A pharmaceutical composition for efficiently eradicating Helicobacter pylori, its preparation method and its application

Abstract

The present invention relates to a pharmaceutical composition for efficiently eradicating Helicobacter pylori. The pharmaceutical composition comprises 830-1150 parts by weight of chicken egg yolk immunoglobulin, 230-360 parts by weight of whey protein, 230-360 parts by weight of barley grass extract, 8-100 parts by weight of probiotics, 30-700 parts by weight of amino acids, 50-100 parts by weight of turmeric extract, and a pharmaceutically acceptable carrier. The number of viable probiotics in a unit dose of the composition is ≥1×10 8 The present invention can effectively eradicate Helicobacter pylori, significantly improve gastrointestinal function, significantly reduce the recurrence rate of Helicobacter pylori infection in subjects, and has the advantages of being safe, effective, and having no side effects.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and in particular relates to a pharmaceutical composition for efficiently eradicating Helicobacter pylori, a preparation method thereof, and an application thereof. Background Art

[0002] Helicobacter pylori (Hp) is a spiral-shaped, microanaerobic bacterium first detected in patients with chronic active gastritis in 1983. It adheres to the gastric mucosa and intercellular spaces. The H. pylori infection rate in my country exceeds 50%, affecting individuals ranging in age from 6 months to 70 years, primarily in the middle-aged and elderly. Children are also susceptible to H. pylori infection, with the infection rate increasing by 0.5%-1% annually. Therefore, awareness of H. pylori infection prevention during childhood is crucial. Once infected with H. pylori, the body is generally difficult to eliminate. Most infected individuals develop lifelong and recurrent infections, leading to gastritis, chronic gastritis, peptic ulcers, atrophic gastritis, gastric precancerous lesions, lymphoproliferative gastric lymphoma, and gastric cancer. Chronic gastritis has the highest incidence rate, with patients experiencing varying degrees of bloating, acid reflux, belching, anemia, bad breath, and intestinal metaplasia. Studies have confirmed that intestinal metaplasia of the gastric mucosa is closely related to gastric cancer. In 2017, the World Health Organization's International Agency for Research on Cancer classified Helicobacter pylori as a Class 1 carcinogen.

[0003] Helicobacter pylori is contagious. Humans are the only source of infection for Helicobacter pylori, and Helicobacter pylori can reflux into the oral cavity through the stomach and esophagus. Saliva becomes the main transmission medium for Helicobacter pylori. Currently, the international standard triple therapy (STT, which is a combination of bismuth, metronidazole and either tetracycline or amoxicillin) is widely used to treat Helicobacter pylori infection. However, triple therapy destroys intestinal flora and kills probiotics, and with the abuse of antibiotics, the resistance of Helicobacter pylori increases, and the eradication rate of Helicobacter pylori drops to 80%. As a result, the recurrence rate and adverse reaction rate of this therapy remain high. It has defects such as antibiotic resistance, large side effects, and high recurrence rate, and is not suitable for the treatment of infected children.

[0004] Anti-Helicobacter pylori chicken egg yolk immunoglobulin (IgY) is a Helicobacter pylori inhibitor. It is produced by immunizing laying hens with either inactivated or attenuated Helicobacter pylori or Helicobacter pylori surface antigens, resulting in the presence of anti-Helicobacter pylori immunoglobulin in their egg yolk. IgY exhibits excellent stability at temperatures ≤65°C and a pH range of 4-11, and exhibits excellent resistance to heat, acid, alkali, and hyperosmotic temperatures. It also maintains activity in a 60% high-concentration sucrose solution.

[0005] Whey protein is a food nutrient enhancer extracted from cow's milk. It has high affinity and can compete with bacteria for iron ions in the body, inhibit the growth of Helicobacter pylori, and gradually eliminate Helicobacter pylori and reverse the degree of gastritis. It has a good repair effect on gastric mucosal damage caused by Hp.

[0006] Extracted from young barley sprouts, chlorophyll is rich in essential nutrients, including minerals, amino acids, enzymes, vitamins, flavonoids, soluble dietary fiber, natural chlorophyll, and hexacosanol. It comprehensively balances cellular nutrition, regulates the body's pH, invigorates cells, accelerates self-repair, enhances immunity, strengthens the body's immune system, and aids recovery from illness. Chlorophyll has a potent anti-inflammatory effect, promoting granulation and wound healing in ulcers, protecting the stomach lining, and resisting pepsin, making it a promising treatment for chronic gastritis.

[0007] Literature 1 (Li Zhi et al., Observation on the efficacy of live Bacillus coagulans tablets in the rescue treatment of Helicobacter pylori with bismuth-containing quadruple regimen, "Drug Efficacy and Observation", late January 2019) disclosed that live Bacillus coagulans tablets combined with bismuth-containing quadruple regimen in the rescue treatment of Helicobacter pylori can improve the eradication rate of Helicobacter pylori after initial treatment failure and reduce adverse reactions, which is worthy of clinical promotion. Studies have confirmed that Bacillus coagulans (viable count ≥1.0*10 8 It has the following beneficial effects in the gastrointestinal tract: first, it reproduces in large quantities, improves intestinal flora and gastrointestinal motility, competitively affects the colonization and survival of Hp in the gastric mucosa, promotes the effective recovery of the intestinal mucosa, maintains cell stability, and enhances the ability of the intestinal mucosa to resist pathogens and toxins; second, it decomposes polysaccharides to produce oligosaccharides, promotes the growth of beneficial bacteria such as bifidobacteria, inhibits the growth of harmful bacteria, and maintains the balance of digestive tract microecology; third, it produces a large amount of prebiotic factors, antibacterial coagulants, lactic acid, amino acids, vitamins, antibacterial substances, digestive enzymes, etc. in the body, absorbs harmful substances such as ammonia and hydrogen sulfide produced by Hp It has the functions of improving gastrointestinal nutrition and increasing nutrient absorption; fourthly, it ferments glucose, sucrose, maltose, mannitol and other sugars, secretes a large amount of L-lactic acid and lowers the pH of the gastrointestinal tract, effectively inhibits the effects of pathogenic bacteria (such as Helicobacter pylori) on the absorption and utilization of the digestive tract, and promotes the gastrointestinal absorption and utilization of nutrients; fifthly, it has anti-inflammatory effects, promotes the regeneration of granulation tissue in ulcer wounds, and accelerates the healing of ulcer wounds; sixthly, it promotes the phagocytic function of human mononuclear macrophages, enhances the body's immunity and humoral immunity, improves the nonspecific immunity and specific immunity and immune balance of the gastrointestinal tract, and effectively inhibits Helicobacter pylori.

