Soluble modified starch for hollow hard capsule shell, preparation method of soluble modified starch and hollow hard capsule shell

Abstract

According to the soluble modified starch for the hollow hard capsule shell, the preparation method of the soluble modified starch and the hollow hard capsule shell, a compound modification process of acidolysis, etherification and pulse low-temperature plasma treatment is adopted, a starch molecular chain structure is improved, functional groups are introduced, the modified starch has good biocompatibility and degradability, and the soluble modified starch can be used for preparing the hollow hard capsule shell. Safety and nontoxicity are realized. The forming quality of the hollow hard capsule prepared from the modified starch can be effectively improved; the capsule product is high in appearance transparency, good in tightness in application, excellent in disintegration performance, stable in property, long in storage period and high in loading finished product rate during filling and filling. The preparation process is simple, and industrial production is easy.

Description

Technical Field

[0001] This application relates to the technical field of pharmaceutical excipients, and specifically relates to a soluble modified starch for a hollow hard capsule shell, a preparation method thereof, and a hollow hard capsule shell. Background Art

[0002] A capsule is an outer shell used to protect medicines. Usually, these medicines are generally powders or granules that are irritating to the esophagus and gastric mucosa, have a bad taste, are volatile, are easily decomposed by saliva in the mouth, and are easily inhaled into the trachea. Loading these medicines into capsules not only protects the medicinal properties of the medicines from being damaged, but also protects the digestive organs and respiratory tract. If the capsule shell is removed, it may cause drug loss, drug waste, reduced drug efficacy, etc. Capsules achieve the therapeutic effect by delivering therapeutic substances in an oral form instead of tablets. The advantages of capsules over tablets are that they can not only deliver solids, but also deliver non-aqueous liquids and semi-solids as solid dosage forms of unit doses. In addition, some medicines need to be dissolved and absorbed in the intestine, and the acid-resistant capsule shell can protect the medicine from being destroyed by gastric acid and enter the intestine. Capsule products have been widely used in the fields of medicine, health products, etc. According to the capsule shell materials, they can be divided into animal gelatin capsules and plant capsules. So far, animal gelatin capsules still dominate the market.

[0003] However, the capsule shell made of gelatin is prone to residual animal protein, which will react with the content medicine and has a strong stimulating effect on the stomach and intestines. At the same time, gelatin capsules are prone to breeding microorganisms, are fragile, and are prone to adhesion in a high-humidity environment. Due to the problem of raw material sources, gelatin capsules are rejected by special groups and have many potential safety problems. In addition, the raw material sources of gelatin capsules are complex, the quality is difficult to control, the storage property is poor, and it is easy to change, which determines that it has many insurmountable defects in performance and safety.

[0004] With the penetration of the concept of pure natural, plant-derived capsules have increasingly become a new choice for capsule dosage forms worldwide. At present, three types of new plant capsule products with different raw materials have been formed internationally, represented by cellulose esters (such as hydroxypropyl methylcellulose, etc.), plant polysaccharides (such as pullulan polysaccharide, alginic acid, carrageenan, and agar, etc.), and plant starches (such as modified corn starch, potato starch, and sweet potato starch, etc.). Plant capsules have many outstanding advantages compared with animal gelatin hollow capsules, which are helpful to the health of consumers, and are especially suitable for anti-inflammatory drugs, traditional Chinese medicines, and high-grade health products, etc., making the products have higher added value and competitiveness.

[0005] As a good film-forming material, natural starch is a very promising capsule shell material because of its wide source, low price, and very good biocompatibility and degradability. A starch capsule refers to a capsule agent with starch and its derivatives as the capsule material. Compared with gelatin capsule shells, starch capsule shells have the following advantages:

[0006] 1) The solubility of the capsule shell is independent of pH and is suitable for making enteric capsules;

[0007] 2) The capsule shell has good water retention, and the moisture content will not change drastically with humidity. The capsule shell is not easily softened or brittle;

[0008] 3) The safety of the capsule shell is very good, and there will be no problems such as excessive heavy metals and mad cow virus in terms of quality;

[0009] 4) The water resistance and oxygen barrier properties of the capsule shell are superior to those of gelatin capsules, which can prevent the contents from absorbing water or oxidizing, and can load drugs with strong hygroscopicity or reducibility;

[0010] 5) Starch is widely sourced and inexpensive. By improving the production process, the cost can be greatly reduced, making it easy to promote.

