CN112353935A

CN112353935A - A preparation for preventing and treating helicobacter pylori

Info

Publication number: CN112353935A
Application number: CN202011522471.0A
Authority: CN
Inventors: 张广明
Original assignee: Nanjing Kangrong Health Technology Co ltd
Current assignee: Nanjing Kangrong Health Technology Co ltd
Priority date: 2020-12-21
Filing date: 2020-12-21
Publication date: 2021-02-12

Abstract

The application provides a can prevent and treat oral cavity stomach helicobacter pylori preparation, this helicobacter pylori preparation adopts lactoferrin and polylysine to mix, and the formulation of adoption is the spray, and this kind of compatibility can increase substantially to the helicobacter pylori people effect of killing through studying, and the spray formulation can be when killing oral cavity helicobacter pylori, leads to swallowing drinking water etc. simultaneously, can make this preparation reach in the stomach, alright like this with supplementary helicobacter pylori of killing in the stomach.

Description

A preparation for preventing and treating helicobacter pylori

Technical Field

The application relates to the field of medical treatment, in particular to a preparation for preventing and treating helicobacter pylori, belonging to the field of medicines.

Background

Helicobacter pylori is a bacterium that is helicoidal, micro-anaerobic, and has very strict requirements for growth conditions. The first successful isolation from biopsy tissue from the gastric mucosa of patients with chronic active gastritis in 1983 is the only microorganism species currently known to survive in the human stomach.

The helicobacter pylori disease includes gastritis, peptic ulcer, lymphoproliferative gastric lymphoma, etc. caused by helicobacter pylori infection, and the poor prognosis of the helicobacter pylori disease is gastric cancer. Gastric cancer is one of the most common malignancies worldwide, and ranks second among the causes of cancer death. In our country, approximately 16 million people die of stomach cancer every year. Prevention and control of gastric cancer has been attracting increasing attention. Studies have shown that helicobacter pylori lives in the pylorus region of the human stomach and is one of the most common bacterial pathogens. Most of the world's population is infected with H.pylori, and in some countries almost 90% of people are infected with this bacterium. People are usually infected at early age, reaching 50% under 5 years of age. This bacterial infection first causes chronic gastritis and leads to gastric ulcers and gastric atrophy, and in severe cases gastric cancer. According to statistics, the incidence rate of atrophic gastritis and gastric cancer of people with early age of the initial helicobacter pylori infection is high, and the helicobacter pylori infection and the death rate of gastric cancer are in parallel. Therefore, experts think that people who find helicobacter pylori infection as soon as possible can kill helicobacter pylori with antibiotics timely and effectively, and the method has great significance for preventing and controlling gastric cancer.

For the killing of helicobacter pylori, the current common method is triple therapy, and then quadruple therapy is developed. The dosing period is 2 weeks minimum. Because the medicine is taken for a long time and the dosage is large, if the medicine can not be eradicated once, the medicine resistance is easy to generate, and the clinical effect is poor. Currently, there is no touch in the treatment of Hp infection to eradicate Hp as another important issue-Hp colonizing the oral cavity. Clinical intragastric Hp treatment results in the widespread use of antibiotics, which become a cause of inducing Hp resistance. Comparison of commonly used antibiotic resistance: furazolidone (0-0.1%), amoxicillin (0-6.8%), tetracycline (0-7.3%), levofloxacin (20-54.8%), clarithromycin (13.9-52.6%) and metronidazole (41.6-99.5%).

The applicant provided in patent CN111184858 an oral spray consisting of lactoferrin and polylysine, which can kill helicobacter pylori in oral cavity after use and prevent helicobacter pylori in oral cavity from causing gastric helicobacter pylori reinfection. The application method comprises spraying the medicine into oral cavity, and swallowing the collected liquid medicine into stomach with saliva or drinking water. The applicant carries out further research on the basis of the patent CN111184858, and research results show that the buccal tablet can achieve the same effect except for the oral spray. When the spray is used for spraying the oral cavity, no water or food needs to be taken within 15 minutes after the spray is sprayed in order to keep the medicine in the oral cavity for a long time. In actual operation, a small part of people can drink or eat water immediately after blowing, so that the concentration of the medicine in the oral cavity is reduced, and the oral curative effect is reduced. The oral buccal tablet developed by the applicant can overcome the defect, is long in the buccal process, and can fully ensure the time and the concentration of the medicine in the oral cavity. In addition, under normal conditions, in the process of using the buccal tablet, normal people can not drink water because the oral cavity contains objects. The applicant further studies on the basis of patent CN111184858 and finds that besides the compatibility of lactoferrin and polylysine, the compatibility of the livetin anti-HPIgY and polylysine or the acylation and amination reaction of lactoferrin and polylysine into polymer to prepare corresponding preparation also shows strong bactericidal effect on helicobacter pylori. The study of patent CN111184858 finds that the killing effect of lactoferrin and polylysine is much stronger than that of single component or single component of synergistic agent when the lactoferrin and the polylysine are used together. And the killing time is much shorter, and more than 70 percent of helicobacter pylori can be killed within 10 minutes through in vitro tests. The research of the invention finds that the matching use of the eggplantin anti-HPIgY and the polylysine has killing effect on the helicobacter pylori which is many times stronger than that of a single eggplantin anti-HPIgY component or a polylysine matching synergist. The patent CN100360566 research shows that 200mg capsules prepared by crude yolk globulin anti-HPIgY are needed to be taken 2-3 times a day, 3 capsules are taken each time when the yolk globulin anti-HPIgY is used for preventing helicobacter pylori infection, namely, the daily dosage is 1200 mg-1800 mg. It follows that the dosage used is very large and that the daily average dosage will be larger if used therapeutically.

