Hydroxypropyl high-amylose starch, preparation method thereof and application of hydroxypropyl high-amylose starch in capsule preparation

Abstract

The invention relates to the technical field of medicine and health care products, and discloses hydroxypropyl high-amylose starch and a preparation method thereof.The hydroxypropyl high-amylose starch is prepared from natural high-amylose corn starch serving as a main raw material through a microwave heating combined enzyme method, hydroxyl is fully exposed due to the honeycomb structure of the porous starch, and the high-amylose starch is prepared. The preparation method comprises the following steps: firstly, preparing porous starch, providing more sites for a hydroxypropyl substitution reaction, then further increasing the contact collision rate of the porous starch and epoxypropane by adopting a pulsed electric field, improving the substitution degree and efficiency, and finally obtaining the hydroxypropyl high-amylose starch. The composite plant hollow capsule prepared by the invention is moderate in wall thickness, high in hardness, good in compatibility among various components and strong in mechanical property, the disintegration time is less than 5min, and the composite plant hollow capsule meets the standard requirements of Pharmacopoeia of the People's Republic of China and is of a typical amorphous structure. The method has the characteristics of low price, good quality and the like, and has good popularization prospects.

Description

Technical Field

[0001] The invention relates to the technical field of medicine, health and health products, and in particular to hydroxypropyl high-amylose starch and a preparation method thereof and application thereof in capsule preparation. Background Art

[0002] Capsules are one of the most common oral preparations. The hard capsule shell of hollow capsules can not only protect the drug from the impact of external forces during storage and transportation, but also mask the bitterness and irritating smell of the drug. They are widely used in the fields of medicines and nutritional products, and the market demand continues to grow. In 2020, the global hollow capsule market value reached US$2.3827 billion, and it is expected to reach US$5.2304 billion in 2030. The commonly used hollow capsules on the market are gelatin capsules, which have the characteristics of good disintegration performance, fast drug release, and high bioavailability.

[0003] With the deepening of research, gelatin capsules have also exposed shortcomings such as poor water retention, short storage time and low mechanical properties; cross-linking may occur in gelatin capsules during storage, which affects their disintegration and dissolution. In addition, since gelatin comes from animal protein, it is not suitable for vegetarians; in the production and processing of gelatin capsules, microbial contamination or pathogenic bacteria may also occur. For example, the "toxic capsules" prepared by gelatin exposed in China have excessive chromium content, which seriously threatens human health. Therefore, plant capsules with higher safety have attracted people's attention. Plant capsules have outstanding advantages over animal gelatin capsules in terms of applicability, safety, stability, and environmental protection. Since the emergence of plant hollow capsules, the proportion of plant capsules used in medicines and health products in developed countries has increased. At present, there are two main types of plant capsules produced at home and abroad: hydroxypropyl methylcellulose hollow capsules and sodium alginate hollow capsules. However, these two types of plant capsules are relatively expensive and difficult to promote in my country due to price issues.

[0004] Hydroxypropyl starch (HPS) has low cost, good film-forming property and water solubility, and can be used to prepare plant capsules. Hydroxypropylation of high-amylose starch can enhance its anti-rupture ability, reduce the tensile strength of starch film, and increase elongation and rupture strength; it also has film-forming and water-retaining properties, oxygen will not penetrate at 25°C and a wide range of relative humidity, and the film is transparent and edible; at the same time, the introduction of hydroxypropyl can effectively inhibit the aging and regeneration of starch. Compared with hydroxypropyl starch, hydroxypropyl high-amylose starch contains a higher proportion of amylose, has better water solubility, stability, viscosity and gelation, and combines the structural characteristics of the helical cavity of amylose with the advantages of the hydroxypropyl group. With the increase of the etherification level, the effect is getting better and better.

