Chitosan-embedded probiotic gel microcapsules, preparation method and application thereof in preparation of anti-helicobacter pylori infection drugs

Abstract

The present application belongs to the technical field of biological medicine, and particularly relates to a chitosan-embedded probiotic gel microcapsule, a preparation method thereof and application of the microcapsule in preparation of an anti-Helicobacter pylori infection medicament. The superfine chitosan powder is used as a coating of the probiotic gel microcapsule, which is conducive to maintaining a high pH value in the microcapsule for a long time and providing a good living environment for the probiotic bacteria. Moreover, after the microcapsule enters the body, the peripheral chitosan powder first contacts the strong acid environment in the gastric juice, thereby providing a certain buffer barrier for the probiotic bacteria and the strong acid environment, so that the probiotic bacteria are prevented from being inactivated by the strong acid gastric acid. Meanwhile, the protonated chitosan shell plays a bridging role to make the microcapsule adsorbed on the gastric wall, thereby increasing the residence time of the microcapsule in the stomach, prolonging the time for the probiotic bacteria such as Bacillus natto to exert an ecological effect in the gastric juice, and finally achieving a good inhibitory effect on Helicobacter pylori.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biological medicine, and particularly relates to a chitosan-embedded probiotic gel microcapsule, a preparation method thereof and application thereof in preparation of an anti-Helicobacter pylori infection medicament. BACKGROUND

[0002] Helicobacter pylori (Hp) is a Gram-negative microaerophilic bacterium that colonizes the gastric mucosa and can cause gastritis, peptic ulcer, gastric cancer and many other diseases. Among them, Helicobacter pylori-related gastric cancer is one of the most common malignancies in humans, which seriously threatens human health. Therefore, the eradication of Helicobacter pylori is particularly important.

[0003] At present, antibiotics are mainly used to treat Helicobacter pylori, but with the use of antibiotics, the drug resistance of Helicobacter pylori has also greatly increased. In addition, the use of antibiotics can also easily cause intestinal microecological disorders and other adverse consequences.

[0004] The treatment and prevention of Helicobacter pylori infection with microecological preparations has become a research hotspot in recent years. For example, Li Xinying et al. used Bacillus subtilis double viable bacteria capsules combined with bismuth-containing quadruple therapy to treat Helicobacter pylori infection; and patent CN119144513A used Lactobacillus plantarum to inhibit the activity of Helicobacter pylori.

[0005] Although microbial preparations have the advantages of mild effect and no toxic side effects, most microorganisms are difficult to survive or have a very low survival rate in the strong acidic environment of the stomach cavity. For example, the survival rate of Lactobacillus plantarum disclosed in patent CN119144513A in artificial gastric juice with pH=3.0 for 3 h was 55.2%, and the survival rate in artificial gastric juice with pH=2.5 for 3 h was only 33.2%, which makes the use of microbial preparations for the treatment of Helicobacter pylori ineffective.

[0006] Using chitosan to wrap microorganisms is a good technical means to improve the stability of microbial strains.

[0007] Chitosan, as a natural polyglucosamine with abundant sources, has been confirmed by many studies to have broad-spectrum antibacterial effect, and there is evidence that chitosan also has a certain inhibitory effect on Helicobacter pylori. For example, Xie Yong et al. verified the in vitro anti-Helicobacter pylori infection ability of chitosan in the article "In Vitro Anti-Helicobacter Pylori Effect of Chitosan and Its Derivatives and Influencing Factors", which proved that chitosan and carboxymethyl chitosan had universal antibacterial effect on 3 standard strains of Hp in vitro and had high inhibitory effect under acidic conditions. They further verified the in vivo anti-Helicobacter pylori effect of chitosan, although single chitosan showed certain in vivo anti-Helicobacter pylori effect, but the effect was very limited, with a cure rate of only 58.3%.

