A medicine for treating Helicobacter pylori infection

Abstract

The present invention relates to the field of medical technology and discloses a drug for treating Helicobacter pylori infection. The drug comprises a substance A and a pharmaceutically acceptable excipient. The structural formula of substance A is shown in formula (I). Substance A has a strong bactericidal effect against Helicobacter pylori and can be used to treat and prevent Helicobacter pylori infection. Furthermore, substance A, due to its specific structure, can achieve efficient bactericidal effects in vivo while also rapidly degrading, with degradation products being rapidly excreted. Substance A and its common degradation products are practically non-toxic and highly safe. Substance A is not absorbed by the human body, has no side effects, and does not induce drug resistance in Helicobacter pylori.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a medicine for treating Helicobacter pylori infection. Background Art

[0002] Clinically, most patients with gastritis and gastric ulcers are infected with Helicobacter pylori. Severe cases can also cause chronic pharyngitis, oral ulcers and other diseases. The infection occurs in people of different races and regions in the world. The infection rate increases with age, about 80% in developing countries and about 40% in developed countries. The rate is slightly higher in men than in women, and higher in pets than in humans.

[0003] Currently, treatment options for Helicobacter pylori positive patients fall into two main categories: antibiotics, supplemented with acid suppressants (bismuth), and proton pump inhibitors. Two other antibiotics, amoxicillin and metronidazole, are the most commonly used. These medications require long treatment cycles, involve multiple medication types, and can have significant side effects.

[0004] Quaternary ammonium salt disinfectant belongs to cationic surfactant, has sterilization and decontamination effect, is generally used for the cleaning and disinfection of non-critical articles in the hospital, also can be used for hand disinfection, is dissolved in ethanol and can strengthen its bactericidal effect as skin disinfectant, and it is usually used in article or external disinfection.Because this class compound can change the permeability of bacterial cell membrane, often they are composited with other disinfectants to improve its bactericidal effect and sterilization speed.Although also have document disclose the quaternary ammonium salt of specific structure and can be coordinated with other materials for suppressing helicobacter pylori, it is generally in vitro or for the helicobacter pylori in the oral cavity, and its therapeutic effect still needs to improve. Summary of the Invention

[0005] Based on the technical problems existing in the background technology, the present invention proposes a drug for treating Helicobacter pylori infection. The substance a described in the present invention has a good bactericidal effect on Helicobacter pylori and can be used to treat and prevent Helicobacter pylori infection; and the specific structure of substance a can achieve efficient bactericidal effect in the body while being able to quickly degrade, and the degradation products can be quickly excreted from the body without residue in the body. Substance a and its common degradation products are actually non-toxic, highly safe, and have a low safety risk when used on the human body; substance a can be rapidly degraded in the body, and the degradation products are fatty acid-like / fatty acids and dicholine. 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, the raw materials of which include: substance a and pharmaceutically acceptable excipients; the structural formula of substance a is shown in formula (I): Formula (I);

[0007] Wherein, R1 and R2 are independently selected from one of C6-C12 alkyl groups, and X is Cl, Br, I or NO3 - One of the following;

[0008] R3 is any one of the following structures: ;

[0009] R4, R5, R6, and R7 are independently selected from one of C1-C4 saturated alkyl groups.

[0010] Preferably, R1 and R2 are independently selected from one of C6-C12 saturated straight-chain alkyl groups.

[0011] Preferably, R3 is .

[0012] Preferably, R4, R5, R6, and R7 are all methyl.

[0013] Preferably, R1 and R2 are C8 saturated straight-chain alkyl groups.

[0014] Preferably, the structural formula of substance a is as shown in one of formulas (II)-(III): Formula (II), which is named compound 10; Formula (III), and it was named Compound 11.

[0015] Preferably, the dosage form of the drug is an oral preparation, a respiratory tract administration dosage form, a skin administration dosage form, a mucosal administration dosage form or a cavity administration dosage form.

[0016] The oral preparations may be in the form of powders, tablets, granules, capsules, solutions, emulsions, suspensions, and the like.

[0017] The above-mentioned respiratory tract administration dosage form can be a spray, aerosol, powder spray, etc.

[0018] The dosage form for skin administration may be a solution for external use, a lotion, a liniment, an ointment, a plaster, a paste, a patch, etc.

[0019] The dosage form for mucosal administration can be eye drops, nasal drops, eye ointments, gargles, sublingual tablets, adhesive tablets, patches, etc.

[0020] The dosage forms for intracavitary administration can be suppositories, aerosols, effervescent tablets, drops and pills.