[0005] At present, the domestic production demand for hydroxypropyl high-amylose corn starch is relatively large. Compared with the international advanced technology, my country's production equipment, process and technology are backward, product quality cannot be guaranteed, starch hydroxyl substitution degree is low, and production efficiency is low. Therefore. It is of great significance to explore a preparation method that can effectively improve the hydroxyl substitution degree in hydroxypropyl high-amylose corn starch and prepare a capsule with good stability, high safety, and low storage humidity and temperature requirements. Summary of the invention

[0006] In view of the problems and shortcomings in the prior art, the present invention aims to provide a hydroxypropyl high-amylose starch and a preparation method thereof and application thereof in capsule preparation.

[0007] Based on the above purpose, the present invention adopts the following technical solution:

[0008] The first aspect of the present invention provides a method for preparing hydroxypropyl high-amylose starch, comprising the following steps:

[0009] (1) After subjecting a high-amylose starch solution to microwave heating, a composite enzyme is added to the high-amylose starch solution for enzymolysis, the enzyme is inactivated and centrifuged, a precipitate is collected, and the precipitate is dried to obtain porous starch, wherein the composite enzyme comprises α-amylase and pullulanase in a mass ratio of (4-6):1;

[0010] (2) preparing the porous starch into starch milk, adjusting the pH of the starch milk to 8-10, and then adding a gelatinizer to the starch milk for gelatinization;

[0011] (3) adding an etherifying agent to the gelatinized reaction system, and placing the reaction system in a pulsed electric field for etherification reaction, wherein the pH of the reaction system is controlled to be 8-10 during the etherification reaction;

[0012] (4) After the etherification reaction is completed, a cross-linking agent is added to the reaction system to carry out a cross-linking reaction. After the cross-linking reaction is completed, the pH of the reaction solution is adjusted to 6-8, and then the reaction solution is filtered to collect the filtrate. The filtrate is dried to obtain hydroxypropyl high-amylose starch.

[0013] Preferably, the mass ratio of the high-amylose starch to the complex enzyme in step (1) is (80-100): (0.5-2).

[0014] Preferably, the pasting agent in step (2) is anhydrous sodium sulfate, the etherifying agent in step (3) is epichlorohydrin, and the cross-linking agent in step (4) is sodium trimetaphosphate solution.

[0015] Preferably, the microwave power in step (1) is 300-500 W, and the microwave time is 25-40 min.

[0016] Preferably, the electric field strength of the pulse electric field in step (4) is 20-30 kV / cm, the pulse width is 40-80 μs, the frequency is 500-1000 Hz, and the pulse reaction time is 30-60 min.

[0017] Preferably, the mass ratio of the gelatinizer to the high-amylose starch is (40-50):(1-2), the mass ratio of the etherifying agent to the high-amylose starch is (8-10):(1-2), and preferably, the mass ratio of the cross-linking agent to the high-amylose starch is (8-10):(3-5).

[0018] Preferably, the amylose content in the high amylose starch in step (1) is higher than 50%.

[0019] Preferably, the mass fraction of the sodium trimetaphosphate solution is 12%. Preferably, in step (2), the pH of the starch milk is adjusted to 8-10 with a sodium hydroxide solution.

[0020] Preferably, in step (3), during the etherification reaction, a sodium hydroxide solution is used to control the pH of the reaction system to 8-10.

[0021] Preferably, in step (4), after the cross-linking reaction is completed, the pH of the solution is adjusted to 6-8 with hydrochloric acid.

[0022] Preferably, the mass fraction of the high-amylose starch solution in step (1) is 20%-35%.

[0023] Preferably, the enzymatic hydrolysis temperature in step (1) is 50-70°C and the time is 10-20 min.

[0024] Preferably, the enzymatic hydrolysis in step (1) is followed by standing for 3-4 hours.

[0025] Preferably, when the etherifying agent is added in step (3), the temperature of the reaction system is 30-45°C.

[0026] Preferably, the starch milk in step (2) is obtained by adding ethanol solution to porous starch and mixing.

[0027] Preferably, the mass ratio of the ethanol solution to the high-amylose starch in step (1) is (4-5):(5-6).