[0008] And, since chitosan can be better dissolved in acidic solution, the traditional chitosan coating is all dissolved after chitosan (usually more dissolved in acidic solution) is used, although this operation makes the toughness and strength of chitosan capsules improved, but since the amino group of chitosan is protonated before entering the body, the chitosan used as a coating material by the traditional method only has the effect of wrapping microorganisms, and the buffering effect of chitosan itself to neutralize gastric acid is difficult to play. +

[0009] Of course, in order to ensure the integrity of chitosan after entering the body, the prior art often modifies chitosan chemically first, and then uses the modified chitosan to wrap microorganisms, such as patents CN101940554A, CN116675785A, CN102687857A, etc. are all modified by chemical method before use, which greatly improves the complexity of chitosan embedding microbial inoculant process, greatly increases the production cost, and also has no ideal effect of neutralizing and buffering gastric acid. SUMMARY

[0010] In order to solve the above technical problems, the present application provides a chitosan-embedded probiotic gel microcapsule, a preparation method and its application in preparing anti-Helicobacter pylori infection drugs, more specifically, a chitosan-embedded Bacillus natto gel microcapsule and its application in preparing drugs for preventing and / or treating Helicobacter pylori infection.

[0011] The first aspect of the present application is to provide a chitosan-embedded probiotic gel microcapsule, wherein chitosan powder is used as a coating material for the probiotic gel microcapsule, and the probiotic bacteria include but are not limited to any one of Bacillus natto, Lactobacillus plantarum, Lactobacillus acidophilus, Bacillus megaterium, Lactobacillus acidophilus, Bacillus subtilis, and Streptococcus thermophilus.

[0012] As a preferred embodiment, the probiotic gel is obtained by wrapping probiotic bacteria with edible gum, and the edible gum is selected from at least one of sodium alginate, fucoidan, gelatin, carrageenan, gum arabic, agar, pectin, konjac gum, guar gum, sodium carboxymethyl cellulose, pullulan, xanthan gum, and chitosan.

[0013] As a preferred embodiment, the particle size of the chitosan powder is 100-200 mesh.

[0014] As a preferred embodiment, the content of probiotic bacteria in the chitosan-embedded probiotic gel microcapsule is 1×10 8 -1×10 10 ​CFU / g, and the particle size of the microcapsule is 300-500 μm.

[0015] A second aspect of the present application provides the use of the chitosan-embedded probiotic gel microcapsule, in particular, the use of the chitosan-embedded probiotic gel microcapsule in the preparation of a medicine for resisting bacterial or viral infection in the body, wherein the bacteria include any one of Helicobacter pylori, Salmonella, Shigella, Clostridium difficile, and the viruses include any one of rotavirus, norovirus, and enteric adenovirus.

[0016] A third aspect of the present application provides a medicine capable of preventing and / or treating Helicobacter pylori infection, wherein the medicine comprises the chitosan-embedded probiotic gel microcapsule described above. Preferably, the medicine can further comprise common pharmaceutical excipients, such as sweeteners, thickening agents, disintegrating agents, lubricants, and the like.

[0017] Further preferably, in the above-mentioned medicine, the probiotic is Bacillus natto.

[0018] Chitosan has been a common coating material for microbial agents, but traditional chitosan coating is to dissolve chitosan in an acidic solution and then coat the microbial agent. However, during the dissolution of chitosan in the acidic solution, H + has been combined to the amino group in the chitosan molecule, so that the chitosan molecule as a coating has formed a positively charged protonated structure. Therefore, when the dissolved chitosan is used to coat the probiotic, the positively charged chitosan molecule can only weakly block the diffusion of H + in the gastric juice, and cannot further absorb free H + , so as to buffer the pH value and adjust the pH environment of the probiotic in the microsphere.

[0019] In the present application, the probiotic gel is directly coated with superfine chitosan powder. The chitosan-embedded probiotic gel microcapsule provided by the present application has the following action mechanism:

[0020] Firstly, the probiotic gel obtained after the edible gel coats the probiotic has good adhesion to chitosan powder, so that a layer of chitosan powder coating is formed on the outer layer of the probiotic gel, without the need for dissolving chitosan and then coating, which reduces the cost of solvent and equipment and the difficulty of process operation.

