阅读说明：本技术 一种冬虫夏草破壁制剂及其制备方法 (Cordyceps sinensis wall-breaking preparation and preparation method thereof ) 是由 汪小东 孙杨杨 钱正明 李周 庄东芳 舒加菊 武万兴 李文佳 于 2021-09-08 设计创作，主要内容包括：本发明涉及中药制剂技术领域,具体公开了一种冬虫夏草的破壁制剂以及冬虫夏草破壁制剂的制备方法。本发明的冬虫夏草破壁制剂由冬虫夏草全草经粉碎获得粗粉,所述粗粉经湿法球磨、喷雾干燥、制粒制得破壁制剂。本发明提供的冬虫夏草的破壁制剂,在制备过程中不对冬虫夏草的生物活性物质产生破坏,并且服用方便,溶出效果好,储存不易结块变质。(The invention relates to the technical field of traditional Chinese medicine preparations, and particularly discloses a cordyceps sinensis wall-broken preparation and a preparation method thereof. The cordyceps wall-breaking preparation is prepared by crushing cordyceps whole grass to obtain coarse powder, and performing wet ball milling, spray drying and granulation on the coarse powder to obtain the wall-breaking preparation. The wall-broken preparation of cordyceps sinensis provided by the invention does not damage bioactive substances of cordyceps sinensis in the preparation process, is convenient to take and good in dissolving effect, and is not easy to agglomerate and deteriorate after being stored.)

1. A method for preparing a cordyceps sinensis wall-breaking preparation is characterized in that cordyceps sinensis whole grass is crushed to obtain coarse powder, and the coarse powder is subjected to wet ball milling, spray drying and granulation to prepare the wall-breaking preparation.

2. The method according to claim 1, wherein the coarse powder is a undersize product of a No. 2 sieve after the whole plant of Cordyceps sinensis is pulverized.

3. The preparation method of claim 1, wherein the wet ball milling is to grind a mixture of coarse powder and water in a ball milling tank, and the particle size D90 in the slurry of the wall-broken powder of Cordyceps sinensis is not more than 45 μm; preferably, the grinding time is 10-90 min, more preferably 30-90 min.

4. The preparation method according to claim 3, wherein the mass percentage of the coarse powder in the mixture of the coarse powder and the water is 5-15%, preferably 10%.

5. The method according to claim 3, wherein ball milling beads having a particle size of 0.1 to 5mm, preferably 0.8mm, are added to the ball milling pot during milling, and the mass of the ball milling beads is 1 to 5 times, preferably 2 to 3 times, the mass of the mixture of the coarse powder and water in the ball milling pot.

6. The preparation method according to claim 1, wherein the spray drying is to dry the cordyceps sinensis wall-broken powder slurry obtained by ball milling by a spray dryer to obtain cordyceps sinensis wall-broken powder dry powder; preferably, the cordyceps sinensis wall-broken powder slurry obtained by ball milling is homogenized and then spray-dried; and/or the air outlet temperature of the spray dryer is 60-70 ℃, and the air volume of the circular air blower is 34-42 m³The pumping speed is 250-1000 ml/h.

7. The preparation method according to claim 1, wherein the granulation is to granulate the dry powder of the cordyceps wall-broken powder obtained by spray drying with purified water, and the particle size of the prepared granules is between 250 and 850 μm; preferably, the amount of the purified water is 15-50% of the weight of the cordyceps wall-breaking powder dry powder, and more preferably 30%.

8. The preparation method according to claim 7, wherein the cordyceps wall-broken powder dry powder is mixed with purified water during granulation, then is extruded into wet granules by a granulator, is dried until the water content of the granules is 2-10%, and is sieved to obtain the cordyceps wall-broken preparation; preferably, the granulator whole grain screen has a diameter of 0.6-2.0mm, more preferably 1.0 mm; and/or the drying temperature is 40-60 ℃.

9. The method of manufacturing according to claim 8, wherein the granulator is a high shear granulator or an oscillating granulator.

10. The wall-broken preparation of cordyceps sinensis prepared by the preparation method of any one of claims 1 to 9.

Technical Field

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a preparation of cordyceps sinensis.

Background

Cordyceps sinensis is a complex of stroma of Cordyceps sinensis (belonging to Clavicipitaceae) parasitic on larva of insect belonging to Hepialidae and larva. Cordyceps has effects in regulating immune system, resisting tumor, relieving fatigue, invigorating lung and kidney, stopping bleeding, eliminating phlegm, and replenishing essence and qi.

At present, the main edible methods of the cordyceps sinensis comprise pulverizing, soaking in wine, soaking in water and the like. Since the active ingredients of cordyceps sinensis have not been completely elucidated so far, only the extract thereof is used in the form of wine or water, and thus some of the medicinal effects may be lost. If the fine powder of Cordyceps sinensis or whole plant is used as a whole, since the fine powder particles of the fine powder of Cordyceps sinensis (such as the product obtained in comparative example 2) are often composed of several or several tens of cells, the dissolution of the active ingredient needs to cross the layer-by-layer obstacle, which is difficult to dissolve, and the dissolution of the active ingredient of the whole plant of Cordyceps sinensis needs to cross more obstacle. The traditional decocting method is easy to damage the heat-sensitive components in the cordyceps sinensis, and the effective components are not completely decocted, so that the loss of the effective components can be caused. The cordyceps sinensis is prepared into superfine powder, so that the utilization rate of effective components is improved, but the increase of the specific surface area of the powder easily causes obvious adverse phenomena such as moisture absorption, agglomeration, adsorption, flying and the like, and causes inconvenience in taking and easy degeneration during storage. Therefore, on the basis of preparing the superfine powder, the superfine powder needs to be further processed and modified so as to effectively overcome the adverse factors and maximize the treatment and health care effects of the cordyceps sinensis.

The existing cordyceps sinensis preparation technology is mostly formed by mixing other medicinal materials or adding auxiliary materials, which is also unfavorable for the absorption of effective components. In particular, the cordyceps sinensis is used as a precious medicinal material and is prepared into a pure powder preparation which is more easily accepted by consumers. The problems of low yield, uneven texture, easy crushing of the particles into powder, incomplete disintegration and the like of the pure cordyceps sinensis powder particles prepared by using the conventional superfine grinding fine powder exist, and further improvement is needed.

Disclosure of Invention

The invention mainly solves the technical problem of providing a wall-broken preparation of cordyceps sinensis and a preparation method of the wall-broken preparation. The preparation has no damage to bioactive substances of Cordyceps, and has the advantages of convenient administration, good dissolution effect, and convenient storage.

