阅读说明：本技术 肠溶海藻植物空心胶囊用超低粘度褐藻胶的制备及其应用 (Preparation and application of ultralow-viscosity algin for enteric seaweed plant hollow capsules ) 是由 程跃谟 吴仕鹏 缪锦来 张璇 于云霞 于 2021-11-02 设计创作，主要内容包括：本发明属于海藻多糖领域,涉及肠溶海藻植物空心胶囊用超低粘度褐藻胶的制备及其应用,包括：以褐藻胶为原料经过酸化降解、氧化降解、中和、脱水、粉碎、烘干。以超低粘度褐藻胶、淀粉、羟丙基甲基纤维素、保湿剂、助凝剂为原料,经过溶胶、养胶、蘸胶、钙化包衣、烘干、冷却、脱模、切割、套合等制成肠溶海藻植物空心胶囊。本发明利用胶囊胚蘸取钙离子溶液后在胶囊外形成水不溶性褐藻酸钙包衣,褐藻酸钙在胃酸环境中会反应形成褐藻酸,褐藻酸具有水不溶的特性,可以有效保持胶囊在胃环境中不崩解,胶囊进入到肠道环境中,褐藻酸会发生反应形成可溶性褐藻酸盐,胶囊壳发生崩解,药效达到释放,具有胃不溶而可以肠溶的特性,性质稳定。(The invention belongs to the field of algal polysaccharides, and relates to a preparation method and an application of ultra-low viscosity algin for an enteric seaweed plant hollow capsule, wherein the preparation method comprises the following steps: algin is taken as a raw material and is subjected to acidification degradation, oxidative degradation, neutralization, dehydration, crushing and drying. The enteric seaweed plant empty capsule is prepared by taking ultralow-viscosity algin, starch, hydroxypropyl methylcellulose, a humectant and a coagulant aid as raw materials through sol, gel curing, gel dipping, calcification coating, drying, cooling, demoulding, cutting, sleeving and the like. According to the invention, the capsule embryo is dipped in the calcium ion solution and then coated with the water-insoluble calcium alginate outside the capsule, the calcium alginate can react in a gastric acid environment to form alginic acid, the alginic acid has the characteristic of water insolubility and can effectively keep the capsule not to disintegrate in a gastric environment, the capsule enters an intestinal environment, the alginic acid can react to form soluble alginate, the capsule shell disintegrates, the drug effect is released, and the capsule has the characteristic of enteric solubility due to gastric insolubility, and has stable property.)

1. A preparation method of ultralow-viscosity algin for enteric seaweed plant empty capsules is characterized by comprising the following steps:

the method comprises the following steps of taking algin as a raw material, and performing acidification degradation, oxidative degradation, neutralization, dehydration, crushing and drying to obtain the ultralow-viscosity algin;

wherein, the specific steps of oxidative degradation are as follows: in the crushing process, hydrogen peroxide is sprayed on the dehydrated alginic acid blocks, and the alginic acid blocks are degraded at normal temperature.

2. The preparation method of the ultra-low viscosity algin for the enteric seaweed plant empty capsule as claimed in claim 1, wherein the mass concentration of the hydrogen peroxide is 30-35%.

3. The method for preparing the ultra-low viscosity algin for the enteric seaweed plant empty capsule as claimed in claim 1, wherein the time of oxidative degradation is 24h-72 h.

4. The method for preparing the ultra-low viscosity algin for the enteric seaweed plant empty capsule as claimed in claim 1, wherein the acidification degradation condition is as follows: adding hydrochloric acid after the algin is dissolved, adjusting the pH to 1-3, keeping the temperature at 60-70 ℃, carrying out acidic degradation for 8-10 h, and dehydrating to obtain alginic acid blocks.

5. The ultra-low viscosity algin for enteric seaweed plant empty capsules prepared by the method of any one of claims 1 to 4, wherein the viscosity of the ultra-low viscosity algin is less than or equal to 50 mPa-s.

6. An enteric seaweed plant empty capsule is characterized by comprising the following raw materials in parts by weight: 15 to 35 parts of ultra-low viscosity algin, 1.5 to 2.5 parts of starch, 75 to 88 parts of hydroxypropyl methylcellulose and 2 to 4 parts of humectant according to the claim 5;

in the coating process, the capsule embryo is soaked in coagulant aid to form a coating;

the coagulant aid is a composite calcium ion solution.