[0008] CN106075436B discloses a non-antibiotic oral preparation for Helicobacter pylori, which is composed of chlorophyll from chicken egg yolk immunoglobulin, lactoferrin, and chlorophyll from barley green. This preparation treats Helicobacter pylori infection without the use of antibiotics, improves cure rates, eliminates the potential for pathogens to develop drug resistance and relapse after recovery, and reduces the incidence of adverse reactions. However, this preparation has a slow effect on improving symptoms such as indigestion, acid reflux, belching, bloating, anemia, bad breath, and intestinal metaplasia caused by Helicobacter pylori, and still needs to improve cure rates and reduce relapse rates. For this reason, there is an urgent need to develop a pharmaceutical composition that can efficiently eradicate Helicobacter pylori, improve the eradication rate of Helicobacter pylori, reduce relapse rates, and reduce the incidence of adverse reactions, so as to significantly improve the gastrointestinal discomfort symptoms caused by Helicobacter pylori. Summary of the Invention

[0009] The present invention aims to provide a pharmaceutical composition for efficiently eradicating Helicobacter pylori, comprising 830-1150 parts by weight of chicken egg yolk immunoglobulin, 230-360 parts by weight of whey protein, 230-360 parts by weight of barley grass extract, 8-100 parts by weight of probiotics, 30-700 parts by weight of amino acids, 50-100 parts by weight of turmeric extract, and a pharmaceutically acceptable carrier, wherein the number of viable probiotics in a unit dose of the composition is ≥1×10 8 CFU / g, the probiotics are selected from any one or a combination of Bacillus coagulans, Saccharomyces boulardii, Lactobacillus, Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium lactis, Bacillus rhamnosus, yeast, probiotic spore bacteria, Clostridium butyricum, Lactobacillus, Bifidobacterium, and Actinomycetes, and the amino acids are selected from any one or a combination of aspartic acid, threonine, serine, glutamic acid, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, γ-aminobutyric acid, histidine, tryptophan, lysine, arginine, proline, glutamine, and lysine hydrochloride.

[0010] In a preferred technical solution of the present invention, the composition contains 840-1100 parts by weight of chicken egg yolk immunoglobulin, 235-355 parts by weight of whey protein, 235-355 parts by weight of barley grass extract, 9-60 parts by weight of probiotics, 35-500 parts by weight of amino acids and 55-95 parts by weight of turmeric extract.

[0011] In a preferred technical solution of the present invention, the composition contains 889 parts by weight of chicken egg yolk immunoglobulin, 240 parts by weight of whey protein, 240 parts by weight of barley grass extract, 30 parts by weight of Bacillus coagulans, 100 parts by weight of γ-aminobutyric acid and 75 parts by weight of turmeric extract.

[0012] In a preferred technical solution of the present invention, the composition contains 1000 parts by weight of chicken yolk immunoglobulin, 300 parts by weight of whey protein, 300 parts by weight of barley grass extract, 10 parts by weight of Bacillus coagulans, 40 parts by weight of glutamine and 60 parts by weight of turmeric extract.

[0013] In a preferred technical solution of the present invention, the composition contains 850 parts by weight of chicken egg yolk immunoglobulin, 350 parts by weight of whey protein, 350 parts by weight of barley grass extract, 50 parts by weight of Bacillus coagulans, 200 parts by weight of lysine hydrochloride and 90 parts by weight of turmeric extract.

[0014] In the preferred technical solution of the present invention, the probiotics in the composition are Bacillus coagulans, and the number of viable bacteria is ≥ 1×10 8 CFU / g, preferably viable bacteria count ≥1×10 10 CFU / g, preferably ≥1×10 11 CFU / g.

[0015] In a preferred technical solution of the present invention, the pharmaceutically acceptable carrier is selected from any one or a combination of fillers, disintegrants, binders, solubilizers, antioxidants, lubricants, acid-base regulators, preservatives, dispersants, emulsifiers, wetting agents, flavoring agents, fragrance agents, dietary fiber, and nutritional enhancers.

[0016] In a preferred technical solution of the present invention, the dietary fiber is selected from any one or a combination of non-starch polysaccharides, plant polysaccharides, microbial polysaccharides, resistant oligosaccharides, and resistant starch; preferably, the dietary fiber is selected from any one or a combination of cellulose, hemicellulose, pectin, guar gum, xanthan gum, fructooligosaccharides, galacto-oligosaccharides, resistant dextrin, and resistant starch.

[0017] In the preferred technical solution of the present invention, the nutritional enhancer is selected from amino acids and nitrogen-containing compounds, vitamins, and minerals. Preferably, the nutritional enhancer is selected from whole milk powder, L-lysine hydrochloride, L-lysine aspartate, L-carnitine, taurine, vitamin A, vitamin D, vitamin E, vitamin K, vitamin C, vitamin B, calcium citrate, calcium gluconate, calcium carbonate, ferrous lactate, ferrous gluconate, zinc gluconate, zinc lactate, and zinc sulfate, or any one or a combination thereof.