[0011] Starch capsules have the above advantages. However, there are still great problems and challenges in the related research of starch capsules. For example, the starch paste obtained by heating and gelatinization has poor solubility, low transparency, and too high viscosity. After the temperature is lowered, the starch paste is prone to aging and forming gels, and the film-forming property and mechanical properties of the prepared starch film are poor. Nevertheless, the great prospects of starch capsules still attract many scholars to conduct related research on improving the properties of starch materials for capsule shells. Summary of the Invention

[0012] The embodiments of the present application provide a soluble modified starch for the shell of a hollow hard capsule, its preparation method, and the shell of a hollow hard capsule to solve the problems existing in the related technology. The technical solutions are as follows:

[0013] In the first aspect, the embodiments of the present application provide a preparation method for a soluble modified starch for the shell of a hollow hard capsule, including the following steps:

[0014] Disperse starch in water to form a starch milk; the starch milk is sequentially subjected to acidolysis treatment, etherification treatment, and pulsed low-temperature plasma treatment to obtain the soluble modified starch for the shell of the hollow hard capsule.

[0015] In one embodiment, after the starch milk is subjected to acidolysis-enzymolysis-etherification treatment, it is then subjected to pulsed low-temperature plasma treatment to obtain the soluble modified starch for the shell of the hollow hard capsule.

[0016] In one embodiment, the starch is one or a combination of two or more of corn starch, tapioca starch, or potato starch.

[0017] In one embodiment, the process of acidolysis treatment is: add a selected acid catalyst to the starch milk, adjust the pH value to 2.0 - 4.0, the reaction temperature is 40 - 60 °C; the reaction time is 1 - 3 h;

[0018] The acid catalyst is one or a combination of two or more of hydrochloric acid, sulfuric acid or nitric acid. Preferably, the molar concentration of the acid is 0.05 - 2 mol / L.

[0019] In one embodiment, the etherification process is as follows: an alkali solution is added to the starch milk after acidolysis to adjust the pH value to alkaline, and then an etherifying agent solution is added, and the reaction is carried out at 50 - 70 °C for 3 - 5 h.

[0020] The alkali solution is an aqueous solution of sodium hydroxide and / or potassium hydroxide. Preferably, the content of sodium hydroxide and / or potassium hydroxide added is 0.5% - 2% of the mass of dry starch.

[0021] In one embodiment, the etherifying reagent is one or a combination of two or more of propylene oxide, ethylene oxide or chloroacetic acid;

[0022] The addition amount of the etherifying reagent is 5% - 15% of the mass of dry starch.

[0023] In one embodiment, before the pulsed low-temperature plasma treatment, the etherified starch is neutralized, washed, dried and pulverized.

[0024] In one embodiment, the conditions for pulsed low-temperature plasma treatment are: treatment at 40 - 60 W for 1 - 10 min.

[0025] In one embodiment, the enzymolysis process is as follows: the acidified starch is added with an enzymolysis reagent, and enzymolyzed starch is obtained after reacting for 2 - 6 h.

[0026] In one embodiment, the enzymolysis reagent is one or a combination of two or more of α-amylase, β-amylase, pullulanase, isoamylase.

[0027] In one embodiment, the addition amount of the enzymolysis reagent is 0.5% - 5% of the mass of dry starch.

[0028] In a second aspect, the embodiments of the present application provide a soluble denatured starch for the shell of a hollow hard capsule, which is prepared by the preparation method of the soluble denatured starch for the shell of a hollow hard capsule described in any one of the above.

[0029] In one embodiment, the viscosity of the 20% glue solution is 2000 - 4000 mPa·s; the viscosity of the 25% glue solution is 2500 - 5000 mPa·s; the viscosity of the 30% glue solution is 3500 - 6500 mPa·s.

[0030] In a third aspect, the embodiments of the present application provide a shell of a hollow hard capsule, which is prepared from the soluble denatured starch for the shell of a hollow hard capsule described above.