7. The enteric seaweed plant empty capsule as claimed in claim 6, wherein the composite calcium ion solution is a mixed solution of calcium citrate and calcium glutamate, preferably, the mass ratio of the calcium citrate to the calcium glutamate is 1-3: 1-3.

8. The enteric seaweed plant empty capsule of claim 6, wherein the concentration of the complex calcium ion solution is 0.1-0.5M/L.

9. A preparation method of an enteric seaweed plant empty capsule is characterized by comprising the following steps:

the preparation method comprises the following steps of taking ultralow-viscosity algin, starch, hydroxypropyl methylcellulose, a humectant and a coagulant aid as raw materials, and carrying out sol, gel curing, gel dipping, calcification coating, drying, cooling, demoulding, cutting and sleeving on the raw materials;

the calcification coating comprises the following specific steps: and (3) when the capsule embryo is in a semi-dry state, immersing the capsule embryo for about 6-8s by using the composite calcium ion solution, and lifting to form a coating.

10. Application of enteric seaweed plant empty capsules in preparation of capsule medicines.

Technical Field

The invention belongs to the field of algal polysaccharides, and particularly relates to preparation and application of ultra-low viscosity algin for an enteric seaweed plant hollow capsule.

Background

The information in this background section is only for enhancement of understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.

The existing traditional gelatin capsules have the problems and potential safety hazards that are difficult to overcome due to the complex sources and difficult controllability of the sources, such as strong hygroscopicity and easy microbial contamination, and are well known in the industry; at the same time, certain religious groups have significant rejection of pharmaceutical agents filled with gelatin capsules.

Disclosure of Invention

In order to overcome the problems, the invention provides a preparation method and application of ultra-low viscosity algin for an enteric seaweed plant empty capsule.

In order to achieve the technical purpose, the invention adopts the following technical scheme:

the invention provides a preparation method of ultralow-viscosity algin for an enteric seaweed plant empty capsule, which comprises the following steps:

the method comprises the following steps of taking algin as a raw material, and performing acidification degradation, oxidative degradation, neutralization, dehydration, crushing and drying to obtain the ultralow-viscosity algin;

wherein, the specific steps of oxidative degradation are as follows: in the crushing process, hydrogen peroxide is sprayed on the dehydrated alginic acid blocks, and the alginic acid blocks are degraded at normal temperature.

In a second aspect of the invention, the ultra-low viscosity algin for the enteric seaweed plant empty capsule prepared by the method is provided, and the viscosity of the ultra-low viscosity algin is less than or equal to 50mPa^.s。

The third aspect of the invention provides an enteric seaweed plant empty capsule which is prepared from the following raw materials in parts by weight: 15-35 parts of ultralow-viscosity algin, 1.5-2.5 parts of starch, 75-88 parts of hydroxypropyl methyl cellulose and 2-4 parts of humectant;

in the coating process, the capsule embryo is soaked in coagulant aid to form a coating;

the coagulant aid is a composite calcium ion solution.

In a fourth aspect of the invention, a preparation method of an enteric seaweed plant empty capsule is provided, which comprises the following steps:

the preparation method comprises the following steps of taking ultralow-viscosity algin, starch, hydroxypropyl methylcellulose, a humectant and a coagulant aid as raw materials, and carrying out sol, gel curing, gel dipping, calcification coating, drying, cooling, demoulding, cutting and sleeving on the raw materials;

the calcification coating comprises the following specific steps: and (3) when the capsule embryo is in a semi-dry state, immersing the capsule embryo for about 6-8s by using the composite calcium ion solution, and lifting to form a coating.

In a fifth aspect of the invention, the application of the enteric seaweed plant empty capsules in preparing capsule medicines is provided.

The invention has the beneficial effects that:

(1) the enteric seaweed plant empty capsule prepared by using the algin is derived from pure natural plants, does not contain animal components, does not have the potential threat of animal epidemic diseases such as mad cow disease, foot and mouth disease and the like, and does not have the problem of residues of antibiotics, feed additives and the like in an animal body. In the aspect of heavy metal content, because gelatin raw materials are not used, the possibility of external chromium source pollution is completely avoided. The seaweed plant empty capsule does not contain a nitrogen source necessary for the growth and the propagation of microorganisms, so the product does not need to be added with a preservative and has a certain self-cleaning function.

