Enterococcus faecium probiotic-prebiotics composite tablet and preparation method thereof

Abstract

The invention provides an enterococcus faecium probiotic-prebiotics composite tablet and a preparation method thereof, and belongs to the technical field of microbial preparations. The tablet is prepared by taking enterococcus faecium (preservation number: CGMCC NO.33919) as a core active component, matching prebiotics adapted to the intestinal tracts of old people, a high-stability protective agent and mild auxiliary materials through a specific process. The tablet can efficiently adjust the intestinal flora structure of the old people, inhibit the proliferation of harmful bacteria in the intestinal tract and enhance the intestinal barrier function of the old people, so that the functional diarrhea and antibiotic-related diarrhea of the old people are relieved, and the tablet is moderate in hardness, easy to swallow, free of intestinal irritation and high in normal-temperature storage stability; the problems that an existing intestinal preparation is poor in adaptability to intestinal tracts of old people, strain activity is prone to inactivation, and swallowing is difficult are solved.

Description

Technical Field

[0001] This invention relates to the field of microbial preparation technology, specifically to an Enterococcus faecalis probiotic-prebiotic compound tablet and its preparation method, which is suitable for improving the intestinal health of the elderly. Background Technology

[0002] As people age, their intestinal function gradually declines, primarily manifested in reduced digestive enzyme secretion, decreased intestinal barrier function, and reduced gut microbiota diversity. These changes easily lead to gut microbiota imbalance, which can cause problems such as functional diarrhea and antibiotic-associated diarrhea, significantly impacting the quality of life and health of the elderly. Furthermore, the weakened chewing and swallowing abilities of older adults make them more sensitive to highly irritating medications or supplements, often resulting in poor user experience and efficacy of traditional gut health products in this population.

[0003] Currently available intestinal preparations have numerous compatibility issues, failing to fully meet the specific needs of elderly individuals for maintaining intestinal health. Firstly, strain protection systems are generally insufficient; most preparations exhibit poor stability under normal temperature storage conditions (such as in the home environment of elderly individuals), with the number of live bacteria significantly decreasing after three months of storage, typically below 60%, making it difficult to guarantee long-term efficacy. Secondly, existing preparations often contain polysaccharides or irritating binders, which can easily cause bloating or intestinal discomfort, potentially exacerbating intestinal problems in the elderly. Furthermore, the dosage form design is inadequate; most tablets are hard (usually >5kg) and heavy (mostly >1g), making it easy for elderly individuals to choke during swallowing, significantly reducing adherence.

[0004] Meanwhile, many intestinal preparations fail to fully consider the specificity of the gut microbiota in the elderly and lack a synergistic "probiotic-prebiotic" system, resulting in limited and unsustainable regulatory effects. Probiotics are a class of live microorganisms beneficial to health, capable of balancing the gut microbiota, inhibiting the proliferation of harmful bacteria, and promoting improved intestinal function. Prebiotics, on the other hand, are specific food components or substances that are not easily digested by the human body and can selectively promote the growth of beneficial bacteria in the gut or enhance their activity. The synergistic effect of probiotics and prebiotics is of great significance in maintaining gut microecological balance, improving functional diarrhea, and enhancing overall gut health.

[0005] Patent CN108514121A discloses a probiotic and prebiotic compound product for laxative and detoxifying purposes, including probiotic components such as Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus, Bacillus subtilis, Enterococcus faecalis, and Clostridium butyricum. However, these formulations do not fully consider the specificity of the intestinal flora and physical condition of the elderly, thus having certain limitations in practical applications. Different strains may compete for activity or interfere with each other, leading to a weakening of the function of some probiotics and failing to achieve a synergistic effect. Furthermore, an excessive number of strains may increase the technical difficulty in formulation production, affecting strain stability and survival rate. Intestinal preparations for the elderly have higher requirements for the stability of live bacteria under room temperature storage conditions; failure to maintain the number of live bacteria will further reduce the effectiveness of use.

[0006] To address the aforementioned issues, we have developed a Enterococcus faecalis gut health improvement tablet specifically tailored to the gut characteristics of the elderly. This tablet features high stability, ease of swallowing, and a design that combines probiotics and prebiotics for synergistic effects. It will provide a superior gut health solution for the elderly population and has significant practical application value. Summary of the Invention

[0007] To address the shortcomings of existing probiotic and prebiotic compound products tailored to the intestinal characteristics of the elderly, this invention provides a tablet prepared using a patented Enterococcus faecalis (accession number: CGMCC NO.: 33919) as the core active ingredient, combined with prebiotics suitable for the intestinal characteristics of the elderly, a highly stable protectant, and mild excipients, through a specific process.

