0065] The method for the test on the killing of Helicobacter pylori in simulated gastric acid is as follows: Take each group of substances and place them in simulated gastric acid at 37°C for 2 h. Dilute them in a two-fold manner starting from 0.1% w / w, and take the minimum concentration that reaches a bactericidal rate of 99.999% as the minimum bactericidal concentration of the compound. Compare the 2-h minimum bactericidal concentrations of compounds 1-12, compounds 13-16, and the substances in Comparative Examples 4-9 against Helicobacter pylori.

[0066]

[0067] As can be seen from Table 3, Compounds 1-12 have a good effect on killing Helicobacter pylori, and their minimum bactericidal concentration is much lower than that of Compounds 13-16 (Comparative Examples 1-3); it is also much lower than that of commercially available quaternary ammonium salts (Comparative Examples 4-9); this shows that the ability of Compounds 1-12 to kill Helicobacter pylori is significantly higher than that of Comparative Examples 1-9. From the comparison between Compounds 10-11 and Compounds 14-16, it can be seen that when sulfur element is not contained, even if the alkyl chain lengths of R1 and R2 in Compound 14 are the same as those in Compound 11, the effect of killing Helicobacter pylori will still be significantly reduced; while when sulfur element is contained, if the alkyl chain lengths of R1 and R2 in Compound 15 are too long or the chain length of R3 in Compound 16 is too long, the effect of killing Helicobacter pylori will be significantly reduced.

[0068] Experiment 3 In order to explore the mechanism of Substance a in killing Helicobacter pylori, since Compounds 1-12 have the same parent nucleus structure, the inventor selected Compound 11 from Compounds 1-12 as a representative, carried out quantum mechanics calculations and simulations on the binding force between Compound 11 and the cell membrane phospholipid bilayer, and used benzalkonium chloride as a control group. The results are as Figure 1-2 shown.

[0069] Figure 1 Fig. is the interaction diagram of benzalkonium chloride and the phospholipid bilayer.

[0070] Figure 2 Fig. is the interaction diagram of Compound 11 and the phospholipid bilayer.

[0071] The research results show that: in addition to the charge (long-range) interaction between benzalkonium chloride and phospholipid molecules, there is no obvious orbital (short-range) interaction. The energy decrease value of this system due to the interaction is 18.6 kcal / mol; In addition to the long-range charge interaction between Compound 11 and phospholipid molecules, there is an obvious interaction between the non-bonding orbital n of the sulfur atom and the P=O of the phospholipid molecule (as shown by the part circled by the circle in Figure 2 ), which causes the change of the head structure of the phospholipid molecule. The energy decrease value of this system due to the interaction is 19.1 kcal / mol, which is greater than that of benzalkonium chloride.

[0072] This shows that Compound 11 and the cell membrane structure not only have long-range interaction, but also can change the electronic structure of phospholipid molecules through orbital interaction, are more likely to interact with the phospholipid molecules of microorganisms, cause the deformation of phospholipid molecules, damage the bacterial cell membrane, and ultimately lead to the inactivation of bacteria.

[0073] In summary, the principle of substance a in killing Helicobacter pylori is as follows: the cationic group in the molecule of substance a adsorbs the negatively charged Helicobacter pylori through electrostatic force, hydrogen bond force, and hydrophobic binding, etc., aggregates on the cell wall, produces a chamber resistance effect, resulting in the inhibition of the growth of Helicobacter pylori and its death; at the same time, there is an obvious interaction between the non-bonding orbital n of the sulfur atom in the structure and the P=O of the phospholipid molecule, which causes a large deformation of the substance a molecule in the cell membrane of Helicobacter pylori, changes the cell membrane permeability, destroys the cell structure, and causes the dissolution and death of Helicobacter pylori cells. The orbitals have obvious interactions, resulting in a large deformation of the substance a molecule in the cell membrane of Helicobacter pylori, changing the cell membrane permeability, destroying the cell structure, and causing the dissolution and death of Helicobacter pylori cells.

[0074] Experiment 4 Compound 10, compound 11, and the degradation product of compound 10 (the structural formula of the degradation product is ) were selected to investigate their toxicological properties. Entrusted to the Anhui Provincial Center for Disease Control and Prevention, in accordance with the "Procedures and Methods for Toxicological Evaluation of Disinfectant Safety (GB / T38496.6.1 - 2020)" and the SOP system of the center, the Horn's method was used for the experiment.

[0075] The test results were as follows: judged according to the acute toxicity evaluation standard of the "Procedures and Methods for Toxicological Evaluation of Disinfectant Safety (GB / T38496.6.1 - 2020)", the acute oral toxicity tests (mice) of compound 10, compound 11, and the degradation product of compound 10 were all > 5000 mg / kg, all were actually non-toxic, had high safety, and had a low safety risk when applied to humans.

[0076] For the existing benzalkonium chloride, didodecyldimethylammonium chloride, and benzethonium chloride, the acute oral toxicity tests of their raw materials were all < 500 mg / kg, which were of medium toxicity. See Table 4 for details.