(2) The main capsule wall material of the enteric seaweed plant hollow capsule is plant polysaccharide extracted from brown algae, and the superior performance of physicochemical property overcomes and avoids the defect of gelatin. The capsule has low water content, can maintain excellent physical properties below 8 percent, and is far lower than the water requirement of about 15 percent of the gelatin hollow capsule. The enteric seaweed plant hollow capsule is not easy to transfer self moisture, is not easy to absorb medicine moisture, and can effectively inhibit external water vapor from entering, thereby ensuring that the medicine is not deteriorated due to moisture absorption and water absorption.

(3) The enteric seaweed plant hollow capsule has the advantages of excellent physical properties, good toughness, high strength, difficult weathering and brittle fracture, loose operation conditions for filling medicines, and long effective period of 48 months which is far longer than that of a gelatin capsule (usually 9-12 months). In the dissolving process, the enteric seaweed plant hollow capsule can not absorb water to swell, so that abdominal distension and inappetence of a patient caused by a large amount of medicine taking are avoided; the gelatin capsule can absorb 5-10 times of water when dissolved.

(4) The enteric seaweed plant empty capsule has chemical inertness, does not generate reactions such as cross-linking and condensation with filling medicines, and can effectively ensure the disintegration, dissolution and bioavailability of the capsule; the gelatin capsule has active groups such as amino and carboxyl because the capsule wall material belongs to protein substances, and the gelatin capsule can cause the deterioration and the color change of the medicine after reacting with certain medicines, thereby influencing the curative effect of the medicine.

(5) The algin is used as medicine and medicine intermediate, and has effects of reducing blood lipid, resisting oxidation, reducing blood sugar, resisting tumor, virus, mutation, radiation and enhancing immunity; as a high-efficiency biological adsorbent, the biological adsorbent can improve the phagocytic capacity of blood cells and has certain improvement effect on the activity of lysozyme.

(6) Due to the difference of pH values of intestines and stomach of a human body (from stomach pH value of 1.0-3.0 to small intestine pH value of 6.5-7.0 to colon pH value of 7.0-8.0), the algin can react in a simulated stomach strong acid environment to generate water-insoluble alginate gel, and when the pH value is increased to an intestinal environment, the alginate can form soluble alginate, so that the algin has pH responsiveness and can realize drug effect positioning release as a capsule shell raw material. The algin produced by the traditional process has high viscosity, the viscosity of the glue solution is too high to influence the glue dipping effect, so the addition amount of the common algin as a capsule raw material is low, the pH response disintegration can not be achieved, the stable enteric effect can not be realized, and the drug effect can not reach the positioning release.

(7) The existing enteric hollow capsule mostly adopts a production mode of artificially synthesizing a high polymer material and coating by taking acetone as a solvent, and the invention innovatively adopts a process technology of taking calcium ions as a coating, avoids the use of an organic solvent and realizes green biological manufacturing. According to the invention, the capsule embryo is dipped in the calcium ion solution and then coated with the water-insoluble calcium alginate outside the capsule, the calcium alginate can react in a gastric acid environment to form alginic acid, the alginic acid has the characteristic of water insolubility and can effectively keep the capsule not to disintegrate in a gastric environment, the capsule enters an intestinal environment, the alginic acid can react to form soluble alginate, the capsule shell disintegrates, and the drug effect is released, so that the prepared capsule shell has the characteristic of stomach insolubility and enteric solubility, and is stable in property.

(8) The research of the invention finds that: compared with the traditional calcium chloride, calcium acetate, calcium gluconate and calcium lactate, the compound calcium ion solution formed by combining the calcium citrate and the calcium glutamate has better gastric insolubility and enteric property (namely, the compound calcium ion solution is more difficult to disintegrate in the stomach environment and is easier to release in the intestinal environment), and can realize faster and more stable positioning release in the intestinal environment. The operation method is simple, low in cost, universal and easy for large-scale production.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this specification, are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the invention and together with the description serve to explain the invention and not to limit the invention.

