A high-activity nattokinase composition and preparation method thereof

Abstract

The invention relates to natto derivatives, in particular to a high-activity nattokinase composition and a preparation method thereof. The high-activity nattokinase composition comprises the following parts by weight: 20-30 parts of bagasse fiber, 160-240 parts of soy protein isolate, 64-96 parts of chia seed colloid particles, 60 parts of high-activity nattokinase dry powder, 16-24 parts of glucose, 92-138 parts of enteric coating agent and 140-210 parts of deionized water; the preparation method of the high-activity nattokinase composition comprises: mixing bagasse fiber, soy protein isolate, high-activity nattokinase dry powder, glucose and deionized water to obtain a first paste; mixing the first paste with chia seed colloid particles to obtain a second paste; preparing the second paste into a medicine core; coating the medicine core with an enteric coating agent, and drying to obtain a finished product; soy protein isolate, as a competitive substrate of nattokinase, combines with trypsin to reduce the probability of nattokinase being hydrolyzed in the intestine, protects the nattokinase, and indirectly improves the absorption rate of the intestine to nattokinase.

Description

Technical Field

[0001] The invention relates to natto derivatives, in particular to a high-activity nattokinase composition and a preparation method thereof. Background Art

[0002] Nattokinase is a fibrinolytic enzyme that is widely used as a thrombolytic drug because of its thrombolytic effect. Its main source is natto products made through fermentation.

[0003] Traditional nattokinase product is the dry powder obtained by crude extraction of natto, and then the dry powder is coated with capsule or coating agent, and its enzyme activity content of each nattokinase product is generally only 100-200FU. The daily dosage of nattokinase for therapeutic purposes is generally 8000-14000FU, and in theory, traditional nattokinase product needs to eat 40-140 tablets every day, and practicality is not high. Although traditional nattokinase product effective content is not high, due to the natto crude extract must contain materials such as dietary fiber, colloid (because the dietary fiber contained by natto is mostly small-particle dietary fiber, its actual defecation function is not outstanding either, so only in the case of high dose, can obvious defecation effect be produced), and the crowd of long-term use of nattokinase is middle-aged and elderly people, and this type of crowd is except having cardiovascular problems, and also widely exists sub-healthy states such as constipation. Therefore, some patients still choose to take traditional nattokinase products to promote defecation while thrombolysis.

[0004] In view of the problem that the effective content of traditional nattokinase products is not high, the industry has made improvements. The fermentation broth is obtained by fermentation tank and enzyme activator technology, and then concentrated by hollow fiber membrane ultrafiltration and freeze-dried to obtain high-activity nattokinase dry powder, which is then coated with a coating agent. The enzyme activity content of each tablet can reach 1000-3000FU, which is the so-called high-activity nattokinase. Since the effective concentration is greatly improved, the number of tablets taken can be reduced. But obviously, due to the process of ultrafiltration of fermentation broth, high-activity nattokinase products no longer have the effect of helping defecation.

[0005] In addition, although the enzyme activity content of existing high-activity nattokinase products is very high, the absorption rate of oral high-activity nattokinase needs to be improved because the nattokinase solution in the intestine is hydrolyzed by trypsin. Summary of the invention

[0006] In view of the shortcomings of the prior art, one of the objects of the present invention is to provide a high-activity nattokinase composition, which can reduce the probability of nattokinase being hydrolyzed by intestinal trypsin and promote intestinal defecation.

[0007] A second object of the present invention is to provide a method for preparing a highly active nattokinase composition.

[0008] The third object of the present invention is to provide a method for taking a high-activity nattokinase composition.

[0009] One of the purposes of the present invention is achieved through the following technical solutions:

[0010] A high-activity nattokinase composition is prepared from the following raw materials in parts by weight:

[0011] 20-30 parts of bagasse fiber, 160-240 parts of soy protein isolate, 64-96 parts of chia seed colloid particles, 60 parts of high-activity nattokinase dry powder, 16-24 parts of glucose, 92-138 parts of enteric coating agent and 140-210 parts of deionized water.

