Drying method of coprophilous fungus multi-layer dropping pills

Abstract

The invention belongs to the technical field of medicament preparation, and provides a drying method of coprophilous fungus multi-layer dropping pills. The drying method comprises the following steps: firstly, providing coprophilous fungus multi-layer dropping pills; carrying out centrifugal deoiling on the coprophilous fungus multi-layer dropping pills by using a deoiling agent, and then carrying out separation treatment to obtain deoiled dropping pills; the deoiling agent is a mixture of fumed silica, soybean fibers and oat cellulose; performing forced air drying on the deoiled dropping pills to obtain pre-dried dropping pills; and carrying out negative pressure drying on the pre-dried dropping pill to obtain the Huanglong dropping pill. According to the drying method provided by the invention, centrifugal deoiling, forced air drying and negative pressure drying are performed in sequence, so that the water activity of the Huanglong dropping pills is further reduced. The data of the embodiment shows that the water activity aw of the Huanglong dropping pill is 0.08-0.14, and the Huanglong dropping pill has excellent tolerance, especially in-vitro simulated gastrointestinal tolerance, and also has excellent stability.

Description

Technical Field

[0001] The invention relates to the technical field of medicament preparation, and in particular to a method for drying fecal bacteria multi-layer drop pills. Background Art

[0002] "Fecal microbiota transplantation" (FMT) refers to transplanting the functional flora in the feces of healthy people into the intestines of patients to rebuild new intestinal flora and achieve the treatment of intestinal and extra-intestinal diseases. It can treat intestinal diseases such as Clostridium difficile infection, refractory diarrhea, constipation, gastroenteritis, Crohn's disease, ulcerative gastroenteritis, and extra-intestinal diseases such as obesity, asthma, obesity, autism, depression, diabetes, cancer and other difficult and complicated diseases.

[0003] Fecal microbiota transplantation administration routes are divided into three types: upper gastrointestinal tract, middle gastrointestinal tract and lower gastrointestinal tract. The upper gastrointestinal tract route mainly refers to oral fecal microbiota capsules, which have the advantages of non-invasiveness and high patient acceptance. The middle gastrointestinal tract route mainly includes nasogastric tubes, nasojejunal tubes and nasoduodenal tubes, which are particularly suitable for patients with colon inflammation, but intubation will cause discomfort to patients and this route cannot evaluate the patient's intestinal mucosa and collect tissue samples. The lower gastrointestinal tract route mainly includes colonoscopy and retention enema, which reduces patient discomfort compared to intubation, and because intestinal cleansing is required before surgery, the colon condition can be located and beneficial bacteria can be delivered to the targeted area, but the disadvantage is that it can only be infused in the distal colon. The above three methods have similar therapeutic effects, and the oral fecal microbiota capsule method is the most easily accepted by patients, so it has the broadest application prospects.

[0004] Huanglong Drop Pills are made of freeze-dried fecal bacteria powder as raw materials. Seamless drop pills are prepared using a new drop pill preparation technology, and then the seamless drop pills are dried to obtain; the results of the in vitro disintegration test of Huanglong Drop Pills showed that they were intact for 2 hours in an acidic environment with a pH of 1.2, and still had good integrity for 4 hours in an environment with a pH of 6.8, and the storage conditions were simple. Water activity is crucial to the efficacy and storage of Huanglong Drop Pills. Huanglong Drop Pills have high water activity, which makes it inconvenient to store and affects the efficacy. Drying the seamless drop pills is a key step that affects the water activity of Huanglong Drop Pills. How to set the drying parameters to ensure the activity of the freeze-dried bacterial powder in Huanglong Drop Pills and low water activity is the focus of existing research on the preparation of Huanglong Drop Pills.

[0005] The Chinese patent with publication number CN115671067A discloses a use of Huanglong dripping pills for treating and preventing irritable bowel syndrome, which discloses dripping a multilayer material into a cooling liquid to obtain a concentric structure seamless dripping pill, and then drying the obtained concentric structure seamless dripping pills at 15°C to 20°C for 10 to 12 hours to remove the outer layer of moisture to obtain the dripping pills. The water activity (aw) of the Huanglong dripping pills obtained by the above drying method is high, which is 0.15 to 0.20. Summary of the invention

[0006] In view of this, the object of the present invention is to provide a method for drying fecal bacteria multilayer pills. The Huanglong pills obtained by the drying method provided by the present invention have low water activity.

