Composition, oral tablet, preparation method and application thereof

Abstract

The present application discloses a composition, oral tablets and their preparation method and application, and belongs to the field of food and drug technology. The composition includes sodium sulfate, magnesium sulfate and potassium chloride, and the weight ratio of the sodium sulfate, magnesium sulfate and potassium chloride is (5-10): (1-2): (0.5-1.5); the particle size of the sodium sulfate is less than 700 μm, the purity is not less than 98%, and the moisture content is less than 0.5%; the particle size of the magnesium sulfate is less than 700 μm, the purity is not less than 98.5%, and the moisture content is less than 5.0%; the particle size of the potassium chloride is less than 700 μm, the purity is not less than 98.5%, and the moisture content is less than 1.0%. Each component function is fully exerted, improves the intestinal environment, restores intestinal health, and alleviates functional constipation.

Description

Technical Field

[0001] The present application relates to a composition, an oral tablet, a preparation method and application thereof, and belongs to the technical field of food and medicine. Background Art

[0002] Functional constipation is a functional intestinal disorder caused by non-organic pathology. Its main symptoms include decreased bowel movement frequency, difficulty in defecation, prolonged bowel movement, a feeling of incomplete defecation, and dry, hard stools. With the accelerated pace of modern life, changes in dietary patterns, and the influence of psychological and social factors, the number of patients suffering from chronic constipation is increasing. Long-term constipation can cause anxiety, depression, and other emotional disturbances, leading to hemorrhoids and an increased risk of cancer, cardiovascular disease, and cerebrovascular disease. Therefore, active research on constipation is of great significance.

[0003] Currently, the main treatments for functional constipation include therapeutic methods and medication. Therapeutic methods involve daily adjustments to diet, fluid intake, and exercise, along with abdominal massage, acupressure, and external application of the Shenque acupoint to improve constipation symptoms. While these methods are somewhat effective, they suffer from drawbacks such as slow onset and a tendency to rebound. Medication, typically using laxatives such as polyethylene glycol and aloe vera, can cause significant side effects such as abdominal distension, abdominal pain, intestinal nerve damage, and melanosis coli with long-term use.

[0004] Probiotics are live microorganisms that, when administered in sufficient quantities, can confer health benefits on the host. When sufficient numbers of probiotics pass through the upper digestive tract and colonize the large intestine, they can have numerous beneficial effects, such as regulating the balance of intestinal flora, enhancing immunity, and reducing the risk of diabetes, cardiovascular disease, gastrointestinal diseases, and various cancers. However, during processing, storage, and digestion, probiotics are susceptible to factors such as oxygen, pH, temperature, moisture, gastric acid, and bile salts, resulting in reduced survival and activity, thus limiting their large-scale application. Summary of the Invention

[0005] In order to solve the above problems, a composition, an oral tablet, a preparation method and application thereof are provided, which improve the resistance of probiotics to harsh environments and their survival and colonization in the intestines, and enable the functions of each component in the oral tablets to be fully exerted, thereby improving the intestinal environment, restoring intestinal health, and alleviating functional constipation.

[0006] The present invention adopts the following technical solutions:

[0007] According to one aspect of the present application, a composition is provided, comprising sodium sulfate, magnesium sulfate and potassium chloride, wherein the weight ratio of sodium sulfate, magnesium sulfate and potassium chloride is (5-10): (1-2): (0.5-1.5);

[0008] The sodium sulfate has a particle size of less than 700 μm, a purity of not less than 98%, and a moisture content of less than 0.5%;

[0009] The magnesium sulfate has a particle size of 700 μm or less, a purity of not less than 98.5%, and a moisture content of 5.0% or less;

[0010] The potassium chloride has a particle size of less than 700 μm, a purity of not less than 98.5%, and a moisture content of less than 1.0%.

[0011] According to another aspect of the present application, an oral tablet is provided, comprising the above-mentioned composition.

[0012] Optionally, the oral tablet further comprises the following components in parts by weight: 3-8 parts of magnesium oxide, 13-18 parts of embedded probiotics, 17-24 parts of citric acid, 15-22 parts of sugar substitute additives, 5-10 parts of spices, and 28-35 parts of excipients;

[0013] The embedded probiotics include an inner embedding layer and an outer embedding layer, the inner embedding layer contains probiotics, and the outer embedding layer is wrapped around the outer surface of the inner embedding layer.

[0014] Optionally, the method for preparing the embedded probiotics comprises the following steps:

[0015] S1. Resuspend a single probiotic strain in phosphate buffered saline and incubate at 35-42°C for 10-20 min, then centrifuge and discard the supernatant.