In order to solve the technical problems, the invention adopts a technical scheme that: a method for preparing wall-broken preparation of Cordyceps comprises pulverizing whole plant of Cordyceps to obtain coarse powder, ball-milling the coarse powder with wet method, spray drying, and granulating to obtain wall-broken preparation.

In a preferred embodiment of the present invention, the coarse powder is a undersize product obtained by pulverizing whole cordyceps sinensis and sieving with a No. 2 sieve. The mesh opening of the No. 2 sieve is 850 +/-29 mu m.

In a preferred embodiment of the invention, the wet ball milling is to grind a mixture of the coarse powder and water in a ball milling tank, and the particle size D90 in the cordyceps sinensis wall-broken powder slurry obtained by grinding is not more than 45 μm.

Preferably, the grinding time is 10-90 min, more preferably 30-90 min.

In a preferred embodiment of the present invention, the mass percentage of the coarse powder in the mixture of the coarse powder and water is 5 to 15%, preferably 10%.

In a preferred embodiment of the present invention, ball milling beads having a particle diameter of 0.1 to 5mm, preferably 0.8mm, and a mass of 1 to 5 times, preferably 2 to 3 times, that of a mixture of the coarse powder and water in the ball milling pot are added to the ball milling pot during milling.

As a preferred embodiment of the invention, the spray drying is to dry the cordyceps sinensis wall-broken powder slurry obtained by ball milling through a spray dryer to prepare cordyceps sinensis wall-broken powder dry powder; preferably, the cordyceps sinensis wall-broken powder slurry obtained by ball milling is homogenized and then spray-dried.

Preferably, the air outlet temperature of the spray dryer is 60-70 ℃, and the air volume of the circular air blower is 34-42 m³The pumping speed is 250-1000 ml/h.

More preferably, the air outlet temperature of the spray dryer is 65-70 ℃, and the air volume of the circular air blower is 40-42 m³The pump speed is 500-800 ml/h.

As a preferred embodiment of the invention, the granulation is to granulate the dry powder of the cordyceps wall-broken powder obtained by spray drying by using purified water, and the particle size of the prepared granules is between 250 and 850 mu m.

Preferably, the amount of the purified water is 15-50% of the weight of the cordyceps wall-breaking powder dry powder, and more preferably 30%.

As a preferred embodiment of the invention, during granulation, the cordyceps wall-broken powder dry powder is mixed with purified water, then is extruded by a granulator to be made into wet granules, then is dried until the water content of the granules is 2-10%, and then is sieved to obtain the cordyceps wall-broken preparation.

Preferably, the granulator has a whole grain screen diameter of 0.6-2.0mm, more preferably 1.0 mm.

Preferably, the drying temperature is 40-60 ℃.

Preferably, the granulator is a high shear granulator or an oscillating granulator.

As a preferred embodiment of the present invention, a wall-broken preparation of Cordyceps sinensis is obtained by a preparation method comprising the steps of:

(1) primary crushing: pulverizing Cordyceps whole plant with pulverizer, and sieving with No. 2 sieve to obtain coarse powder;

(2) ball milling: mixing the coarse powder with purified water, wherein the mass percentage of the coarse powder in the mixture is 5-15%, then placing the mixture into a ball milling tank, and then placing zirconium dioxide ball milling beads, 2-3 times of the weight of the mixture of the coarse powder and the water, into the ball milling tank; grinding is started, the tank body is enabled to do rapid multidimensional swing motion, the grinding time is 30-90 min, and then the cordyceps sinensis wall-broken powder slurry is obtained by screen separation, wherein the particle size D90 of the contained particles is less than or equal to 45 mu m;

(3) spray drying: homogenizing the cordyceps sinensis wall-broken powder slurry obtained in the step (2), and drying by using a spray dryer to obtain cordyceps sinensis wall-broken powder dry powder; the parameters of the spray dryer were: the air inlet temperature is 120-140 ℃, the air outlet temperature is 60-70 ℃, and the air quantity of the circular air blower is 42m³The pump speed is 500-1000 ml/h; during the spray drying process, the cordyceps wall-broken homogenate is in a magnetic stirring state;

(4) and (3) granulating: and (3) adding purified water into the cordyceps wall-breaking powder dry powder obtained in the step (3) for granulation, wherein the amount of the purified water is 30% of the mass of the cordyceps wall-breaking powder dry powder, then extruding the mixture through a granulator to prepare wet granules, the mesh diameter of the granulator is 1.0mm, drying the wet granules at 50 ℃ for 1h to ensure that the water content of the granules is between 2% and 10%, and then sieving the granules to prepare the cordyceps wall-breaking preparation, wherein the particle size of the granules is between 250 and 850 mu m.

The wall-broken preparation of cordyceps sinensis is prepared by any one of the preparation methods.

According to the wall-broken preparation of cordyceps sinensis, a ball mill is used for wet ball milling and crushing in the preparation process, so that the dissolution of cordyceps sinensis water-soluble components such as cordyceps polysaccharide is facilitated, and the dissolved components generate viscosity, so that an adhesive which needs to be added in conventional granulation is replaced, and pure powder granulation is realized; because of the existence of water, the ball milling efficiency is high and heat is not generated basically, thereby avoiding the damage to the active ingredients of the cordyceps sinensis, and external refrigeration equipment is not needed, so as to achieve the purpose of saving cost. Specifically, because the ball milling time is short and water exists, only a small amount of heat is generated, and after the ball milling is finished, the temperature of the material is less than or equal to 30 ℃, which is close to the room temperature, thereby avoiding the high-temperature damage to the cordyceps sinensis components. Of course, the same ball milling effect can be achieved by properly reducing the ball milling ratio and increasing the ball milling time.

In the preparation process, the cordyceps wall-broken slurry is dried into dry wall-broken powder by adopting a spray drying technology, the problems of wall sticking and caking of materials during spray drying are solved by controlling drying parameters, high-yield spray drying without adding auxiliary materials can be realized, the steps are simple, the process is stable, and the loss of effective components is less. Specifically, the outlet air temperature of spray drying is controlled at 60-70 ℃, and cannot be too high; during grinding, the mass percentage of the coarse powder in the mixture of the coarse powder and water is controlled to be 5-15%, the concentration of the cordyceps sinensis in the slurry after grinding and homogenization is 5-15%, and tests show that when the concentration reaches above 15%, the viscosity is rapidly increased, so that spraying difficulty is caused; when the concentration of the cordyceps sinensis is too low, dried powder particles are too fine and are easy to be adsorbed on a drying tower, so that the yield is reduced.