[0031] The advantages or beneficial effects in the above technical solutions at least include:

[0032] The preparation method of the hollow hard capsule shell of the present application using soluble modified starch adopts a composite modification process of acid hydrolysis, or enzymatic hydrolysis, etherification and pulsed low-temperature plasma treatment to improve the starch molecular chain structure and introduce functional groups. The modified starch has good biocompatibility and biodegradability, and is safe and non-toxic. It can effectively improve the forming quality of the hollow hard capsule prepared from the modified starch; the appearance of the capsule product has high transparency, good tightness in application, excellent disintegration performance, stable properties, long storage period, and high finished product rate of loading medicine on the machine during filling. The preparation process of the present invention is simple and easy for industrial production.

[0033] The above summary is only for the purpose of the specification and is not intended to be limiting in any way. In addition to the illustrative aspects, embodiments and features described above, further aspects, embodiments and features of the present application will be readily apparent by reference to the drawings and the following detailed description. Brief Description of the Drawings

[0034] In the drawings, unless otherwise specified, the same reference numerals throughout the several views represent the same or similar components or elements. These drawings are not necessarily drawn to scale. It should be understood that these drawings only depict some embodiments disclosed in the present application and should not be regarded as limiting the scope of the present application.

[0035] Figure 1 A starch capsule product prepared from the soluble modified starch for the hollow hard capsule shell prepared in Example 1 of the present application;

[0036] Figure 2 A starch capsule product prepared from the soluble modified starch for the hollow hard capsule shell prepared in Example 2 of the present application;

[0037] Figure 3 A starch capsule product prepared from the soluble modified starch for the hollow hard capsule shell prepared in Example 3 of the present application;

[0038] Figure 4 A product diagram of a gelatin capsule on the market. Detailed Description of the Embodiments

[0039] In the following, only some exemplary embodiments are simply described. As those skilled in the art can recognize, the described embodiments can be modified in various different ways without departing from the spirit or scope of the present application. Therefore, the drawings and the description are considered to be exemplary in nature and not restrictive.

[0040] For a long time, gelatin capsules have occupied the main capsule market. However, with the in-depth application of gelatin capsules and the increasing severity of problematic capsules, there are many defects in performance and safety that are difficult to overcome. With the penetration of the concept of natural purity, plant-based capsules are increasingly becoming a new choice for capsule dosage forms worldwide. When using non-gelatin materials to make capsules, the first choice of capsule raw material is cellulose. Cellulose is non-toxic to the human body, has a rich source and a low price, and is suitable for making capsules. However, the physical and chemical properties of the "methyl cellulose" type of capsule shells produced are far inferior to those of gelatin capsules.

[0041] The first plant capsule was successfully developed and launched by Pfizer in the United States. It is a plant capsule with hydroxypropyl methylcellulose (HPMC) as the main raw material. Plant capsules with HPMC as the raw material are all made using a unique dipping mold process and drying technology, which is significantly different from the forming process of traditional gelatin capsules; among them, the requirements for the raw material source are high, and the synthesis process is relatively complex, resulting in a high market price of hydroxypropyl methylcellulose, which is basically equivalent to that of gelatin. Therefore, it is imperative to find more cost-effective plant-based hollow capsule raw materials.

[0042] Natural starch is the most abundant, economical, and renewable biopolymer, with the advantages of being natural, safe, non-toxic, cheap and easily available, and biodegradable. Essentially, starch is a storage biopolymer used for plant regeneration and is usually used as the main source of carbohydrates for human nutrition. It has been widely used in industries such as pharmaceuticals, food, textiles, and papermaking, and is considered the most potential substitute for capsule raw materials.

[0043] Due to the poor water absorption of natural starch, it is prone to retrogradation and aging, the viscosity of the prepared glue solution is high and not conducive to dipping, the film is brittle after film formation, and the product yield is low. Moreover, it is difficult to obtain a hollow hard capsule shell with high strength and resistance to filling, which cannot meet the requirements of some capsule uses. Therefore, it is difficult to directly use it to prepare the shell of hollow hard capsules.

[0044] The present invention aims to provide a preparation method of soluble modified starch for the shell of hollow hard capsules to solve the above problems existing in the prior art.

[0045] The embodiments of the present application provide a preparation method of soluble modified starch for the shell of hollow hard capsules, including the following steps:

[0046] Disperse starch in water to form a starch milk; the starch milk is sequentially subjected to acid hydrolysis treatment, etherification treatment, and pulsed low-temperature plasma treatment to obtain the soluble modified starch for the shell of hollow hard capsules.