[0021] Preferably, the 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, defoaming agents, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants, deflocculants, filter aids, and release retardants.

[0022] The preparation method of the above-mentioned substance a can refer to the preparation method described in the patent with application number 202210890033.2 and invention name "A degradable gemini quaternary ammonium salt, its preparation method, and fungicide".

[0023] Preferably, 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 ingredient is one or more of compound a; more preferably, the active ingredient is one or more of compound 10 and compound 11.

[0024] Preferably, the raw materials include, by weight: 0.05 parts of active ingredients, 0-1 parts of gum, 0-0.5 parts of wax liquid, 1-0.5 parts of sweetener, and 0.02 parts of flavor.

[0025] Compared with the currently commonly used triple and quadruple antibiotics, which not only damage the stomach but also take a long time to take, the inventors found that compound a can still effectively kill Helicobacter pylori when used in a very small dose, and compound a can be degraded in a short time. The degradation products are fatty acid-like / fatty acid and dicholine. 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 needing to be taken for two days, once a day.

[0026] In addition, the acute oral toxicity test (mice) of compound a and its degradation products were both greater than 5000 mg / kg, indicating that they were practically non-toxic and highly safe.

[0027] Preferably, the gum is a natural gum or a glycerol resin.

[0028] Preferably, when the gum is 0, the wax liquid is 0.

[0029] Preferably, when the amount of gum is 0, the sweetener is one or more of sucrose and fructose.

[0030] Preferably, when the weight portion of the gum is greater than 0, the sweetener is one or more of sorbitol, mannitol, maltitol and xylitol.

[0031] Preferably, the flavor is one or more of mint flavor, peach flavor, and lemon flavor.

[0032] Preferably, the wax liquid is beeswax.

[0033] Preferably, when the content of the gum is 0, the method of using the composition for treating Helicobacter pylori infection is: orally dissolving the composition and then swallowing it.

[0034] Preferably, when the weight portion of the gum is greater than 0, the method of using the composition for treating Helicobacter pylori infection is: chewing until it has no taste and then spitting it out.

[0035] Compound a tastes bitter, and adding sweeteners improves the taste.

[0036] When chewing, compound a can be considered completely chewed out when there is no taste in the mouth, and can be spit out.

[0037] Since Helicobacter pylori primarily resides in the stomach, but also in the mouth and esophagus, comprehensive eradication from the mouth to the stomach is crucial. Existing treatments typically involve direct oral administration or swallowing, which only lasts a short time in the mouth and cannot fully eradicate the bacteria from the mouth to the stomach.

[0038] By combining various raw materials, the drug can be used in a solid form by oral dispensing or chewing, which allows the active ingredients to stay in the oral cavity for a longer period of time, thereby achieving comprehensive sterilization from the oral cavity to the stomach; the above-mentioned drug only needs to be used on an empty stomach 2 hours before breakfast, and continuous use for two days can completely eliminate Helicobacter pylori in the body. The use cycle is very short, the side effects on the human body are small, and the therapeutic effect is significant.

[0039] The gum, wax liquid, sweetener and essence of the present invention are all of medicinal grade.

[0040] Preferably, the preparation method thereof includes method A or method B;

[0041] When the amount of the gum is 0, method A is used, comprising the following steps: taking the raw materials, mixing them uniformly, heating and melting them, and mixing them uniformly to obtain a drug for treating Helicobacter pylori infection;

[0042] When the weight of the resin is greater than 0, method B is adopted, comprising the following steps: taking the active ingredient, resin, 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.

[0043] Preferably, in both method A and method B, the temperature is heated to 140-160°C.

[0044] 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 used in a very small amount, the substance a still has a good effect of killing Helicobacter pylori, and its bactericidal effect is far better than that of existing quaternary ammonium salts.

[0045] The research found that the cationic groups in the substance a molecule adsorbed negatively charged Helicobacter pylori through electrostatic force, hydrogen bond force and hydrophobic binding, and gathered on the cell wall, producing a chamber resistance effect, which inhibited the growth of Helicobacter pylori and caused its death. At the same time, the non-bonding orbital n of the sulfur atom in the structure and the P=O of the phospholipid molecule The orbitals have obvious interactions, causing the substance a molecule to produce a large deformation in the Helicobacter pylori cell membrane, changing the permeability of the cell membrane, destroying the cell structure, and causing the Helicobacter pylori cells to dissolve and die.