[0018] In a preferred technical solution of the present invention, the filler is selected from any one of lactose, powdered sugar, dextrin, starch or its derivatives, cellulose, microcrystalline cellulose, sodium carboxymethyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, calcium sulfate, calcium phosphate, calcium hydrogen phosphate, precipitated calcium carbonate, sorbitol, glycine, sodium carboxymethyl starch, sodium starch glycolate, pregelatinized starch, modified starch, hydroxypropyl starch, and corn starch, or a combination thereof.

[0019] In a preferred technical solution of the present invention, the disintegrant is selected from any one of starch, sodium carboxymethyl starch, sodium starch glycolate, pregelatinized starch, modified starch, hydroxypropyl starch, corn starch, polyvinyl pyrrolidone, cross-linked polyvinyl pyrrolidone, and microcrystalline cellulose, or a combination thereof.

[0020] In a preferred technical solution of the present invention, the binder is selected from any one of syrup, gum arabic, gelatin, sorbitol, tragacanth gum, cellulose, microcrystalline cellulose, sodium carboxymethyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, gelatin slurry, syrup, starch, sodium carboxymethyl starch, sodium starch glycolate, pregelatinized starch, modified starch, hydroxypropyl starch, corn starch, starch slurry, and polyvinyl pyrrolidone, or a combination thereof.

[0021] In a preferred technical solution of the present invention, the lubricant is selected from any one of micropowdered silica gel, magnesium stearate, talc, aluminum hydroxide, boric acid, hydrogenated vegetable oil, and polyethylene glycol, or a combination thereof.

[0022] In a preferred technical solution of the present invention, the wetting agent is selected from any one of sodium lauryl sulfate, water, alcohol, or a combination thereof.

[0023] In a preferred technical solution of the present invention, the emulsifier is selected from any one of polysorbate 80, sorbitan monophosphate, Pluronic F-68, lecithin, and soybean lecithin, or a combination thereof.

[0024] In a preferred technical solution of the present invention, the acid-base regulator is selected from any one of citric acid, sodium citrate, malic acid, sodium malate, hydrochloric acid, acetic acid, sodium acetate, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, carbonic acid, sodium carbonate, sulfonic acid, sodium sulfonate, glutamic acid, tartaric acid, sodium tartrate, lactic acid, sodium lactate, fumaric acid, sodium fumarate, itaconic acid, ascorbic acid, sodium ascorbate, nicotinic acid, sodium nicotinate, fumaric acid, α-ketoglutaric acid, fruit acid, sodium fruit acid, acetic acid, oxalic acid, succinic acid, carbon dioxide, citric acid, and sodium citrate, or a combination thereof.

[0025] In a preferred technical solution of the present invention, the concentration of the acid-base regulator is 0.5-8 mol / L, preferably 0.8-6 mol / L, and more preferably 1-5 mol / L.

[0026] In a preferred technical solution of the present invention, the solubilizer is selected from any one of glycerol and Tween-80 or a combination thereof.

[0027] In a preferred technical solution of the present invention, the antioxidant is selected from any one of potassium sorbate, sodium sulfite, sodium bisulfite, sodium metabisulfite, and dibutyl benzoate, or a combination thereof.

[0028] In a preferred technical solution of the present invention, the composition optionally contains 0.01%-0.2% (w / w) of a preservative, and the preservative is selected from any one of potassium sorbate, sodium benzoate, ethylparaben, methylparaben, calcium propionate, sodium lactate, or a combination thereof.

[0029] In a preferred technical solution of the present invention, the composition contains 0.03%-0.15% (w / w), preferably 0.05%-0.1% (w / w), of preservatives.

[0030] In a preferred technical solution of the present invention, the composition contains a flavoring agent, and the flavoring agent is selected from any one of sucrose, simple syrup, mannitol, sorbitol, saccharin sodium, aspartame, sucralose, steviol glycosides, glucose, xylitol, and maltitol, or a combination thereof.

[0031] In a preferred technical solution of the present invention, the flavoring agent is selected from any one of spices, edible spices, and edible flavors, or a combination thereof.

[0032] In the preferred technical solution of the present invention, the composition of the present invention can be in various dosage forms well known in the art, and can be prepared using conventional formulation techniques in the art.

[0033] In a preferred technical solution of the present invention, the composition is an oral preparation.

[0034] In the preferred technical solution of the present invention, the oral preparation is selected from any one of oral liquid preparations, syrups, suspensions, tablets, capsules, granules, pills, powders, dripping pills, mixtures, dews, effervescents, pastes, emulsions, teas, compressed candies, and chewable tablets.

[0035] Another object of the present invention is to provide a compressed candy for efficiently eradicating Helicobacter pylori, wherein the compressed candy contains 830-1150 parts by weight of chicken egg yolk immunoglobulin, 230-360 parts by weight of whey protein, 230-360 parts by weight of barley grass extract, 8-100 parts by weight of probiotics, 30-700 parts by weight of amino acids, 50-100 parts by weight of turmeric extract, 2700-3300 parts by weight of sorbitol, 2700-3400 parts by weight of whole milk powder, 900-1500 parts by weight of resistant dextrin, 280-330 parts by weight of ginger powder, 350-400 parts by weight of oligofructose, 280-340 parts by weight of xylitol, and 10-80 parts by weight of magnesium stearate, wherein the number of viable probiotic bacteria in a unit dose of the composition is ≥1×10 8CFU / g, the probiotics are selected from any one or a combination of Bacillus coagulans, Saccharomyces boulardii, Lactobacillus, Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium lactis, Bacillus rhamnosus, yeast, probiotic spore bacteria, Clostridium butyricum, Lactobacillus, Bifidobacterium, and Actinomycetes, and the amino acids are selected from any one or a combination of aspartic acid, threonine, serine, glutamic acid, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, γ-aminobutyric acid, histidine, tryptophan, lysine, arginine, proline, glutamine, and lysine hydrochloride.