FIG. 1 is a flow chart of the process for preparing ultra-low viscosity algin of the present invention;

FIG. 2 is a process flow chart of the preparation of the enteric seaweed plant empty capsule of the present invention;

FIG. 3 is a graph showing the effect of the dosage of ultra-low viscosity algin on the enteric capsule shell in the experimental examples of the present invention;

FIG. 4 shows the effect of the amount of starch on the enteric capsule shell in the experimental examples of the present invention;

FIG. 5 is a graph showing the effect of glycerol dosage on enteric capsule shells in experimental examples of the present invention;

FIG. 6 is a graph showing the effect of dipping temperature on enteric capsule shells in the experimental examples of the present invention.

Detailed Description

It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

The invention provides a preparation method of ultralow-viscosity algin for an enteric seaweed plant empty capsule, which comprises the following steps:

the method comprises the following steps of taking algin as a raw material, and performing acidification degradation, oxidative degradation, neutralization, dehydration, crushing and drying to obtain the ultralow-viscosity algin;

wherein, the specific steps of oxidative degradation are as follows: in the crushing process, hydrogen peroxide is sprayed on the dehydrated alginic acid blocks, and the alginic acid blocks are degraded at normal temperature.

In some embodiments, the hydrogen peroxide solution has a mass concentration of 30% to 35%.

In some embodiments, the time for oxidative degradation is from 24h to 72 h.

In some embodiments, the conditions of the acidification degradation are: adding hydrochloric acid after the algin is dissolved, adjusting the pH to 1-3, keeping the temperature at 60-70 ℃, carrying out acidic degradation for 8-10 h, and dehydrating to obtain alginic acid blocks.

In some embodiments, the viscosity of the ultra-low viscosity algin is 50mPa or less^.s。

The invention also provides an enteric seaweed plant empty capsule which is prepared from the following raw materials in parts by weight: 15 to 35 parts of ultra-low viscosity algin, 1.5 to 2.5 parts of starch, 75 to 88 parts of hydroxypropyl methylcellulose and 2 to 4 parts of humectant according to the claim 5;

in the coating process, the capsule embryo is soaked in coagulant aid to form a coating;

the coagulant aid is a composite calcium ion solution.

In some embodiments, the composite calcium ion solution is a mixed solution of calcium citrate and calcium glutamate, and preferably, the mass ratio of the calcium citrate to the calcium glutamate is 1-3: 1-3.

In some embodiments, the concentration of the complex calcium ion solution is 0.1-0.5M/L.

2. Preparation of enteric seaweed plant hollow capsule

15-35% of ultralow-viscosity algin (the viscosity is less than or equal to 50 mPa.s);

1.5 to 2.5 percent of starch;

75% -88% of hydroxypropyl methyl cellulose;

humectant (glycerin) 2% -4%;

the sum of the percentages of the raw materials is one hundred percent.

The concentration of coagulant aid (mixed solution of calcium citrate and calcium glutamate) and composite calcium ion solution is 0.1-0.5M/L.

The present invention is described in further detail below with reference to specific examples, which are intended to be illustrative of the invention and not limiting.

Example 1:

firstly, preparing the ultra-low viscosity algin

The method takes algin as a raw material and comprises the following steps of acidification degradation, oxidative degradation, neutralization, dehydration, crushing and drying:

(1) degradation by acidification

Dissolving algin, adding hydrochloric acid, adjusting pH to 2, keeping temperature at 65 deg.C, performing acidic degradation for 8h, stirring during soaking to mix well, and dehydrating with 250 mesh sieve to obtain alginic acid block.

(2) Oxidative degradation

Spraying hydrogen peroxide with the concentration of 35% in the process of crushing the dehydrated alginic acid blocks, wherein the adding amount is 1.8% of the mass of the alginic acid blocks, storing at normal temperature, and degrading for 48 hours;

(3) neutralization

Adding ethanol into the dehydrated acid blocks, stirring, adding 27.5% sodium hydroxide for neutralization, and dehydrating when the pH is measured to be 8 to obtain dehydrated rubber blocks;

(4) dewatering

Adding ethanol into the glue solution obtained by suction filtration, filtering by a 400-mesh screen, and dehydrating to obtain a dehydrated glue block;

(5) pulverizing, and oven drying

And crushing the dehydrated glue blocks, and drying in a drying system after crushing to obtain the ultralow-viscosity algin.