The invention also discovers that the stability of the prepared cordyceps sinensis wall-broken preparation finished product cannot be improved by adopting other crushing and drying modes except wet ball milling and spray drying or singly adopting ball milling or spray drying, and the stability of the cordyceps sinensis wall-broken product can be greatly improved by combining the wet ball milling and the spray drying, so that unexpected technical effects are generated.

The invention adopts wet ball milling, can obviously improve the dissolution of cordyceps sinensis polysaccharide compared with other crushing modes and dry ball milling modes, and has unexpected effect.

The preparation method of the cordyceps sinensis wall-broken preparation combines the properties of active ingredients of cordyceps sinensis, and the granules with excellent properties are prepared by a simple, convenient and efficient method. The prepared wall-broken preparation of the cordyceps sinensis is not added with any auxiliary materials and preservatives, has simple process and high yield, and meets the requirement of consumers on products without additives; the preparation has high granule dissolution rate, good fluidity, good preservation of Cordyceps flavor, crisp taste, convenient administration, and rapid disintegration in oral cavity without granule feeling after direct oral administration; the active ingredients of the cordyceps are reserved, the dissolution rate of the cordyceps polysaccharide can reach more than 90 percent, and the bioavailability of the cordyceps is greatly improved.

The invention also effectively solves the problem that the steps of soaking, stewing and the like are required to cause loss of bioactive substances when the cordyceps sinensis is taken; solves the problems of partial use obstacle and inconvenient administration of the cordyceps sinensis due to appearance; solves the problems that the pure powder of the cordyceps sinensis is easy to absorb moisture, agglomerate and deteriorate when being stored, and is easy to fly and adhere when being taken.

Drawings

FIG. 1 is a photograph showing the microscopic examination of fine powder (passing through 100 mesh) of Cordyceps sinensis in Experimental example 1 of the present invention, wherein the scale is 100 μm;

FIG. 2 is another photograph showing microscopic examination of fine powder (passing through 100 mesh) of Cordyceps sinensis in Experimental example 1 of the present invention, wherein the scale is 100 μm;

FIG. 3 is a detection picture of microscopic examination of the wall-broken powder of Cordyceps sinensis after ball milling in Experimental example 1, wherein the scale in the picture is 100 μm;

FIG. 4 is another detection picture of wall-broken powder microscopic examination after ball milling of Cordyceps sinensis in Experimental example 1 of the present invention, wherein the scale in the figure is 100 μm;

FIG. 5 is a graph showing the dissolution profile of Cordyceps sinensis polysaccharide in Experimental example 7 of the present invention.

Detailed Description

The technical solution of the present invention will be described in detail by specific examples.

Example 1

The wall-broken preparation of cordyceps sinensis provided by the embodiment is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis whole grass, crushing the cordyceps sinensis whole grass by a crusher, and screening the crushed cordyceps sinensis whole grass by a No. 2 sieve to obtain coarse powder;

(2) ball milling: mixing the coarse powder with purified water, wherein the mass percent of the coarse powder in the mixture is 5%, then placing the mixture into a ball milling tank, and then placing zirconium dioxide ball milling beads, the weight of which is 3 times of that of the mixture of the coarse powder and the water, into the ball milling tank, wherein the particle size of the ball milling beads is 0.8 mm; then, grinding for 30min, then separating by using a screen to obtain cordyceps sinensis wall-broken powder slurry, and detecting the particle size of the cordyceps sinensis wall-broken powder slurry;

(3) spray drying: homogenizing the cordyceps sinensis wall-broken powder slurry obtained in the step (2), drying by using a spray dryer, wherein the concentration of cordyceps sinensis in the homogenized cordyceps sinensis wall-broken powder slurry is 5%, and spray drying to obtain cordyceps sinensis wall-broken powder dry powder; the parameters of the spray dryer were: the air inlet temperature is 130 ℃, the air outlet temperature is 65 ℃, and the air quantity of the circular air blower is 42m³The pump speed is 500 ml/h;

(4) and (3) granulating: and (3) adding purified water into the cordyceps wall-breaking powder dry powder obtained in the step (3) to prepare a soft material, wherein the amount of the purified water is 30% of the mass of the cordyceps wall-breaking powder dry powder, then extruding the mixture through a granulator to prepare wet granules, wherein the mesh diameter of the granulator is 1.0mm, drying the wet granules at 50 ℃ for 1h to ensure that the water content of the granules is between 2% and 10%, and then sieving the granules to prepare the cordyceps wall-breaking preparation.

The conditions of ball milling, spray drying, granulation and the obtained finished product in the preparation process were respectively detected, and the results are shown in table 1.

Wherein, the determination method of the angle of repose and the disintegration time limit in the table is as follows:

angle of repose measurement: the evaluation by HM-1001A powder physical property tester shows that the powder has a best repose angle of 30 degrees or less, a good repose angle of 31 to 35 degrees, and a good repose angle of 36 to 40 degrees.

Time limit of water collapse: weighing 0.25g of wall-broken particles, adding 200mL of hot water, stirring while observing until no large particles exist, and recording the time.

Oral cavity collapse time limit: selecting 3 evaluators, taking 0.25g of wall-broken granules for each person, buccal administration till no granule feeling in oral cavity, recording time, and taking average value.

In other examples and comparative examples, the methods for measuring the angle of repose and the disintegration time were the same as in this example.

TABLE 1

Because the particle size of the cordyceps wall-broken preparation is smaller than the particle size which can be sensed by the oral cavity, no granular sensation exists after complete disintegration; the product retains the good flavor of Cordyceps, has no fine powder, and can be taken orally without choking throat.

Example 2

The wall-broken preparation of cordyceps sinensis provided by the embodiment is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis whole grass, crushing the cordyceps sinensis whole grass by a crusher, and screening the crushed cordyceps sinensis whole grass by a No. 2 sieve to obtain coarse powder;

(2) ball milling: mixing the coarse powder with purified water, wherein the mass percent of the coarse powder in the mixture is 10%, then placing the mixture into a ball milling tank, and then placing zirconium dioxide ball milling beads, the weight of which is 3 times of that of the mixture of the coarse powder and the water, into the ball milling tank, wherein the particle size of the ball milling beads is 0.3 mm; then, grinding for 30min, then separating by using a screen to obtain cordyceps sinensis wall-broken powder slurry, and detecting the particle size of the cordyceps sinensis wall-broken powder slurry;

(3) spray drying: homogenizing the cordyceps sinensis wall-broken powder slurry obtained in the step (2), drying by using a spray dryer, wherein the concentration of cordyceps sinensis in the homogenized cordyceps sinensis wall-broken powder slurry is 10%, and spray drying to obtain cordyceps sinensis wall-broken powder dry powder; the parameters of the spray dryer were: the air inlet temperature is 130 ℃, the air outlet temperature is 65 ℃, and the air quantity of the circular air blower is 42m³The pump speed is 800 ml/h;

(4) and (3) granulating: and (3) adding purified water into the cordyceps wall-breaking powder dry powder obtained in the step (3) to prepare a soft material, wherein the amount of the purified water is 30% of the mass of the cordyceps wall-breaking powder dry powder, then extruding the mixture through a granulator to prepare wet granules, wherein the mesh diameter of the granulator is 1.0mm, drying the wet granules at 50 ℃ for 1h to ensure that the water content of the granules is between 2% and 10%, and then sieving the granules to prepare the cordyceps wall-breaking preparation.