[0047] By adopting combined modification processes such as acid hydrolysis, etherification, and pulsed low-temperature plasma treatment, the molecular chain structure of starch molecules is improved and functional groups are introduced to achieve modification. The modified starch has good biocompatibility and degradability, is safe and non-toxic, and can effectively improve the forming quality of starch-based hollow hard capsules; the capsule products have high transparency, good tightness during application, excellent disintegration performance, stable properties, long storage period, and high finished product rate of loading drugs onto the machine during filling.

[0048] As one of the implementation manners, the starch raw material undergoes a pretreatment process: selecting high-purity starch to ensure the uniformity of its molecular structure.

[0049] As one of the implementation manners, starch is dispersed in water to form a starch milk, which is to uniformly disperse starch powder in deionized water and form a stable starch milk through heating and mechanical stirring to provide an ideal reaction medium for subsequent reactions.

[0050] As one of the implementation manners, after the starch milk is subjected to acid hydrolysis - enzymatic hydrolysis - etherification treatment and then pulsed low-temperature plasma treatment, the soluble modified starch for the hollow hard capsule shell is obtained. Enzymatic hydrolysis can further modify the starch.

[0051] As one of the implementation manners, the process of enzymatic hydrolysis is: adding the acidified starch to the enzymatic hydrolysis reagent and obtaining enzymatically hydrolyzed starch after reacting for 2 - 6 h.

[0052] As one of the implementation manners, the enzymatic hydrolysis reagent is one or a combination of two or more of α-amylase, β-amylase, pullulanase, and isoamylase.

[0053] As one of the implementation manners, the addition amount of the enzymatic hydrolysis reagent is 0.5% - 5% of the mass of dry starch.

[0054] As one of the implementation manners, the starch is one or a combination of two or more of corn starch, cassava starch, or potato starch. Corn starch, cassava starch, or potato starch has a wider raw material source and is more in line with economic benefits.

[0055] As one of the implementation manners, the process of acid hydrolysis is: adding a selected acid catalyst to the starch milk, adjusting the pH value to 2.0 - 4.0, with the reaction temperature being 40 - 60°C; the reaction time is 1 - 3 h. Start the hydrolysis and restructuring reaction under the control of temperature and pH conditions; precisely control the breakage and recombination of starch chains by adjusting the acid concentration and reaction time to obtain ideal solubility and stability, and obtain acid-hydrolyzed starch milk.

[0056] As one of the implementation manners, the acid catalyst is one or a combination of two or more of hydrochloric acid, sulfuric acid or nitric acid. Hydrochloric acid, sulfuric acid or nitric acid are all dilute solutions. Too high concentration will cause the denaturation or carbonization of starch. Therefore, dilute solutions are used for acid hydrolysis. Preferably, the molar concentration of the acid is 0.05 - 2 mol / L.

[0057] As one of the implementation manners, the etherification process is as follows: Add an alkali solution to the starch milk after acid hydrolysis to adjust the pH value to alkaline, then add an etherifying agent solution, and react at 50 - 70 °C for 3 - 5 h;

[0058] The alkali solution is an aqueous solution of sodium hydroxide and / or potassium hydroxide. Preferably, the content of sodium hydroxide and / or potassium hydroxide added is 0.5% - 2% of the mass of dry starch.

[0059] Etherification is carried out in an alkaline environment, and a non-ionic starch derivative is obtained by the etherification reaction of starch.

[0060] As one of the implementation manners, the etherifying reagent is one or a combination of two or more of propylene oxide, ethylene oxide or chloroacetic acid. When the etherifying agent is propylene oxide, because a hydrophilic hydroxypropyl group is introduced into the molecular chain, the action of hydrogen bonds in starch is weakened, and the fluidity, transparency and water retention of pasty starch are also improved. The reaction process is as follows:

[0061]

[0062] As one of the implementation manners, the addition amount of the etherifying reagent is 5% - 15% of the mass of dry starch. The degree of etherification affects the performance of the modified starch. Therefore, the addition amount of the etherifying reagent is controlled within a certain range.