[0016] S2, mixing the single probiotic suspension and the plant polyphenol solution in Tris-HCl buffer, and reacting in a dark environment for 1-3 hours, and then washing with phosphate buffer to form an inner embedding layer;

[0017] S3. Add Tween 80 to phosphate buffer and mix evenly. Then add glycerol and oligosaccharide and stir ultrasonically at 60-80°C for 1-2 minutes to obtain solution A. Add Persian gum to phosphate buffer and mix evenly to obtain solution B. After mixing solution A and solution B evenly, add protamine and continue mixing to obtain solution C.

[0018] S4. Add the inner embedding layer obtained in S2 to solution C, stir and mix for 5-15 minutes, and then freeze-dry to form an outer embedding layer.

[0019] Optionally, in S2, the concentration of the probiotic suspension is 1.2×10 8 -7.6×10 8 CFU / mL;

[0020] The concentration of the plant polyphenol solution is 0.1-1 mg / mL.

[0021] Optionally, the probiotics are bifidobacteria and / or lactobacilli;

[0022] The plant polyphenol is protocatechuic acid, chlorogenic acid or caffeic acid;

[0023] The oligosaccharide is at least one of xylooligosaccharide, galactooligosaccharide, fructooligosaccharide and lactulose.

[0024] Optionally, in S3, the weight ratio of the oligosaccharide to protamine is 1:(3-8);

[0025] The added weight of the Persian gum is 3-8% of the protamine.

[0026] Optionally, the sugar substitute additive is at least one of xylitol, sorbitol and erythritol;

[0027] The spice is at least one of vanilla, cloves, cinnamon, rose and mint;

[0028] The auxiliary material is at least one of starch, milk powder, maltodextrin, microcrystalline cellulose and magnesium stearate.

[0029] According to another aspect of the present application, a method for preparing an oral tablet is provided, which is used to prepare an oral tablet as described above, comprising the following steps:

[0030] (1) Sodium sulfate, magnesium sulfate, potassium chloride, magnesium oxide, citric acid, sugar substitute additives and spices are respectively passed through a 60-100 mesh sieve and mixed uniformly according to the formula ratio to obtain a mixture 1;

[0031] (2) Mixture 1 is put into a fluidized bed one-step granulator for granulation and granulation, with an air inlet volume of 110-120m 3 / h, the inlet air temperature is 50-70℃, the atomization pressure is 1.0-1.2bar, and the liquid feeding speed is 4-6mL / min to obtain mixture 2;

[0032] (3) Mix the mixture 2, the embedded probiotics and the auxiliary materials in accordance with the formula ratio, and then compress the mixture into tablets using a tablet press to obtain oral tablets.

[0033] According to another aspect of the present application, there is provided an application of any of the above-described oral tablets for cleaning the intestine, improving the intestinal environment and alleviating functional constipation, wherein the daily dosage of the oral tablet is 0.1-0.5 g / kg.

[0034] The beneficial effects of this application include but are not limited to:

[0035] 1. In the oral tablets of the present application, sodium sulfate is a bulk laxative that is not easily absorbed in the intestine. It forms a hypertonic solution in the intestine and absorbs a large amount of water, which increases the volume and pressure of the intestinal cavity, thereby irritating the intestinal wall, promoting peristalsis, and causing diarrhea. Magnesium oxide and citric acid react with water to form an osmotic laxative, magnesium citrate, after dissolving in water, which enhances the bowel cleansing effect while also improving the taste. The combined use of these two laxative ingredients can prevent users from becoming dependent on a single laxative, while effectively increasing the volume and water content of stool, making it easier to excrete stool and reducing the discomfort of intestinal dryness and constipation.

[0036] 2. In the oral tablets of the present application, the embedded probiotics can adjust the balance of the intestinal flora, help the intestines quickly establish a normal and healthy flora after a large amount of excretion, reduce the invasion and colonization opportunities of pathogenic bacteria, and play the role of occupying each other, competing for nutrients, and fighting each other, thereby ensuring that the body is not invaded by pathogenic bacteria; magnesium sulfate and potassium chloride can timely replenish the electrolytes lost by the body during diarrhea and reduce the occurrence of adverse reactions; the addition of sugar substitutes and spices can improve the taste and flavor of the oral tablets and increase public acceptance; the added excipients ensure the molding of the oral tablets, improve production efficiency and product quality stability; the combined effect of various components not only relieves functional constipation and achieves intestinal cleansing, but also improves the balance of intestinal flora and the integrity of the intestinal barrier, and promotes intestinal health.