[0046] In addition, substance a has a specific structure, which allows it to achieve efficient sterilization in the body while being rapidly degraded, and the degradation products are quickly excreted from the body without leaving any residue in the body; and the acute oral toxicity test (on mice) of substance a and its common degradation products are all >5000 mg / kg, which are practically non-toxic, highly safe, and have a low safety risk when used on humans; the degradation products of substance a are fatty acid-like substances / fatty acids and dicholine, which will not be absorbed by the human body, have no side effects, and will not cause Helicobacter pylori to develop drug resistance, and substance a has a short treatment cycle for Helicobacter pylori infection and a fast efficacy. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 Diagram of the interaction between benzalkonium chloride and phospholipid molecular layer.

[0048] Figure 2 Diagram of the interaction between compound 11 and phospholipid molecular layer.

[0049] Figure 3 These are the degradation rate results of compound 10, compound 13, and Efumora. DETAILED DESCRIPTION

[0050] The technical solution of the present invention is described in detail below through specific embodiments.

[0051] Example 1

[0052] Compound 1-9 was prepared according to Example 1-9 in the invention patent application number 202210890033.2.

[0053] Example 2

[0054] Preparation of compounds 10 and 11

[0055] 0.02 mol of dimethylaminoethyl acrylate, 0.02 mol of 1-octanethiol, 0.01 mol of 1,3-dibromopropane and 10 mL of ethanol were added to a single-necked flask, and stirred at 60°C under normal pressure for 12 h. The solvent was then distilled off under reduced pressure, and the mixture was washed with acetone 2-3 times and freeze-dried to obtain compound 10.

[0056] Compound 11 was prepared according to the method of compound 10 by replacing 1,3-dibromopropane with 1,3-dichloropropane.

[0057] Example 3

[0058] Preparation of compound 12

[0059] A 1 wt% aqueous solution of compound 10 was added with silver nitrate and mixed (the molar ratio of compound 10 to silver nitrate was 1:2). The mixture was stirred at room temperature in the dark for 2 h, and the supernatant was collected by centrifugation and freeze-dried to obtain compound 12.

[0060] Comparative Example 1

[0061] Preparation of compound 13

[0062] Compound 13 was prepared by replacing "dimethylaminoethyl acrylate" with "dimethylaminoethyl methacrylate" and following the method for compound 10.

[0063] Comparative Example 2

[0064] Preparation of compound 14

[0065] 0.1 mol of lauric acid was added to a four-necked flask equipped with a magnetic stirrer, a thermometer was inserted, and after the fractionation apparatus was built, an oil bath was set at 70°C, and heating and stirring were performed until the lauric acid was completely melted. A certain amount of p-toluenesulfonic acid and hypophosphorous acid were then added as catalysts, and nitrogen was introduced for protection. 0.18 mol of N, N-dimethylethanolamine was added dropwise using a constant pressure funnel, and then the temperature was raised to 160°C and stirred for esterification reaction. The acid value was measured every hour during the reaction, and the reaction was stopped when the acid value did not change much after 7 hours of reaction. The product was cooled to room temperature, and a 50 wt% potassium hydroxide aqueous solution was added. The product was stirred at 75°C for 30 minutes to remove impurities, and then the product was transferred to a pear-shaped separating funnel. CCl4 was added for extraction, and the product was allowed to stand for 12 hours. The lower layer of liquid was removed and the CCl4 was removed by rotary evaporation to obtain an intermediate.

[0066] The intermediate, 1,3-dichloropropane, and isopropanol were added sequentially to a three-necked flask equipped with a thermometer and a reflux apparatus. After stirring at room temperature for 15 minutes, the initial amine value was measured. The system temperature was raised to 100°C and refluxed with stirring for 6 hours, during which the amine value was measured every hour. After the reaction was completed, the isopropanol was evaporated under reduced pressure to obtain a crude product. The product was recrystallized from a mixed solvent of isopropanol and ethyl acetate to obtain compound 14.

[0067] Comparative Example 3

[0068] Preparation of compounds 15 and 16

[0069] Compound 15 was prepared by replacing "1-octanethiol" with "tetradecathiol" according to the method of compound 10.

[0070] Compound 16 was prepared by replacing "1,3-dibromopropane" with "1,7-dibromoheptane" according to the method of compound 10.

[0071] The structural formulas of the above compounds 1-16 are shown in Table 1.

[0072] Comparative Example 4

[0073] Dodecyldimethylbenzyl ammonium chloride and dioctyldimethylammonium chloride are mixed in a weight ratio of 1:1 to obtain a fungicide.