[0012] The main body of bagasse fiber is insoluble dietary fiber, which has the effect of promoting defecation, but the bagasse fiber in the present invention is not directly used to promote defecation. The particle size of bagasse fiber in the present invention is less than 0.5 mm. It is known that insoluble dietary fiber with too small a particle size is difficult to play a significant role in promoting defecation, while dietary fiber with large particle size, such as husks, wheat bran, etc., is difficult to swallow and easily scratches the intestinal mucosa. The significance of using bagasse fiber in the present invention is to evenly arrange small-particle bagasse fiber to the core, so that the core structure is similar to large-particle dietary fiber particles such as husks, with a rough surface and an overall particle size sufficient to stimulate intestinal peristalsis and secrete digestive juices. The soy protein isolate in the present invention serves as a plasticizer for the core, and also serves as a reinforcing agent for bagasse fiber and as a protective agent for highly active nattokinase after entering the intestine. In the present invention, the chia seed colloid particles serve as a swelling agent, which gradually swells from the outside to the inside after the coating agent disintegrates, and peels off the other components of the core layer by layer. In the present invention, glucose supplements energy for protein absorption by the intestine.

[0013] The second object of the present invention is achieved by the following technical solutions:

[0014] A method for preparing a highly active nattokinase composition comprises the following steps:

[0015] S1 weighs the raw materials;

[0016] S2: mixing bagasse fiber, soy protein isolate, high-activity nattokinase dry powder, glucose and deionized water to obtain a first paste;

[0017] S3: mixing the first paste with the chia seed colloid particles to obtain a second paste;

[0018] S4 prepares the second paste into a medicine core;

[0019] S5: coating the drug core with an enteric coating agent and drying to obtain a finished product.

[0020] Preferably, step S1 also includes the preparation of bagasse fiber: first, the bagasse obtained from the sugar industry is washed and sterilized under high pressure, and crushed into particles with a particle size of ≤0.5mm; the bagasse is put into an 8wt% sulfuric acid aqueous solution and boiled for 45-55min, and then the bagasse is picked up and rinsed with clean water and drained; the bagasse is put into a 4wt% sodium hydroxide aqueous solution and boiled for 15-30min, and then the bagasse is picked up and rinsed with clean water and drained, and the bagasse pH is tested to be between 6-8 for use as bagasse fiber. If the pH exceeds the standard, it is continued to be rinsed with clean water and drained until it meets the pH standard.

[0021] Preferably, step S1 further comprises the preparation of chia seed colloid particles: adding water 10 times its weight to the chia seeds, fully soaking the chia seeds in a 37°C environment, stirring the mixture of chia seeds and water at 40×g centrifugal force, centrifuging the mixture at 400×g centrifugal force for 30 min in a 25°C environment, separating through an 18-mesh sieve to obtain a gelatinous liquid, centrifuging the separated gelatinous liquid at 400×g centrifugal force for 10 min, taking the supernatant, freeze-drying at -24°C for 48 hours, and crushing it into microparticles with a particle size of 0.3-0.6 mm to obtain chia seed colloid particles, which are sealed and stored at 4°C for standby use.

[0022] Preferably, the mixing and stirring method in step S2 is: add the formula amount of deionized water and bagasse fiber to the stirrer, stir at a speed of 1000-2500r / min for 5-15min in an environment of 35-45°C, and add soy protein isolate, high-activity nattokinase dry powder and glucose in sequence during the stirring process, and the feeding interval is 30s. The advantage is that the bagasse fiber is first wetted to greatly increase its density, and it is used as hard small particles to help stirring in the stirrer to improve the stirring efficiency; in addition, the bagasse fiber is first contacted with the soy protein isolate, and some soy protein isolate molecules or broken polypeptide molecules are combined with the hydroxyl groups widely present on the surface of the bagasse fiber through amino groups and carboxyl groups, thereby greatly improving the mechanical strength of the bagasse fiber, enhancing toughness, and reducing the probability of the bagasse fiber breaking during subsequent extrusion granulation, drying or coating.

[0023] Preferably, the mixing and stirring method in step S3 is: adding the first paste to the stirrer, stirring at a speed of 200-300 r / min for 15-20 min in an environment of 15-25° C., adding chia seed colloid particles to the first paste in small amounts and multiple times during the stirring process, and completing the addition of chia seed colloid particles within 5 minutes after the start of stirring. Adding in small amounts and multiple times can prevent the chia seed colloid particles from aggregating after absorbing water.

[0024] Preferably, the preparation method of the medicine core in step S4 is: placing the second paste in an extruder for extrusion and granulation, then spheronizing with a spheronizer, and finally freeze-drying to obtain the medicine core. The circular design makes the shrinkage rate of the medicine core in all directions relatively consistent when drying, avoiding the generation of large shrinkage seams that affect the subsequent disintegration order in the intestine.