[0007] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0008] The present invention provides a method for drying fecal bacteria multilayer pellets, comprising the following steps:

[0009] Provide fecal bacteria multi-layer pellets;

[0010] The fecal bacteria multilayer pellets are centrifugally deoiled by using a deoiling agent, and then separated to obtain deoiled pellets; the deoiling agent is a mixture of fumed silica, soybean fiber and oat cellulose;

[0011] The de-oiled pellets are subjected to air blast drying to obtain pre-dried Huanglong pellets;

[0012] The pre-dried Huanglong dripping pills are subjected to negative pressure drying to obtain Huanglong dripping pills.

[0013] Preferably, the mass ratio of the fumed silica, soybean fiber and oat cellulose is 1:1-2:1-2.

[0014] Preferably, the mass ratio of the fecal bacteria multi-layer pellets to the deoiling agent is 1:1 to 3.

[0015] Preferably, the rotation speed of the centrifugal deoiling is 500-1200 rpm, and the time is 10-15 min.

[0016] Preferably, the separation treatment time is 3 to 8 minutes;

[0017] The separation process is carried out in a drying drum, and the rotation speed of the drying drum is 5 to 10 rpm.

[0018] Preferably, the rotation speed of the blast drying is 4 to 10 rpm, and the time is 5.5 to 7.5 hours; the blast gas of the blast drying is sterile air;

[0019] The blast drying is carried out in a drying drum, the wall of which is provided with holes with a diameter of 0.5 to 1.5 mm, and a pure cotton oil-absorbing cloth is installed in the drying drum;

[0020] The pure cotton oil-absorbing cloth was changed every 30 minutes during the first 60 minutes of the blast drying.

[0021] Preferably, the water activity of the pre-dried Huanglong dripping pills is 0.15 to 0.2.

[0022] Preferably, the negative pressure drying has a pressure of 0 to 0.02 MPa, a temperature of 25 to 28° C., a humidity of 3 to 15%, and a time of 60 to 180 min.

[0023] Preferably, the negative pressure drying is carried out in a drying drum, and the rotation speed of the drying drum is 4 to 10 rpm;

[0024] The drying drum is filled with a desiccant, which is a mixture of color-changing silica gel and anhydrous calcium chloride, and the mass ratio of the color-changing silica gel to the anhydrous calcium chloride is 1:1-3.

[0025] Preferably, the water activity of the Huanglong Drop Pills is 0.08-0.14.

[0026] The present invention provides a method for drying fecal bacteria multilayer dropping pills, comprising the following steps: providing fecal bacteria multilayer dropping pills; centrifugally deoiling the fecal bacteria multilayer dropping pills with a deoiling agent, and then performing separation treatment to obtain deoiled dropping pills; the deoiling agent is a mixture of fumed silica, soybean fiber and oat cellulose; air-drying the deoiled dropping pills to obtain pre-dried Huanglong dropping pills; and negative pressure drying the pre-dried Huanglong dropping pills to obtain Huanglong dropping pills.

[0027] The drying method provided by the present invention further reduces the water activity of Huanglong Drop Pills by centrifugal deoiling, blast drying and negative pressure drying in sequence. The data of the embodiment show that the water activity aw of the obtained Huanglong Drop Pills is 0.08-0.14, has excellent tolerance, especially in vitro simulated gastrointestinal tolerance, and also has excellent stability.

[0028] Furthermore, the drying method provided by the present invention takes a short time and has a high working effect. DETAILED DESCRIPTION

[0029] The present invention provides a method for drying fecal bacteria multilayer pellets, comprising the following steps:

[0030] Provide fecal bacteria multi-layer pellets;

[0031] The fecal bacteria multilayer pellets are centrifugally deoiled by using a deoiling agent, and then separated to obtain deoiled pellets; the deoiling agent is a mixture of fumed silica, soybean fiber and oat cellulose;

[0032] The de-oiled pellets are subjected to air blast drying to obtain pre-dried Huanglong pellets;

[0033] The pre-dried Huanglong dripping pills are subjected to negative pressure drying to obtain Huanglong dripping pills.