[0021] Secondly, the probiotic is coated in the microsphere to form a microcapsule after the gel treatment, and after entering the body, the chitosan powder on the outer layer of the microcapsule first contacts the strong acid in the gastric juice, rapidly combines with H +, promote the dissolution of the outer layer of chitosan powder, thereby avoiding the direct contact of probiotics in the microcapsule with the strong acidic gastric juice environment, providing a certain buffer time for the contact of probiotics with the strong acidic environment, as the water pressure inside and outside the microcapsule gradually balances, the diffusion power of H + Also gradually weakens, and the chitosan powder gradually neutralizes the H + Inside the capsule and part of the H + Outside the capsule periphery in the dissolution process, and the sodium alginate or fucoidan inside the capsule can also absorb part of the H + , so that the pH value in the vicinity of the microcapsule is relatively high.

[0022] Thirdly, with the dissolution of chitosan, most of the chitosan will form a protective film on the stomach wall, thereby competitively inhibiting the adhesion of Helicobacter pylori to the binding sites on the stomach wall, preventing the adhesion of Helicobacter pylori on the stomach wall, and the dissolved chitosan adhered to the stomach wall can promote the healing of the ulcer site.

[0023] Fourthly, a part of the chitosan in the chitosan-embedded probiotic gel microcapsule will be adsorbed by the negatively charged edible gum such as sodium alginate or fucoidan, and combined on the surface of the probiotic microcapsule in the form of ionic bond, and since the chitosan is positively charged after dissolution, it is beneficial to prevent H + From further diffusing into the microcapsule, thereby ensuring that the pH value in the microcapsule remains high for a long time, which is beneficial to provide a good living environment for probiotics, so that the probiotics can better play the effect in the gastric juice.

[0024] In addition, during the treatment of Helicobacter pylori infection, the chitosan-embedded Bacillus natto gel microcapsule provided by the present application has the following advantages: the chitosan powder on the periphery of the microcapsule is positively charged after protonation, and through electrostatic action, the microcapsule is adsorbed on the stomach wall, prolonging the residence time of the microcapsule in the stomach, and being close to the Helicobacter pylori colonization site, the microcapsule adsorbed on the stomach wall is close to the Helicobacter pylori colonization site for a long time, and continuously releases chitosan and antibacterial substances such as natto kinase and antibacterial peptides in the capsule to destroy the biofilm formed after Helicobacter pylori infection, and the growth and reproduction of Bacillus natto in the microcapsule consume oxygen in the vicinity of the microcapsule, so that the Helicobacter pylori adhered to the stomach wall is exposed to anoxic and bactericidal environment, and the Helicobacter pylori on the stomach wall is inhibited for a long time and then hibernates and finally dies and falls off, and the fallen Helicobacter pylori is easily adsorbed by the positively charged chitosan capsule microspheres, and finally enters the intestine with chyme and is excreted out of the body with feces.

[0025] The fourth aspect of the present application is to provide a preparation method of the chitosan-embedded probiotic gel microcapsule, comprising the following steps:

[0026] S1 culture of probiotics: the probiotics are routinely cultured to the logarithmic phase of the probiotics to obtain a probiotic bacterial solution;

[0027] S2 preparation of probiotic sol solution: 0.5%-2% edible gum is added to the probiotic bacterial solution in S1, and mixed uniformly to obtain a probiotic sol solution;

[0028] S3 preparation of microcapsules: the probiotic sol solution obtained in S2 is pumped into a spray tower to form 60-200 μm probiotic sol droplets, which are sprayed into superfine chitosan powder, mixed by mechanical stirring to form probiotic gel microspheres, and freeze-dried to obtain the chitosan-embedded probiotic gel microcapsules.

[0029] The fifth aspect of the present application is to provide chitosan-embedded Bacillus natto gel microcapsules for preventing and / or treating H. pylori infection, which are prepared by wrapping Bacillus natto with sodium alginate or fucoidan solution as edible gum to form edible gum-embedded Bacillus natto sol solution, then spraying to form 60-200 μm Bacillus natto sol droplets, and finally coating the Bacillus natto sol droplets with chitosan powder.