[0025] Preferably, the aperture of the extrusion head of the extruder in step S4 is 3 mm. Too large an aperture will make the drug core particle size too large and difficult to swallow, while too small an aperture will make the drug core particle size too small and fail to promote defecation.

[0026] Preferably, the freeze drying method in step S4 is: freeze drying at -24°C for 48 hours. It is known that the moisture content of tablets should be less than 6wt%. In this preparation method, chia seed colloid particles are added after mixing other materials. Experiments have shown that the drying time after granulation can be reduced.

[0027] The third object of the present invention is achieved by the following technical solutions:

[0028] A method for taking a high-activity nattokinase composition comprises first taking the high-activity nattokinase composition according to a predetermined dosage, then filling the high-activity nattokinase composition into an empty shell capsule, and taking the composition with warm water, wherein the empty shell capsule is a gastric-soluble capsule. This method can prevent individual tablets from being squeezed and damaged in the throat and stomach and unable to reach the intestines intact; in addition, a single capsule is easier to swallow than multiple tablets.

[0029] Working principle of the present invention:

[0030] In the medicine core, soy protein isolate is mixed with high-activity nattokinase dry powder and glucose as a binder, and is bonded with bagasse fiber and chia seed colloid particles. When the medicine core enters the intestine and is released by the coating agent, the medicine core is a hard particle with a rough surface, which begins to stimulate intestinal secretion and peristalsis. Then the soy protein isolate on the surface of the medicine core begins to absorb water and dissolve, releasing part of the soy protein isolate, high-activity nattokinase dry powder and glucose. This part of the soy protein isolate and nattokinase can bind to trypsin, thereby reducing the risk of nattokinase being hydrolyzed and increasing the probability of nattokinase being absorbed by the intestine. Then the outer layer of chia seed colloid particles swells, and then the adhesive on the outside of the medicine core is cracked, accelerating the release of soy protein isolate and nattokinase, but due to the swelling of the chia seed colloid particles, the volume of the medicine core does not decrease significantly even if it loses part of the adhesive, and the outer layer of bagasse fiber after moisture absorption provides a rough texture for the main surface of the medicine core, so it can continue to stimulate the intestine to strengthen secretion and peristalsis. The chia seed colloid particles in the deep layer then swell, expanding the outer chia seed particles, bagasse fibers and adhesive and separating them from the main body of the medicine core, until the medicine core is basically disintegrated after multiple rounds of swelling and cracking.

[0031] The beneficial effects of the present invention are as follows: first, soy protein isolate is used as a plasticizer instead of dextrin to construct the overall shape of the medicine core; second, the soy protein isolate also serves as a reinforcing agent for bagasse fiber to improve the mechanical strength of the bagasse fiber; finally, the soy protein isolate acts as a competitive substrate of nattokinase and combines with trypsin to reduce the probability of nattokinase being hydrolyzed in the intestine, thereby protecting nattokinase and indirectly improving the intestinal absorption rate of nattokinase. DETAILED DESCRIPTION

[0032] The following is further described in conjunction with specific implementation methods:

[0033] Example 1

[0034] A method for preparing a highly active nattokinase composition comprises the following steps:

[0035] Preparation of bagasse fiber: First, wash the bagasse obtained from the sugar industry, sterilize it under high pressure, and crush it into particles with a particle size of ≤0.5mm; put the bagasse into 8wt% sulfuric acid aqueous solution and boil it for 46min, pick it up and rinse it with clean water, and drain it; put the bagasse into 4wt% sodium hydroxide aqueous solution and boil it for 16min, pick it up and rinse it with clean water, and drain it. Test the pH of the bagasse and find that it is between 6-8 as bagasse fiber. If it exceeds the pH standard, continue to rinse it with clean water and drain it until it meets the pH standard.

[0036] Preparation of chia seed colloid particles: add 10 times the weight of water to chia seeds, fully soak the chia seeds at 37°C, then stir the mixture of chia seeds and water at 40×g, centrifuge the mixture at 400×g for 30 minutes at 25°C, separate through an 18-mesh sieve to obtain a gelatinous liquid, centrifuge the separated gelatinous liquid at 400×g for 10 minutes, take the supernatant, freeze-dry at -24°C for 48 hours, and crush into microparticles with a particle size of 0.3-0.6 mm to obtain chia seed colloid particles, which are sealed and stored at 4°C for later use.