[0063] As one of the implementation manners, before the pulsed low-temperature plasma treatment, the etherified starch is neutralized, washed, dried and pulverized. In this implementation manner, neutralization is carried out using dilute hydrochloric acid or dilute sulfuric acid until neutral. The washing process uses water. The methods of drying and pulverization are not specifically limited.

[0064] As one of the implementation manners, the conditions of the pulsed low-temperature plasma treatment are: treating at 40 - 60 W for 1 - 10 min. Through the pulsed plasma treatment with instantaneous high voltage, the physicochemical properties and digestion characteristics of starch can be effectively changed, the solubility, relative crystallinity and gelatinization temperature can be increased, and the puffing degree and viscosity can be reduced, and the sterilization treatment can be effectively realized with less influence on the quality of starch, and a pharmaceutical-grade modified starch product can be obtained.

[0065] The present application also provides a soluble modified starch for the shell of a hollow hard capsule, which is prepared by the preparation method of the soluble modified starch for the shell of a hollow hard capsule described in any one of the above.

[0066] As one of the embodiments, the viscosity of the 20% glue solution is 2000 - 4000 mpa.s; the viscosity of the 25% glue solution is 2500 - 5000 mpa.s; the viscosity of the 30% glue solution is 3500 - 6500 mpa.s. The viscosity of the soluble modified starch for the shell of the hollow hard capsule prepared in the present application is within a relatively large range, and different concentrations can be configured according to the viscosity requirements.

[0067] The present application also provides a shell of a hollow hard capsule, which is prepared from the soluble modified starch for the shell of a hollow hard capsule described above. The appearance of the capsule shell product has high transparency, good tightness in application, excellent disintegration performance, stable properties, a long storage period, and a high finished product rate when loading medicine on the machine during filling.

[0068] The following is a further description with specific examples.

[0069] Example 1

[0070] Disperse 100 g of corn starch in 500 mL of water, stir evenly at high speed to obtain a starch milk; feed the prepared starch milk into a high-pressure homogenizer for homogenization treatment, and control the homogenization pressure between 60 MPa and 200 MPa; add a selected acid catalyst to the starch milk, adjust the pH value to 2.0 - 4.0, and the reaction temperature is 40 - 60 °C; after reacting for 1 - 3 hours, obtain acid-hydrolyzed starch; add an alkali solution to the acid-hydrolyzed starch milk to adjust the pH value to alkaline, then add an etherifying agent solution, and react at 50 - 70 °C for 3 - 5 hours to complete the etherification reaction of the molecules, obtaining etherified starch; neutralize, wash, dry, and pulverize the etherified starch solution, and then treat it on a pulsed plasma processor at 40 - 60 W for 1 - 10 min to obtain the soluble modified starch for the shell of the hollow hard capsule.

[0071] Example 2

[0072] Disperse 100 g of refined tapioca starch in 500 mL of water and stir evenly to obtain a starch milk; Feed the prepared starch milk into a high-pressure homogenizer for homogenization, and control the homogenization pressure between 60 MPa and 200 MPa; Add an alkali solution to the starch milk to adjust the pH value to alkaline, then add an etherifying agent solution, and react at 50 - 70 °C for 3 - 5 hours to complete the etherification reaction of the molecules; Add a selected acid catalyst to the starch milk, adjust the pH value to 2.0 - 4.0, and the reaction temperature is 40 - 60 °C; After reacting for 1 - 3 hours, acid-hydrolyzed starch is obtained; Neutralize, wash, dry, and pulverize the soluble modified starch solution, and then treat it on a pulsed plasma processor at 40 - 60 W for 1 - 10 min to obtain the soluble modified starch for the hollow hard capsule shell.

[0073] Example 3

[0074] Disperse 100 g of refined tapioca starch in 500 mL of water and stir evenly to obtain a starch milk; Feed the prepared starch milk into a high-pressure homogenizer for homogenization, and control the homogenization pressure between 60 MPa and 200 MPa; Add a selected acid catalyst to the starch milk for reaction, then adjust the pH value to 5.0 - 6.0, and the reaction temperature is 40 - 60 °C; Add a mixture of α-amylase, β-amylase, pullulanase, isoamylase, etc. in equal proportions, and the addition amount is 3% of the dry starch mass, and react for 2 - 6 hours to obtain enzymatically hydrolyzed starch; Add an alkali solution to the enzymatically hydrolyzed starch milk to adjust the pH value to alkaline, then add an etherifying agent solution, and react at 50 - 70 °C for 3 - 5 hours to complete the etherification reaction of the molecules; Pulsed low-temperature plasma treatment: Neutralize, wash, dry, and pulverize the soluble modified starch solution, and then treat it on a pulsed plasma processor at 40 - 60 W for 1 - 10 min to obtain the soluble modified starch for the hollow hard capsule shell.