The conditions of ball milling, spray drying, granulation and the obtained finished product in the preparation process were respectively detected, and the results are shown in table 2.

TABLE 2

Example 3

The wall-broken preparation of cordyceps sinensis provided by the embodiment is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis, drying until the water content is less than or equal to 5%, crushing by a crusher, and sieving by a No. 2 sieve to obtain coarse powder;

(2) ball milling: mixing the coarse powder with purified water, wherein the mass percent of the coarse powder in the mixture is 5%, then placing the mixture into a ball milling tank, and then placing zirconium dioxide ball milling beads, the weight of which is 3 times of that of the mixture of the coarse powder and the water, into the ball milling tank, wherein the particle size of the ball milling beads is 0.8 mm; then, grinding for 30min, then separating by using a screen to obtain cordyceps sinensis wall-broken powder slurry, and detecting the particle size of the cordyceps sinensis wall-broken powder slurry;

(3) spray drying: homogenizing the cordyceps sinensis wall-broken powder slurry obtained in the step (2), drying by using a spray dryer, wherein the concentration of cordyceps sinensis in the homogenized cordyceps sinensis wall-broken powder slurry is 5%, and spray drying to obtain cordyceps sinensis wall-broken powder dry powder; the parameters of the spray dryer were: the air inlet temperature is 140 ℃, the air outlet temperature is 70 ℃, and the air quantity of the circular air blower is 42m³The pump speed is 500 ml/h;

(4) and (3) granulating: and (3) adding purified water into the cordyceps wall-breaking powder dry powder obtained in the step (3) to prepare a soft material, wherein the amount of the purified water is 50% of the mass of the cordyceps wall-breaking powder dry powder, then extruding the mixture through a granulator to prepare wet granules, wherein the mesh diameter of the granulator is 1.0mm, drying the wet granules at 50 ℃ for 1h to ensure that the water content of the granules is between 2% and 10%, and then sieving the granules to prepare the cordyceps wall-breaking preparation.

The conditions of ball milling, spray drying, granulation and the obtained finished product in the preparation process were respectively detected, and the results are shown in table 3.

TABLE 3

The amount of purified water added during granulation is increased, the prepared soft material has higher water content and high viscosity, more soft materials are adhered to a screen of a granulator during granulation, and the disintegration rate of the prepared granules is reduced.

Example 4

The wall-broken preparation of cordyceps sinensis provided by the embodiment is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis, drying until the water content is less than or equal to 5%, crushing by a crusher, and sieving by a No. 2 sieve to obtain coarse powder;

(2) ball milling: mixing the coarse powder with purified water, wherein the mass percent of the coarse powder in the mixture is 15%, then placing the mixture into a ball milling tank, and then placing zirconium dioxide ball milling beads, the weight of which is 3 times of that of the mixture of the coarse powder and the water, into the ball milling tank, wherein the particle size of the ball milling beads is 0.8 mm; then, grinding for 30min, then separating by using a screen to obtain cordyceps sinensis wall-broken powder slurry, and detecting the particle size of the cordyceps sinensis wall-broken powder slurry;

(3) spray drying: homogenizing the cordyceps sinensis wall-broken powder slurry obtained in the step (2), drying by using a spray dryer, wherein the concentration of cordyceps sinensis in the homogenized cordyceps sinensis wall-broken powder slurry is 15%, and spray drying to obtain cordyceps sinensis wall-broken powder dry powder; the parameters of the spray dryer were: the air inlet temperature is 140 ℃, the air outlet temperature is 70 ℃, and the air quantity of the circular air blower is 42m³The pump speed is 500 ml/h;

(4) and (3) granulating: and (3) adding purified water into the cordyceps wall-breaking powder dry powder obtained in the step (3) to prepare a soft material, wherein the amount of the purified water is 20% of the mass of the cordyceps wall-breaking powder dry powder, then extruding the mixture through a granulator to prepare wet granules, wherein the mesh diameter of the granulator is 1.0mm, drying the wet granules at 50 ℃ for 1h to ensure that the water content of the granules is between 2% and 10%, and then sieving the granules to prepare the cordyceps wall-breaking preparation.

The conditions of ball milling, spray drying, granulation and the obtained finished product in the preparation process were respectively detected, and the results are shown in table 4.

TABLE 4

The amount of purified water added during granulation is reduced, the moisture content of the prepared soft material is lower, the generated viscosity is not enough, and the fine powder is slightly increased.

Comparative example 1: preparation method without granulating step

The preparation of the cordyceps sinensis provided by the comparative example is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis, drying until the water content is less than or equal to 5%, crushing by a crusher, and sieving by a No. 2 sieve to obtain coarse powder;

(2) ball milling: mixing the coarse powder with purified water, wherein the mass percent of the coarse powder in the mixture is 15%, then placing the mixture into a ball milling tank, and then placing zirconium dioxide ball milling beads, the weight of which is 3 times of that of the mixture of the coarse powder and the water, into the ball milling tank, wherein the particle size of the ball milling beads is 0.8 mm; then, grinding for 30min, then separating by using a screen to obtain cordyceps sinensis wall-broken powder slurry, and detecting the particle size of the cordyceps sinensis wall-broken powder slurry;

(3) spray drying: homogenizing the cordyceps sinensis wall-broken powder slurry obtained in the step (2), drying by using a spray dryer, wherein the concentration of cordyceps sinensis in the homogenized cordyceps sinensis wall-broken powder slurry is 15%, and spray drying to obtain cordyceps sinensis wall-broken powder dry powder; the parameters of the spray dryer were: the air inlet temperature is 130 ℃, the air outlet temperature is 60 ℃, and the air quantity of the ring air blower is 42m³The pump speed was 500 ml/h.

No granulation step was performed.

The conditions of ball milling, spray drying and the obtained dry powder of the cordyceps wall-broken powder in the preparation process were respectively detected, and the results are shown in table 5.