[0074] Comparative Examples 5-9 are commercially available chitosan quaternary ammonium salt, benzalkonium chloride, didecyldimethylammonium chloride, benzethonium chloride, and Efumora.

[0075] Test 1

[0076] Compounds 1-12 were tested for killing Helicobacter pylori in simulated gastric acid. The results are shown in Table 2.

[0077] The method of the Helicobacter pylori killing test in simulated gastric acid is as follows: each group of substances is placed in simulated gastric acid at 37°C for 2 hours to examine its killing effect on Helicobacter pylori. The concentration of each group of substances is the same, 0.1% w / w.

[0078]

[0079] It can be seen from Table 2 that compounds 1-12 have a good effect of killing Helicobacter pylori, and the sterilization rate reaches 99.9999% in 2 hours at a concentration of 0.1% w / w.

[0080] Test 2

[0081] Compounds 1-12 were subjected to a Helicobacter pylori killing test in simulated gastric acid and compared with compounds 13-16 and the substances in comparative examples 4-9. The results are shown in Table 3.

[0082] The method of the Helicobacter pylori killing test in simulated gastric acid is as follows: take each group of substances and place them in simulated gastric acid at 37°C for 2 hours, and dilute them in multiples starting from 0.1% w / w. The minimum concentration that achieves a bactericidal rate of 99.999% is the minimum bactericidal concentration of the compound, and the 2-hour minimum bactericidal concentrations of compounds 1-12, compounds 13-16, and the substances in comparative examples 4-9 against Helicobacter pylori are compared.

[0083]

[0084] As can be seen from Table 3, compounds 1-12 have a good effect of killing Helicobacter pylori, and their minimum bactericidal concentrations are much lower than those of compounds 13-16 (Comparative Examples 1-3) and much lower than those of existing commercially available quaternary ammonium salts (Comparative Examples 4-9). This indicates that the ability of compounds 1-12 to kill Helicobacter pylori is significantly higher than that of comparative examples 1-9.

[0085] A comparison of compounds 10-11 and compounds 14-16 shows that: when there is no sulfur element, even if the alkyl chain lengths of R1 and R2 in compound 14 are the same as those in compound 11, its effect in killing Helicobacter pylori will still be greatly reduced; and when there is sulfur element, the alkyl chain lengths of R1 and R2 in compound 15 are too long, and the chain length of R3 in compound 16 is too long, and their effects in killing Helicobacter pylori will be greatly reduced.

[0086] Test 3

[0087] In order to explore the mechanism of substance a in killing Helicobacter pylori, the inventors selected compound 11 from compounds 1-12 as a representative because compounds 1-12 have the same core structure. The binding force of compound 11 with the cell membrane phospholipid bilayer was calculated and simulated by quantum mechanics, and benzalkonium chloride was used as a control group. The results are as follows Figure 1-2 shown.

[0088] Figure 1 Diagram of the interaction between benzalkonium chloride and phospholipid molecular layer.

[0089] Figure 2 Diagram of the interaction between compound 11 and phospholipid molecular layer.

[0090] The results showed that, in addition to charge (long-range) interactions, there were no significant orbital (short-range) interactions between benzalkonium chloride and phospholipid molecules. The energy drop of the system due to the interaction was 18.6 kcal / mol.

[0091] In addition to the long-range charge interaction between compound 11 and phospholipid molecules, the non-bonding orbital n of the sulfur atom and the P=O of the phospholipid molecule The orbitals have significant interactions (e.g. Figure 2The circled part in the figure causes the head structure of the phospholipid molecule to change. The energy of the system decreases by 19.1 kcal / mol due to the interaction, which is greater than that of benzalkonium chloride.

[0092] This indicates that compound 11 not only has long-range interactions with the cell membrane structure, but can also change the electronic structure of phospholipid molecules through orbital interactions, making it easier to interact with the phospholipid molecules of microorganisms, causing the phospholipid molecules to deform, destroying the bacterial cell membrane, and ultimately causing the bacteria to inactivate.

[0093] In summary, the principle of substance a killing Helicobacter pylori is as follows: the cationic groups in the substance a molecule adsorb negatively charged Helicobacter pylori through electrostatic force, hydrogen bond force and hydrophobic binding, and aggregate on the cell wall, producing a chamber resistance effect, which inhibits the growth of Helicobacter pylori and causes its death; at the same time, the non-bonding orbital n of the sulfur atom in the structure and the P=O of the phospholipid molecule The orbitals have obvious interactions, causing the substance a molecule to produce a large deformation in the Helicobacter pylori cell membrane, changing the permeability of the cell membrane, destroying the cell structure, and causing the Helicobacter pylori cells to dissolve and die.