[0008] In a first aspect, the present invention provides an Enterococcus faecium probiotic-prebiotic complex tablet comprising the following components: 5-20% Enterococcus faecium probiotic powder, 15-20% galacto-oligosaccharides, 10-15% preservative, 35-40% microcrystalline cellulose, 5-10% hydroxypropyl methylcellulose, and 2-3% magnesium stearate. The Enterococcus faecium probiotic mentioned is Enterococcus faecium, accession number: CGMCC NO.: 33919, accession date: March 21, 2025, depositary institution: China General Microbiological Culture Collection Center; The degree of polymerization of the oligogalactose is 3-5; The Enterococcus faecalis probiotic powder contains galactooligosaccharides in a ratio of 1:1.5~2. The protective agent is trehalose and skim milk powder in a ratio of 1:1.5~3.

[0009] Galacto-oligosaccharides can specifically promote the proliferation of beneficial bacteria in the gut of the elderly; trehalose and skim milk powder are combined to form a highly effective probiotic protectant, which can maintain cell membrane integrity and reduce freeze-drying damage; hydroxypropyl methylcellulose is an excipient suitable for the elderly, with no special contraindications, no components that may cause bloating throughout the process, and is suitable for the gut environment of the elderly.

[0010] According to a specific embodiment of the present invention, the tablet hardness is 3~4 kg.

[0011] According to a specific embodiment of the present invention, the tablet weight is 0.6~0.8g.

[0012] According to a specific embodiment of the present invention, the tablet disintegration time is ≤30 min.

[0013] Secondly, the present invention provides a method for preparing Enterococcus faecium probiotic-prebiotic complex tablets, comprising the following steps: (1) Pretreatment of bacterial powder: Enterococcus faecalis probiotic powder and protectant (trehalose + skim milk powder) are added to a sterile mixer and stirred at 170 r / min for 20 min to obtain premixed bacterial powder; (2) Pretreatment of excipients: Mix galacto-oligosaccharides, microcrystalline cellulose and hydroxypropyl methylcellulose, add purified water to make soft material, granulate through an 18-mesh sieve, and dry in an oven at 42°C to obtain excipient granules; (3) Total mixing: Add the premixed bacterial powder, excipient granules, and magnesium stearate to the mixer, stir at 160 r / min for 23 min, and granulate through a 20 mesh sieve to obtain total mixed granules; (4) Tableting: Put the total mixed particles into the tableting machine and compress them into tablets.

[0014] According to a specific embodiment of the present invention, the temperature is controlled to be ≤35℃ and the humidity to be ≤30% throughout the process.

[0015] According to a specific embodiment of the present invention, after granulation in step (2), the granulation is dried at low temperature until the moisture content is ≤5%.

[0016] According to a specific embodiment of the present invention, after granulation in step (2), the granulation is dried at low temperature to a moisture content of 2.5%.

[0017] According to a specific embodiment of the present invention, the tableting pressure in step (4) is 28~35kN.

[0018] Employing a "low-temperature stepwise granulation-gentle tableting" process, with temperature controlled at ≤35℃ and humidity at ≤30% throughout the process to prevent live bacteria inactivation: In the pretreatment stage, Enterococcus faecalis probiotic powder is premixed with a compound preservative in a specific ratio. After granulation, it is dried at low temperature until the moisture content is ≤5%. Environmental parameters are strictly controlled throughout the mixing and tableting process, and finally, the product is individually vacuum-packed in aluminum foil. This low-temperature process significantly improves the survival rate of probiotics, aligning with the mechanism of action of the trehalose-skimmed milk powder compound preservative.

[0019] According to a specific embodiment of the present invention, the viable bacteria retention rate of Enterococcus faecium probiotic-prebiotic complex tablets is ≥85% when stored at room temperature (20-25℃) for 6 months. Beneficial effects

[0020] This invention provides a *Enterococcus faecium* probiotic-prebiotic complex tablet specifically designed for the elderly. Through the addition of a scientifically formulated ratio of *Enterococcus faecium* and galactooligosaccharides, a synergistic system of probiotics and prebiotics is formed, effectively inhibiting harmful intestinal bacteria and promoting the proliferation of beneficial bacteria, thereby improving the intestinal microecological balance and alleviating common intestinal health problems in the elderly, such as diarrhea. Furthermore, the innovative use of trehalose and skim milk powder as a protective agent, combined with a "low-temperature stepwise granulation-mild tableting" process, effectively improves the survival rate of probiotics. The viable bacteria retention rate reaches over 85% after 6 months of storage at room temperature, ensuring the stability and long-term efficacy of the formulation. The optimized tablet hardness, weight, and rapid disintegration characteristics significantly improve the suitability for elderly users, avoiding swallowing difficulties and digestive discomfort. This provides a novel solution for the intestinal health of the elderly, possessing significant clinical application value and broad market prospects. Attached Figure Description

[0021] Figure 1 This is a graph showing the number of live probiotics under different proportions of protectant in Example 4.