[0030] The beneficial effects of the present application are:

[0031] (1) chitosan dry powder is used as the outer coating of the chitosan-embedded probiotic gel microcapsules, on the one hand, the chitosan dry powder can bind H + , thereby ensuring that the probiotic gel microcapsules contain a small amount of free H + , which is beneficial to maintaining a high pH value in the microspheres for a long time, providing a good living environment for probiotics;

[0032] On the other hand, when the chitosan powder-coated microcapsules enter the stomach cavity, the outer layer of chitosan dry powder first contacts the gastric acid and slowly dissolves in the gastric acid, avoiding direct contact of the probiotics in the microcapsules with the strong acid environment of the gastric juice, providing a short buffer time for the contact of the probiotics with the strong acid environment, reducing the damage of the strong acid environment of the gastric acid to Bacillus natto and other probiotics, thereby facilitating the microecological effect of Bacillus natto in the stomach to inhibit and kill H. pylori;

[0033] In addition, the dissolved chitosan powder can inhibit H. pylori and form a film on the gastrointestinal wall to protect the gastrointestinal health and promote the healing of inflammation or wounds;

[0034] (2) The preparation process of the probiotic gel microcapsule is simple, and the production cost is low. BRIEF DESCRIPTION OF DRAWINGS

[0035] Figure 1 A structure diagram of the chitosan-embedded probiotic gel microcapsule provided by the present application;

[0036] Figure 2 A real object diagram of the chitosan-embedded Bacillus natto gel microcapsule provided by Example 1 of the present application;

[0037] Figure 3 An enlarged schematic diagram of the chitosan-embedded Bacillus natto gel microcapsule provided by Example 1 of the present application;

[0038] Figure 4 Optical micrographs of Bacillus natto in the logarithmic phase and in simulated gastric juice in Example 1 of the present application; wherein (A) is a growth state diagram of Bacillus natto in the logarithmic phase in the culture solution; and (B) is a growth state diagram of Bacillus natto in the chitosan-embedded Bacillus natto gel microcapsule prepared by the method of the present embodiment. DETAILED DESCRIPTION

[0039] In order to enable those skilled in the art to better understand the present application, the present application will be further described in conjunction with specific embodiments.

[0040] Example 1

[0041] A chitosan-embedded Bacillus natto gel microcapsule, and a preparation method thereof, specifically includes the following steps:

[0042] S1 Culturing of Bacillus natto: The Bacillus natto is routinely cultured until the logarithmic phase of the Bacillus natto, to obtain a Bacillus natto bacterial solution;

[0043] S2 Preparation of a Bacillus natto sol solution: 2% sodium alginate is added to the Bacillus natto bacterial solution in S1 to obtain a Bacillus natto sol solution;

[0044] S3 Preparation of a microcapsule: the Bacillus natto sol solution in S2 is pumped into a spray tower to form sol droplets of about 60-100 μm, and the sol droplets are coated with 200-mesh chitosan powder, and then freeze-dried to form the chitosan-embedded Bacillus natto gel microcapsule, wherein the content of the Bacillus natto is 1×10 10 CFU / g microcapsule.

[0045] Figure 1 This is a schematic structural diagram of the chitosan-embedded probiotic gel microcapsule provided by the present invention. Figure 2 This is a photo of the chitosan-embedded Bacillus natto gel microcapsules prepared in this example. Figure 3 This is a schematic diagram of the enlarged structure of the Bacillus natto gel microcapsules prepared in this example.

[0046] Figure 1-3 As can be seen, the outer layer of the chitosan-embedded Bacillus natto gel microcapsules prepared by the present invention is coated with ultrafine chitosan dry powder, which wraps the inner layer of Bacillus natto gel. The unique structure of chitosan ensures that the interior of the microcapsule is in a relatively high pH environment, which is conducive to the survival of Bacillus natto.