[0028] The second aspect of the present invention provides the use of hydroxypropyl high-amylose starch prepared by the method described in the first aspect in capsule preparation.

[0029] The third aspect of the present invention provides a method for preparing a composite plant hollow capsule, which comprises: mixing the hydroxypropyl high-amylose starch and flaxseed gum prepared by the method of the first aspect in a mass ratio of (1-3):1, reacting at 50-80°C for 2-3h, then sequentially adding locust bean gum and propylene glycol, heating, heat preservation, dipping in glue to prepare embryos, and drying to obtain the composite plant hollow capsule.

[0030] Preferably, the mass of the locust bean gum is 5%-10% of the mass of the hydroxypropyl high-amylose starch, and the mass of the propylene glycol is 2%-5% of the mass of the hydroxypropyl high-amylose starch.

[0031] The fourth aspect of the present invention provides a composite plant hollow capsule prepared by the method described in the third aspect.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] 1. The present invention uses natural high-amylose corn starch as the main raw material, and adopts microwave heating combined with enzyme method to prepare porous starch. The honeycomb structure of the porous starch fully exposes the hydroxyl group, and further applies a pulse electric field and etherification cross-linking reaction to increase the contact and collision rate between starch and epichlorohydrin, improve the hydroxypropyl substitution degree and efficiency, and the final hydroxypropyl high-amylose starch has moderate viscosity, which is conducive to the molding of the capsule shell.

[0034] 2. Compared with gelatin hollow capsules, the composite plant hollow capsules prepared by the present invention have the following advantages: (1) moderate wall thickness, high light transmittance, good compatibility between various components, low water content, and can be filled with highly hygroscopic drugs; (2) high hardness, disintegration time <5min, in line with the standard requirements of the "Pharmacopoeia of the People's Republic of China"; (3) Gelatin will cross-link with aldehydes, polyphenols, reducing sugars, polyvalent metal ions, etc. in the drug, affecting the solubility of the capsule shell and the release of the drug. The significant advantages of non-gelatin hollow capsules are stable chemical properties, no cross-linking reaction, relatively stable drug release rate, high safety, improved storage stability of drugs, and reduced requirements for storage humidity and temperature conditions; (4) strong mechanical properties, a typical amorphous structure, low price, good quality, etc., with good promotion prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is a scanning electron microscope (SEM) image of the composite plant hollow capsule obtained in Example 2-1; wherein a is a cross section (100 nm); b is a cross section (200 nm); and c is a surface morphology (10 μm);

[0036] Figure 2 This is the X-ray diffraction (XRD) pattern of the composite plant hollow capsule obtained in Example 2-1. DETAILED DESCRIPTION

[0037] In order to make the purpose, technical scheme and advantages of the present invention more clearly understood, the present invention is further described in detail by way of embodiments below. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0038] Example 1

[0039] This example provides four types of hydroxypropyl high-amylose corn starch and preparation methods thereof, namely, Examples 1-1 to 1-4. The hydroxypropyl substitution degree and viscosity stability of the obtained four types of hydroxypropyl high-amylose corn starch are tested. The results are shown in Table 1.

[0040] Example 1-1

[0041] A method for preparing hydroxypropyl high-amylose corn starch specifically comprises the following steps:

[0042] (1) preparing a high-amylose starch solution: dissolving 80 parts of high-amylose corn starch in a sodium citrate buffer solution to prepare a high-amylose starch solution with a mass fraction of 25%;

[0043] (2) Microwave heating: microwave the high amylose starch solution at 300 W for 25 min;

[0044] (3) Enzymatic hydrolysis: After microwave treatment, add 1% of the mass of high-amylose starch composite enzyme, heat at 50°C for 10 min, and then let stand for 3 h. The composite enzyme is composed of α-amylase and pullulanase in a mass ratio of 4:1.