[0075] Comparative Example 1

[0076] Commercially available gelatin hollow hard capsule shell.

[0077] Comparative Example 2

[0078] Comparative Example 2 does not perform acid hydrolysis compared to Example 1, and other methods are the same as those in Example 1.

[0079] Comparative Example 3

[0080] Comparative Example 3 does not perform etherification treatment compared to Example 1, and other methods are the same as those in Example 1.

[0081] Performance test:

[0082] Viscosity tests were carried out on Examples 1 - 3, Comparative Examples 2 - 3, and the raw material starch at 45 °C at different concentrations, and the results are shown in Table 1.

[0083] Table 1

[0084]

[0085] As can be seen from Table 1, the viscosity of the soluble modified starch used for the hollow hard capsule shell prepared in this application is significantly reduced relative to the original starch, and soluble modified starch with different viscosity ranges for the hollow hard capsule shell can be obtained according to the treatment method and by adjusting the concentration of the glue solution; it can meet different usage requirements.

[0086] In Examples 1 and 2, corn starch and refined tapioca starch were used respectively. These two starches are both starches with a large quantity and wide distribution, and both can be modified to prepare products. However, these two starches have different amylopectin / amylose ratios. The amylose content of tapioca starch is much less than that of corn starch. Therefore, the process of first etherifying and then acid-hydrolyzing tapioca starch is to first improve the solubility of the starch and then more effectively modify the amylopectin, so as to improve the water solubility of the modified starch and the film strength and water and oil resistance after film formation.

[0087] In Example 3, since the enzymatic hydrolysis process uses proteins with high catalytic activity, its catalytic hydrolysis and conversion of starch have relatively high specificity. However, due to being a biological catalysis, its modification of starch is still not as obvious as that of inorganic acid hydrolysis. As a result, although a relatively long time was used for modification, the viscosity of its enzymatic hydrolysis product is still significantly higher than that of the acid-hydrolyzed starch product. The soluble modified starch for the hollow hard capsule shell in Examples 1 - 3 and the starches in Comparative Examples 2 - 3 were made into capsule shells. Among them, the capsule shell of Example 1 is as Figure 1 shown; the capsule shell of Example 2 is as Figure 2 shown; the capsule shell of Example 3 is as Figure 3 shown; the commercially available gelatin capsule shell of Comparative Example 1 is as Figure 4 shown. Relevant performance tests were carried out, and the results are shown in Table 2.

[0088] Table 2

[0089]

[0090] Among them, in Comparative Examples 2 and 3, since the prepared glue solution could not achieve high solid and low viscosity, it was impossible to prepare the hollow hard capsule shell.

[0091] As can be seen from Table 2 and Figures 1-3 it can be seen that the hollow hard capsule shell prepared from the soluble modified starch for the hollow hard capsule shell of this application has good solubility, film-forming property, mechanical strength, biocompatibility, degradability, and transparency; while for the existing gelatin products, it can be clearly seen from Figure 4 that the capsule shell turns yellow, which is caused by the photo-oxidation of amino acids in the gelatin.

[0092] The performance results of Comparative Example 2 and Comparative Example 3 show that the soluble modified starch for the shell of the hollow hard capsule of the present application needs to achieve better performance improvement under the synergistic action of acid hydrolysis and etherification.

[0093] In summary, the present application uses an acid hydrolysis / enzyme hydrolysis & etherification and pulsed low-temperature plasma treatment composite modification process to prepare a soluble modified starch for the shell of a hollow hard capsule. By improving the molecular chain structure of starch molecules and introducing functional groups, the molding quality of starch-based hollow hard capsules can be effectively improved. The capsule products have high transparency, good tightness during application, excellent disintegration performance, stable properties, a long storage period, and a high finished product rate when filling and loading on the machine. The modified starch has good biocompatibility and biodegradability, and is safe and non-toxic. The preparation process of the present invention is simple and easy to industrialize.