[0036] In a preferred technical solution of the present invention, the compressed candy contains 840-1100 parts by weight of chicken egg yolk immunoglobulin, 235-355 parts by weight of whey protein, 235-355 parts by weight of barley grass extract, 9-60 parts by weight of probiotics, 35-500 parts by weight of amino acids, 55-95 parts by weight of turmeric extract, 2750-3250 parts by weight of sorbitol, 2750-3350 parts by weight of whole milk powder, 1000-1450 parts by weight of resistant dextrin, 285-320 parts by weight of ginger powder, 355-395 parts by weight of fructooligosaccharide, 285-335 parts by weight of xylitol and 15-75 parts by weight of magnesium stearate.

[0037] In a preferred technical solution of the present invention, the compressed candy contains 889 parts by weight of chicken egg yolk immunoglobulin, 240 parts by weight of whey protein, 240 parts by weight of barley grass extract, 30 parts by weight of Bacillus coagulans, 100 parts by weight of γ-aminobutyric acid, 75 parts by weight of turmeric extract, 3125 parts by weight of sorbitol, 3000 parts by weight of whole milk powder, 1250 parts by weight of resistant dextrin, 313 parts by weight of ginger powder, 375 parts by weight of oligofructose, 313 parts by weight of xylitol and 50 parts by weight of magnesium stearate.

[0038] In a preferred technical solution of the present invention, the compressed candy contains 1000 parts by weight of chicken egg yolk immunoglobulin, 300 parts by weight of whey protein, 300 parts by weight of barley grass extract, 10 parts by weight of Bacillus coagulans, 40 parts by weight of glutamine, 60 parts by weight of turmeric extract, 3000 parts by weight of sorbitol, 2800 parts by weight of whole milk powder, 1400 parts by weight of resistant dextrin, 300 parts by weight of ginger powder, 390 parts by weight of oligofructose, 330 parts by weight of xylitol and 70 parts by weight of magnesium stearate.

[0039] In a preferred technical solution of the present invention, the compressed candy contains 850 parts by weight of chicken egg yolk immunoglobulin, 350 parts by weight of whey protein, 350 parts by weight of barley grass extract, 50 parts by weight of Bacillus coagulans, 200 parts by weight of lysine hydrochloride, 90 parts by weight of turmeric extract, 2800 parts by weight of sorbitol, 3300 parts by weight of whole milk powder, 1050 parts by weight of resistant dextrin, 290 parts by weight of ginger powder, 360 parts by weight of oligofructose, 290 parts by weight of xylitol and 20 parts by weight of magnesium stearate.

[0040] In the preferred technical solution of the present invention, the probiotics in the compressed candy are Bacillus coagulans, with a viable cell count of ≥1×10 8 CFU / g, preferably viable bacteria count ≥1×10 10 CFU / g, preferably ≥1×10 11 CFU / g.

[0041] Another object of the present invention is to provide a method for preparing a compressed candy for efficiently eradicating Helicobacter pylori. The compressed candy contains 830-1150 parts by weight of chicken egg yolk immunoglobulin, 230-360 parts by weight of whey protein, 230-360 parts by weight of barley grass extract, 8-100 parts by weight of probiotics, 30-700 parts by weight of amino acids, 50-100 parts by weight of turmeric extract, 2700-3300 parts by weight of sorbitol, 2700-3400 parts by weight of whole milk powder, 900-1500 parts by weight of resistant dextrin, 280-330 parts by weight of ginger powder, 350-400 parts by weight of oligofructose, 280-340 parts by weight of xylitol, and 10-80 parts by weight of magnesium stearate, wherein the number of viable probiotic bacteria in a unit dose of the composition is ≥1×10 8 CFU / g, the probiotics are selected from any one or a combination of Bacillus coagulans, Saccharomyces boulardii, Lactobacillus, Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium lactis, Bacillus rhamnosus, yeast, probiotic spore bacteria, Clostridium butyricum, Lactobacillus, Bifidobacterium, and actinomycetes; the amino acids are selected from any one or a combination of aspartic acid, threonine, serine, glutamic acid, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, γ-aminobutyric acid, histidine, tryptophan, lysine, arginine, proline, glutamine, and lysine hydrochloride. The method comprises the following steps: weighing required amounts of chicken egg yolk immunoglobulin, whey protein, barley grass extract, Bacillus coagulans, turmeric extract, amino acids, sorbitol, whole milk powder, resistant dextrin, ginger powder, oligofructose, and xylitol, mixing them evenly, granulating, drying, granulating, adding magnesium stearate, mixing evenly, and tableting to obtain the product.

[0042] In the preferred technical solution of the present invention, the magnesium stearate is crushed and passed through a 10-80 mesh sieve for standby use.

[0043] In a preferred technical solution of the present invention, any one of the chicken yolk immunoglobulin, whey protein, barley grass extract, Bacillus coagulans, turmeric extract, amino acids, sorbitol, whole milk powder, resistant dextrin, ginger powder, oligofructose, and xylitol is passed through a 10-80 mesh sieve and set aside.

[0044] In a preferred technical solution of the present invention, the granulation comprises the following steps: weighing the required amounts of chicken yolk immunoglobulin, whey protein, barley grass extract, Bacillus coagulans, turmeric extract, amino acids, sorbitol, whole milk powder, resistant dextrin, ginger powder, oligofructose and xylitol, uniformly mixing them, adding 70%-99% ethanol solution for granulation, and granulating through a 16-60 mesh sieve to obtain wet granules.