[0045] (4) Inactivating the enzyme: After enzymolysis, the reaction system obtained in step (3) is placed in a boiling water bath for 5 minutes, then cooled and centrifuged, and the precipitate is dried to obtain porous starch;

[0046] (5) pH adjustment: the porous starch and 100 parts of ethanol solution are introduced into a round-bottom flask, and the pH is adjusted to 8 with a 10% sodium hydroxide solution;

[0047] (6) Gelatinization: Add 2 parts of anhydrous sodium sulfate to the reaction system after adjusting the pH, and stir evenly;

[0048] (7) Pulsed electric field assisted etherification reaction: Take 10 parts of epichlorohydrin, dilute it 5 times with ethanol, and add the epichlorohydrin solution dropwise to the reaction system of step (6) at 30°C, and complete the dropwise addition within 20 minutes; then use a peristaltic pump to transport the entire system to a PEF treatment chamber, and react for 50 minutes at 20 kV / cm, pulse width 40-80 μs, and 1000 Hz; during the reaction, use 10% sodium hydroxide solution to maintain the pH of the reaction system at 8, the distance between the two plates of the treatment chamber is 0.3 cm, and the diameter of the treatment chamber is 0.3 cm;

[0049] (8) Cross-linking: add 45 parts of 12% sodium trimetaphosphate solution to the reaction system of step (7) and react for 1.5 hours;

[0050] (9) Termination of reaction: After the reaction is completed, the pH is adjusted to 7 with hydrochloric acid, the reaction solution is poured out, and the round-bottom flask is rinsed three times with ethanol solution. The reaction solution and the rinse solution are mixed, filtered, and dried to obtain hydroxypropyl high-amylose starch.

[0051] Example 1-2

[0052] A method for preparing hydroxypropyl high-amylose corn starch specifically comprises the following steps:

[0053] (1) preparing a high-amylose starch solution: dissolving 90 parts of high-amylose corn starch in a sodium citrate buffer solution to prepare a high-amylose starch solution with a mass fraction of 30%;

[0054] (2) Microwave heating: microwave the high amylose starch solution at 400 W for 30 min;

[0055] (3) Enzymatic hydrolysis: After microwave treatment, add 2% of the mass of high-amylose starch composite enzyme, heat at 70°C for 15 min, and then let stand for 3 h. The composite enzyme is composed of α-amylase and pullulanase in a mass ratio of 5:1.

[0056] (4) Inactivating the enzyme: After enzymolysis, the reaction system obtained in step (3) is placed in a boiling water bath for 5 minutes, then cooled and centrifuged, and the precipitate is dried to obtain porous starch;

[0057] (5) pH adjustment: the porous starch and 110 parts of ethanol solution were introduced into a round-bottom flask, and the pH was adjusted to 9 with a 10% sodium hydroxide solution;

[0058] (6) Gelatinization: Add 3 parts of anhydrous sodium sulfate to the reaction system after adjusting the pH, and stir evenly;

[0059] (7) Pulsed electric field assisted etherification reaction: Take 20 parts of epichlorohydrin, dilute it 5 times with ethanol, and add the epichlorohydrin solution dropwise to the reaction system of step (6) at 40° C., and complete the dropwise addition within 20 minutes; then use a peristaltic pump to transport the entire system to a PEF treatment chamber, and react for 30 minutes at 25 kV / cm, a pulse width of 50 μs, and 800 Hz; during the reaction, use 10% sodium hydroxide solution to maintain the pH of the reaction system at 9, the distance between the two plates of the treatment chamber is 0.3 cm, and the diameter of the treatment chamber is 0.3 cm;

[0060] (8) Cross-linking: add 50 parts of 12% sodium trimetaphosphate solution to the reaction system of step (7) and react for 2 hours;

[0061] (9) Termination of reaction: After the reaction is completed, the pH is adjusted to 6 with hydrochloric acid, the reaction solution is poured out, and the round-bottom flask is rinsed three times with ethanol solution. The reaction solution and the rinse solution are mixed, filtered, and dried to obtain hydroxypropyl high-amylose starch.