The same in vitro and in vivo bacterial method as in patent CN111184858 is adopted: in the same time, the same amount of helicobacter pylori is killed, the effective concentration of the combination of the eggplants anti-HPIgY and the polylysine is 1.95mg/ml based on the eggplants anti-HPIgY, the effective concentration of the combination of the lactoferrin and the polylysine is 1.32mg/ml based on the lactoferrin, the effective concentration of the lactoferrin polylysine polymer is 1.87mg/ml, the effective concentration of the single eggplants anti-HPIgY is 92.46mg/ml, the effective concentration of the single polylysine is 63.78mg/ml, and the effective concentration of the single lactoferrin is 72.15 mg/ml. Therefore, no matter lactoferrin or eggplants anti-HPIgY is compatible with polylysine or forms a polymer through polymerization, the antibacterial effect of the polymer on helicobacter pylori is increased by dozens of times and dozens of times, and a new idea is provided for the research and development of clinical helicobacter pylori resistant medicines.

The bacteriostatic test shows that: the bacteriostasis rate of the lactoferrin and polylysine compound preparation, the livetin anti-HPIgY and polylysine compound preparation or the lactoferrin polylysine polymer to helicobacter pylori reaches more than 98 percent, so the lactoferrin and polylysine compound preparation, the livetin anti-HPIgY and polylysine compound preparation or the lactoferrin polylysine polymer can be prepared into clinical preparations which can be used for clinical HP treatment, and the clinical HP antibiotic use can be greatly reduced. The bacteriostatic action of the lactoferrin and polylysine compound preparation, the livetin anti-HPIgY and polylysine compound preparation and the lactoferrin polylysine polymer on staphylococcus aureus, escherichia coli and candida albicans is respectively tested, and the results show that the action effect of the lactoferrin and polylysine compound preparation, the livetin anti-HPIgY and polylysine compound preparation and the lactoferrin polylysine polymer on the bacteria is poorer than that of helicobacter pylori in effectiveness. This may be associated with lactoferrin, an iron-binding glycoprotein with both egyprotein anti-HPIgY, polylysine as a cationic surfactant, which increases the permeability of the helicobacter pylori cell membrane, lactoferrin, an iron-binding glycoprotein with both egyprotein anti-HPIgY, which competes with helicobacter pylori for iron, which increased permeability of the helicobacter pylori cell membrane may help helicobacter pylori lose iron-resistant iron to survive. Staphylococcus aureus, Escherichia coli and Candida albicans are not iron-dependent bacteria, so that the lactoferrin and polylysine compound preparation, the livetin anti-HPIgY and polylysine compound preparation or the lactoferrin polylysine polymer has stronger effect on helicobacter pylori and weaker effect on other bacteria.

Disclosure of Invention

The object of the present invention is to provide a preparation for the treatment of helicobacter pylori infection, which has no or extremely low side effects and has an extremely high selectivity for helicobacter pylori. The preparation can kill helicobacter pylori in oral cavity and stomach simultaneously. Realizes simultaneous treatment of pylorus helicobacterium and stomachs.

The preparation can kill helicobacter pylori, and is characterized in that the preparation is oral spray, oral lozenge, oral effervescent tablet and oral sugar, wherein the oral spray and the oral lozenge are preferred.

The preparation for killing helicobacter pylori is characterized in that the preparation is taken through oral cavity, stays in the oral cavity for a long time, sufficiently eliminates the helicobacter pylori in the oral cavity, and then is swallowed or swallowed along with saliva or drinking water to the stomach, thereby killing the helicobacter pylori in the stomach.

The preparation for killing helicobacter pylori is characterized in that the preparation mainly comprises one or more of polymers of lactoferrin plus polylysine, livetin plus polylysine and lactoferrin polylysine.

As mentioned above, the preparation can kill helicobacter pylori, and is characterized in that the stability of the preparation under the acidic condition is better than that under the alkaline condition.

The preparation can kill helicobacter pylori as described above, and is characterized in that the preparation can kill helicobacter pylori in combination with existing medicines.

The preparation can kill helicobacter pylori, and is characterized in that the preparation can be used for killing helicobacter pylori alone.

As described above, the agent for killing helicobacter pylori is characterized by being excellent in the therapeutic effect on oral ulcer, aphtha, angular stomatitis and halitosis.