[0037] Weigh 21 parts of bagasse fiber, 170 parts of soy protein isolate, 68 parts of chia seed colloid particles, 60 parts of high-activity nattokinase dry powder, 17 parts of glucose, 98 parts of enteric coating agent and 149 parts of deionized water according to weight.

[0038] Bagasse fiber, soy protein isolate, high-activity nattokinase dry powder, glucose and deionized water are mixed and stirred to obtain a first paste; the mixing and stirring method is: add the formulated amount of deionized water and bagasse fiber into the stirrer, stir at a speed of 1100r / min for 6 minutes in an environment of 36°C, and add soy protein isolate, high-activity nattokinase dry powder and glucose in sequence during the stirring process, with an interval of 30s between additions.

[0039] The first paste is mixed and stirred with chia seed colloid particles to obtain a second paste; the mixing and stirring method is: add the first paste to the stirrer, stir at a speed of 210r / min for 16 minutes in an environment of 16°C, add chia seed colloid particles to the first paste in small amounts and multiple times during the stirring process, and complete the addition of chia seed colloid particles within 5 minutes after the start of stirring.

[0040] The second paste is made into a medicine core; the preparation method of the medicine core is: the second paste is placed in an extruder for extrusion and granulation, then spheronized by a spheronizer, and finally freeze-dried to obtain the medicine core. The aperture of the extruder head is 3 mm. The freeze-drying method is: freeze-drying at -24°C for 48 hours.

[0041] The drug core is coated with an enteric coating agent and dried to obtain a finished product. The enteric coating agent adopts a conventional enteric coating agent and a conventional coating method.

[0042] Example 2

[0043] A method for preparing a highly active nattokinase composition comprises the following steps:

[0044] Preparation of bagasse fiber: First, wash the bagasse obtained from the sugar industry, sterilize it under high pressure, and crush it into particles with a particle size of ≤0.5mm; put the bagasse into 8wt% sulfuric acid aqueous solution and boil it for 54min, pick it up and rinse it with clean water, and drain it; put the bagasse into 4wt% sodium hydroxide aqueous solution and boil it for 29min, pick it up and rinse it with clean water, and drain it. Test the pH of the bagasse and find that it is between 6-8 as bagasse fiber. If it exceeds the pH standard, continue to rinse it with clean water and drain it until it meets the pH standard.

[0045] Preparation of chia seed colloid particles: add 10 times the weight of water to chia seeds, fully soak the chia seeds at 37°C, then stir the mixture of chia seeds and water at 40×g, centrifuge the mixture at 400×g for 30 minutes at 25°C, separate through an 18-mesh sieve to obtain a gelatinous liquid, centrifuge the separated gelatinous liquid at 400×g for 10 minutes, take the supernatant, freeze-dry at -24°C for 48 hours, and crush into microparticles with a particle size of 0.3-0.6 mm to obtain chia seed colloid particles, which are sealed and stored at 4°C for later use.

[0046] Weigh 28 parts of bagasse fiber, 230 parts of soy protein isolate, 92 parts of chia seed colloid particles, 60 parts of high-activity nattokinase dry powder, 23 parts of glucose, 132 parts of enteric coating agent and 201 parts of deionized water according to weight.

[0047] Bagasse fiber, soy protein isolate, high-activity nattokinase dry powder, glucose and deionized water are mixed and stirred to obtain a first paste; the mixing and stirring method is: add the formulated amount of deionized water and bagasse fiber into the stirrer, stir at a speed of 240r / min for 14 minutes in an environment of 44°C, and add soy protein isolate, high-activity nattokinase dry powder and glucose in sequence during the stirring process, with an interval of 30s between additions.

[0048] The first paste is mixed and stirred with chia seed colloid particles to obtain a second paste; the mixing and stirring method is: add the first paste to the stirrer, stir at a speed of 290r / min for 19 minutes in an environment of 24°C, and add chia seed colloid particles to the first paste in small amounts and multiple times during the stirring process, and complete the addition of chia seed colloid particles within 5 minutes after the start of stirring.

[0049] The second paste is made into a medicine core; the preparation method of the medicine core is: the second paste is placed in an extruder for extrusion and granulation, then spheronized by a spheronizer, and finally freeze-dried to obtain the medicine core. The aperture of the extruder head is 3 mm. The freeze-drying method is: freeze-drying at -24°C for 48 hours.