[0062] Examples 1-3

[0063] A method for preparing hydroxypropyl high-amylose corn starch specifically comprises the following steps:

[0064] (1) preparing a high-amylose starch solution: dissolving 100 parts of high-amylose corn starch in a sodium citrate buffer solution to prepare a high-amylose starch solution with a mass fraction of 35%;

[0065] (2) Microwave heating: microwave the high amylose starch solution at 500 W for 40 min;

[0066] (3) Enzymatic hydrolysis: After microwave treatment, add 2% of the mass of high-amylose starch composite enzyme, heat at 70°C for 20 min, and then let stand for 3 h. The composite enzyme is composed of α-amylase and pullulanase in a mass ratio of 6:1.

[0067] (4) Inactivating the enzyme: After enzymolysis, the reaction system obtained in step (3) is placed in a boiling water bath for 5 minutes, then cooled and centrifuged, and the precipitate is dried to obtain porous starch;

[0068] (5) pH adjustment: the porous starch and 120 parts of ethanol solution are introduced into a round-bottom flask, and the pH is adjusted to 10 with a 10% sodium hydroxide solution;

[0069] (6) Gelatinization: Add 4 parts of anhydrous sodium sulfate to the reaction system after adjusting the pH, and stir evenly;

[0070] (7) Pulsed electric field assisted etherification reaction: Take 20 parts of epichlorohydrin, dilute it 5 times with ethanol, and add the epichlorohydrin solution dropwise to the reaction system of step (6) at 45°C, and complete the dropwise addition within 20 minutes; then use a peristaltic pump to transport the entire system to a PEF treatment chamber, and react for 60 minutes at 30 kV / cm, pulse width 60 μs, and 900 Hz; during the reaction, use 10% sodium hydroxide solution to maintain the pH of the reaction system at 10, the distance between the two plates of the treatment chamber is 0.3 cm, and the diameter of the treatment chamber is 0.3 cm;

[0071] (8) Cross-linking: add 30 parts of 12% sodium trimetaphosphate solution to the reaction system of step (7) and react for 1 hour;

[0072] (9) Termination of reaction: After the reaction is completed, the pH is adjusted to 8 with hydrochloric acid, the reaction solution is poured out, and the round-bottom flask is rinsed three times with ethanol solution. The reaction solution and the rinse solution are mixed, filtered, and dried to obtain hydroxypropyl high-amylose starch.

[0073] Examples 1-4

[0074] A method for preparing hydroxypropyl high-amylose corn starch specifically comprises the following steps:

[0075] (1) preparing a high-amylose starch solution: dissolving 90 parts of high-amylose corn starch in a sodium citrate buffer solution to prepare a high-amylose starch solution with a mass fraction of 30%;

[0076] (2) Microwave heating: microwave the high amylose starch solution at 400 W for 30 min;

[0077] (3) Enzymatic hydrolysis: After microwave treatment, add 1.5% of the mass of high-amylose starch composite enzyme, heat at 60°C for 15 min, and then stand for 3.5 h. The composite enzyme is composed of α-amylase and pullulanase in a mass ratio of 6:1.

[0078] (4) Inactivating the enzyme: After enzymolysis, the reaction system obtained in step (3) is placed in a boiling water bath for 5 minutes, then cooled and centrifuged, and the precipitate is dried to obtain porous starch;

[0079] (5) pH adjustment: the porous starch and 100 parts of the ethanol solution are introduced into a round-bottom flask, and the pH is adjusted to 9 with a 10% sodium hydroxide solution;

[0080] (6) Gelatinization: Add 4 parts of anhydrous sodium sulfate to the reaction system after adjusting the pH, and stir evenly;