[0034] In the present invention, unless otherwise specified, the raw materials used in the present invention are preferably commercially available products.

[0035] The invention provides fecal bacteria multi-layer drop pills.

[0036] In the present invention, the fecal bacteria multilayer drop pills refer to undried Huanglong drop pills, which have a multilayer structure but have not been dried. The present invention does not specifically limit the preparation method of the fecal bacteria multilayer drop pills, and operations familiar to those skilled in the art can be used.

[0037] After providing the fecal bacteria multilayer pellets, the present invention uses a deoiling agent to centrifugally deoil the fecal bacteria multilayer pellets, and then performs separation treatment to obtain deoiled pellets; the deoiling agent is a mixture of fumed silica, soybean fiber and oat cellulose.

[0038] In the present invention, the mass ratio of the fumed silica, soybean fiber and oat cellulose is preferably 1:1-2:1-2, and more preferably 1:1:1. In the present invention, the preparation method of the deoiling agent preferably comprises the following steps: mixing fumed silica, soybean fiber and oat cellulose, and obtaining the mixture by vacuum drying and cooling. The vacuum drying temperature is preferably 40-60°C, and more preferably 50°C; the time is preferably 4-6h, and more preferably 5h. The vacuum drying is preferably carried out in a vacuum drying oven. In the present invention, the mass ratio of the fecal bacteria multilayer pellets and the deoiling agent is preferably 1:1-3, and more preferably 1:1.

[0039] In the present invention, the rotation speed of the centrifugal deoiling is preferably 500-1200 rpm, more preferably 800-1000 rpm; the time is preferably 10-15 min, more preferably 11-14 min, and more preferably 12-13 min. In the present invention, the centrifugal deoiling preferably includes: putting the deoiling agent and the fecal bacteria multilayer pellets into a sterile bag, and then placing the sterile bag in a centrifuge for centrifugal deoiling.

[0040] In the present invention, the separation treatment time is preferably 3 to 8 minutes. In the present invention, the separation treatment is preferably carried out in a drying drum, and a hole is provided on the wall of the drying drum, and the hole diameter is preferably 0.5 to 1.5 mm; the rotation speed of the drying drum is preferably 5 to 10 rpm. In the present invention, the drum in the drying drum is preferably pretreated before use, and the pretreatment preferably includes boiling water and drying in sequence, and the boiling time is preferably 30 to 45 minutes. The drying gas is preferably sterile air, and the pressure of the sterile air is preferably 0.2 to 0.3 MPa. In the present invention, the separation treatment can separate the deoiling agent and the deoiled pellets.

[0041] After obtaining the deoiled dropping pills, the present invention performs air blast drying on the deoiled dropping pills to obtain pre-dried Huanglong dropping pills.

[0042] In the present invention, the rotation speed of the blast drying is preferably 4 to 10 rpm, and the time is preferably 5.5 to 7.5 hours. In the present invention, the blast gas for the blast drying is preferably sterile air.

[0043] In the present invention, the blast drying is preferably carried out in a drying drum, the wall of the drying drum is provided with holes, the hole diameter is preferably 0.5-1.5 mm, and the drying drum is preferably equipped with a pure cotton oil-absorbing cloth. In the present invention, the pure cotton oil-absorbing cloth is preferably pretreated before use, and the pretreatment includes steam sterilization and drying in sequence, and the temperature of the steam sterilization is preferably 121°C, and the time is preferably 20 minutes; the temperature of the drying is preferably 45-50°C, and the time is preferably 2-3 hours. In the present invention, the drum in the drying drum is preferably pretreated before use, and the pretreatment preferably includes boiling water and drying in sequence, and the boiling time is preferably 30-45 minutes. The drying gas is preferably sterile air, and the pressure of the sterile air is preferably 0.2-0.3MPa.

[0044] In the present invention, the pure cotton oil-absorbing cloth is preferably replaced every 30 minutes during the first 60 minutes of the blast drying.

[0045] In the present invention, the water activity (aw) of the pre-dried Huanglong dripping pills is preferably 0.15 to 0.2.