[0045] In the preferred technical solution of the present invention, 85%-97% ethanol solution is added for granulation, and 20-40 mesh screen is used for granulation.

[0046] In a preferred technical solution of the present invention, the drying temperature is ≤60°C, preferably 40-60°C.

[0047] In a preferred technical solution of the present invention, the drying is selected from any one of reduced pressure drying, vacuum drying, spray drying or a combination thereof.

[0048] In the preferred technical solution of the present invention, the moisture content of the compressed candy is 5%-8%.

[0049] In the preferred technical solution of the present invention, the tablet weight of the compressed candy is 300-900 mg and the hardness is 200-400N.

[0050] In the preferred technical solution of the present invention, the tablet weight of the compressed candy is 350-850 mg and the hardness is 250-350N.

[0051] In the preferred technical solution of the present invention, the tablet weight of the compressed candy is 800 mg and the hardness is 300N.

[0052] Another object of the present invention is to use the composition or compressed candy of the present invention in the preparation of a product for eradicating symptoms associated with Helicobacter pylori infection and / or improving gastrointestinal function, wherein the product is selected from any one of health products, functional foods, and foods for special medical purposes (FSMP) or a combination thereof.

[0053] In a preferred technical solution of the present invention, the Helicobacter pylori infection-related symptoms are selected from any one of acute gastritis, chronic gastritis, peptic ulcer, gastric cancer, atrophic gastritis, gastric cancer, gastric mucosa-associated lymphoid tissue lymphoma, or their complications.

[0054] In a preferred technical solution of the present invention, the peptic ulcer is selected from any one of gastric ulcer, duodenal ulcer, esophageal ulcer, gastrojejunostomy ulcer, Meckel's diverticulum ulcer of gastric mucosa, or their complications.

[0055] In the preferred technical solution of the present invention, the improvement of gastrointestinal function is selected from any one of improving bloating, acid reflux, belching, anemia, bad breath, intestinal metaplasia, constipation, indigestion, gastric ulcer, antral gastritis, stomach pain, bloating, and peptic ulcer.

[0056] In a preferred technical solution of the present invention, the product is selected from any one of tablets, capsules, granules, oral liquids, suspensions, pills, powders, dripping pills, syrups, mixtures, dews, effervescent tablets, emulsions, teas, compressed candies, and chewable tablets, or a combination thereof, preferably compressed candies.

[0057] In the preferred technical solution of the present invention, the dosage of the composition of the present invention is related to factors such as the age, gender, health status, treatment status, and combined medication of the subject. The recommended dosage of probiotics is ≥1×10 8 CFU / day.

[0058] Unless otherwise specified, when the present invention relates to the percentage between liquids, the percentages are volume / volume percentages; when the present invention relates to the percentage between liquids and solids, the percentages are volume / weight percentages; when the present invention relates to the percentage between solids and liquids, the percentages are weight / volume percentages; and the rest are weight / weight percentages.

[0059] Compared with the prior art, the present invention has the following beneficial technical effects:

[0060] The present invention scientifically screens the types and amounts of chicken egg yolk immunoglobulin, whey protein, barley grass extract, probiotics, turmeric extract and amino acids in the composition, synergistically utilizes the effective ingredients to promote the body's utilization of chicken egg yolk immunoglobulin to fight Helicobacter pylori, comprehensively balance the gastrointestinal flora, improve gastrointestinal function and enhance the gastrointestinal self-immunity, competitively inhibit the colonization and survival of Helicobacter pylori, efficiently eradicate Helicobacter pylori, regulate gastric acid secretion, accelerate the self-repair speed of the gastrointestinal tract, effectively prevent and treat gastric precancerous lesions, reduce adverse reaction rates, improve cure rates, significantly improve gastrointestinal function, effectively relieve gastrointestinal discomfort symptoms such as acidity, bloating, belching, anemia, bad breath, intestinal metaplasia, significantly reduce the subjects' reinfection with Helicobacter pylori and significantly reduce the recurrence rate, and has the advantages of being safe, effective and having no side effects.

[0061] The preparation method of the present invention has the advantages of simple operation, low production cost, and ease of industrial production. DETAILED DESCRIPTION

[0062] The present invention will be described in detail below with reference to the following examples, which are only used to illustrate the technical solutions of the present invention and are not intended to limit the essence of the present invention.

[0063] Chicken yolk immunoglobulin was purchased from Youlikang (Jiangsu) Biopharmaceutical Co., Ltd.; whey protein was purchased from Shaanxi Jinrun Biotechnology Co., Ltd.; barley grass extract was purchased from Qingdao Gengyun Centennial Biotechnology Co., Ltd.; the viable count of Bacillus coagulans was ≥1×10 11 CFU / g; Turmeric extract was purchased from Henan Zhongda Hengyuan Biotechnology Co., Ltd.