[0094] Test 4

[0095] Select compound 10, compound 11, and the degradation product of compound 10 (the structural formula of the degradation product is ), to examine its toxicological properties, the Anhui Provincial Center for Disease Control and Prevention was commissioned to conduct the test using the Horn method in accordance with the "Procedures and Methods for Safety Toxicological Evaluation of Disinfectants (GB / T38496.6.1-2020)" and the control center's SOP system.

[0096] The test results are: According to the acute toxicity evaluation standards of "(GB / T38496.6.1-2020) Procedures and Methods for Toxicological Evaluation of Safety of Disinfectants", the acute oral toxicity tests (mice) of compound 10, compound 11, and the degradation products of compound 10 are all >5000 mg / kg, which are actually non-toxic, highly safe, and have low safety risks for human use.

[0097] The acute oral toxicity test results of existing raw materials for benzalkonium chloride, didecyldimethylammonium chloride, and benzethonium chloride are all less than 500 mg / kg, indicating moderate toxicity. See Table 4 for details.

[0098]

[0099] Note: a) Extremely toxic: LD 50 <1mg / kg, b) extremely toxic: LD 50 =1~50mg / kg, c) Moderate toxicity: LD 50=51~500mg / kg, d) Low toxicity: LD 50 =501~5000mg / kg, e) non-toxic: LD 50 >5000mg / kg.

[0100] Test 5

[0101] Compound 10, Compound 13, and Efumora were used to investigate their degradation rates. The specific investigation method was as follows: each of the above substances was prepared into a 1 wt% solution with pond water. Samples were taken regularly and the ratio of the peak integrated area before and after degradation of the quaternary ammonium salt terminal trimethyl hydrogen (the retention time of the quaternary ammonium salt terminal trimethyl hydrogen before and after degradation was detected by nuclear magnetic hydrogen spectrum was calculated to calculate the degradation rate. The results are shown in Figure 2. Figure 3 shown.

[0102] The structural formula of Evmora is shown below: .

[0103] Figure 3 These are the degradation rate results of compound 10, compound 13, and Efumora.

[0104] Depend on Figure 3 It can be seen that when the ester group contains a branched alkyl group, its degradation rate will be greatly reduced.

[0105] The Guangdong Provincial Microbiological Analysis and Testing Center was commissioned to conduct an acute oral toxicity test on Efumora in mice in accordance with the "Procedures and Methods for Toxicological Evaluation of Disinfectant Safety (GB / T38496.6.1-2020)". The results showed that the acute oral toxicity of Efumora in mice was LD50 in males. 50 =2710 mg / kg, low toxicity; female LD 50 =1710 mg / kg, which is low toxicity; it can be seen that the toxicity of Efumora is higher than that of compound 10 (actually non-toxic).

[0106] The inventors have found through research that when the ester group contains a branched alkyl group (such as a methyl group), its degradation rate in the body will be reduced, thereby increasing its toxicity;

[0107] The present invention discovered that substance a has a specific structure, which can achieve efficient sterilization in the body while being able to degrade rapidly, and the degradation products are quickly excreted from the body without any residue in the body. In addition, substance a and its degradation products are actually non-toxic and highly safe, and the safety risk of application to the human body is low.

[0108] Example 4

[0109] A medicine for treating Helicobacter pylori infection, comprising the following raw materials 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.

[0110] The preparation method of the above-mentioned composition for treating Helicobacter pylori infection comprises the following steps: adding compound 10, natural gum, xylitol, and mint essence into a blender, stirring and mixing to obtain a paste, then heating to 140-160° C. to expand the paste, then adding wax liquid, stirring and mixing to make it elastic and easy to chew in the mouth, then adding it into a mold to form it, and then cooling and setting it to obtain a composition for treating Helicobacter pylori infection.

[0111] Example 5

[0112] A composition for treating Helicobacter pylori infection, comprising the following raw materials in parts by weight: 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.

[0113] The preparation method of the above-mentioned composition for treating Helicobacter pylori infection comprises the following steps: adding compound 11, glycerol resin, sorbitol, and mint essence into a blender, stirring and mixing to obtain a paste, then heating to 140-160° C. to expand the paste, then adding wax liquid, stirring and mixing to make it elastic and easy to chew in the mouth, then adding it into a mold to form it, and then cooling and setting it to obtain a composition for treating Helicobacter pylori infection.