[0046] After obtaining the pre-dried Huanglong dropping pills, the present invention performs negative pressure drying on the pre-dried Huanglong dropping pills to obtain Huanglong dropping pills.

[0047] In the present invention, the pressure of the negative pressure drying is preferably 0-0.02 MPa, the temperature is preferably 25-28° C., the humidity is preferably 3-15%, and the time is preferably 60-180 min.

[0048] In the present invention, the negative pressure drying is preferably carried out in a drying drum, and the rotation speed of the drying drum is preferably 4 to 10 rpm.

[0049] In the present invention, the drying drum is preferably filled with a desiccant, and the desiccant is preferably a mixture of color-changing silica gel and anhydrous calcium chloride, and the mass ratio of the color-changing silica gel to the anhydrous calcium chloride is preferably 1:1-3. In the present invention, the particle sizes of the color-changing silica gel and the anhydrous calcium chloride are independently preferably 5-8 mm. In the present invention, the preparation method of the desiccant preferably comprises the following steps: mixing the color-changing silica gel and the anhydrous calcium chloride, and drying to obtain the desiccant; the drying temperature is preferably 150-170°C, and the time is preferably 6-8 hours.

[0050] After the negative pressure drying, the present invention preferably further comprises screening the obtained material. In the present invention, the screening is preferably carried out in an anaerobic glove box.

[0051] In the present invention, the water activity of the Huanglong Dropping Pills is preferably 0.08 to 0.14; the particle size of the Huanglong Dropping Pills is preferably 1.8 to 2.5 mm.

[0052] The drying method of the fecal bacteria multilayer pellets provided by the present invention is described in detail below in conjunction with the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0053] Example 1

[0054] First, 200 g of fumed silica, 200 g of soybean fiber and 200 g of oat cellulose were mixed, and then vacuum dried at 50° C. for 5 h, cooled to room temperature and packed into a sterile bag.

[0055] Then, 600 g of the fecal bacteria multilayer pellets prepared by the pellet machine were put into a sterile bag and centrifuged in a centrifuge at 1000 rpm for 12 minutes to remove oil.

[0056] Pretreatment of the drying drum: The drying drum was boiled in boiling water for 45 minutes and then blown dry with 0.3MPa sterile filtered air.

[0057] After centrifugal deoiling, the material in the sterile bag is poured into a pre-treated drying drum (pore diameter of 0.5-1.5 mm), separated at a speed of 6 rpm for 5 min, and the deoiling agent is removed by sieving to obtain deoiled pellets.

[0058] The deoiled pills were placed in a drying drum (the drying drum was pretreated before use, the pretreatment being that the drying drum was boiled in boiling water for 45 minutes and then dried with 0.3 MPa sterile filtered air; and pure cotton oil-absorbing cloth was loaded into the drying drum, the pure cotton oil-absorbing cloth was steam sterilized at 121°C for 20 minutes and dried at 45°C for 2.5 hours), and dried at 6 rpm for 6.5 hours under the condition of blowing in sterile air, wherein the pure cotton oil-absorbing cloth was changed every 30 minutes for the first 60 minutes, to obtain pre-dried Huanglong pills, and the water activity of the pre-dried Huanglong pills was tested, and the result was that the water activity aw was 0.158.

[0059] Mix 200g of color-changing silica gel (particle size is 6mm) and 200g of anhydrous calcium chloride (particle size is 6mm), dry at 115°C for 2.5h and cool to room temperature to obtain a desiccant; put the desiccant into a drying drum (the drying drum is pretreated before use, the pretreatment is that the drying drum is boiled in boiling water for 45min, and then blown dry with 0.3MPa sterile filtered air), control the temperature of the drying drum at 28°C, the humidity at 5%, the rotation speed at 5rpm, evacuate, ensure that the pressure of the drying drum is a negative pressure of 0.02MPa, and perform negative pressure drying for 120min to obtain Huanglong Drop Pills, and detect the water activity of the obtained Huanglong Drop Pills. The result is that the water activity aw of the obtained Huanglong Drop Pills is 0.092.

[0060] The final Huanglong pills were sieved in an anaerobic glove box to obtain Huanglong pills 1 with a particle size of 1.8 to 2.5 mm.