[0064] Example 1 Preparation of the compressed candy of the present invention

[0065] Composition of compressed candy:

[0066] Components Dosage (g) Chicken yolk immunoglobulin 889 whey protein 240 Barley Grass Extract 240 Bacillus coagulans 30 Turmeric extract 75 γ-aminobutyric acid 100 sorbitol 3125 whole milk powder 3000 Resistant dextrin 1250 ginger powder 313 Fructooligosaccharides 375 Xylitol 313 magnesium stearate 50

[0067] The preparation of compressed candy comprises the following steps:

[0068] 1) After the magnesium stearate is crushed, it is passed through a 16-mesh sieve and set aside;

[0069] 2) Chicken egg yolk immunoglobulin, whey protein, barley grass extract, Bacillus coagulans, turmeric extract, γ-aminobutyric acid, sorbitol, whole milk powder, resistant dextrin, ginger powder, oligofructose, and xylitol are passed through a 30-mesh sieve and set aside;

[0070] 3) Weighing the required amounts of chicken egg yolk immunoglobulin, whey protein, barley grass extract, Bacillus coagulans, turmeric extract, γ-aminobutyric acid, sorbitol, whole milk powder, resistant dextrin, ginger powder, oligofructose, and xylitol, uniformly mixing them, spraying them with 95% ethanol solution while stirring, and granulating them using a 30-mesh screen in an oscillating granulator to obtain wet granules;

[0071] 4) The obtained wet granules were dried under reduced pressure at 40°C to control the moisture content to 6%, and the obtained dry granules were passed through a 20-mesh sieve and sized;

[0072] 5) The granules are uniformly mixed with a required amount of magnesium stearate, and then tabletted to obtain a tablet candy having a tablet weight of 800 mg and a hardness of 300 N.

[0073] Example 2 Preparation of the compressed candy of the present invention

[0074] Composition of compressed candy:

[0075] Components Dosage (g) Chicken yolk immunoglobulin 1000 whey protein 300 Barley Grass Extract 300 Bacillus coagulans 10 Turmeric extract 60 Glutamine 40 sorbitol 3000 whole milk powder 2800 Resistant dextrin 1400 ginger powder 300 Fructooligosaccharides 390 Xylitol 330 magnesium stearate 70

[0076] The preparation of compressed candy comprises the following steps:

[0077] 1) After the magnesium stearate is crushed, it is passed through an 18-mesh sieve and set aside;

[0078] 2) Chicken egg yolk immunoglobulin, whey protein, barley grass extract, Bacillus coagulans, turmeric extract, glutamine, sorbitol, whole milk powder, resistant dextrin, ginger powder, oligofructose, and xylitol are passed through a 40-mesh sieve and set aside;

[0079] 3) Weighing the required amounts of chicken egg yolk immunoglobulin, whey protein, barley grass extract, Bacillus coagulans, turmeric extract, glutamine, sorbitol, whole milk powder, resistant dextrin, ginger powder, oligofructose, and xylitol, uniformly mixing them, spraying them with 97% ethanol solution while stirring, and granulating them using a 40-mesh screen in an oscillating granulator to obtain wet granules;

[0080] 4) The obtained wet granules were dried under reduced pressure at 55°C to control the moisture content to 8%, and the obtained dry granules were passed through a 30-mesh sieve and sized;

[0081] 5) The granules are uniformly mixed with a required amount of magnesium stearate, and then tabletted to obtain a tablet candy having a tablet weight of 800 mg and a hardness of 300 N.

[0082] Example 3 Preparation of Tablet Candy of the Present Invention

[0083] Composition of compressed candy:

[0084]

[0085]

[0086] The preparation of compressed candy comprises the following steps:

[0087] 1) After the magnesium stearate is crushed, it is passed through a 16-mesh sieve and set aside;

[0088] 2) Chicken egg yolk immunoglobulin, whey protein, barley grass extract, Bacillus coagulans, turmeric extract, lysine hydrochloride, sorbitol, whole milk powder, resistant dextrin, ginger powder, oligofructose, and xylitol are passed through a 40-mesh sieve and set aside;

[0089] 3) Weighing the required amounts of chicken egg yolk immunoglobulin, whey protein, barley grass extract, Bacillus coagulans, turmeric extract, lysine hydrochloride, sorbitol, whole milk powder, resistant dextrin, ginger powder, oligofructose, and xylitol, uniformly mixing them, spraying them with 99% ethanol solution while stirring, and granulating them using a 30-mesh screen in an oscillating granulator to obtain wet granules;

[0090] 4) The obtained wet granules were dried under reduced pressure at 45°C to control the moisture content to 5%, and the obtained dry granules were passed through a 20-mesh sieve and sized;

[0091] 5) The granules are uniformly mixed with a required amount of magnesium stearate, and then tabletted to obtain a tablet candy having a tablet weight of 800 mg and a hardness of 300 N.

[0092] Comparative Example 1 Preparation of the compressed candy of the present invention

[0093] Composition of compressed candy:

[0094]

[0095]

[0096] The preparation of compressed candy comprises the following steps:

[0097] 1) After the magnesium stearate is crushed, it is passed through a 16-mesh sieve and set aside;

[0098] 2) Chicken egg yolk immunoglobulin, whey protein, barley grass extract, sorbitol, whole milk powder, resistant dextrin, oligofructose and xylitol are passed through a 30-mesh sieve and set aside;

[0099] 3) Weighing the required amounts of chicken egg yolk immunoglobulin, whey protein, barley grass extract, sorbitol, whole milk powder, resistant dextrin, oligofructose, and xylitol, uniformly mixing them, spraying them with 95% ethanol solution while stirring, and granulating them using a 30-mesh screen in an oscillating granulator to obtain wet granules;

[0100] 4) The obtained wet granules were dried under reduced pressure at 40°C to control the moisture content to 6%, and the obtained dry granules were passed through a 20-mesh sieve and sized;

[0101] 5) The granules are uniformly mixed with a required amount of magnesium stearate, and then tabletted to obtain a tablet candy having a tablet weight of 760 mg and a hardness of 300 N.

[0102] Test Example 1 Study on the effect of the composition of the present invention in eliminating Helicobacter pylori

[0103] Fifty volunteers diagnosed with Helicobacter pylori infection were randomly divided into five groups, each with 10 participants aged 18 to 80 years, with an average age of 40. All participants experienced varying degrees of bloating, acid reflux, belching, and bad breath. The participants took two tablets twice daily for two weeks.