[0037] 3. In the oral tablets of the present application, the inner layer is formed by oxidative polymerization of plant polyphenols on the probiotics. When the probiotic cells are exposed to the phenolic solution, the manganese ions released by the probiotic cells act as a catalyst for this process to activate the oxidation of plant polyphenols and induce their polymerization on the surface of the bacteria, wherein the phenolic compounds are oxidized into quinones, followed by cross-coupling reactions and polymerization assembly, which have a good protective effect on the probiotics and improve their survival rate, colonization ability and antioxidant properties in the intestine; oligosaccharides and protamine are compounded to complement each other and are embedded in the inner layer. A stable gel network structure is formed on the outer surface of the inner embedding layer, and Persian gum makes the gel network structure tightly adsorbed on the outer surface of the inner embedding layer, protecting the inner embedding layer from damage under harsh conditions. At the same time, the moisture retention ability of Persian gum prevents the embedded probiotics from excessive drying during storage, thereby having better storage stability. In this way, not only the action time of the probiotics is prolonged, but also the body can be supplemented with probiotics and prebiotics at the same time. The two work together to maintain a balance in the intestinal microecological environment, prevent and improve constipation and diarrhea, enhance immunity, and maintain human health.

[0038] 4. The oral tablet preparation method of the present application uses a fluidized bed one-step granulation process to increase the fluidity and compressibility of the material. The granulated particles are mixed with the embedded probiotics and then compressed into tablets, which reduces the damage to the embedded probiotics caused by tablet compression. Compared with ordinary tablets, the oral tablets prepared by the preparation method of the present application can be directly chewed in the mouth until they are broken, resulting in a product with a larger surface area. Moreover, they do not need to disintegrate, dissolve faster, and have higher bioavailability, making them particularly suitable for the elderly and children with poor gastrointestinal function. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The drawings described herein are used to provide a further understanding of the present application and constitute a part of the present application. The illustrative embodiments of the present application and their descriptions are used to explain the present application and do not constitute an improper limitation on the present application. In the drawings:

[0040] Figure 1 This is a diagram showing the effect of relieving constipation according to an embodiment of the present application. DETAILED DESCRIPTION

[0041] The endpoints of the ranges and any values ​​disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered to be specifically disclosed herein.

[0042] If the specific conditions are not specified in the examples, the experiments were carried out under conventional conditions or those recommended by the manufacturer. The raw materials or instruments used, if the manufacturers are not specified, are all conventional products that can be purchased commercially.

[0043] In the present application, the lactobacillus is at least one of Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus lactis, and Lactobacillus acidophilus; preferably Lactobacillus acidophilus, the strain deposit number of Lactobacillus acidophilus is CGMCC 21371;

[0044] The bifidobacterium is at least one of Bifidobacterium bifidum, Bifidobacterium lactis and Bifidobacterium longum; preferably Bifidobacterium lactis, and the strain collection number of Bifidobacterium lactis is CGMCC 18093.

[0045] Example 1

[0046] A method for preparing an oral tablet comprises the following steps:

[0047] (1) By weight, 25 parts of sodium sulfate (particle size 700 μm, purity 98%, moisture content 0.5%), 4 parts of magnesium sulfate (particle size 700 μm, purity 98.5%, moisture content 5.0%), 2 parts of potassium chloride (particle size 700 μm, purity 98.5%, moisture content 1.0%), 3 parts of magnesium oxide, 17 parts of citric acid, 15 parts of xylitol, 3 parts of vanilla and 2 parts of cinnamon were respectively passed through a 60-mesh sieve and mixed uniformly to obtain a mixture 1;

[0048] (2) Mixture 1 is put into a fluidized bed one-step granulator for granulation and granulation. The air inlet volume is 110m 3 / h, the inlet air temperature is 50℃, the atomizing pressure is 1.0bar, and the liquid feeding speed is 4mL / min to obtain mixture 2;

[0049] (3) Mixture 2 was uniformly mixed with 13 parts of embedded probiotics, 10 parts of maltodextrin, 10 parts of microcrystalline cellulose, and 8 parts of magnesium stearate, and then tableted using a tablet press to obtain oral tablets;

[0050] The preparation method of the embedded probiotics comprises the following steps:

[0051] S1. Resuspend the Lactobacillus acidophilus strain in phosphate buffer and incubate at 35°C for 10 min, then centrifuge at 4000 rpm for 10 min and discard the supernatant;

[0052] S2, the concentration is 1.2×10 8 A Lactobacillus acidophilus suspension of 100 CFU / mL and a protocatechuic acid solution of 0.1 mg / mL were mixed in a Tris-HCl buffer solution and reacted in a dark environment for 1 hour. After the reaction, the mixture was washed with a phosphate buffer solution to form an inner embedding layer.