[0094] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples", etc. means that the specific features, structures, materials, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. Moreover, the specific features, structures, materials, or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments or examples described in this specification and the features of different embodiments or examples.

[0095] In addition, the terms "first" and "second" are only used for descriptive purposes and cannot be understood as indicating or implying relative importance or implicitly indicating the quantity of the indicated technical features. Thus, the features defined with "first" and "second" may explicitly or implicitly include at least one of the features. In the description of the present application, "a plurality" means two or more, unless otherwise specifically defined.

[0096] The above is only the specific implementation manner of the present application, but the protection scope of the present application is not limited thereto. Any person skilled in the art can easily think of various changes or substitutions within the technical scope disclosed by the present application, and these should all be covered by the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. A preparation method of soluble modified starch for the shell of hollow hard capsules, characterized in that, It includes the following steps: Disperse starch in water to form a starch milk; after the starch milk is subjected to acidolysis-etherification treatment or etherification-acidolysis treatment, and then subjected to pulsed low-temperature plasma treatment, the soluble denatured starch for the hollow hard capsule shell is obtained.

2. The preparation method of the soluble denatured starch for the hollow hard capsule shell according to claim 1, characterized in that After the starch milk is subjected to acidolysis-enzymolysis-etherification treatment, and then subjected to pulsed low-temperature plasma treatment, the soluble denatured starch for the hollow hard capsule shell is obtained.

3. The preparation method of the soluble denatured starch for the hollow hard capsule shell according to claim 1, characterized in that The starch is one or a combination of two or more of corn starch, cassava starch or potato starch.

4. The preparation method of the soluble denatured starch for the hollow hard capsule shell according to claim 1, characterized in that The process of acidolysis treatment is: adding a selected acid catalyst to the starch milk, adjusting the pH value to 2.0-4.0, the reaction temperature is 40-60°C; the reaction time is 1-3h; The acid catalyst is one or a combination of two or more of hydrochloric acid, sulfuric acid or nitric acid.

5. The preparation method of the soluble denatured starch for the hollow hard capsule shell according to claim 1, characterized in that The process of etherification treatment is: adding an alkali solution to the starch milk after acidolysis or enzymolysis treatment to adjust the pH value to alkaline, and then adding an etherifying agent solution, and reacting at 50-70°C for 3-5h; The alkali solution is an aqueous solution of sodium hydroxide and / or potassium hydroxide.

6. The preparation method of the soluble denatured starch for the hollow hard capsule shell according to claim 4, characterized in that The etherifying reagent is one or a combination of two or more of propylene oxide, ethylene oxide or chloroacetic acid; The addition amount of the etherifying reagent is 5%-15% of the mass of dry starch.

7. The preparation method of the soluble denatured starch for the hollow hard capsule shell according to claim 1, characterized in that Before pulsed low-temperature plasma treatment, neutralize, wash, dry and pulverize the starch after etherification treatment; the conditions of pulsed low-temperature plasma treatment are: treat at 40-60W for 1-10min.

8. The preparation method of the soluble denatured starch for the hollow hard capsule shell according to claim 2, characterized in that The process of enzymolysis treatment is: adding an enzymolysis reagent to the acidified starch, and obtaining enzymolyzed starch after reacting for 2-6h; The enzymolysis reagent is one or a combination of two or more of α-amylase, β-amylase, pullulanase, isoamylase; The addition amount of the enzymolysis reagent is 0.5%-5% of the mass of dry starch.

9. A soluble denatured starch for the shell of a hollow hard capsule, characterized in that, Prepared by the preparation method of the soluble denatured starch for the hollow hard capsule shell according to any one of claims 1-8; The viscosity of the 20% glue solution of the soluble denatured starch for the hollow hard capsule shell is 2000-4000 mPa·s; the viscosity of the 25% glue solution is 2500-5000 mPa·s; the viscosity of the 30% glue solution is 3500-6500 mPa·s.

10. A hollow hard capsule shell, characterized in that, Prepared from the soluble denatured starch for the hollow hard capsule shell according to claim 9.

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