Secondly, preparing the enteric seaweed plant empty capsule

20 percent of ultralow-viscosity algin (the viscosity is less than or equal to 50mPa.s)

2 percent of starch

Hydroxypropyl methylcellulose 75%

Humectant (glycerin) 3%

The concentration of coagulant aid (mixed solution of calcium citrate and calcium glutamate) and composite calcium ion solution is 0.3M/L.

The enteric seaweed plant hollow capsule is prepared by using ultralow-viscosity algin, starch, hydroxypropyl methylcellulose, a humectant and a coagulant aid as raw materials and performing sol, gel curing, gel dipping, calcification coating, drying, cooling, demolding, cutting, registering, light inspection, metering and packaging.

(1) Sol and gel curing: weighing the materials according to the prescription amount, slowly adding the materials into a sol tank, uniformly mixing, adding purified water, stirring and soaking for 20min, adding glycerol, continuously stirring to fully absorb water, expand and dissolve, heating to 95 ℃, starting a vacuum pump valve, stirring while vacuumizing to remove bubbles, keeping the temperature of the sol in the sol tank at 97 ℃, stirring at high temperature for 3.5h, and starting cooling. Stirring the sol at 90 ℃ for 3.5 hours until the sol solution is completely dissolved, cooling the sol solution to 50 ℃, stirring at constant temperature for 1 hour until the viscosity of the sol solution meets 1500-one-viscosity 4000mPa.s, and maintaining the sol for 16 hours for later use.

(2) Dipping glue: selecting capsule mould with suitable type, soaking the mould into the glue solution to dip capsule blank when the temperature of the glue solution is reduced to 45 deg.C, lubricating the mould with appropriate amount of lubricant (such as vegetable oil) before dipping glue, and uniformly sticking the glue solution on the mould.

(3) Calcified coating: and (3) when the capsule embryo is in a semi-dry state, immersing the capsule embryo for about 6s by using the composite calcium ion solution, and slowly lifting to form a coating. According to the characteristics of the algin gel, a composite calcium ion solution is selected to crosslink and calcify the capsule blank to form a calcium alginate coating.

(4) Drying, cooling, demolding, cutting, registering, optical inspection, metering and packaging and gold detection: drying with hot wind at 40 deg.C for 1.2 hr, and cooling in 25 deg.C stabilizing box with relative humidity of 55% for 30 min. And (4) after cooling, separating the capsule from the die, then cutting, sleeving the two capsule hemispheres together, and metering and packaging after optical inspection is qualified.

Example 2:

firstly, preparing the ultra-low viscosity algin

Algin is taken as a raw material and is subjected to acidification degradation, oxidative degradation, neutralization, dehydration, crushing and drying.

(1) Degradation by acidification

Dissolving algin, adding hydrochloric acid, adjusting pH to 1, keeping temperature at 60 deg.C, performing acidic degradation for 8h, stirring during soaking to mix well, and dewatering with 200 mesh filter screen to obtain alginic acid block.

(2) Oxidative degradation

Spraying hydrogen peroxide with the concentration of 35% in the process of crushing the dehydrated alginic acid blocks, wherein the adding amount is 0.2% of the mass of the alginic acid blocks, storing at normal temperature, and degrading for 72 hours;

(3) neutralization

Adding ethanol into the dehydrated acid blocks, stirring, adding 25% by mass of sodium hydroxide for neutralization, and dehydrating when the pH is measured to be 7.5 to obtain dehydrated rubber blocks;

(4) dewatering

Adding ethanol into the glue solution obtained by suction filtration, filtering by a 400-mesh screen, and dehydrating to obtain a dehydrated glue block;

(5) pulverizing, and oven drying

And crushing the dehydrated glue blocks, and drying in a drying system after crushing to obtain the ultralow-viscosity algin.