TABLE 5

Comparative example 2: preparation method by superfine grinding

The preparation of the cordyceps sinensis provided by the comparative example is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis, drying until the water content is less than or equal to 5%, crushing by a crusher, and sieving by a No. 2 sieve to obtain coarse powder;

(2) superfine grinding: pulverizing the coarse powder with a vibrating rod type ultrafine pulverizer, sieving with a 100-mesh sieve, and detecting the particle size;

(3) and (3) granulating: adding purified water into the cordyceps sinensis dry powder obtained in the step (2) to prepare a soft material, wherein the amount of the purified water is 30% of the mass of the cordyceps sinensis wall-breaking powder dry powder, extruding the soft material through a granulator to prepare wet granules, wherein the mesh diameter of the granulator is 1.0mm, drying the wet granules at 50 ℃ for 1h to ensure that the water content of the granules is between 2% and 10%, and then sieving the granules to prepare the preparation.

The crushing condition, the granulation condition and the obtained finished product condition in the preparation process were respectively detected, and the results are shown in table 6.

TABLE 6

The vibrating rod type ultrafine pulverizer is more common ultrafine pulverizing equipment, but the pulverizing effect is not as good as ball milling, the particle size of the pulverized ultrafine powder is larger, the granulation forming rate is not high, and the particle size of the ultrafine powder is larger than that of the ultrafine powder which can be sensed by an oral cavity, so that the ultrafine powder has obvious granular sense when being tasted in the mouth.

Comparative example 3: preparation method with air outlet temperature of 90 DEG C

The preparation of the cordyceps sinensis provided by the comparative example is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis, drying until the water content is less than or equal to 5%, crushing by a crusher, and sieving by a No. 2 sieve to obtain coarse powder;

(2) ball milling: mixing the coarse powder with purified water, wherein the mass percent of the coarse powder in the mixture is 15%, then placing the mixture into a ball milling tank, and then placing zirconium dioxide ball milling beads, the weight of which is 3 times of that of the mixture of the coarse powder and the water, into the ball milling tank, wherein the particle size of the ball milling beads is 0.8 mm; then, grinding for 30min, then separating by using a screen to obtain cordyceps sinensis wall-broken powder slurry, and detecting the particle size of the cordyceps sinensis wall-broken powder slurry;

(3) spray drying: homogenizing the cordyceps sinensis wall-broken powder slurry obtained in the step (2), drying by using a spray dryer, wherein the concentration of cordyceps sinensis in the homogenized cordyceps sinensis wall-broken powder slurry is 15%, and spray drying to obtain cordyceps sinensis wall-broken powder dry powder; the parameters of the spray dryer were: the air inlet temperature is 160 ℃, the air outlet temperature is 90 ℃, and the air quantity of the circular air blower is 42m³The pump speed is 500 ml/h;

(4) and (3) granulating: and (3) adding purified water into the cordyceps wall-breaking powder dry powder obtained in the step (3) to prepare a soft material, wherein the amount of the purified water is 30% of the mass of the cordyceps wall-breaking powder dry powder, then extruding the mixture through a granulator to prepare wet granules, wherein the mesh diameter of the granulator is 1.0mm, drying the wet granules at 50 ℃ for 1h to ensure that the water content of the granules is between 2% and 10%, and then sieving the granules to prepare the cordyceps preparation.

The conditions of ball milling, spray drying, granulation and the obtained finished product in the preparation process were respectively detected, and the results are shown in table 7.

TABLE 7

When the air outlet temperature rises, a large amount of cordyceps wall-broken powder can be adhered to the drying tower, the cordyceps adhered to the drying tower is gradually coked along with the spray drying, the coked material can fall off from time to time and enter the collector, the material in the collector is burnt, and the situation that the cordyceps wall-broken powder cannot be completely disintegrated can also occur in the disintegration time limit.

Comparative example 4: investigation of amount of purified water used in granulation step

The preparation of the cordyceps sinensis provided by the comparative example is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis, drying until the water content is less than or equal to 5%, crushing by a crusher, and sieving by a No. 2 sieve to obtain coarse powder;

(2) ball milling: mixing the coarse powder with purified water, wherein the mass percent of the coarse powder in the mixture is 15%, then placing the mixture into a ball milling tank, and then placing zirconium dioxide ball milling beads, the weight of which is 3 times of that of the mixture of the coarse powder and the water, into the ball milling tank, wherein the particle size of the ball milling beads is 0.8 mm; then, grinding for 30min, then separating by using a screen to obtain cordyceps sinensis wall-broken powder slurry, and detecting the particle size of the cordyceps sinensis wall-broken powder slurry;

(3) spray drying: homogenizing the cordyceps sinensis wall-broken powder slurry obtained in the step (2), drying by using a spray dryer, wherein the concentration of cordyceps sinensis in the homogenized cordyceps sinensis wall-broken powder slurry is 15%, and spray drying to obtain cordyceps sinensis wall-broken powder dry powder; the parameters of the spray dryer were: the air inlet temperature is 130 ℃, the air outlet temperature is 65 ℃, and the air quantity of the circular air blower is 42m³The pump speed is 500 ml/h;

(4) and (3) granulating: and (3) adding purified water into the cordyceps wall-breaking powder dry powder obtained in the step (3) to prepare a soft material, wherein the amount of the purified water is 10% of the mass of the cordyceps wall-breaking powder dry powder, then extruding the mixture through a granulator to prepare wet granules, wherein the mesh diameter of the granulator is 1.0mm, drying the wet granules at 50 ℃ for 1h to ensure that the water content of the granules is between 2% and 10%, and then sieving the granules to prepare the cordyceps preparation.

The conditions of ball milling, spray drying, granulation and the obtained finished product in the preparation process were respectively detected, and the results are shown in table 8.

TABLE 8

Comparative example 5: examination of drying method (vacuum drying)

The preparation of the cordyceps sinensis provided by the comparative example is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis, drying until the water content is less than or equal to 5%, crushing by a crusher, and sieving by a No. 2 sieve to obtain coarse powder;

(2) ball milling: mixing the coarse powder with purified water, wherein the mass percent of the coarse powder in the mixture is 15%, then placing the mixture into a ball milling tank, and then placing zirconium dioxide ball milling beads, the weight of which is 3 times of that of the mixture of the coarse powder and the water, into the ball milling tank, wherein the particle size of the ball milling beads is 0.8 mm; then, grinding for 30min, then separating by using a screen to obtain cordyceps sinensis wall-broken powder slurry, and detecting the particle size of the cordyceps sinensis wall-broken powder slurry;

(3) and (3) vacuum drying: drying the cordyceps sinensis wall-broken powder slurry obtained in the step (2) by a vacuum dryer, wherein the parameters of vacuum drying are as follows: drying at 65 deg.C under-0.1 Mpa until no water beads are coagulated;

(4) and (3) granulating: and (3) crushing the cordyceps sinensis dry powder obtained in the step (3), adding purified water to prepare a soft material, extruding the soft material through a granulator to prepare wet granules, wherein the amount of the purified water is 30% of the mass of the cordyceps sinensis wall-broken powder, the mesh diameter of a screen of the granulator is 1.0mm, drying the wet granules at 50 ℃ for 1h to ensure that the water content of the granules is between 2% and 10%, and then sieving to prepare the cordyceps sinensis preparation.