[0047] The growth state of Bacillus natto in different environments was observed using an optical microscope. Figure 4 As shown, (A) is a diagram showing the growth status of Bacillus natto in the logarithmic phase in the culture medium; (B) is a diagram showing the growth status of Bacillus natto in the chitosan-embedded Bacillus natto gel microcapsules prepared by the method of this embodiment, Figure 4 The magnification of the microscope was ×800.

[0048] from Figure 4 It can be seen from the figure that when Bacillus natto is cultured to the logarithmic phase, the individuals of Bacillus natto are small, with high density and strong activity. In this embodiment, chitosan powder is used to encapsulate Bacillus natto sol droplets to obtain microcapsules. After 6 hours in a simulated gastric fluid (pH = 1.5) environment, Bacillus natto still exists in a vegetative form, with larger individuals and parts affected by the gel aggregated together. The activity is weaker than that in the non-encapsulated state. These characteristics may be due to the restriction of the gel. The split individuals are not separated in time and appear to be larger. The viscous properties of the gel restrict the movement of Bacillus natto.

[0049] Example 2

[0050] A chitosan-embedded Bacillus natto gel microcapsule, the preparation method specifically comprising the following steps:

[0051] S1. Cultivation of Bacillus natto: performing conventional culture on Bacillus natto until the logarithmic phase of Bacillus natto to obtain a Bacillus natto bacterial liquid;

[0052] Preparation of S2 Bacillus natto sol solution: adding sodium alginate with a final concentration of 1.5% to the Bacillus natto bacterial solution in S1 to obtain a Bacillus natto sol solution;

[0053] Preparation of the S3 microcapsule: the Bacillus natto sol solution in S2 is pumped into a spray tower to form sol droplets of 100-200 μm, the Bacillus natto sol droplets are coated with 150-mesh chitosan powder, and are freeze-dried to form the chitosan-embedded Bacillus natto gel microcapsule, wherein the content of Bacillus natto is 1 x 10 10 CFU / g microcapsule.

[0054] Example 3

[0055] A chitosan-embedded Bacillus natto gel microcapsule, the preparation method specifically comprising the following steps:

[0056] S1 Culturing of Bacillus natto: the Bacillus natto is routinely cultured until the logarithmic phase of the Bacillus natto, to obtain a Bacillus natto bacterial solution;

[0057] S2 Preparation of a Bacillus natto sol solution: 1% sodium alginate is added to the Bacillus natto bacterial solution in S1 to obtain a Bacillus natto sol solution;

[0058] S3 Preparation of the microcapsule: the Bacillus natto sol solution in S2 is pumped into a spray tower to form sol droplets of 100-200 μm, the Bacillus natto sol droplets are coated with 150-mesh chitosan powder, and are freeze-dried to form the chitosan-embedded Bacillus natto gel microcapsule, wherein the content of Bacillus natto is 1 x 10 10 CFU / g microcapsule.

[0059] Example 4

[0060] A chitosan-embedded Bacillus natto gel microcapsule, the preparation method specifically comprising the following steps:

[0061] S1 Culturing of Bacillus natto: the Bacillus natto is routinely cultured until the logarithmic phase of the Bacillus natto, to obtain a Bacillus natto bacterial solution;

[0062] S2 Preparation of a Bacillus natto sol solution: 2% fucoidan is added to the Bacillus natto bacterial solution in S1 to obtain a Bacillus natto sol solution;

[0063] S3 Preparation of the microcapsule: the Bacillus natto sol solution in S2 is pumped into a spray tower to form sol droplets of 100-200 μm, the Bacillus natto sol droplets are coated with 150-mesh chitosan powder, and are freeze-dried to form the chitosan-embedded Bacillus natto gel microcapsule, wherein the content of Bacillus natto is 1 x 10 10 CFU / g microcapsule.