[0104] Test Group 1: Oral administration of the compressed candy of Example 1.

[0105] Test Group 2: Oral administration of the compressed candy of Example 2.

[0106] Test Group 3: Oral administration of the compressed candy of Example 3.

[0107] Control group 1: Orally take the compressed candy of Comparative Example 1.

[0108] Control group 2: Orally administered the composition prepared in Example 4 of CN106075436B.

[0109] Evaluation criteria for the efficacy of relieving gastrointestinal discomfort symptoms:

[0110] Cure: Physical signs are completely improved, the subject has no adverse feelings, is in a good mood and is in high spirits.

[0111] Markedly effective: Physical signs were significantly improved, the subjects had basically no adverse feelings, were in a good mood, and were in high spirits.

[0112] Effective: Physical signs have changed significantly, with occasional slight discomfort but acceptable, better mood and more energy.

[0113] Ineffective: No changes in physical signs, symptoms remain the same, with depression and listlessness.

[0114] During the trial, the presence of adverse reactions was determined through interviews. After drug discontinuation, the improvement of the subjects' gastrointestinal discomfort symptoms was recorded, and the results are shown in Table 1.

[0115] Table 1

[0116] Grouping Number of people treated cure Significant effect efficient invalid Experimental group 1 10 6 3 1 0 Experimental Group 2 10 5 2 3 0 Experimental Group 3 10 5 3 2 0 Control group 1 10 4 3 2 1 Control group 2 10 3 3 2 2

[0117] After stopping the drug, 14 C-urea breath test to evaluate the cure of Helicobacter pylori. 14 Relapse was detected by C-urea breath test. The results are shown in Table 2.

[0118] Table 2

[0119] Grouping Number of people treated Number of people cured Number of adverse reactions Number of relapses Experimental group 1 10 6 0 1 Experimental Group 2 10 5 0 1 Experimental Group 3 10 5 0 1 Control group 1 10 4 0 1 Control group 2 10 3 0 2

[0120] The composition of the present invention can effectively eradicate Helicobacter pylori infection and relieve gastrointestinal discomfort symptoms, effectively solving the problems of existing Helicobacter pylori inhibition drugs such as large dosage, long treatment time, and insignificant relief of gastrointestinal discomfort symptoms, thereby alleviating the pain of medication for subjects and improving their medication compliance.

[0121] Test Example 2 Study on the effect of the composition of the present invention on preventing and treating intestinal metaplasia of gastric mucosa

[0122] Twenty subjects with chronic atrophic gastritis associated with intestinal metaplasia caused by Helicobacter pylori were randomly divided into two groups: a test group of 10 subjects and a control group of 10 subjects, aged 18-80 years (average age 40 years). The test group received the composition prepared in Example 1, while the control group received the composition prepared in Example 4 of CN106075436B. The subjects took two tablets twice daily for seven months. The results of the treatment and prevention of intestinal metaplasia in the gastric mucosa are shown in Table 3.

[0123] Efficacy evaluation criteria:

[0124] Cure: Clinical symptoms are alleviated or disappear, gastroscopy shows that the mucosa returns to normal with no blood vessels visible, and the pathological results are chronic atrophic gastritis.

[0125] Effective: Clinical symptoms are alleviated or disappeared, gastroscopy shows grade 1 local gastric blood vessels, and pathological results show inflammation of the lamina propria.

[0126] Ineffective: The pathology does not meet the effective criteria and the symptoms do not improve.

[0127] Table 3

[0128] Group Number of subjects (people) Heal (a person) Effective (people) Invalid (person) Efficiency experimental group 10 10 0 0 100％ control group 10 5 1 4 60％

[0129] The above description is merely an example of the implementation of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A pharmaceutical composition for inhibiting Helicobacter pylori, comprising 830-1150 parts by weight of anti-Helicobacter pylori chicken egg yolk immunoglobulin, 230-360 parts by weight of whey protein, 230-360 parts by weight of barley grass extract, 8-100 parts by weight of probiotics, 40-200 parts by weight of amino acids, 50-100 parts by weight of turmeric extract, 280-330 parts of ginger powder, and a pharmaceutically acceptable carrier, wherein: The number of viable probiotic bacteria in a unit dose composition is ≥ 1×10 11 CFU / g, the probiotic is Bacillus coagulans, and the amino acid is selected from any one of γ-aminobutyric acid, glutamine, and lysine hydrochloride.

2. The composition according to claim 1, comprising 840-1100 parts by weight of anti-Helicobacter pylori chicken egg yolk immunoglobulin, 235-355 parts by weight of whey protein, 235-355 parts by weight of barley grass extract, 9-60 parts by weight of probiotics, 40-200 parts by weight of amino acids, 55-95 parts by weight of turmeric extract and 285-320 parts by weight of ginger powder.

3. The composition according to claim 2, comprising 889 parts by weight of anti-Helicobacter pylori chicken egg yolk immunoglobulin, 240 parts by weight of whey protein, 240 parts by weight of barley grass extract, 30 parts by weight of Bacillus coagulans, 100 parts by weight of gamma-aminobutyric acid, 75 parts by weight of turmeric extract and 313 parts by weight of ginger powder.

4. The composition according to claim 2, comprising 1000 parts by weight of anti-Helicobacter pylori chicken egg yolk immunoglobulin, 300 parts by weight of whey protein, 300 parts by weight of barley grass extract, 10 parts by weight of Bacillus coagulans, 40 parts by weight of glutamine, 60 parts by weight of turmeric extract and 300 parts by weight of ginger powder.