[0053] S3. Add 1.5 wt% Tween 80 to phosphate buffer and mix evenly, then add 3 wt% glycerol and xylo-oligosaccharide, and stir ultrasonically at 60°C for 2 min to obtain solution A; add 4 wt% Persian gum to phosphate buffer and mix evenly to obtain solution B; after mixing solution A and solution B evenly, add protamine, with the weight ratio of xylo-oligosaccharide to protamine being 1:3, and continue mixing to obtain solution C;

[0054] S4. Add the inner embedding layer obtained in S2 to solution C, stir and mix for 5 minutes, and then freeze-dry to form an outer embedding layer.

[0055] Example 2

[0056] A method for preparing an oral tablet comprises the following steps:

[0057] (1) By weight, 42 parts of sodium sulfate (particle size 600 μm, purity 98.4%, moisture content 0.2%), 8 parts of magnesium sulfate (particle size 600 μm, purity 98.8%, moisture content 3%), 4 parts of potassium chloride (particle size 600 μm, purity 98.8%, moisture content 0.6%), 5 parts of magnesium oxide, 20 parts of citric acid, 18 parts of erythritol, 3 parts of vanilla, 2 parts of cloves and 3 parts of rose were respectively passed through an 80-mesh sieve and mixed uniformly to obtain a mixture 1;

[0058] (2) Mixture 1 is put into a fluidized bed one-step granulator for granulation and granulation, with an air inlet volume of 115m 3 / h, the air inlet temperature is 60℃, the atomizing pressure is 1.1bar, and the liquid inlet speed is 5mL / min to obtain mixture 2;

[0059] (3) Mixture 2 was uniformly mixed with 15 parts of embedded probiotics, 10 parts of starch, 8 parts of milk powder, 6 parts of microcrystalline cellulose, and 6 parts of magnesium stearate, and then tableted using a tablet press to obtain oral tablets;

[0060] The preparation method of the embedded probiotics comprises the following steps:

[0061] S1. Resuspend the Lactobacillus acidophilus strain in phosphate buffer and incubate at 38°C for 15 min, then centrifuge at 6000 rpm for 8 min and discard the supernatant;

[0062] The Bifidobacterium lactis strain was resuspended in phosphate buffer and incubated at 40°C for 15 min, then centrifuged at 6000 rpm for 8 min, and the supernatant was discarded;

[0063] S2, the concentration is 7.6×10 8 A Lactobacillus acidophilus suspension with a concentration of CFU / mL and a chlorogenic acid solution with a concentration of 0.5 mg / mL were mixed in a Tris-HCl buffer solution and reacted in a dark environment for 2 hours. After the reaction, the mixture was washed with a phosphate buffer solution to form an inner embedding layer 1;

[0064] The concentration was 7.6×10 8 A suspension of Bifidobacterium lactis with a concentration of 0.5 CFU / mL and a chlorogenic acid solution with a concentration of 0.5 mg / mL were mixed in a Tris-HCl buffer solution and reacted in a dark environment for 2 hours. After the reaction, the mixture was washed with a phosphate buffer solution to form an inner embedding layer 2;

[0065] S3. Add 1.5 wt% Tween 80 to phosphate buffer and mix evenly, then add 3 wt% glycerol and oligofructose, and stir ultrasonically at 70°C for 1.5 min to obtain solution A; add 5 wt% Persian gum to phosphate buffer and mix evenly to obtain solution B; after mixing solution A and solution B evenly, add protamine, with the weight ratio of oligofructose to protamine being 1:5, and continue mixing to obtain solution C;

[0066] S4. The inner embedding layer 1 and the inner embedding layer 2 obtained in S2 are added to the solution C, stirred and mixed for 10 minutes, and then freeze-dried to form an outer embedding layer.