[0064] Example 5

[0065] A chitosan-embedded lactobacillus gel microcapsule, the preparation method specifically comprising the following steps:

[0066] S1 Culturing of lactobacillus: The lactobacillus is routinely cultured to the logarithmic phase to obtain a lactobacillus bacterial solution;

[0067] S2 Preparation of lactobacillus sol solution: 2% sodium alginate is added to the lactobacillus bacterial solution in S1 to obtain a lactobacillus sol solution;

[0068] S3 Preparation of microcapsules: the lactobacillus sol solution in S2 is pumped into a spray tower to form sol droplets of 60-100 μm, the lactobacillus sol droplets are coated with 200-mesh chitosan powder, and are freeze-dried to form the chitosan-embedded lactobacillus gel microcapsule, wherein the content of lactobacillus is 1×10 10 CFU / g microcapsule.

[0069] Comparative Example 1

[0070] A chitosan-embedded bacillus natto gel microcapsule, the preparation method specifically comprising the following steps:

[0071] S1 Culturing of bacillus natto: The bacillus natto is routinely cultured to the logarithmic phase to obtain a bacillus natto bacterial solution;

[0072] S2 Preparation of bacillus natto sol solution: 2% sodium alginate is added to the bacillus natto bacterial solution in S1 to obtain a bacillus natto sol solution;

[0073] S3 Preparation of microcapsules: the lactobacillus sol solution in S2 is pumped into a spray tower to form sol droplets of 60-100 μm, the lactobacillus sol droplets are coated with 200-mesh chitosan powder, and are freeze-dried to form the chitosan-embedded lactobacillus gel microcapsule, wherein the content of lactobacillus is 1×10 10 CFU / g.

[0074] The chitosan-embedded probiotic gel microcapsules prepared in each example and comparative example are used for clinical research.

[0075] Research object: patients who visit a hospital due to digestive system symptoms in 2023-2024 are selected, and 13 C breath test 13280 cases were selected as the research objects, including 152 male cases and 128 female cases, with the age of 8-72 years old and the average age of 39 years old; 280 cases included 205 cases of chronic gastritis and 75 cases of peptic ulcer, and all the above patients were initial treatment cases.

[0076] Grouping and treatment: 280 patients were randomly grouped according to the order of visiting by using the completely random design method, and were divided into 8 groups, with 35 people in each group.

[0077] The blank group took placebo at time, and the taking method was the same as that of the experimental group; the placebo was a microcapsule prepared by using sodium alginate sol and starch without embedding any microorganism;

[0078] The traditional triple therapy treatment group was given triple therapy treatment (20 mg of Losec twice a day, 1.0 g of amoxicillin twice a day, and 0.1 g of furazolidone three times a day);

[0079] Each experimental group took the chitosan-embedded probiotic gel microcapsule prepared in each embodiment and the comparative example, and the treatment mode was 0.5 g each time, 3 times a day, for a total of 6 weeks.

[0080] Each group was reexamined after the treatment 13 C-UBT, whether the helicobacter pylori was eradicated was judged according to the detection result.

[0081] Reexamination of the treatment period less than 6 weeks 13 C-UBT result is negative, reexamination after 30 days of drug withdrawal 13 C-UBT result is still negative, and it is judged as cured; if it is not cured, continue to take medicine until 6 weeks after the treatment 13 C-UBT result is negative, and it is judged as cured.

[0082] The treatment effects of the drugs of each group on helicobacter pylori are shown in Table 1.

[0083] Table 1 Treatment effect of chitosan-embedded probiotic gel microcapsule

[0084] Experimental group 2 weeks healing case 3 weeks healing case 4 weeks healing case 6 weeks healing case Healing rate (%) Blank group (placebo group) 0 0 0 1 2.8 Example 1 17 20 21 27 77.1 Example 2 14 17 18 25 71.4 Example 3 13 15 18 21 60 Example 4 18 22 25 28 80 Example 5 9 13 18 18 51.4 Comparative example 1 3 5 5 6 17.1 Traditional triple therapy 15 18 20 25 71.4

[0085] The results show that the treatment effect of the chitosan-embedded bacillus natto gel microcapsule prepared in embodiments 1-4 on helicobacter pylori is much higher than that of the chitosan-embedded lactobacillus gel microcapsule in embodiment 5, and in particular, after the microcapsule in embodiment 4 is used for treatment, only 7 patients are not completely cured after 6 weeks, but the Hp detection amount and clinical symptoms of the 7 patients are obviously improved after 6 weeks.