[0022] Figure 2 This is the physical property verification spectrum of the tablet in Example 5. Detailed Implementation

[0023] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of protection of the present invention. After reading this invention, any modifications of the present invention in various equivalent forms, or direct or indirect applications in other related technical fields, made by those skilled in the art, shall fall within the scope defined by the appended claims. Example 1

[0024] Prepare Enterococcus faecalis probiotic-prebiotic complex tablets according to the following mass percentages: Element Quality percentage (%) <![CDATA[Enterococcus faecium probiotic powder (viable count 1.2×10 10 CFU / g)]]> 10 Galacto-oligosaccharides (degree of polymerization 3-5) 18 Protectant (trehalose:skimmed milk powder = 1:1.5) 14 microcrystalline cellulose 38 Hydroxypropyl methylcellulose 7 magnesium stearate 3 Preparation steps: (1) Pretreatment of bacterial powder: 10 kg of Enterococcus faecalis probiotic powder and 14 kg of protectant (5.6 kg of trehalose + 8.4 kg of skim milk powder) were added to an aseptic mixer, and the temperature was controlled at 26℃ and the humidity at 30%. The mixture was stirred at 170 r / min for 20 min to obtain 24 kg of premixed bacterial powder. (2) Pretreatment of excipients: Mix 18kg of galactooligosaccharide, 38kg of microcrystalline cellulose and 7kg of hydroxypropyl methylcellulose, add purified water (63kg×9%=5.67kg) to make soft material, granulate through an 18-mesh sieve, and dry in an oven at 42℃ until the moisture content of the particles is 2.5% to obtain 65.67kg of excipient particles. (3) Total mixing: Add 24 kg of premixed bacterial powder, 65.67 kg of excipient granules and 3 kg of magnesium stearate to a mixer, stir at 160 r / min for 23 min, and granulate through a 20 mesh sieve to obtain 92.67 kg of total mixed granules; (4) Tableting: Put the total mixed particles into the tablet press, set the tableting pressure to 32kN, and press the tablet.

[0025] The tablets were pressed to obtain tablets with a weight of 0.7g and a hardness of 3.5kg, and a total of about 132,385 tablets were produced. Example 2

[0026] Increasing the amount of hydroxypropyl methylcellulose (from 7% to 10%) and decreasing the amount of microcrystalline cellulose (from 38% to 35%), combined with a low tableting pressure of 28kN, enhances the adhesive effect of hydroxypropyl methylcellulose, which can maintain tablet formability under low pressure.

[0027] Prepare Enterococcus faecalis probiotic-prebiotic complex tablets according to the following mass percentages: Element Quality percentage (%) <![CDATA[Enterococcus faecium probiotic powder (viable count 1.2×10 10 CFU / g)]]> 10 Galacto-oligosaccharides (degree of polymerization 3-5) 18 Protectant (trehalose:skimmed milk powder = 1:1.5) 14 microcrystalline cellulose 35 Hydroxypropyl methylcellulose 10 magnesium stearate 3 Preparation steps: (1) Pretreatment of bacterial powder: 10 kg of Enterococcus faecalis probiotic powder and 14 kg of protectant (5.6 kg of trehalose + 8.4 kg of skim milk powder) were added to an aseptic mixer, and the temperature was controlled at 25℃ and the humidity at 28%. The mixture was stirred at 165 r / min for 22 min to obtain 24 kg of premixed bacterial powder. (2) Pretreatment of excipients: Mix 18kg of galactooligosaccharide, 35kg of microcrystalline cellulose and 10kg of hydroxypropyl methylcellulose, add purified water (63kg×11%=6.93kg) to make soft material, granulate through an 18-mesh sieve, and dry in an oven at 40℃ until the moisture content of the particles is 2.2% to obtain 66.93kg of excipient particles; (3) Total mixing: Add 24 kg of premixed bacterial powder, 66.93 kg of excipient granules and 3 kg of magnesium stearate to a mixer, stir at 155 r / min for 25 min, and granulate through a 20 mesh sieve to obtain 93.93 kg of total mixed granules; (4) Tableting: Put the total mixed particles into the tablet press, set the tableting pressure to 28kN, and press the tablet.