Secondly, preparing the enteric seaweed plant empty capsule

15 percent of ultralow-viscosity algin (the viscosity is less than or equal to 50mPa.s)

1.5 percent of starch

Hydroxypropyl methylcellulose 81.5%

Humectant (glycerin) 2%

Coagulant aid (mixed solution of calcium citrate and calcium glutamate) composite calcium ion solution with concentration of 0.1M/L

The enteric seaweed plant hollow capsule is prepared by using ultralow-viscosity algin, starch, hydroxypropyl methylcellulose, a humectant and a coagulant aid as raw materials and performing sol, gel curing, gel dipping, calcification coating, drying, cooling, demolding, cutting, registering, light inspection, metering and packaging.

(1) Sol and gel curing: weighing the materials according to the prescription amount, slowly adding the materials into a sol tank, uniformly mixing, adding purified water, stirring and soaking for 20min, adding glycerol, continuously stirring to fully absorb water, expand and dissolve, heating to 95 ℃, starting a vacuum pump valve, stirring while vacuumizing to remove bubbles, keeping the temperature of the sol in the sol tank at 95 ℃, stirring at high temperature for 4h, and starting cooling. Stirring the sol at 90 ℃ for 3 hours until the sol solution is completely dissolved, cooling the sol solution to 40 ℃, stirring at constant temperature for 1 hour until the viscosity of the sol solution meets 1500-one-viscosity 4000mPa.s, and maintaining the sol for 24 hours for later use.

(2) Dipping glue: selecting capsule mould with suitable type, soaking the mould into the glue solution to dip capsule blank when the temperature of the glue solution is reduced to 38 deg.C, lubricating the mould with appropriate amount of lubricant (such as vegetable oil) before dipping glue, and uniformly sticking the glue solution on the mould.

(3) Calcified coating: and (3) when the capsule embryo is in a semi-dry state, immersing the capsule embryo for about 6s by using the composite calcium ion solution, and slowly lifting to form a coating. According to the characteristics of the algin gel, a composite calcium ion solution is selected to crosslink and calcify the capsule blank to form a calcium alginate coating.

(4) Drying, cooling, demolding, cutting, registering, optical inspection, metering and packaging and gold detection: drying with hot wind at 35 deg.C for 1.5h, and cooling in 25 deg.C stabilizing box with relative humidity of 55% for 30 min. And (4) after cooling, separating the capsule from the die, then cutting, sleeving the two capsule hemispheres together, and metering and packaging after optical inspection is qualified.

Example 3:

firstly, preparing the ultra-low viscosity algin

Algin is taken as a raw material and is subjected to acidification degradation, oxidative degradation, neutralization, dehydration, crushing and drying.

(1) Degradation by acidification

Dissolving algin, adding hydrochloric acid, adjusting pH to 3, keeping temperature at 70 deg.C, performing acidic degradation for 8h, stirring during soaking to mix well, and dewatering with 300 mesh filter screen to obtain alginic acid block.

(2) Oxidative degradation

Spraying hydrogen peroxide with the concentration of 35% in the process of crushing the dehydrated alginic acid blocks, wherein the adding amount is 3.5% of the mass of the alginic acid blocks, storing at normal temperature, and degrading for 24 hours;

(3) neutralization

Adding ethanol into the dehydrated acid blocks, stirring, adding 30% by mass of sodium hydroxide for neutralization, and dehydrating when the pH is measured to be 8.5 to obtain dehydrated rubber blocks;

(4) dewatering

Adding ethanol into the glue solution obtained by suction filtration, filtering by a 400-mesh screen, and dehydrating to obtain a dehydrated glue block;

(5) pulverizing, and oven drying

And crushing the dehydrated glue blocks, and drying in a drying system after crushing to obtain the ultralow-viscosity algin.

Secondly, preparing the enteric seaweed plant empty capsule

18.5 percent of ultralow-viscosity algin (the viscosity is less than or equal to 50mPa.s)

2.5 percent of starch

Hydroxypropyl methylcellulose 75%

Humectant (glycerin) 4%

Coagulant aid (mixed solution of calcium citrate and calcium glutamate) composite calcium ion solution with concentration of 0.5M/L

The enteric seaweed plant hollow capsule is prepared by using ultralow-viscosity algin, starch, hydroxypropyl methylcellulose, a humectant and a coagulant aid as raw materials and performing sol, gel curing, gel dipping, calcification coating, drying, cooling, demolding, cutting, registering, light inspection, metering and packaging.