5. The composition according to claim 2, comprising 850 parts by weight of anti-Helicobacter pylori chicken egg yolk immunoglobulin, 350 parts by weight of whey protein, 350 parts by weight of barley grass extract, 50 parts by weight of Bacillus coagulans, 200 parts by weight of lysine hydrochloride, 90 parts by weight of turmeric extract and 290 parts by weight of ginger powder.

6. The composition of claim 1, wherein the pharmaceutically acceptable carrier is selected from any one of fillers, disintegrants, binders, solubilizers, antioxidants, lubricants, acid-base regulators, preservatives, dispersants, emulsifiers, wetting agents, flavoring agents, fragrances, dietary fiber, and nutritional enhancers, or a combination thereof.

7. The composition of claim 6, wherein the dietary fiber is selected from any one of non-starch polysaccharides, resistant oligosaccharides, and resistant starch, or a combination thereof.

8. The composition of claim 6, wherein the dietary fiber is selected from any one of cellulose, hemicellulose, pectin, guar gum, xanthan gum, fructooligosaccharides, galacto-oligosaccharides, resistant dextrin, and resistant starch, or a combination thereof.

9. The composition according to claim 6, wherein the nutritional enhancer is selected from any one of amino acids, vitamins, and minerals or a combination thereof.

10. The composition of claim 6, wherein the nutritional enhancer is selected from any one of whole milk powder, L-lysine aspartate, L-carnitine, taurine, vitamin A, vitamin D, vitamin E, vitamin K, vitamin C, vitamin B, calcium citrate, calcium gluconate, calcium carbonate, ferrous lactate, ferrous gluconate, zinc gluconate, zinc lactate, and zinc sulfate, or a combination thereof.

11. The composition of claim 6, wherein the filler is selected from any one of lactose, powdered sugar, dextrin, starch, cellulose, calcium sulfate, calcium phosphate, calcium hydrogen phosphate, precipitated calcium carbonate, sorbitol, and glycine, or a combination thereof.

12. The composition according to claim 6, wherein the disintegrant is selected from any one of starch, polyvinyl pyrrolidone, cross-linked polyvinyl pyrrolidone, microcrystalline cellulose or a combination thereof.

13. The composition of claim 6, wherein the binder is selected from any one of syrup, gum arabic, gelatin, sorbitol, tragacanth, cellulose, gelatin paste, starch, and polyvinyl pyrrolidone, or a combination thereof.

14. The composition of claim 6, wherein the lubricant is selected from any one of micropowdered silica gel, magnesium stearate, talc, aluminum hydroxide, boric acid, hydrogenated vegetable oil, and polyethylene glycol, or a combination thereof.

15. The composition of claim 6, wherein the wetting agent is selected from any one of sodium lauryl sulfate, water, and alcohol, or a combination thereof.

16. The composition of claim 6, wherein the emulsifier is selected from any one of polysorbate 80, Pluronic F-68, lecithin, and soybean lecithin, or a combination thereof.

17. The composition of claim 6, wherein the acid-base regulator is selected from any one of citric acid, sodium citrate, malic acid, sodium malate, hydrochloric acid, acetic acid, sodium acetate, phosphoric acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, carbonic acid, sodium carbonate, sulfonic acid, sodium sulfonate, glutamic acid, tartaric acid, sodium tartrate, lactic acid, sodium lactate, fumaric acid, sodium fumarate, itaconic acid, ascorbic acid, sodium ascorbate, nicotinic acid, sodium nicotinate, fumaric acid, α-ketoglutaric acid, fruit acid, sodium fruit acid, acetic acid, oxalic acid, succinic acid, carbon dioxide, citric acid, and sodium citrate, or a combination thereof. The composition according to claim 6 , wherein the concentration of the acid-base regulator is 0.5-8 mol / L. The composition according to claim 18 , wherein the concentration of the acid-base regulator is 0.8-6 mol / L.

20. The composition according to claim 19, wherein the concentration of the acid-base regulator is 1-5 mol / L.

21. The composition of claim 6, wherein the solubilizing agent is selected from any one of glycerol and Tween-80 or a combination thereof.

22. The composition of claim 6, wherein the antioxidant is selected from any one of potassium sorbate, sodium sulfite, sodium bisulfite, sodium metabisulfite, and dibutyl benzoate, or a combination thereof.

23. The composition according to claim 6, comprising 0.01%-0.2% (w / w) of a preservative, wherein the preservative is selected from any one of potassium sorbate, sodium benzoate, ethylparaben, methylparaben, calcium propionate, and sodium lactate, or a combination thereof.

24. The composition of claim 23, comprising 0.03% to 0.15% (w / w) of a preservative.

25. The composition of claim 24, comprising 0.05% to 0.1% (w / w) of a preservative.

26. The composition of claim 6, comprising a flavoring agent selected from any one of sucrose, simple syrup, mannitol, sorbitol, saccharin sodium, aspartame, sucralose, steviol glycosides, glucose, xylitol, and maltitol, or a combination thereof.

27. The composition of claim 6, wherein the flavoring agent is selected from any one of spices and edible flavors or a combination thereof.

28. The composition according to any one of claims 1 to 27, which is an oral preparation.

29. The composition of claim 28, wherein the oral preparation is selected from any one of syrup, suspension, tablet, capsule, granule, pill, powder, effervescent, paste, and emulsion.

30. Use of the pharmaceutical composition for inhibiting Helicobacter pylori according to any one of claims 1 to 27 for preparing a product for inhibiting Helicobacter pylori and improving gastrointestinal function, wherein the improvement of gastrointestinal function is selected from any one of improving bloating, acid reflux, belching, bad breath, and intestinal metaplasia.

31. The use according to claim 30, wherein the product is selected from any one of tablets, capsules, granules, oral liquids, pills, powders, effervescents, emulsions, syrups, and suspensions.

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