The conditions of ball milling, vacuum drying, granulation and the obtained finished product in the preparation process were respectively detected, and the results are shown in table 9.

TABLE 9

After vacuum drying, the cordyceps sinensis turns into black brown, is recombined into compact cutin-like sheets, cannot be easily disintegrated into a particulate state, cannot be completely restored into a broken wall powder state after being crushed by a universal crusher, and has obvious bad tastes of rancid gas and the like on a finished product due to long time required by vacuum drying, so that the flavor is greatly influenced.

Comparative example 6: examination of drying method (Freeze drying)

The preparation of the cordyceps sinensis provided by the comparative example is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis, drying until the water content is less than or equal to 5%, crushing by a crusher, and sieving by a No. 2 sieve to obtain coarse powder;

(2) ball milling: mixing the coarse powder with purified water, wherein the mass percent of the coarse powder in the mixture is 15%, then placing the mixture into a ball milling tank, and then placing zirconium dioxide ball milling beads, the weight of which is 3 times of that of the mixture of the coarse powder and the water, into the ball milling tank, wherein the particle size of the ball milling beads is 0.8 mm; then, grinding for 30min, then separating by using a screen to obtain cordyceps sinensis wall-broken powder slurry, and detecting the particle size of the cordyceps sinensis wall-broken powder slurry;

(3) and (3) freeze drying: placing the cordyceps sinensis wall-broken powder slurry obtained in the step (2) on a freezing tray, and drying by using a freeze dryer, wherein the freeze drying parameters are as follows: pre-freezing for 5 hours at the temperature of minus 40 ℃ under normal pressure; 0.13mbar and sublimation drying at-10 ℃ for 30 hours; resolving and drying at 0.13mbar and 25 ℃ for 5 hours;

(4) and (3) granulating: and (3) crushing the cordyceps sinensis dry powder obtained in the step (3), adding purified water to prepare a soft material, extruding the soft material through a granulator to prepare wet granules, wherein the amount of the purified water is 30% of the mass of the cordyceps sinensis wall-broken powder, the mesh diameter of a screen of the granulator is 1.0mm, drying the wet granules at 50 ℃ for 1h to ensure that the water content of the granules is between 2% and 10%, and then sieving to prepare the cordyceps sinensis preparation.

The conditions of ball milling, freeze-drying, granulation and the obtained finished product in the preparation process were respectively detected, and the results are shown in table 10.

Watch 10

The finished product obtained by freeze drying is in a lamellar shape, granulation is carried out after crushing, and the material is fluffy and easy to fly, so that great loss is caused during crushing and granulation. It should be noted that the freeze-drying period is very long, taking pilot-scale spray dryer and freeze dryer for experiment as examples, the whole process requires 40 hours, at most 3L of Cordyceps slurry can be dried, the same material only requires 6 hours for drying by using the spray dryer, and no additional pulverization step is needed, so that a lot of time and energy can be saved. Furthermore, freeze-drying produces particles that are less fluid than spray-drying, presumably related to the microstructure of the material.

Comparative example 7: preparation method adopting dry ball milling

The preparation of the cordyceps sinensis provided by the comparative example is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis whole grass, crushing the cordyceps sinensis whole grass by a crusher, and screening the crushed cordyceps sinensis whole grass by a No. 2 sieve to obtain coarse powder;

(2) ball milling: placing the coarse powder into a ball milling tank, and then placing zirconium dioxide ball milling beads with the weight being 3 times of that of the coarse powder into the ball milling tank, wherein the particle size of the ball milling beads is 0.8 mm; then, grinding for 60min, separating out the cordyceps sinensis dry powder, and detecting the particle size of the cordyceps sinensis dry powder;

(3) and (3) granulating: and (3) adding purified water into the cordyceps sinensis dry powder obtained in the step (2) to prepare a soft material, wherein the amount of the purified water is 30% of the mass of the cordyceps sinensis dry powder, extruding the mixture through a granulator to prepare wet granules, wherein the mesh diameter of the granulator is 1.0mm, drying the wet granules at 50 ℃ for 1h to ensure that the water content of the granules is between 2% and 10%, and then sieving the granules to prepare the cordyceps sinensis preparation.

The conditions of ball milling, granulation and the obtained finished product in the preparation process were respectively detected, and the results are shown in table 11.

TABLE 11

During the test, the temperature in the ball mill tank can obviously rise at the end of the test because no water is added in the ball mill.

Comparative example 8: investigation of coarse powder content in ball milling step

The preparation of the cordyceps sinensis provided by the comparative example is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis, drying until the water content is less than or equal to 5%, crushing by a crusher, and sieving by a No. 2 sieve to obtain coarse powder;

(2) ball milling: mixing the coarse powder with purified water, wherein the mass percent of the coarse powder in the mixture is 20%, then placing the mixture into a ball milling tank, and then placing zirconium dioxide ball milling beads, the weight of which is 3 times of that of the mixture of the coarse powder and the water, into the ball milling tank, wherein the particle size of the ball milling beads is 0.8 mm; grinding for 30min, separating with a screen to obtain Cordyceps broken powder slurry, and detecting the particle size of the Cordyceps broken powder slurry D90-34.42 μm;

(3) spray drying: homogenizing the cordyceps sinensis wall-broken powder slurry obtained in the step (2), drying by using a spray dryer, wherein the concentration of cordyceps sinensis in the homogenized cordyceps sinensis wall-broken powder slurry is 20%, and spray drying to obtain cordyceps sinensis wall-broken powder dry powder; the parameters of the spray dryer were: the air inlet temperature is 130 ℃, the air outlet temperature is 60 ℃, and the air quantity of the ring air blower is 42m³The pump speed was 300 ml/h.

Because the concentration of the cordyceps sinensis is high (20%) during ball milling, the cordyceps sinensis slurry after ball milling contains a lot of fine bubbles, the shape of the cordyceps sinensis slurry is similar to whipped cream, the cordyceps sinensis slurry is in a semi-solid state, materials cannot be successfully sprayed out, and spray drying fails. Diluting the slurry to 1% with pure water, and spray drying according to the above parameters, so that the powder sprayed from the Cordyceps slurry with concentration of 1% almost sticks to the wall of the spray drying tower and is difficult to collect.