Detailed Description

Example 1 taking 1 part of lactoferrin, 1 part of polylysine and 0.05 part of tween, adding 50 parts of purified water, stirring to completely dissolve the lactoferrin, adding a proper amount of flavoring agent, adjusting the pH value of the solution to 2.5-4.0, filtering, and subpackaging in a spray bottle, wherein the specification is as follows: 30 ml/bottle.

Example 2 taking and mixing 50 parts of purified water, stirring to completely dissolve the eggplants, namely HPIGY2 parts, polylysine 1 part and tween 0.05 part, adding a proper amount of flavoring agent, adjusting the pH value of the solution to 2.5-4.0, filtering, and subpackaging in a spray bottle according to the specification: 30 ml/bottle.

Example 3 taking 1 part of lactoferrin polylysine polymer and 0.05 part of tween, adding 50 parts of purified water, stirring to completely dissolve the polymers, adding a proper amount of flavoring agent, adjusting the pH value of the solution to 2.5-4.0, filtering, and subpackaging in a spray bottle, wherein the specification is as follows: 30 ml/bottle.

Example 4 Lactoferrin 1 part, polylysine 1 part, lactose 2 parts, mannitol 1 part, microcrystalline cellulose 0.5 part were mixed well, granulated with 25% ethanol solution, tabletted, tablet weight 0.482 g.

Test I, stability

Using example 1, a solution a having a pH of 3.68 and a solution B having a pH of 7.93 were prepared, and left at 40 ℃ for 6 months, and the contents of lactoferrin and polylysine as main components were measured at the beginning of (0 day) 1, 2, 3, and 6 months, respectively, and the results are shown in table 1:

TABLE 1 Lactoferrin polylysine solution stability

From the above experiments it can be seen that the lactoferrin polylysine solution is more stable under acidic conditions than under more basic conditions.

Test II, therapeutic Effect on HP infection

Selecting 86 HP infected patients, wherein the age is 4-10 years old, and the clinical symptoms are as follows: abdominal pain, vomiting, halitosis, stomach distention and poor appetite. HP infection was confirmed by antigen detection. The samples of example 1 were administered as a mouth spray, four times a day, 5 puffs at a time. No water or meal can be taken 30 minutes after the spraying. The application is continued for 4 weeks. The patient was observed for remission or disappearance of clinical symptoms during treatment and was antigen tested again after 4 weeks. As a result: the clinical symptoms are totally eliminated in 76 cases, and 7 cases with remission and 3 cases without effect are provided. The negative antigen test was 62 cases, accounting for 72.1%, and the remaining positive 24 cases, accounting for 27.9%.

Experiment three, the treatment effect on angular stomatitis and oral ulcer

140 patients with angular stomatitis or canker sores were dosed with the sample of example 1 as a mouth spray four times a day with 5 sprays. No water or meal can be taken 30 minutes after the spraying. The treatment time was 7 days, and the treatment results are shown in table 2.

TABLE 2 treatment Effect of patients with angular stomatitis and oral ulcer

	Recovery method	Show effect	Invalidation	Total effective rate (%)	Inefficiency (%)
						Angular cheilitis	46 examples of	62 example (c)	6 examples of	91.18％	8.82％
Oral ulcer	53 cases of	68 examples of	4 examples of	94.44％	5.56％

The foregoing is a more detailed description of the present application in connection with specific embodiments thereof, and it is not intended that the present application be limited to the specific embodiments thereof. For those skilled in the art to which the present application pertains, several simple deductions or substitutions may be made without departing from the spirit of the present application, which should be considered as belonging to the protection scope of the present application.

Claims

1. A preparation for treating helicobacter pylori infection, which has no or extremely low side effects and has an extremely high selectivity for helicobacter pylori.

2. Helicobacter pylori formulation according to claim 1, characterized in that the formulation is a mouth spray, a mouth lozenge, an effervescent tablet, a mouth sugar, wherein mouth spray and mouth lozenge are preferred.

3. A helicobacter pylori preparation according to claim 2, wherein the preparation is administered orally, left in the mouth for a prolonged period of time sufficient to eliminate helicobacter pylori in the mouth, and then swallowed, or swallowed with saliva or drinking water, into the stomach, thereby killing helicobacter pylori in the stomach.

4. Helicobacter pylori preparation according to claim 1, wherein the preparation comprises as the main component one or more polymers selected from the group consisting of lactoferrin plus polylysine, livetin-HPIGY plus polylysine, and lactoferrin polylysine.

5. A helicobacter pylori formulation according to claim 1, wherein the formulation is more stable under mildly acidic conditions than under mildly alkaline conditions.

6. A helicobacter pylori preparation according to claim 1, wherein the preparation is used in combination with an existing drug to kill helicobacter pylori.

7. A helicobacter pylori preparation according to claim 1, characterized in that the preparation can also be used alone for the killing of helicobacter pylori.

8. Helicobacter pylori formulation according to claim 1, characterized in that it has an excellent therapeutic effect on oral ulcers, aphthous stomatitis, angular stomatitis and halitosis.