[0086] The chitosan-embedded lactobacillus gel microcapsules in Example 5 also have a certain healing effect, but the effect is not significant, which may be because the oxygen consumption capacity of lactobacillus is relatively weak, and it cannot create an anaerobic environment for helicobacter pylori.

[0087] In addition, after taking the microcapsules prepared in Examples 1-4 of the present application for two weeks, the detection amount of Hp of all the test patients is obviously decreased.

[0088] The differences between the above examples and the comparative examples are shown in Table 2.

[0089] Table 2 Differences in raw materials between examples and comparative examples

[0090] Probiotic species Edible gum species and content Sol droplet particle size (μm) Chitosan particle size (mesh) Example 1 Bacillus natto 2% sodium alginate 60-100 200 Example 2 Bacillus natto 1.5% sodium alginate 100-200 150 Example 3 Bacillus natto 1% sodium alginate 100-200 100 Example 4 Bacillus natto 2% fucoidan 60-100 200 Example 5 Lactobacillus 2% sodium alginate 60-100 200 Comparative example 1 Bacillus natto 2% sodium alginate 60-100 200

[0091] As can be seen from Table 2, in Examples 1-3, the concentration of edible gum gradually decreases during the preparation of chitosan-embedded bacillus natto gel microcapsules, the particle size of the sol droplets and chitosan gradually increases, and at the same time, the cure rate of the microcapsules for helicobacter pylori shows a decreasing trend.

[0092] Example 4 only changes the composition of edible gum during the preparation of gel microcapsules compared with Example 1, replacing sodium alginate with fucoidan, and the cure rate of the obtained microcapsules for helicobacter pylori is not much different from that of Example 1.

[0093] In addition, Example 5 replaces bacillus natto with lactobacillus based on Example 1, and the bacterial concentration remains unchanged. Due to the difference between lactobacillus and bacillus natto, the cure rate is reduced, which to varying degrees indicates that consuming oxygen in the environment of helicobacter pylori is an important factor for clearing helicobacter pylori infection.

[0094] In Comparative Example 1, the chitosan solution is used to embed the bacillus natto gel to prepare the obtained gel microcapsules, which have a certain therapeutic effect, but the cure effect is the worst in the treatment period. This is because the microcapsules prepared by the conventional process cannot effectively buffer the gastric acid in the stomach cavity, the microorganisms cannot grow and reproduce in the stomach, cannot continuously consume oxygen at the helicobacter pylori colonization site, release bacteriostatic substances, and the survival rate is low, so the therapeutic effect is poor.

Claims

1. A chitosan-encapsulated probiotic gel microcapsule for use against Helicobacter pylori infection, characterized in that, The chitosan powder is used as a coating of the probiotic gel microcapsule, the particle size of the chitosan powder is 200 mesh, and the probiotic is Bacillus natto; The probiotic gel is obtained by wrapping the Bacillus natto with 2% fucoidan; The content of Bacillus natto in the microcapsule is 1×10 10 CFU / g, and the particle size of the microcapsule is 300-500 μm.

2. A process for the preparation of chitosan-entrapped probiotic gel microcapsules as claimed in claim 1, characterized in that, The steps include the following: S1, culture of the probiotic: the probiotic is conventionally cultured to the logarithmic phase to obtain a probiotic bacterial solution, and the probiotic is Bacillus natto; S2, preparation of a probiotic sol solution: 2% edible gum is added to the probiotic bacterial solution in S1, and mixed uniformly to obtain a probiotic sol solution, and the edible gum is fucoidan; S3, preparation of a microcapsule: the probiotic sol solution obtained in S2 is pumped into a spray tower to form probiotic sol droplets, which are sprayed into superfine chitosan powder, mixed by mechanical stirring to form a probiotic gel microsphere, and freeze-dried to obtain the chitosan-embedded probiotic gel microcapsule.

3. The production method according to claim 2, wherein In S3, the particle size of the probiotic sol droplets is 60-200 μm.

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