Comparative example 9: preparation method by using superfine grinding and spray drying

The preparation of the cordyceps sinensis provided by the comparative example is obtained by the preparation method comprising the following steps:

(1) primary crushing: taking clean cordyceps sinensis, drying until the water content is less than or equal to 5%, crushing by a crusher, and sieving by a No. 2 sieve to obtain coarse powder;

(2) superfine grinding: pulverizing the coarse powder with a vibrating rod type ultrafine pulverizer, sieving with a 100-mesh sieve, and detecting the particle size;

(3) spray drying: adding purified water into the cordyceps sinensis dry powder obtained in the step (2), homogenizing, drying by using a spray dryer, wherein the concentration of cordyceps sinensis in the cordyceps sinensis powder slurry after homogenizing is 15%, and performing spray drying to obtain cordyceps sinensis powder dry powder; the parameters of the spray dryer were: the air inlet temperature is 130 ℃, the air outlet temperature is 60 ℃, and the air quantity of the ring air blower is 42m³The pump speed is 500 ml/h;

(4) and (3) granulating: and (3) adding purified water into the cordyceps sinensis dry powder obtained in the step (3) to prepare a soft material, wherein the amount of the purified water is 15% of the mass of the cordyceps sinensis wall-breaking powder dry powder, extruding the soft material through a granulator to prepare wet granules, wherein the mesh diameter of the granulator is 1.0mm, drying the wet granules at 50 ℃ for 1h to ensure that the water content of the granules is between 2% and 10%, and then sieving the granules to prepare the preparation.

The pulverization condition, granulation condition and the obtained finished product condition in the preparation process were respectively detected, and the results are shown in table 12.

TABLE 12

The vibrating rod type ultrafine pulverizer is more common ultrafine pulverizing equipment, but the pulverizing effect is not as good as ball milling, the particle size of the pulverized ultrafine powder is larger, the granulation forming rate is not high, and the particle size of the ultrafine powder is larger than that of the ultrafine powder which can be sensed by an oral cavity, so that the ultrafine powder has obvious granular sense when being tasted in the mouth.

Experimental example 1 comparison of microscopic examination results before and after wall breaking

An appropriate amount of the samples before and after ball milling in example 1 were taken to prepare temporary water-filled tablets, which were observed under a Leica DM750 microscope at a magnification of 400 times, and the results are shown in FIGS. 1 to 4. Wherein, fig. 1 is a detection picture of microscopic examination of cordyceps sinensis fine powder (passing 100 meshes) (a sample before ball milling), fig. 2 is another detection picture of microscopic examination of cordyceps sinensis fine powder (passing 100 meshes) (a sample before ball milling), fig. 3 is a detection picture of microscopic examination of cordyceps sinensis wall-breaking powder after ball milling, and fig. 4 is another detection picture of microscopic examination of cordyceps sinensis wall-breaking powder after ball milling. As can be seen from FIGS. 1 and 2, the non-ball milled fine powder of Cordyceps sinensis is brownish yellow and is irregular blocks with different sizes. As can be seen from FIGS. 3 and 4, the wall-broken powder after ball milling of Cordyceps sinensis is irregular small granules ranging from light yellow to yellow white, and occasionally longer hypha is observed, so that the particle size of Cordyceps sinensis after wall breaking is obviously reduced.

Experimental example 2 particle size distribution

According to the requirements of the quality standard research standard of the traditional Chinese medicine wall-broken decoction pieces in Guangdong province, 0.1g of the finished products in the examples 1, 2, 3 and 4 are taken respectively, 30ml of water is added, ultrasonic treatment is carried out, shaking is carried out for 3min, the particle size is measured by a Malvern 3000 laser particle size analyzer, and as a result, the finished products in the examples 1 to 4 can be rapidly dispersed, and D90 sequentially comprises the following steps: 38.20 μm, 38.59 μm, 39.62 μm, 35.48 μm, and 37.97 μm on average, all less than 45 μm.

EXAMPLE 3 examination of Limit of unbroken cells

According to the requirements of the quality standard research standard of the Chinese medicinal broken wall decoction pieces in Guangdong province, 0.010g of each finished product in the examples 1, 2, 3 and 4 is taken, 0.5ml of chloral hydrate test solution-water (1:1) is added, ultrasonic treatment is carried out until the finished product is completely dissolved, all solutions are sucked and loaded into tablets, the number of particles of complete cells larger than 100 mu m is calculated by detecting each tablet with a microscope of 100 times. The number of the cells without wall breaking of each example is 50, 76, 69 and 87, the average number is 70.5, and the number does not exceed 100, which indicates that the wall breaking degree is high.

Experimental example 4 content measurement and characteristic Profile

Appropriate amounts of the finished product of example 1, the finished product of comparative example 2, the finished product of comparative example 7 and the finished product of comparative example 9 were taken and tested.

Wherein adenosine, heavy metals and harmful elements (lead, cadmium, arsenic, mercury and copper) are detected by a method under Cordyceps of 2020 edition of Chinese pharmacopoeia I; the characteristic spectrum is detected by a method under the item of cordyceps sinensis in the Chinese medicinal material standard of Guangdong province; the cordyceps polysaccharide is detected by adopting a phenol-sulfuric acid method and taking glucose as a standard. The results are shown in Table 13.

TABLE 13 assay and profile comparison

As can be seen from table 13, adenosine, heavy metals and harmful elements (lead, cadmium, arsenic, mercury and copper) of the finished products of example 1, comparative example 2, comparative example 7 and comparative example 9 have characteristic spectra within the specified ranges of the chinese pharmacopoeia and the chinese herbal standards of guangdong province, and the change of each component before and after wall breaking is not large, which proves that the wall breaking process does not cause the change of the material basis of cordyceps sinensis, that is, the wall breaking process can well retain the active ingredients of cordyceps sinensis, and the content of five heavy metals and harmful elements of lead, cadmium, arsenic, mercury and copper is not increased.

Experimental example 5 accelerated stability comparison of Cordyceps products

A proper amount of the finished product of example 1, the finished product of comparative example 2, the finished product of comparative example 5, the finished product of comparative example 6, the finished product of comparative example 7 and the finished product of comparative example 9 are respectively taken, the stability test of the samples is accelerated for three months according to an accelerated test method in 9001 raw material medicament and preparation stability test guiding principles of the 2020 edition, and the organoleptic property and the adenosine content of the samples are detected, and the results are respectively shown in tables 14 and 15.

TABLE 14 accelerated stability sensory comparison

TABLE 15 accelerated stability adenosine content comparison

Note: in the tableIndicating a ten-thousandth number.