[0114] Example 6

[0115] A composition for treating Helicobacter pylori infection, comprising the following raw materials by weight: 0.05 g of compound 10, 1 g of sucrose, and 0.02 g of mint essence.

[0116] The preparation method of the above-mentioned composition for treating Helicobacter pylori infection comprises the following steps: adding compound 10, sucrose and mint essence into a blender, stirring and mixing, then heating to 140-160° C., adding into a mold for forming, and then cooling and setting to obtain a composition for treating Helicobacter pylori infection.

[0117] Example 7

[0118] A composition for treating Helicobacter pylori infection, comprising the following raw materials by weight: 0.05 g of compound 11, 1 g of fructose, and 0.02 g of mint essence.

[0119] The preparation method of the above-mentioned composition for treating Helicobacter pylori infection comprises the following steps: adding compound 11, fructose and mint essence into a blender, stirring and mixing, then heating to 140-160° C., adding into a mold for forming, and then cooling and setting to obtain a composition for treating Helicobacter pylori infection.

[0120] Patients aged 30-45 who tested positive for Helicobacter pylori were selected and tested for Helicobacter pylori using a C13 breath test. The patients then took the medication described in Example 4 on an empty stomach 2 hours before breakfast, chewed it until it was tasteless, and then spitted it out, once daily for 2 consecutive days. Three days after stopping the medication, the C13 breath test was repeated. The test results are shown in Table 5.

[0121] Note: DOB < 4.0 is negative and DOB ≥ 4.0 is positive.

[0122] 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 needing to be taken for two days, once a day.

[0123] The above-mentioned drug only needs to be taken on an empty stomach 2 hours before breakfast for two consecutive days to completely eliminate Helicobacter pylori in the body. The use period is very short, the side effects to the human body are minimal, and the therapeutic effect is significant. By selecting suitable raw materials and combining them together, the above-mentioned drug can be used in a solid form by oral confinement or chewing, which allows the active ingredients to remain in the mouth for a longer time, thereby achieving comprehensive sterilization from the mouth to the stomach.

[0124] In summary:

[0125] 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 used in a very small amount, the substance a still has a good effect of killing Helicobacter pylori, and its bactericidal effect is far better than that of existing quaternary ammonium salts.

[0126] The cationic groups in the substance a molecule adsorb negatively charged Helicobacter pylori through electrostatic forces, hydrogen bonding forces and hydrophobic binding, and aggregate on the cell wall, producing a chamber resistance effect, which inhibits the growth of Helicobacter pylori and causes its death. At the same time, the non-bonding orbital n of the sulfur atom in the structure and the P=O of the phospholipid molecule The orbitals have obvious interactions, causing the substance a molecule to produce a large deformation in the Helicobacter pylori cell membrane, changing the permeability of the cell membrane, destroying the cell structure, and causing the Helicobacter pylori cells to dissolve and die.

[0127] In addition, substance a has a specific structure, which allows it to achieve efficient sterilization in the body while being rapidly degraded, and the degradation products are quickly excreted from the body without leaving any residue in the body; and the acute oral toxicity test (on mice) of substance a and its common degradation products are all >5000 mg / kg, which are practically non-toxic, highly safe, and have a low safety risk when used on humans; the degradation products of substance a are fatty acid-like substances / fatty acids and dicholine, which will not be absorbed by the human body, have no side effects, and will not cause Helicobacter pylori to develop drug resistance, and substance a has a short treatment cycle for Helicobacter pylori infection and a fast efficacy.

[0128] The above description is only a preferred specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with the technical field, within the technical scope disclosed by the present invention, who makes equivalent replacements or changes based on the technical solution and inventive concept of the present invention, should be covered by the scope of protection of the present invention.

Claims

1. Use of substance a in the preparation of a medicament for treating Helicobacter pylori infection, characterized in that: The structural formula of substance a is shown in one of formulas (II)-(III): .

2. The use according to claim 1, characterized in that The raw materials of the drug for treating Helicobacter pylori infection 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.

3. The use according to claim 2, characterized in that Gum is a natural gum or glycerin resin.

4. The use according to claim 2, characterized in that When the gum is 0, the wax liquid is 0.

5. The use according to claim 2, characterized in that: The method for preparing the drug for treating Helicobacter pylori infection 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, mixing them uniformly, heating and melting them, and mixing them uniformly to obtain a drug for treating Helicobacter pylori infection; When the weight of the resin is greater than 0, method B is adopted, comprising the following steps: taking the active ingredient, resin, 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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