[0067] Example 3

[0068] A method for preparing an oral tablet comprises the following steps:

[0069] (1) By weight, 68 parts of sodium sulfate (particle size 500 μm, purity 98.2%, moisture content 0.3%), 15 parts of magnesium sulfate (particle size 500 μm, purity 98.6%, moisture content 4%), 6 parts of potassium chloride (particle size 500 μm, purity 98.6%, moisture content 0.7%), 8 parts of magnesium oxide, 24 parts of citric acid, 22 parts of sorbitol and 10 parts of mint were respectively passed through a 100-mesh sieve and mixed uniformly to obtain a mixture 1;

[0070] (2) Mixture 1 is put into a fluidized bed one-step granulator for granulation and granulation, with an air inlet volume of 120m 3 / h, the inlet air temperature was 70℃, the atomizing pressure was 1.2bar, and the liquid feeding rate was 6mL / min to obtain mixture 2;

[0071] (3) Mixture 2 was uniformly mixed with 18 parts of embedded probiotics, 15 parts of starch, 10 parts of microcrystalline cellulose, and 10 parts of magnesium stearate, and then tableted using a tablet press to obtain oral tablets;

[0072] The preparation method of the embedded probiotics comprises the following steps:

[0073] S1. Resuspend the Bifidobacterium lactis strain in phosphate buffer and incubate at 42°C for 20 min, then centrifuge at 8000 rpm for 5 min and discard the supernatant;

[0074] S2, the concentration is 4.5×10 8 A suspension of Bifidobacterium lactis with a concentration of 100 CFU / mL and a caffeic acid solution with a concentration of 1 mg / mL were mixed in a Tris-HCl buffer and reacted in a dark environment for 3 hours. After the reaction, the mixture was washed with a phosphate buffer to form an inner embedding layer.

[0075] S3. Add 1.5 wt% Tween 80 to phosphate buffer and mix evenly, then add 3 wt% glycerol and lactulose, and stir ultrasonically at 80°C for 1 min to obtain solution A; add 8 wt% Persian gum to phosphate buffer and mix evenly to obtain solution B; after mixing solution A and solution B evenly, add protamine, with the weight ratio of lactulose to protamine being 1:8, and continue mixing to obtain solution C;

[0076] S4. Add the inner embedding layer obtained in S2 to solution C, stir and mix for 15 minutes, and then freeze-dry to form an outer embedding layer.

[0077] Example 4

[0078] The difference from Example 2 is that:

[0079] The preparation method of embedded probiotics comprises the following steps:

[0080] S1. Resuspend the Lactobacillus acidophilus strain in phosphate buffer and incubate at 38°C for 15 min, then centrifuge at 6000 rpm for 8 min and discard the supernatant;

[0081] The Bifidobacterium lactis strain was resuspended in phosphate buffer and incubated at 40°C for 15 min, then centrifuged at 6000 rpm for 8 min, and the supernatant was discarded;

[0082] S2, the concentration is 7.6×10 8 A Lactobacillus acidophilus suspension with a concentration of 0.5 CFU / mL and a chlorogenic acid solution with a concentration of 0.5 mg / mL were mixed in a Tris-HCl buffer solution and reacted in a dark environment for 2 hours. After the reaction, the mixture was washed with a phosphate buffer solution to form an embedding layer 1;

[0083] The concentration was 7.6×10 8 A Bifidobacterium lactis suspension with a concentration of CFU / mL and a chlorogenic acid solution with a concentration of 0.5 mg / mL were mixed in a Tris-HCl buffer solution and reacted in a dark environment for 2 hours. After the reaction, the mixture was washed with a phosphate buffer solution to form an embedding layer 2.

[0084] Example 5

[0085] The difference from Example 2 is that:

[0086] The preparation method of embedded probiotics comprises the following steps:

[0087] S1. Resuspend the Lactobacillus acidophilus strain in phosphate buffer and incubate at 38°C for 15 min, then centrifuge at 6000 rpm for 8 min and discard the supernatant;

[0088] The Bifidobacterium lactis strain was resuspended in phosphate buffer and incubated at 40°C for 15 min, then centrifuged at 6000 rpm for 8 min, and the supernatant was discarded;

[0089] S2. 1.5 wt% Tween 80 was added to a phosphate buffer solution and mixed evenly, followed by adding 3 wt% glycerol and oligofructose, and ultrasonically stirring at 70°C for 1.5 min to obtain a solution A; 5 wt% Persian gum was added to a phosphate buffer solution and mixed evenly to obtain a solution B; after mixing solution A and solution B evenly, protamine was added, with the weight ratio of oligofructose to protamine being 1:5, and the mixing process was continued to obtain a solution C;

[0090] S3. Add the precipitate obtained by centrifugation in S1 to solution C, stir and mix for 10 minutes, and then freeze-dry to form an embedding layer.