[0028] The tablets were pressed to obtain tablets with a weight of 0.6g and a hardness of 3.0kg, and a total of about 156,550 tablets were produced.

[0029] Example 3 By reducing the amount of magnesium stearate (from 3% to 2.5%), fine-tuning the ratio of microcrystalline cellulose to hydroxypropyl methylcellulose, and applying a 35kN high-pressure plate, the reduced amount of magnesium stearate can improve particle adhesion and achieve the target hardness under high pressure.

[0030] Prepare Enterococcus faecalis probiotic-prebiotic complex tablets according to the following mass percentages: Element Quality percentage (%) <![CDATA[Enterococcus faecium probiotic powder (viable count 1.2×10 10 CFU / g)]]> 10 Galacto-oligosaccharides (degree of polymerization 3-5) 18 Protectant (trehalose:skimmed milk powder = 1:1.5) 14 microcrystalline cellulose 39 Hydroxypropyl methylcellulose 6.5 magnesium stearate 2.5 (1) Pretreatment of bacterial powder: 10 kg of Enterococcus faecalis probiotic powder and 14 kg of protectant (5.6 kg of trehalose + 8.4 kg of skim milk powder) were added to an aseptic mixer, and the temperature was controlled at 27℃ and the humidity at 29%. The mixture was stirred at 175 r / min for 18 min to obtain 24 kg of premixed bacterial powder. (2) Pretreatment of excipients: Mix 18kg of galactooligosaccharide, 39kg of microcrystalline cellulose and 6.5kg of hydroxypropyl methylcellulose, add purified water (63.5kg×8.5%=5.4kg) to make soft material, granulate through an 18-mesh sieve, and dry in an oven at 43℃ until the moisture content of the particles is 2.8% to obtain 66.9kg of excipient particles; (3) Total mixing: Add 24 kg of premixed bacterial powder, 66.9 kg of excipient granules and 2.5 kg of magnesium stearate to a mixer, stir at 165 r / min for 20 min, and granulate through a 20 mesh sieve to obtain 93.4 kg of total mixed granules; (4) Tableting: Put the total mixed particles into the tablet press, set the tableting pressure to 35kN, and press the tablet.

[0031] The tablets were pressed to obtain tablets with a weight of 0.8g and a hardness of 4.0kg, and a total of about 116,750 tablets were produced. Example 4: Effect of different protectant ratios on the stability of probiotics

[0032] Prepare tablets with different protective agent ratios according to Table 1. Table 1 Formula number Protectant ratio (trehalose: skim milk powder) Trehalose dosage (kg) Skim milk powder usage (kg) Total amount of protective agent used (kg) Example 1 1：1.5 5.60 8.40 14 Formula 1 1：1 9.33 4.67 14 Formula 2 1：0.5 7.00 7.00 14 Formula 3 1：2 4.67 9.33 14 Formula 4 1：3 3.50 10.05 14 The tablets in Table 1 were stored at 25°C and 60% relative humidity for 6 months, and samples were taken for testing at 0 months, 3 months and 6 months.

[0033] 1. Sample preparation: Take 1000 tablets of each probiotic-prebiotic compound tablet prepared in each group, remove the outer packaging, put them into a pharmaceutical polyethylene bottle and seal it. Set up 3 parallel samples for each group.

[0034] 2. Storage conditions: The sealed sample was placed in a constant temperature and humidity chamber at 25℃ and 60% relative humidity for accelerated stability testing. The storage period was 6 months.

[0035] 3. Sampling and testing: At 0 months (initial), 3 months and 6 months of storage, 10 tablets were randomly selected from each group of parallel samples as test samples, and the viable bacteria count was tested according to the microbial examination method of the Pharmacopoeia of the People's Republic of China.

[0036] Viable bacteria count test procedure: Take one sample and place it in sterile physiological saline. Shake thoroughly to disintegrate and disperse the tablet. Prepare a series of gradient dilutions. Select the appropriate dilution and spread it on MRS agar medium. After anaerobic incubation at 37°C for 48 hours, count the number of colonies and calculate the number of viable bacteria per tablet (CFU / tablet).