(1) Sol and gel curing: weighing the materials according to the prescription amount, slowly adding the materials into a sol tank, uniformly mixing, adding purified water, stirring and soaking for 20min, adding glycerol, continuously stirring to fully absorb water, expand and dissolve, heating to 95 ℃, starting a vacuum pump valve, stirring while vacuumizing to remove bubbles, keeping the temperature of the sol in the sol tank at 100 ℃, stirring at high temperature for 3h, and starting cooling. Stirring the sol at 90 ℃ for 4 hours until the sol solution is completely dissolved, cooling the sol solution to 60 ℃, stirring at constant temperature for 1 hour until the viscosity of the sol solution meets 1500-one-viscosity 4000mPa.s, and maintaining the sol for 8 hours for later use.

(2) Dipping glue: selecting capsule mould with suitable type, soaking the mould into the glue solution to dip capsule blank when the temperature of the glue solution is reduced to 60 deg.C, lubricating the mould with appropriate amount of lubricant (such as vegetable oil) before dipping glue, and uniformly sticking the glue solution on the mould.

(3) Calcified coating: and (3) when the capsule embryo is in a semi-dry state, immersing the capsule embryo for about 8 seconds by using the composite calcium ion solution, and slowly lifting to form a coating. According to the characteristics of the algin gel, a composite calcium ion solution is selected to crosslink and calcify the capsule blank to form a calcium alginate coating.

(4) Drying, cooling, demolding, cutting, registering, optical inspection, metering and packaging and gold detection: drying with hot air at 45 deg.C for 1 hr, and cooling in 25 deg.C stabilizing box with relative humidity of 55% for 30 min. And (4) after cooling, separating the capsule from the die, then cutting, sleeving the two capsule hemispheres together, and metering and packaging after optical inspection is qualified.

Examples of the experiments

On the basis of the embodiment 1, each process parameter is adjusted to obtain the optimal process condition, which specifically comprises the following steps:

(1) influence of calcium ion coating on physicochemical properties of empty capsule

And (4) experimental conclusion: the enteric seaweed plant empty capsule prepared by preparing the blastula through one-step forming and dipping the blastula in the composite calcium ion solution for coating has more stable disintegration performance and achieves the enteric effect, and the concentration of the composite calcium ion solution is 0.1-0.5M/L. (2) The influence of algin compatibility on the physicochemical properties of the hollow capsule

And (4) experimental conclusion: the quality of the prepared capsule is best when the dosage of the algin is 15-35%.

In the above test, when the content of the ultra-low viscosity algin is 10%, 20%, 30% or 40%, the corresponding content of the hydroxypropyl methylcellulose is 65%, 75%, 65% or 55%, respectively, and the content of the other components is not changed.

(3) The compatibility of starch and other auxiliary materials influences the physical and chemical properties of the hollow capsule

And (4) experimental conclusion: the addition amount of starch is preferably 1.5-2.5%.

In the above test, when the amount of starch added was 1%, 1.5%, 2%, 2.5%, and 3%, the corresponding hydroxypropyl methylcellulose content was 76%, 75.5%, 75%, 74.5%, and 74%, respectively, and the content of the other components was unchanged.

(4) The influence of the compatibility of glycerol on the physicochemical properties of the empty capsule

And (4) experimental conclusion: the best effect is achieved when the addition amount of the glycerol is between 2 and 4 percent.

In the above test, when the amount of starch added is 1%, 2%, 3%, 4%, 5%, the corresponding hydroxypropyl methylcellulose content is 77%, 76%, 75%, 74%, 73%, respectively, and the content of other components is unchanged.

(6) Influence of dipping temperature on glue solution and capsule property

And (4) experimental conclusion: the dipping temperature is most suitable for 38-60 ℃.

(7) Effect of coating time on Capsule Shell Properties

Coating time/s	Wall thickness/10-2mm
		5	9.24+0.24
8	10.18+0.16
		10	10.73+0.17

And (4) experimental conclusion: the coating time is most suitable at 6-8 s.

It should be noted that the above-mentioned embodiments are only preferred embodiments of the present invention, and the present invention is not limited thereto, and although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications and equivalents can be made in the technical solutions described in the foregoing embodiments, or equivalents thereof. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.