[0061] The preparation method of the fecal bacteria multilayer pellets comprises the following steps:

[0062] 1. Outer matrix

[0063] The outer layer matrix formula is: 25wt% gelatin (freeze strength 160), 1.5wt% glycerol, 4wt% sucrose, and water added to 100wt%. Preparation of the outer layer matrix: Soak the gelatin in appropriate amount of water (overnight) to dissolve, add glycerol and sucrose, stir to dissolve, and add water to the full amount.

[0064] 2. Middle layer matrix

[0065] Middle layer matrix formula: hardened oil (melting point 39-43°C, measured 43°C) 93wt%, natural vitamin E oil 3wt%, calcium chloride 4wt%. Middle layer matrix preparation: mix all materials evenly and melt at 60°C, homogenize with a 5000r / min homogenizer to obtain.

[0066] 3. Inner capsule material

[0067] Inner capsule material formula: biologically active substances (such as probiotics, intestinal flora, enzymes, and polypeptides, added in an amount of 10-30%; in this example, the feces provided by healthy volunteer B was freeze-dried to obtain intestinal flora powder, and the added amount was 20wt%), natural vitamin E oil 1.8wt%, dipotassium hydrogen phosphate-potassium dihydrogen phosphate (1:5) 1.2wt%, vegetable oil (melting point 37-42°C, measured 38°C) added to 100% (added amount 60-80%, adjusted according to the added amount of biologically active substances). Inner capsule material preparation: melt the vegetable oil, add natural vitamin E oil and micronized dipotassium hydrogen phosphate-potassium dihydrogen phosphate, mix well, then add the biologically active substances, homogenize with a 5000r / min homogenizer, keep warm and stir for use to avoid sedimentation.

[0068] 4. Pill making

[0069] The weight ratio of the outer layer / middle layer / inner layer is 1:3:1.5. On the three-layer pellet equipment, the inner layer material, the middle layer material and the outer layer material are respectively dripped into the inner, middle and outer layers of the three-layer dripper (the dripper temperature is 65°C) into a cooling liquid (liquid paraffin) at 18-20°C to cool and form a three-layer concentric structure seamless pellet (the obtained pellet has a diameter of 2.5mm), thus obtaining a multi-layer pellet of fecal bacteria.

[0070] Comparative Example 1

[0071] 600 g of fecal bacteria multilayer pellets prepared by a pellet machine were dried at 18° C. for 11 h to obtain Huanglong Pills 2.

[0072] Among them, the fecal bacteria multi-layer pellets were taken from the fecal bacteria multi-layer pellets prepared in Example 1, and the batches were consistent.

[0073] Test Example 1

[0074] Stability test of Huanglong dripping pills at 25℃ (0~28d)

[0075] Packaging machine: back-seal granule packaging machine, model DXDK50IIE1, manufacturer is Zhuhai Ruichuang Technology Development Co., Ltd.

[0076] Aluminum foil bag: material PET12 / AL7 / PET12 / PE80, Zhejiang Jinshi Packaging Co., Ltd.

[0077] Deoxidizer: Active substance content 99%, batch number 20210201, Nanjing Weino Preservative Factory.

[0078] Desiccant: Active substance content 99%, batch number 20210201, Nanjing Weino Preservative Factory.

[0079] Date of pill making and drying: 20210727.

[0080] Storage conditions of pills: (25℃±2℃ / 60%RH±5%RH).

[0081] The results are shown in Tables 1 and 2.

[0082] Table 1 Experimental results of water activity of Huanglong pills at 25℃ for 0-28 days

[0083] Water activity at 25℃ 0d 2d 4d 7d 10d 14d 28d Huanglong dripping pill 2 0.164 0.195 0.215 0.226 0.231 0.249 0.255 Huanglong dripping pills 1 0.092 0.126 0.147 0.159 0.168 0.179 0.191

[0084] Table 2 The results of the moisture test of Huanglong Drop Pills at 25℃ for 0-28 days

[0085] 25℃ moisture 0d 2d 4d 7d 10d 14d 28d Huanglong dripping pill 2 1.72％ 2.11％ 2.29％ 2.33％ 2.48％ 2.58％ 2.66％ Huanglong dripping pills 1 0.91％ 1.31％ 1.58％ 1.71％ 1.86％ 1.92％ 2.09％

[0086] By comparing Table 1 and Table 2, it can be seen that the water activity of Huanglong Dropping Pill 1 obtained in Example 1 is lower than that of Huanglong Dropping Pill 2 obtained in Comparative Example 1, indicating that Huanglong Dropping Pill 1 obtained in Example 1 has good tolerability.