[0037] 4. Results Analysis: Record the test data at different time points, calculate the viable count retention rate (viable count retention rate = viable count after storage / initial viable count × 100%), and evaluate the stability of the tablets.

[0038] The results are as follows Figure 1 As shown, in Examples 1, Formula 3, and Formula 4, the viable count at 0 months was 1.2 × 10⁻⁶. 10 CFU / tablet, approximately 1.15 × 10⁻⁶ over 3 months. 10 CFU / tablet, approximately 1.03 × 10⁻⁶ over 6 months. 10 CFU / tablet, with a live bacteria retention rate of up to 85.8%, meets the long-term storage needs of the elderly. Example 5: Physical Performance Verification

[0039] One hundred tablets of probiotic-prebiotic compound tablets prepared in Examples 1-3 were randomly selected. Residual particles and impurities on the tablet surface were removed. The samples were divided into three groups (30 tablets per group, with the remaining 10 tablets used as backup samples). Tablet weight variation, tablet hardness, and disintegration time in simulated gastric fluid were tested according to the requirements of the General Rules, Part IV, of the 2020 edition of the Pharmacopoeia of the People's Republic of China. The specific steps are as follows: 1. Tablet weight difference detection Using an electronic balance with an accuracy of 0.01%, the weight of each tablet in each group of 30 tablets was weighed sequentially, and the weight data of each tablet was recorded. The average weight of the 30 tablets was calculated, and then the percentage difference between the weight of each tablet and the average weight was calculated. The distribution range of the percentage difference in tablet weight was statistically analyzed to determine whether it meets the tablet quality standards.

[0040] 2. Tablet hardness testing Using a YD-1 tablet hardness tester, place the tablet horizontally between the indenter and the base of the hardness tester. Set the indenter to apply pressure at a uniform rate of 2 mm / s. Start the instrument until the tablet breaks. Record the pressure value at this point, which is the hardness of the tablet. Repeat this process for 30 tablets and analyze the fluctuation range of the hardness values.

[0041] 3. Disintegration time detection in artificial gastric fluid (1) Preparation of artificial gastric juice: Take 24 mL of dilute hydrochloric acid, add purified water to dilute to 1000 mL, stir evenly, and then adjust the pH to 1.2 with hydrochloric acid or sodium hydroxide solution to obtain artificial gastric juice; (2) Disintegration time limit test: According to the disintegration time limit test method in General Chapter 0921 of the Chinese Pharmacopoeia, the disintegrator basket was immersed in a beaker containing artificial gastric fluid and the temperature was controlled at 37℃±0.5℃. Six tablets were placed in the glass tube of the basket, the disintegrator was started, and the time for each tablet to completely disintegrate (no residual particles larger than 2mm after disintegration) was observed and recorded. Five groups (30 tablets in total) were tested repeatedly, and the range of disintegration time limit was calculated.

[0042] The results are as follows Figure 2 As shown, the hardness of the tablets is between 3.2-3.8 kg, the disintegration time in artificial gastric juice is ≤28 minutes, and the weight difference is ≤±5%, which meets the swallowing and disintegration needs of the elderly. In vitro microbial regulation verification

[0043] The bacterial suspension obtained after disintegration of the tablets in the formulations in Table 2 below (containing 1×10⁶ Enterococcus faecalis) 8 (CFU / mL) was co-cultured with a gut microbiota mimicry solution from elderly individuals for 24 hours. Table 2 Formula number Probiotic-Prebiotic Ratio Percentage of Enterococcus faecium probiotic powder (%) Galacto-oligosaccharide percentage (%) Formula characteristics Example 1 1：1.5 12 18 Appropriate prebiotic content Formula 1 1：0.5 15 7.5 Low prebiotic content Formula 2 1：2.0 10 20 Slightly higher prebiotic content Formula 3 1：3.0 8 24 Excessive prebiotic content The results are shown in Table 3. Table 3 Formula number Probiotic-Prebiotic Ratio E. coli reduction rate (%) Bifidobacteria increase Gas production (mL / L) Evaluation of the effect of gut microbiota regulation Intestinal burden assessment Example 1 1:1.5 82.3 2.1 9.2 Excellent results, significantly inhibiting harmful bacteria and greatly increasing beneficial bacteria. No obvious burden Formula 1 1:0.5 31.2 1.2 5.8 Poor efficacy, insufficient inhibition of harmful bacteria, and limited proliferation of beneficial bacteria. No burden Formula 2 1:2.0 85.7 2.3 12.5 The effect was optimal, with a slightly better gut microbiota regulation effect than Example 1. slight burden Formula 3 1:3.0 84.9 2.2 18.7 The effect was good, but there was no significant difference compared with Formula Example 1 and Formula 2. The burden has increased significantly. Formula 1 (Enterococcus faecalis probiotic powder: galactooligosaccharide ratio of 1:0.5), which has too low a prebiotic content, only reduced Escherichia coli by 31.2% and increased Bifidobacteria by 1.2 times. The effect of gut microbiota regulation was poor, and the lack of prebiotics could not provide sufficient carbon source for the proliferation of probiotics.