[0050] The drug core is coated with an enteric coating agent and dried to obtain a finished product.

[0051] Example 3

[0052] A method for preparing a highly active nattokinase composition comprises the following steps:

[0053] Preparation of bagasse fiber: First, wash the bagasse obtained from the sugar industry, sterilize it under high pressure, and crush it into particles with a particle size of ≤0.5mm; put the bagasse into 8wt% sulfuric acid aqueous solution and boil it for 50min, pick it up and rinse it with clean water, and drain it; put the bagasse into 4wt% sodium hydroxide aqueous solution and boil it for 23min, pick it up and rinse it with clean water, and drain it. Test the pH of the bagasse and find that it is between 6-8 as bagasse fiber. If it exceeds the pH standard, continue to rinse it with clean water and drain it until it meets the pH standard.

[0054] Preparation of chia seed colloid particles: add 10 times the weight of water to chia seeds, fully soak the chia seeds at 37°C, then stir the mixture of chia seeds and water at 40×g, centrifuge the mixture at 400×g for 30 minutes at 25°C, separate through an 18-mesh sieve to obtain a gelatinous liquid, centrifuge the separated gelatinous liquid at 400×g for 10 minutes, take the supernatant, freeze-dry at -24°C for 48 hours, and crush into microparticles with a particle size of 0.3-0.6 mm to obtain chia seed colloid particles, which are sealed and stored at 4°C for later use.

[0055] Weigh 25 parts of bagasse fiber, 200 parts of soy protein isolate, 80 parts of chia seed colloid particles, 60 parts of high-activity nattokinase dry powder, 20 parts of glucose, 115.5 parts of enteric coating agent and 175 parts of deionized water according to weight.

[0056] Bagasse fiber, soy protein isolate, high-activity nattokinase dry powder, glucose and deionized water are mixed and stirred to obtain a first paste; the mixing and stirring method is: add a formulated amount of deionized water and bagasse fiber into a stirrer, stir at a speed of 2000r / min for 10 minutes in an environment of 40°C, and during the stirring process, add soy protein isolate, high-activity nattokinase dry powder and glucose in sequence, with an interval of 30s between additions.

[0057] The first paste is mixed and stirred with chia seed colloid particles to obtain a second paste; the mixing and stirring method is: add the first paste to the stirrer, stir at a speed of 250r / min for 17 minutes in an environment of 20°C, and add chia seed colloid particles to the first paste in small amounts and multiple times during the stirring process, and complete the addition of chia seed colloid particles within 5 minutes after the start of stirring.

[0058] The second paste is made into a medicine core; the preparation method of the medicine core is: the second paste is placed in an extruder for extrusion and granulation, then spheronized by a spheronizer, and finally freeze-dried to obtain the medicine core. The aperture of the extruder head is 3 mm. The freeze-drying method is: freeze-drying at -24°C for 48 hours.

[0059] The drug core is coated with an enteric coating agent and dried to obtain a finished product.

[0060] Example 4

[0061] The composition obtained in Example 3 was filled into gastric soluble capsules.

[0062] Comparative Example 1

[0063] The soy protein isolate in Example 3 was replaced with an equal weight of β-cyclodextrin. The remaining steps were the same as in Example 3.

[0064] Comparative Example 2

[0065] The same weight of bagasse fiber, soy protein isolate, chia seed colloid particles, high-activity nattokinase dry powder and glucose as in Example 3 were filled into enteric-coated capsules.

[0066] Comparative Example 3

[0067] When mixing, bagasse fiber, soy protein isolate, high-activity nattokinase dry powder, glucose, chia seed colloid particles and deionized water are mixed and stirred to obtain a paste. The remaining steps are the same as those in Example 3, that is, the mixing is done once, and the chia seed colloid particles are no longer added later.

[0068] Experimental study on the protective effect of soy protein isolate on nattokinase

[0069] Purpose:

[0070] Verify the protective effect of soy protein isolate on nattokinase in the intestinal environment.