As can be seen from tables 14 and 15, in the three-month accelerated stability test, the adenosine reduction ratio of the finished product of example 1 was 9%, the adenosine reduction ratio of the finished product of comparative example 2 (employing ultra-fine pulverization) was 14.8%, the adenosine reduction ratio of the finished product of comparative example 5 (employing wet ball milling and vacuum drying) was 15.0%, the adenosine reduction ratio of the finished product of comparative example 6 (employing wet ball milling and freeze drying) was 26.7%, the adenosine reduction ratio of the finished product of comparative example 7 (employing dry ball milling preparation method) was 17%, and the adenosine reduction ratio of the finished product of comparative example 9 (employing ultra-fine pulverization and spray drying) was 20%; the fishy smell of the cordyceps sinensis gradually increased during the placement of the finished product of comparative example 2, the finished product of comparative example 5, the finished product of comparative example 6, the finished product of comparative example 7 and the finished product of comparative example 9 until the cordyceps sinensis has a rancid smell or rancid smell, which indicates that the quality of the cordyceps sinensis is reduced.

The adenosine stability results of comparative example 2 and comparative example 9 show that spray drying alone cannot improve the adenosine stability, while the results of tables 14 and 15 show that the process of example 1 can slow down the adenosine reduction rate and sensory tests show that the process can slow down the property change process of the cordyceps sinensis, which proves that the stability of the cordyceps sinensis can be greatly improved by adopting a preparation method combining a drying mode except spray drying and wet ball milling, or a preparation method combining a crushing mode except wet ball milling and spray drying, or adopting wet ball milling or spray drying alone, and the stability of the cordyceps sinensis can not be improved, so that the synergistic effect is achieved, and the technical effects are unexpected.

Experimental example 6 comparison of SOD enzyme Activity accelerated stability test

A proper amount of the finished product of example 1, the finished product of comparative example 5, the finished product of comparative example 7 and the finished product of comparative example 9 are respectively taken, an accelerated three-month stability test is carried out according to an accelerated test method in the standard of the stability test of 9001 raw material medicaments and preparations in the general pharmacopoeia of China (four) of 2020 edition, and the SOD enzyme activity of the samples is detected, and the results are shown in Table 16.

TABLE 16 accelerated stability SOD enzyme Activity comparison

Accelerated month	Comparative example 5 finished product	Comparative example 7 finished product	Comparative example 9 finished product	EXAMPLE 1 finished product
					0	13454.1U/g	13648.7U/g	13257.4U/g	13487.5U/g
1	9176.3U/g	9345.1U/g	9248.4U/g	10921.3U/g
					2	5842.1U/g	6012.9U/g	5916.7U/g	8245.1U/g
3	2852.4U/g	2957.6U/g	2846.8U/g	4687.2U/g

As can be seen from the results in table 16, in the accelerated three-month stability test, the SOD enzyme activity reduction rate of the finished product of example 1 was 65.2%, the SOD enzyme activity reduction rate of the finished product of comparative example 5 was 78.8%, the SOD enzyme activity reduction rate of the finished product of comparative example 7 was 78.3%, and the SOD enzyme activity reduction rate of the finished product of comparative example 9 was 78.5%; the results show that the process of example 1 can slow down the rate of SOD enzyme activity reduction, and prove that the stability of the product cannot be improved by adopting wet ball milling alone or spray drying alone, but the stability of the cordyceps can be greatly improved by combining the wet ball milling with the spray drying, so that synergistic effects are achieved, and unexpected technical effects are achieved.

Experimental example 7 dissolution comparison of Cordyceps polysaccharide

250mg of the finished product of example 1, the finished product of comparative example 2, the finished product of comparative example 7 and the finished product of comparative example 9 are taken and precisely weighed. Then determining the dissolution rate according to a small cup method in 0931 dissolution rate and release rate determination methods of general rules of Chinese pharmacopoeia (four departments) of 2020 edition; the detection method of Cordyceps polysaccharide is phenol-sulfuric acid method, and comprises detecting with glucose as standard, and calculating with polysaccharide content of content measurement as 100%, the dissolution rate of Cordyceps polysaccharide is shown in Table 17, and the dissolution curve of Cordyceps polysaccharide is shown in FIG. 5.

TABLE 17 dissolution comparison of Cordyceps polysaccharides

Cordyceps Polysaccharide (CP) is the main component of Cordyceps, and has multiple biological activities of regulating immunity, resisting tumor, resisting oxidation, reducing blood sugar, reducing blood lipid, delaying aging, and protecting liver. Modern medicine has proved that the cordyceps polysaccharide can effectively treat various diseases, and has wide application prospect due to high drug effect and low toxic and side effect.

As can be seen from FIG. 5, the dissolution rate of Cordyceps sinensis polysaccharide after wall breaking of Cordyceps sinensis is greatly increased, and the dissolution rate of polysaccharide reaches more than 80% within 5 minutes; the final dissolution rate was also much higher than that of comparative example 2, comparative example 7 and comparative example 9, P < 0.01 by T test, and the dissolution rate of the finished product of example 1 was very significantly different from that of comparative example 2, comparative example 7 and comparative example 9. The process is proved to successfully retain the active ingredients of the cordyceps, promote the dissolution of cordyceps polysaccharide and greatly improve the bioavailability.

Although the particle size of the comparative example 7 reaches the wall-broken level (D90 is less than or equal to 45 mu m), the dissolution rate is not improved much compared with that of the comparative example 2, which shows that wet ball milling is an important factor for improving the dissolution rate of cordyceps polysaccharide, and the wet ball milling can obviously improve the dissolution rate of cordyceps polysaccharide, so that the technical effect is unexpected.

Cordyceps sinensis polysaccharide is mainly present in the cell interior of Cordyceps sinensis, and is also commonly called Cordyceps sinensis intracellular polysaccharide. The extraction of cordyceps polysaccharide usually needs to be carried out for 1 to 5 hours at a temperature of 80 to 100 ℃ in the prior art, and then the complete extraction can be basically carried out. The cordyceps polysaccharide is very limited in utilization when taken in the form of common powder or whole grass. Extracting polysaccharide by a certain method is an effective method for improving the utilization rate of cordyceps polysaccharide, but other effective components contained in cordyceps sinensis, such as cordyceps sinensis protein, adenosine, unsaturated fatty acid, SOD enzyme and the like, are lost. Experiments prove that the granular preparation prepared by the method can furthest reserve and utilize the active ingredients of the cordyceps sinensis.

Although the invention has been described in detail hereinabove by way of general description, specific embodiments and experiments, it will be apparent to those skilled in the art that many modifications and improvements can be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.