[0091] Example 6

[0092] The difference from Example 2 is that:

[0093] In step S2, chlorogenic acid was replaced with salicylic acid.

[0094] Example 7

[0095] The difference from Example 2 is that:

[0096] S3. 1.5 wt% Tween 80 was added to phosphate buffer and mixed evenly. 3 wt% glycerol and oligofructose were then added, and ultrasonic stirring was performed at 70° C. for 1.5 min to obtain solution A. Protamine was added to solution A in a weight ratio of oligofructose to protamine of 1:5, and the mixture was further mixed to obtain solution B.

[0097] S4. The inner embedding layer 1 and the inner embedding layer 2 obtained in S2 are added to solution B, stirred and mixed for 10 minutes, and then freeze-dried to form an outer embedding layer.

[0098] Example 8

[0099] The difference from Example 2 is that:

[0100] No magnesium oxide was added in step (1).

[0101] Example 9

[0102] The difference from Example 2 is that:

[0103] The weight ratio of fructooligosaccharide to protamine is 1:10.

[0104] Comparative Example 1

[0105] The difference from Example 2 is that:

[0106] The embedded probiotics in step (3) were replaced with 7.6×10 8 CFU / g Lactobacillus acidophilus powder and 7.6×10 8 CFU / g of Bifidobacterium lactis powder, and the preparation method of the encapsulated probiotics is not disclosed.

[0107] Comparative Example 2

[0108] The difference from Example 2 is that:

[0109] A method for preparing an oral tablet comprises the following steps:

[0110] (1) By weight, 42 parts of sodium sulfate (particle size 600 μm, purity 98.4%, moisture content 0.2%), 8 parts of magnesium sulfate (particle size 600 μm, purity 98.8%, moisture content 3%), 4 parts of potassium chloride (particle size 600 μm, purity 98.8%, moisture content 0.6%), 5 parts of magnesium oxide, 20 parts of citric acid, 18 parts of erythritol, 3 parts of vanilla, 2 parts of cloves and 3 parts of rose were respectively passed through an 80-mesh sieve and mixed uniformly to obtain a mixture 1;

[0111] (2) Mixture 1 is mixed evenly with 15 parts of embedded probiotics, 10 parts of starch, 8 parts of milk powder, 6 parts of microcrystalline cellulose and 6 parts of magnesium stearate, and then compressed by a tablet press to obtain oral tablets.

[0112] The oral tablets obtained by the preparation methods of Examples 1-9 and Comparative Examples 1-2 were tested, and the test methods and results are shown below.

[0113] 1. Quality evaluation

[0114] Angle of repose: Weigh 100g of the material to be tested (excluding ingredients containing probiotics) and slowly add it from the top of the funnel. The inclination angle of the conical accumulation formed by the material leaking from the bottom of the funnel on the horizontal plane is the angle of repose.

[0115] Hardness: measured using an intelligent hardness tester.

[0116] Friability: Take 10 oral tablets, use a hair dryer to gently blow away the powder on the surface of the tablets, accurately weigh their mass, then place them in a cylinder, rotate them 100 times, take them out, blow away the powder on the surface of the tablets in the same way, then accurately weigh their mass, calculate their lost weight, and calculate their friability.

[0117] Taste rating: 50 subjects were randomly selected to rate the taste or overall taste of the oral tablets. A good taste or flavor was assigned a score of 10, while an unacceptable taste was assigned a score of 0. The average score was taken, and the highest score was assigned to the best taste.

[0118] Table 1

[0119]

[0120]

[0121] As can be seen from Table 1, the oral tablets obtained by the preparation method of the present application have a good mouthfeel and taste. The surface area increases after chewing and does not require a disintegration process. The active ingredients can be rapidly dissolved, which is beneficial to the dissolution and absorption of each ingredient in the body, thereby greatly reducing the burden on the gastrointestinal tract. Therefore, it is particularly suitable for the elderly, children, people with swallowing difficulties and people with weak gastrointestinal function.

[0122] 2. Determination of viable bacterial count

[0123] The number of viable bacteria in the oral tablets obtained by the preparation methods of Examples 1-9 and Comparative Examples 1-2 was detected with reference to GB4789.2-2016, and the results are shown in Table 2 below.