[0071] Experimental methods:

[0072] Take the drug cores obtained in Example 3 and Comparative Example 1 (freeze-dried to a water content of less than 6%), all with a specification of 0.5 g / piece. Take 12 beakers, each filled with 100 mL of intestinal environment simulation liquid, and mark them as 1-1, 1-2, 1-3, 1-4, 1-5, 1-6, 2-1, 2-2, 2-3, 2-4, 2-5, 2-6. Groups 1-1, 1-2, 1-3, 1-4, 1-5, and 1-6 are all put into 1 tablet of the drug core obtained in Example 3, and groups 2-2, 2-3, 2-4, 2-5, and 2-6 are all put into 1 tablet of the drug core obtained in Comparative Example 1. The timing starts from the time when the core is put in. In the first minute, 300 mL of the fixing solution is put into the 1-1 and 2-1 groups, and the pH is adjusted to 7 with dilute hydrochloric acid. In the third minute, 300 mL of the fixing solution is put into the 1-2 and 2-2 groups, and the pH is adjusted to 7 with dilute hydrochloric acid. In the sixth minute, 300 mL of the fixing solution is put into the 1-3 and 2-3 groups, and the pH is adjusted to 7 with dilute hydrochloric acid. In the ninth minute, 300 mL of the fixing solution is put into the 1-4 and 2-4 groups, and the pH is adjusted to 7 with dilute hydrochloric acid. In the 12th minute, 300 mL of the fixing solution is put into the 1-5 and 2-5 groups, and the pH is adjusted to 7 with dilute hydrochloric acid. In the 15th minute, 300 mL of the fixing solution is put into the 1-6 and 2-6 groups, and the pH is adjusted to 7 with dilute hydrochloric acid. Finally, the powder obtained after low-temperature drying of each group was tested for the enzyme activity of nattokinase.

[0073] The intestinal environment simulation liquid is: 6.8g of potassium dihydrogen phosphate and 10g of trypsin are mixed with water, and then the pH value is adjusted to 6.8 with 0.4wt% sodium hydroxide solution, and then water is added to make the volume to 1000ml to make the intestinal environment simulation liquid. The fixing liquid is 0.4wt% sodium hydroxide solution. The pH of the fixing liquid is greater than 9, which makes trypsin permanently inactivated, and nattokinase can withstand a high pH environment. Therefore, by adding the fixing liquid to detect the enzyme activity of nattokinase, the activity content of nattokinase in the time period of adding the fixing liquid can be more accurately reflected.

[0074] Experimental results:

[0075] Table 1 Enzyme activity statistics

[0076]

[0077] Experimental summary:

[0078] As can be seen from Table 1, after the core is put into the intestinal environment simulation liquid, the nattokinase in Example 3 and Comparative Example 1 may be hydrolyzed and inactivated by trypsin. When the nattokinase in Example 3 is dissolved in the intestinal environment simulation liquid with the soy protein isolate, since there is soy protein isolate as a competitive substrate for trypsin (both soy protein isolate and nattokinase contain a large amount of lysine and arginine, which are easy to bind to trypsin), and the concentration of soy protein isolate is much greater than that of nattokinase, the amount of nattokinase hydrolyzed and inactivated per unit time is small, which ultimately increases the probability of nattokinase being captured and absorbed by intestinal cells; while in Comparative Example 1, due to the lack of protection of soy protein isolate, most of the nattokinase will be hydrolyzed and inactivated in a short time as long as it is dissolved in the intestinal environment simulation liquid with dextrin, and only a small part of nattokinase can survive and enter the intestinal cells.

[0079] Promote defecation experiment

[0080] Purpose:

[0081] It is verified that the nattokinase composition obtained by the present invention has a substantial defecation promoting effect on the human body.

[0082] Experimental methods:

[0083] Two groups of volunteers, Example 3 and Comparative Example 2, were set up, each group had 15 people, and they took 15 tablets after dinner, the core specification of each was 0.5g, and they were all taken with warm water within 1 hour; the intestinal transit time reduction rate and the increase in stool weight on the day before and the day after taking the medicine were tested. The test method refers to Tomlin, J., & Read, NW (1988). Laxative properties of indigestible plastic particles. BMJ (Clinical research ed.), 297 (6657), 1175-1176.

[0084] https: / / doi.org / 10.1136 / bmj.297.6657.1175.