[0077]

[0078] Note: a) Extremely toxic: LD 50 < 1 mg / kg, b) Highly toxic: LD 50 = 1 - 50 mg / kg, c) Moderately toxic: LD 50 = 51 - 500 mg / kg, d) Slightly toxic: LD 50 = 501 - 5000 mg / kg, e) Non-toxic: LD 50 > 5000 mg / kg.

[0079] Experiment 5 Compound 10, Compound 13, and Evofimora were separately examined for their degradation rates. The specific examination method was as follows: Each of the above substances was separately prepared into a 1 wt% solution with pond water, and samples were taken regularly. The ratio of the peak integration areas of the trimethyl hydrogen at the quaternary ammonium salt end (the retention times of the trimethyl hydrogen at the quaternary ammonium salt end before and after degradation were different) before and after degradation was detected by nuclear magnetic resonance hydrogen spectrum, and the degradation rate was calculated. The results are as Figure 3 shown.

[0080] The structural formula of Evofimora is as follows: .

[0081] Figure 3 are the results of the degradation rates of Compound 10, Compound 13, and Evofimora.

[0082] From Figure 3 it can be seen that when there is a branched alkyl group beside the ester group, its degradation rate will be significantly reduced.

[0083] Entrusted the Guangdong Provincial Center for Microbiological Analysis and Testing, and referring to the "Procedures and Methods for Toxicological Evaluation of the Safety of Disinfectants (GB / T 38496.6.1 - 2020)", the acute oral toxicity test of Evofimora on mice was carried out. The results showed that: The acute oral toxicity of Evofimora in male mice LD 50 = 2710 mg / kg, belonging to low toxicity; the acute oral toxicity of Evofimora in female mice LD 50 = 1710 mg / kg, belonging to low toxicity; it can be seen that the toxicity of Evofimora is higher than that of Compound 10 (practically non-toxic).

[0084] The inventors found through research that: When there is a branched alkyl group (such as a methyl group) beside the ester group, it will reduce its degradation rate in the body, thereby increasing its toxicity; The present invention discovers that Substance a has a specific structure, can achieve efficient sterilization in the body while being able to degrade rapidly, and enables the degradation products to be rapidly excreted from the body, leaving no residue in the body. Moreover, both Substance a and its degradation products are practically non-toxic, with high safety, and the application to the human body has a low safety risk.

[0085] Example 4

[0086] A drug for treating Helicobacter pylori infection, the raw materials of which include, by weight: 0.05 g of Compound 10, 1 g of natural gum, 0.2 g of wax liquid, 0.5 g of xylitol, and 0.02 g of mint essence.

[0087] The preparation method of the above composition for treating Helicobacter pylori infection comprises the following steps: taking Compound 10, natural gum, xylitol, and mint essence, adding them into a blender, stirring and mixing evenly to obtain a paste, then heating it to 140 - 160 °C to make the paste expand, then adding wax liquid, stirring and mixing evenly to make it elastic and easy to chew in the mouth, then adding it into a mold to form, and then cooling and shaping to obtain the composition for treating Helicobacter pylori infection.

[0088] Example 5

[0089] A composition for treating Helicobacter pylori infection, the raw materials of which by weight include: 0.05 g of Compound 11, 1 g of glycerol resin, 0.2 g of wax liquid, 0.5 g of sorbitol, and 0.02 g of lemon essence.

[0090] The preparation method of the above composition for treating Helicobacter pylori infection comprises the following steps: taking Compound 11, glycerol resin, sorbitol, and mint essence, adding them into a blender, stirring and mixing evenly to obtain a paste, then heating it to 140 - 160 °C to make the paste expand, then adding wax liquid, stirring and mixing evenly to make it elastic and easy to chew in the mouth, then adding it into a mold to form, and then cooling and shaping to obtain the composition for treating Helicobacter pylori infection.

[0091] Example 6

[0092] A composition for treating Helicobacter pylori infection, the raw materials of which by weight include: 0.05 g of Compound 10, 1 g of sucrose, and 0.02 g of mint essence.

[0093] The preparation method of the above composition for treating Helicobacter pylori infection comprises the following steps: taking Compound 10, sucrose, and mint essence, adding them into a blender, stirring and mixing evenly, then heating it to 140 - 160 °C, adding it into a mold to form, and then cooling and shaping to obtain the composition for treating Helicobacter pylori infection.

[0094] Example 7

[0095] A composition for treating Helicobacter pylori infection, the raw materials of which by weight include: 0.05 g of Compound 11, 1 g of fructose, and 0.02 g of mint essence.

[0096] The preparation method of the above composition for treating Helicobacter pylori infection comprises the following steps: taking Compound 11, fructose, and mint essence, adding them into a blender, stirring and mixing evenly, then heating it to 140 - 160 °C, adding it into a mold to form, and then cooling and shaping to obtain the composition for treating Helicobacter pylori infection.

[0097] Patients with positive Helicobacter pylori test were selected, aged 30 - 45 years old. The Helicobacter pylori of the patients was detected by C13 breath test. Then, the drug of Example 4 above was used on an empty stomach 2 hours before breakfast, chewed until tasteless and then spit out, once a day for 2 consecutive days. After stopping the drug for 3 days, C13 breath test was carried out again. The test results are shown in Table 5.