[0124] Table 2

[0125] Test number Viable bacteria count (CFU / tablet) Example 1 <![CDATA[0.7×10 8 ]]> Example 2 <![CDATA[6.8×10 8 ]]> Example 3 <![CDATA[3.6×10 8 ]]> Example 4 <![CDATA[5.4×10 6 ]]> Example 5 <![CDATA[2.8×10 6 ]]> Example 6 <![CDATA[6.2×10 7 ]]> Example 7 <![CDATA[4.8×10 7 ]]> Example 8 <![CDATA[6.8×10 8 ]]> Example 9 <![CDATA[0.3×10 8 ]]> Comparative Example 1 <![CDATA[5.8×10 5 ]]> Comparative Example 2 <![CDATA[7.4×10 5 ]]>

[0126] As can be seen from Table 2, the oral tablets obtained by the preparation methods of Examples 1-3 have a high number of viable bacteria, especially the oral tablet of Example 3 has a higher number of viable bacteria. This can increase the abundance of beneficial bacteria in the intestine, inhibit the growth of potential pathogenic bacteria, change the composition of the intestinal flora, and restore intestinal health.

[0127] 3. Constipation relief efficacy test

[0128] 3.1 ICR male mice were randomly divided into six groups: a blank control group, a model control group (loperamide hydrochloride at a dose of 1 mg / kg dissolved in distilled water), a positive control group (polyethylene glycol powder at a dose of 1 g / kg dissolved in distilled water), a low-dose group (the oral tablets of Example 2 at a dose of 0.1 g / kg dissolved in distilled water), a medium-dose group (the oral tablets of Example 2 at a dose of 0.3 g / kg dissolved in distilled water), and a high-dose group (the oral tablets of Example 2 at a dose of 0.5 g / kg dissolved in distilled water). The blank control group received an equal volume of distilled water, while the remaining groups were gavaged with the test substances at a dose of 1 mL / 100 g once daily for 7 consecutive days. After the seventh dose, mice in each group were fasted for 24 hours. The blank control group received distilled water, while the remaining groups received a 1 mL / 100 g loperamide hydrochloride solution by gavage. 30 minutes later, the blank and model control groups were administered Chinese ink, while the remaining four groups were administered Chinese ink containing the corresponding test samples. After 30 minutes, the mice were immediately killed, and the intestinal tube from the pylorus to the cecum was removed. The total length of the small intestine and the ink propagation length were measured. The small intestinal ink propagation rate (P / %) was calculated as ink propagation length (cm) / total small intestine length (cm) × 100. The ink propagation rate was statistically processed and analyzed by variance. The general condition of the mice was observed, and the weight of the mice was recorded. The biosafety of the product was investigated. The results are as follows: Figure 1 shown.

[0129] Depend on Figure 1 It can be seen that compared with the model control group, there was no significant difference between the low-dose group and the positive control group, and the ink propulsion rate of the medium and high-dose groups increased, indicating that the medium and high-dose groups of the sample can promote gastrointestinal motility, among which the high-dose group can significantly improve the intestinal motility of mice and relieve constipation with the best effect; compared with the positive control group, the low-dose group was basically the same, the medium-dose group was better, and the high-dose group had a significant effect on improving intestinal motility.

[0130] The data were expressed as x±s and statistically analyzed using SPSS22.0 software. One-way analysis of variance was used for comparison between groups. When the differences between groups were statistically significant, the least significant difference method was used for pairwise comparison between groups, and p<0.05 indicated a significant difference.

[0131] 3.2 Subjects: aged 20-60 years, with similar constipation levels, and signed informed consent. The subjects were divided into 10 groups, each with 100 subjects (the age distribution of the subjects in each group was uniform). The subjects in each group were orally administered with the oral tablets obtained in Examples 1-9 and Comparative Examples 1-2, two tablets at a time, three times a day; the control group did not take the tablets; the constipation relief rate of each group after taking the corresponding oral tablets for 7 days was calculated (constipation relief rate = number of subjects with constipation relief / total number of subjects in the group). The constipation relief was defined as one bowel movement per day, with smooth and easy bowel movements, and no dry stools or diarrhea. The results are shown in Table 3.

[0132] Table 3

[0133] Test number Constipation relief rate (%) control group 0 Example 1 86.3 Example 2 88.5 Example 3 87.1 Example 4 74.6 Example 5 72.3 Example 6 78.5 Example 7 76.2 Example 8 61.4 Example 9 82.6 Comparative Example 1 65.3 Comparative Example 2 68.5

[0134] As can be seen from Table 3, the oral tablets obtained by the preparation method of the present application can accelerate gastrointestinal motility of the body, especially the oral tablets obtained by the preparation method of Examples 1-3, which have a significant effect in alleviating functional constipation.