[0044] Example 1 (Enterococcus faecalis probiotic powder: galactooligosaccharide ratio of 1:1.5) can reduce Escherichia coli by 82.3% and increase Bifidobacteria by 2.1 times, with a gas production of only 9.2 mL / L and no obvious intestinal burden. It is the optimal ratio that balances the effect of flora regulation and the intestinal tolerance of the elderly.

[0045] Formula 2 (Enterococcus faecium probiotic powder: galactooligosaccharide ratio of 1:2.0), with a slightly higher prebiotic content, showed a slightly better regulatory effect (E. coli decreased by 85.7%, Bifidobacteria increased by 2.3 times), and gas production increased to 12.5 mL / L, resulting in a slight intestinal burden. Formula 3 (Enterococcus faecium probiotic powder: galactooligosaccharide ratio of 1:3.0), with an excessively high prebiotic content, did not significantly improve the regulatory effect, but gas production reached 18.7 mL / L, significantly increasing the intestinal burden and easily causing discomfort such as abdominal distension in the elderly.

[0046] Probiotic-prebiotic complex tablets (Enterococcus faecium probiotic powder: galactooligosaccharide ratio of 1:1.5~2.0) can effectively regulate the intestinal flora structure of the elderly, inhibit harmful bacteria and promote the growth of beneficial bacteria, without increasing the digestive burden on the intestines, providing an experimental basis for relieving diarrhea in the elderly and improving the intestinal microecological balance.

Claims

1. A compound tablet containing Enterococcus faecalis probiotics and prebiotics, characterized in that, It includes the following components: 5-20% Enterococcus faecalis probiotic powder, 15-20% galacto-oligosaccharides, 10-15% preservative, 35-40% microcrystalline cellulose, 5-10% hydroxypropyl methylcellulose, and 2-3% magnesium stearate. The Enterococcus faecalis probiotic is Enterococcus faecalis. Enterococcus faecium Accession number: CGMCC NO.: 33919; The degree of polymerization of the oligogalactose is 3-5; The Enterococcus faecalis probiotic powder contains galactooligosaccharides at a ratio of 1:1.5~2.

0. The protective agent is trehalose and skim milk powder in a ratio of 1:1.5~3.

0.

2. The tablet according to claim 1, characterized in that, The hardness is 3.0~4.0 kg.

3. The tablet according to claim 1, characterized in that, Each tablet weighs 0.6~0.8g.

4. The tablet according to claim 1, characterized in that, Disintegration time ≤ 30 min.

5. A method for preparing the tablet according to claim 1, characterized in that, Includes the following steps: (1) Pretreatment of bacterial powder: Add Enterococcus faecalis probiotic powder and protectant to a sterile mixer and stir at 170 r / min for 20 min to obtain premixed bacterial powder; (2) Pretreatment of excipients: Mix galacto-oligosaccharides, microcrystalline cellulose and hydroxypropyl methylcellulose, add purified water to make soft material, granulate through an 18-mesh sieve, and dry in an oven at 42°C to obtain excipient granules; (3) Total mixing: Add the premixed bacterial powder, excipient granules, and magnesium stearate to the mixer, stir at 160 r / min for 23 min, and granulate through a 20 mesh sieve to obtain total mixed granules; (4) Tableting: Put the total mixed particles into the tableting machine and compress them into tablets.

6. The preparation method according to claim 5, characterized in that, Temperature should be controlled at ≤35℃ throughout the process.

7. The preparation method according to claim 5, characterized in that, Humidity is controlled to be ≤30% throughout the process.

8. The preparation method according to claim 5, characterized in that, After granulation in step (2), the product is dried at low temperature until the moisture content is ≤5%, preferably 2.5%.

9. The preparation method according to claim 5, characterized in that, Step (4) The tableting pressure is 28~35kN.

10. The tablet according to claim 1, characterized in that, Store at room temperature (20-25℃) for 6 months, with a viable bacteria retention rate of ≥85%.

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