[0098] Note: DOB < 4.0 is negative; DOB ≥ 4.0 is positive.

[0099] It can be seen from Table 5 that the composition of the present invention has a good therapeutic effect on Helicobacter pylori infection, and the treatment cycle is very short, only need to take it for two days, once a day.

[0100] For the above drug, it only needs to be used on an empty stomach 2 hours before breakfast and used continuously for two days to completely eliminate Helicobacter pylori in the body. The use cycle is very short, with little side effect on the human body and significant therapeutic effect. By selecting appropriate raw materials and cooperating with each other, the above drug can be used in the form of solid by containing or chewing in the mouth, so that the active ingredients can stay in the mouth for a long time, thus achieving comprehensive sterilization from the mouth to the stomach.

[0101] To sum up: The substance a of the present invention has a good bactericidal effect on Helicobacter pylori and can be used to treat Helicobacter pylori infection; when the substance a is used in a very small amount, it still has a good effect of killing Helicobacter pylori, and its bactericidal effect is much better than that of the existing quaternary ammonium salts.

[0102] The cationic group in the molecule of substance a adsorbs the negatively charged Helicobacter pylori body through electrostatic force, hydrogen bond force and hydrophobic binding, etc., aggregates on the cell wall, produces a chamber resistance effect, resulting in the growth inhibition and death of Helicobacter pylori; at the same time, there is an obvious interaction between the non-bonding orbital n of the sulfur atom in the structure and the P=O of the phospholipid molecule orbital, resulting in a large deformation of the substance a molecule in the cell membrane of Helicobacter pylori, changing the cell membrane permeability, destroying the cell structure, and causing the dissolution and death of Helicobacter pylori cells.

[0103] Moreover, due to its specific structure, substance a can achieve efficient sterilization in the body while being rapidly degraded, and the degradation products can be rapidly excreted from the body without residue in the body; and the acute oral toxicity tests (mice) of substance a and its common degradation products are both > 5000 mg / kg, both are actually non-toxic, with high safety, and the application to the human body has a low safety risk; the degradation products of substance a are fatty acid-like / fatty acids and dicationic choline, substance a will not be absorbed by the human body, has no side effects, will not make Helicobacter pylori produce drug resistance, and the treatment cycle of substance a for Helicobacter pylori infection is very short and the curative effect is fast.

[0104] As described above, it is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution and inventive concept of the present invention, makes equivalent substitutions or changes, and should be covered within the protection scope of the present invention.

Claims

1. A drug for treating Helicobacter pylori infection, characterized in that: The raw materials include: substance a and pharmaceutically acceptable excipients; the structural formula of substance a is shown in formula (I): Formula (I); Wherein, R1 and R2 are independently selected from one of C6-C12 alkyl groups, and X is Cl, Br, I or NO3 - One of; R3 is any one of the following structures: ； R4, R5, R6 and R7 are independently selected from one of C1-C4 saturated alkyl groups.

2. The drug for treating Helicobacter pylori infection according to claim 1, characterized in that: R4, R5, R6 and R7 are all methyl groups.

3. The drug for treating Helicobacter pylori infection according to claim 1, characterized in that: R1 and R2 are C8 saturated straight chain alkyl groups.

4. The drug for treating Helicobacter pylori infection according to claim 1, characterized in that: The structural formula of substance a is shown in one of formulas (II)-(III): Formula (II); Formula (III).

5. The drug for treating Helicobacter pylori infection according to claim 1, characterized in that: The dosage form of the drug is oral preparation, respiratory tract administration dosage form, skin administration dosage form, mucosal administration dosage form or cavity administration dosage form.

6. The drug for treating Helicobacter pylori infection according to claim 1, characterized in that: Pharmaceutically acceptable excipients include: at least one of solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integrators, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants, deflocculating agents, filter aids, and release retardants.

7. The drug for treating Helicobacter pylori infection according to claim 1, characterized in that: The raw materials include, by weight: 0.04-0.06 parts of active ingredients, 0-1 parts of gum, 0-0.5 parts of wax liquid, 1-0.5 parts of sweetener, and 0.01-0.03 parts of flavor; wherein the active ingredients are one or more of substance a.

8. The drug for treating Helicobacter pylori infection according to claim 7, characterized in that: Gum is a natural gum or glycerin resin.

9. The drug for treating Helicobacter pylori infection according to claim 7, characterized in that: When the gum is 0, the wax liquid is 0.

10. The drug for treating Helicobacter pylori infection according to claim 7, characterized in that: The preparation method thereof includes method A or method B; When the amount of the gum is 0, method A is used, comprising the following steps: taking the raw materials and mixing them uniformly, heating and melting the mixture to obtain a drug for treating Helicobacter pylori infection; When the weight of the gum is greater than 0, method B is adopted, which includes the following steps: taking the active ingredient, gum, sweetener, and flavor, mixing them evenly, heating and expanding them, and then adding the wax liquid and mixing them evenly to obtain a drug for treating Helicobacter pylori infection.

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