[0135] The foregoing is merely an embodiment of the present application, and the scope of protection of the present application is not limited by these specific embodiments, but is determined by the claims of the present application. For those skilled in the art, the present application may have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc. made within the technical ideas and principles of the present application should be included in the scope of protection of the present application.

Claims

1. An oral tablet for cleaning the intestines, improving the intestinal environment and relieving functional constipation, characterized in that: The tablet comprises sodium sulfate, magnesium sulfate, and potassium chloride, wherein the weight ratio of sodium sulfate, magnesium sulfate, and potassium chloride is (5-10):(1-2):(0.5-1.5); and, in parts by weight, 3-8 parts of magnesium oxide, 13-18 parts of embedded probiotics, 17-24 parts of citric acid, 15-22 parts of sugar substitute additives, 5-10 parts of spices, and 28-35 parts of other auxiliary materials. The sodium sulfate has a particle size of less than 700 μm, a purity of not less than 98%, and a moisture content of less than 0.5%; The magnesium sulfate has a particle size of 700 μm or less, a purity of not less than 98.5%, and a moisture content of 5.0% or less; The potassium chloride has a particle size of 700 μm or less, a purity of not less than 98.5%, and a moisture content of 1.0% or less; The embedded probiotics include an inner embedding layer and an outer embedding layer, wherein the inner embedding layer contains probiotics, and the outer embedding layer is wrapped around the outer surface of the inner embedding layer; The preparation method of the embedded probiotics comprises the following steps: S1. Resuspend a single probiotic strain in phosphate buffered saline and incubate at 35-42°C for 10-20 min, then centrifuge and discard the supernatant. S2. Mix the above-mentioned single probiotic suspension and plant polyphenol solution in Tris-HCl buffer and react in a dark environment for 1-3 hours. After the reaction, wash with phosphate buffer to form an inner embedding layer; S3. Add Tween 80 to phosphate buffer and mix evenly. Then add glycerol and oligosaccharide and stir ultrasonically at 60-80°C for 1-2 minutes to obtain solution A. Add Persian gum to phosphate buffer and mix evenly to obtain solution B. After mixing solution A and solution B evenly, add protamine and continue mixing to obtain solution C. S4. Add the inner embedding layer obtained in S2 to solution C, stir and mix for 5-15 minutes, and then freeze-dry to form an outer embedding layer.

2. The oral tablet according to claim 1, wherein In S2, the concentration of the probiotic suspension is 1.2×10 8 -7.6×10 8 CFU / mL; The concentration of the plant polyphenol solution is 0.1-1 mg / mL.

3. The oral tablet according to claim 1, wherein The probiotics are bifidobacteria and / or lactobacilli; The plant polyphenol is protocatechuic acid, chlorogenic acid or caffeic acid; The oligosaccharide is at least one of xylooligosaccharide, galactooligosaccharide, fructooligosaccharide and lactulose.

4. The oral tablet according to claim 1, wherein In S3, the weight ratio of the oligosaccharide to protamine is 1:(3-8); The added weight of the Persian gum is 3-8% of the protamine.

5. The oral tablet according to claim 1, wherein The sugar substitute additive is at least one of xylitol, sorbitol and erythritol; The spice is at least one of vanilla, cloves, cinnamon, rose and mint; The other auxiliary materials are at least one of starch, milk powder, maltodextrin, microcrystalline cellulose and magnesium stearate.

6. A method for preparing an oral tablet, characterized in that: The method for preparing an oral tablet according to any one of claims 1 to 5 comprises the following steps: (1) Sodium sulfate, magnesium sulfate, potassium chloride, magnesium oxide, citric acid, sugar substitute additives and spices are sieved through a 60-100 mesh sieve respectively, and then mixed uniformly according to the formula ratio to obtain a mixture 1; (2) Put the mixed material 1 into the fluidized bed one-step granulator for granulation and granulation, with an air inlet volume of 110-120m 3 / h, the inlet air temperature is 50-70℃, the atomization pressure is 1.0-1.2bar, and the liquid feeding speed is 4-6mL / min to obtain mixture 2; (3) Mix the mixture 2 with the embedded probiotics and other excipients according to the formula ratio, and then compress the mixture into tablets using a tablet press to obtain oral tablets.

7. Use of the oral tablet according to any one of claims 1 to 5 in the preparation of a medicament for cleaning the intestine, improving the intestinal environment and relieving functional constipation, wherein the daily dosage of the oral tablet is 0.1-0.5 g / kg.

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