[0085] Experimental results:

[0086] Table 2 Statistics of the decrease rate of intestinal transit time and the increase in stool weight

[0087] Type of pills taken Decrease rate of intestinal transit time, % Increase in defecation weight, g Example 3 19 17 Comparative Example 2 0 2

[0088] Experimental summary:

[0089] As can be seen from Table 2, the nattokinase composition obtained in Example 3 accelerates intestinal transit and increases the amount of defecation, so it has an obvious effect of promoting defecation; while Comparative Example 2 with the same ingredients is difficult to form particles of suitable particle size and rough surface because the raw materials are only filled in capsules and sent to the intestine, and it is difficult to stimulate the intestine to increase secretion and accelerate peristalsis.

[0090] Core drying efficiency experiment

[0091] Purpose:

[0092] It is verified that the feeding method of the present invention can improve the drying efficiency of the medicine core.

[0093] Experimental methods:

[0094] Take the particles extruded by the extruder in Example 3 and Comparative Example 3, with a particle size of 3 mm, 25 particles each, and arrange them on a ceramic sheet with a distance of at least 1 cm between the particles. The two ceramic sheets are respectively placed in two -24°C freeze-drying ovens and the moisture content of the particles is monitored online. When the average moisture content of the particles on the ceramic sheets is lower than 6%, the drying time of this group is recorded.

[0095] Experimental results:

[0096] The drying time of the granules obtained in Example 3 was 42h45min, and the drying time of the granules obtained in Comparative Example 3 was 45h1min.

[0097] Experimental summary:

[0098] The experiment shows that adding the water-absorbing chia seed colloid particles later can reduce the drying time of the medicine core, which is helpful to improve production efficiency.

[0099] The above embodiments and descriptions are only for illustrating the principles and best embodiments of the present invention. Without departing from the spirit and scope of the present invention, the present invention may be subject to various changes and improvements, all of which fall within the scope of the present invention to be protected.

Claims

1. A highly active nattokinase composition, characterized in that, The preparation method comprises the following steps: Preparation of bagasse fiber: First, wash the bagasse obtained from the sugar industry, sterilize it under high pressure, and crush it into particles with a particle size of ≤0.5mm; put the bagasse into an 8wt% sulfuric acid aqueous solution and boil it for 50min, pick it up and rinse it with clean water and drain it; put the bagasse into a 4wt% sodium hydroxide aqueous solution and boil it for 23min, pick it up and rinse it with clean water and drain it, test the bagasse pH between 6-8 as bagasse fiber, and continue to rinse it with clean water and drain it if it exceeds the pH standard until it meets the pH standard; Preparation of chia seed colloid particles: add 10 times of water by weight to chia seeds, fully soak the chia seeds in a 37°C environment, stir the mixture of chia seeds and water at 40×g centrifugal force, centrifuge the mixture at 400×g centrifugal force for 30 minutes at 25°C, separate through an 18-mesh sieve to obtain a colloid solution, centrifuge the separated colloid solution at 400×g centrifugal force for 10 minutes, take the supernatant, freeze-dry at -24°C for 48 hours, crush into microparticles with a particle size of 0.3-0.6 mm to obtain chia seed colloid particles, and seal and store at 4°C for standby use; Weigh 25 parts of bagasse fiber, 200 parts of soy protein isolate, 80 parts of chia seed colloid particles, 60 parts of high-activity nattokinase dry powder, 20 parts of glucose, 115.5 parts of enteric coating agent and 175 parts of deionized water according to weight parts; Bagasse fiber, soy protein isolate, high-activity nattokinase dry powder, glucose and deionized water are mixed and stirred to obtain a first paste; the mixing and stirring method is: adding a formula amount of deionized water and bagasse fiber to a stirrer, stirring at a speed of 2000r / min for 10min in an environment of 40°C, and adding soy protein isolate, high-activity nattokinase dry powder and glucose in sequence during the stirring process, with an interval of 30s between feedings; The first paste is mixed and stirred with chia seed colloid particles to obtain a second paste; the mixing and stirring method is: adding the first paste to a stirrer, stirring at a speed of 250r / min for 17 minutes in an environment of 20°C, and adding chia seed colloid particles to the first paste in small amounts and multiple times during the stirring process, and the addition of chia seed colloid particles is completed within 5 minutes after the start of stirring; The second paste is made into a medicine core; the preparation method of the medicine core is: the second paste is placed in an extruder for extrusion and granulation, then spheronization is performed by a spheronization machine, and finally freeze-drying to obtain the medicine core; the aperture of the extruder head is 3 mm; the freeze-drying method is: freeze-drying at -24°C for 48 hours; The drug core is coated with an enteric coating agent and dried to obtain a finished product.

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