[0087] Test Example 2

[0088] Microbiological experiments

[0089] Buffer: 0.9% NaCl solution containing 0.05% tween-80 (sterilized at 121°C for 15 min).

[0090] Preparation of Huanglong pill solution: 0.5 g of Huanglong pill was added to 49.5 g of sterilized buffer and homogenized at 18000 rpm for 80 s.

[0091] Culture medium: ① Plate count agar (PCA) (HB0101, Haibo Biotechnology Co., Ltd.); ② Wilkins-Chalgren agar (WCA) (HB0261, Haibo Biotechnology Co., Ltd.); ③ MRS medium (027315, Guangdong Huankai Microbiological Technology Co., Ltd.), and the supporting reagents SR0370 mupirocin lithium salt and cysteine ​​hydrochloride need to be added according to the instructions.

[0092] Cultivation method: The prepared Huanglong pill solution was diluted with buffer gradient to the appropriate concentration and then applied: PCA was used to culture total aerobic bacteria, and the culture was carried out at 37°C after application; WCA was used to culture total anaerobic bacteria, and the culture was carried out at 37°C after application; MRA was used to culture bifidobacteria, and the culture was carried out at 37°C after application. Plate counts were performed after 48 hours, and the results are shown in Tables 3 and 4.

[0093] Among them, bifidobacteria were cultured with reference to the national standard GB4789.34-2016 using MRS medium + mupirocin lithium salt and cysteine ​​hydrochloride.

[0094] Table 3 Results of microbiological tests on Huanglong Pills 2 at 25°C, 0-28 days

[0095]

[0096]

[0097] Table 4 Microbiological test results of Huanglong Drop Pills 1 at 25℃, 0-28d

[0098]

[0099]

[0100] By comparing Table 3 and Table 4, it can be seen that the stability of Huanglong Drop Pills 1 obtained by the drying method provided by the present invention is better than that of Huanglong Drop Pills 2 obtained in Comparative Example 1.

[0101] Test Example 3

[0102] In vitro simulated gastrointestinal tolerance test

[0103] The third method (small cup method) of "0931 Dissolution and Release Determination Method" in Part IV of the 2020 edition of the Chinese Pharmacopoeia was used to perform a dissolution test with 200 mL of dissolution medium at a rotation speed of 50 rpm. After 2 hours of simulated gastric fluid, the pellets were transferred to simulated intestinal fluid for 4 hours and sampled. According to the "Probiotic Live Bacteria Count Detection Method", the survival rate of the microorganisms of the test samples after dissolution treatment was determined (the relative survival rate was calculated as 100% without dissolution treatment, i.e., the microbial survival rate at 0 h, expressed as the average of 6 dissolution cups).

[0104] The preparation method of the dissolution medium simulated gastric fluid is as follows: take 3.84 mL of hydrochloric acid, add about 800 mL of water and 10 g of pepsin, shake well, and dilute with water to 1000 mL.

[0105] The preparation method of dissolution medium simulated intestinal fluid is as follows: take 6.8g of potassium dihydrogen phosphate, add 500mL to dissolve it, and adjust the pH value to 6.8 with 0.1mol / L sodium hydroxide solution; take 10g of pancreatic enzyme and 3g of bile salt, add appropriate amount of water to dissolve them, mix the two liquids, and dilute with water to 1000mL.

[0106] Table 5 Huanglong Drop Pills in vitro simulated gastrointestinal tolerance test

[0107]

[0108]

[0109] Huanglong Pills 2 were treated with pH 1.2 gastric acid solution plus enzyme for 2 hours, and the total anaerobic bacteria survival rate was 79.1%. After being treated with pH 6.8 phosphate plus pancreatic enzyme buffer for 4 hours, the survival rate was 39.2%.

[0110] Huanglong Drop Pills 2 were treated with pH 1.2 gastric acid solution plus enzyme for 2 hours, and the total aerobic bacteria survival rate was 66.8%. After being treated with pH 6.8 phosphate plus pancreatic enzyme buffer for 4 hours, the survival rate was 37.4%.

[0111] Huanglong Pills 2 were treated with pH 1.2 gastric acid solution plus enzyme for 2 hours, and the survival rate of bifidobacteria was 81.6%. After being treated with pH 6.8 phosphate plus pancreatic enzyme buffer for 4 hours, the survival rate was 50.1%.

[0112] Huanglong Drop Pills 1 were treated with pH 1.2 gastric acid solution plus enzyme for 2 hours, and the total anaerobic bacteria survival rate was 82.6%. After being treated with pH 6.8 phosphate plus pancreatic enzyme buffer for 4 hours, the survival rate was 41.1%.

[0113] Huanglong Drop Pills 1 were treated with pH 1.2 gastric acid solution plus enzyme for 2 hours, and the total aerobic bacteria survival rate was 71.2%. After being treated with pH 6.8 phosphate plus pancreatic enzyme buffer for 4 hours, the survival rate was 39.9%.

[0114] Huanglong Drop Pills 1 were treated with pH 1.2 gastric acid solution plus enzyme for 2 hours, and the survival rate of bifidobacteria was 86.7%. After being treated with pH 6.8 phosphate plus pancreatic enzyme buffer for 4 hours, the survival rate was 52.6%.

[0115] The Huanglong Dropping Pills 1 obtained by the drying method provided by the present invention have better tolerance effect than the Huanglong Dropping Pills 2 obtained in Comparative Example 1.

[0116] The above is only a preferred embodiment 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 principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for drying fecal bacteria multilayer pellets, characterized in that: The following steps are involved: Provide fecal bacteria multi-layer pellets; The fecal bacteria multilayer pellets are centrifugally deoiled by using a deoiling agent, and then separated to obtain deoiled pellets; the deoiling agent is a mixture of fumed silica, soybean fiber and oat cellulose; The de-oiled pellets are subjected to air blast drying to obtain pre-dried Huanglong pellets; The pre-dried Huanglong dripping pills are subjected to negative pressure drying to obtain Huanglong dripping pills.

2. The drying method according to claim 1, characterized in that The mass ratio of the fumed silica, soybean fiber and oat cellulose is 1:1-2:1-2.

3. The drying method according to claim 1 or 2, characterized in that: The mass ratio of the fecal bacteria multilayer pellets to the deoiling agent is 1:1-3.

4. The drying method according to claim 1, characterized in that The rotation speed of the centrifugal deoiling is 500-1200 rpm, and the time is 10-15 minutes.

5. The drying method according to claim 1, characterized in that: The separation treatment time is 3 to 8 minutes; The separation process is carried out in a drying drum, and the rotation speed of the drying drum is 5 to 10 rpm.

6. The drying method according to claim 1, characterized in that: The rotation speed of the blast drying is 4 to 10 rpm, and the time of the blast drying is 5.5 to 7.5 hours; the blast gas of the blast drying is sterile air; The blast drying is carried out in a drying drum, the wall of which is provided with holes with a diameter of 0.5 to 1.5 mm, and a pure cotton oil-absorbing cloth is installed in the drying drum; The pure cotton oil-absorbing cloth was changed every 30 minutes during the first 60 minutes of the blast drying.

7. The drying method according to claim 1 or 6, characterized in that: The water activity of the pre-dried Huanglong dripping pills is 0.15-0.

2.

8. The drying method according to claim 1, characterized in that: The negative pressure drying has a pressure of 0-0.02 MPa, a temperature of 25-28° C., a humidity of 3-15%, and a time of 60-180 min.

9. The drying method according to claim 1 or 8, characterized in that: The negative pressure drying is carried out in a drying drum, and the rotation speed of the drying drum is 4 to 10 rpm; The drying drum is filled with a desiccant, which is a mixture of color-changing silica gel and anhydrous calcium chloride, and the mass ratio of the color-changing silica gel to the anhydrous calcium chloride is 1:1-3.

10. The drying method according to claim 1, characterized in that: The water activity of the Huanglong dripping pills is 0.08-0.14.

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