[0081] (7) Pulsed electric field assisted etherification reaction: Take 10 parts of epichlorohydrin, dilute it 5 times with ethanol, and add the epichlorohydrin solution dropwise to the reaction system of step (6) at 35°C, and complete the dropwise addition within 20 minutes; then use a peristaltic pump to transport the entire system to a PEF treatment chamber, and react for 50 minutes at 20 kV / cm, pulse width 40 μs, and 1000 Hz; during the reaction, use 10% sodium hydroxide solution to maintain the pH of the reaction system at 9, the distance between the two plates of the treatment chamber is 0.3 cm, and the diameter of the treatment chamber is 0.3 cm;

[0082] (8) Cross-linking: add 35 parts of 12% sodium trimetaphosphate solution to the reaction system of step (7) and react for 2 hours;

[0083] (9) Termination of reaction: After the reaction is completed, the pH is adjusted to 7 with hydrochloric acid, the reaction solution is poured out, and the round-bottom flask is rinsed three times with ethanol solution. The reaction solution and the rinse solution are mixed, filtered, and dried to obtain hydroxypropyl high-amylose starch.

[0084] The viscosity stability determination method is as follows: weigh the same weight of hydroxypropyl high amylose starch samples and high amylose starch 22.59g of Examples 1-1 to 1-4, add 50mL of distilled water, and prepare a 5% suspension; heat to gelatinization, heating rate is 1.5℃ / min, and then keep the sample at 95℃ for 30min, then cool to 30℃, cooling rate is 1.5℃ / min, and sample after cooling. Use a rotary viscometer to rotate for 5min to measure the viscosity, the results are shown in Table 1.

[0085] The hydroxypropyl substitution degree of the hydroxypropyl high amylose corn starch obtained in Examples 1-1 to 1-4 was tested with reference to the relevant part of the food additive hydroxypropyl starch in the national food safety standard GB 29930-2013. The results are shown in Table 1.

[0086] Table 1 Viscosity and degree of hydroxypropyl substitution of hydroxypropyl high amylose corn starch obtained in Examples 1-1 to 1-4

[0087] sample Viscosity / Pa s Hydroxypropyl substitution degree / % Example 1-1 0.281 14.7 Example 1-2 0.332 18.3 Examples 1-3 0.356 23.2 Examples 1-4 0.201 14.8

[0088] As can be seen from Table 1, the hydroxypropyl substitution degree of the four high-amylose corn starches prepared in Example 1 is between 14.7% and 23.2%. As the hydroxypropyl substitution degree increases, the viscosity has a certain increasing trend. This is because the hydroxypropyl group is a hydrophilic group, which can make water molecules more easily penetrate into the starch molecules, so that the starch molecules are fully expanded, thereby causing the viscosity of the glue to increase; the viscosity of the four high-amylose corn starches is in the range of 0.201-0.332 Pa s, which is conducive to the molding of the capsule shell.

[0089] Example 2

[0090] This example provides four methods for preparing composite plant hollow capsules, namely, Examples 2-1 to 2-4, and uses gelatin hollow capsules (commercially available) as a control, and tests the wall thickness and light transmittance, water content, friability, disintegration time, stability and characterization of the prepared composite plant hollow capsules.

[0091] Example 2-1

[0092] A preparation method of a composite plant hollow capsule, the preparation method comprising: adding hydroxypropyl high-amylose corn starch and linseed gum obtained in Example 1-1 in a mass ratio of 1:1 into a round-bottom flask, reacting at 50°C for 2h, then adding 6% of the mass of hydroxypropyl high-amylose corn starch and 4% of propylene glycol, stirring at 80°C for 1h, standing at 50°C for 30min, dipping in glue to prepare embryos, placing capsule shells in a 45°C oven to dry for 2.5h, shelling, cutting and fitting, to obtain composite plant hollow capsules.

[0093] Example 2-2

[0094] A preparation method of a composite plant hollow capsule, the preparation method comprising: adding hydroxypropyl high-amylose corn starch and linseed gum obtained in Example 1-2 in a mass ratio of 2:1 into a round-bottom flask, reacting at 70°C for 3h, then adding locust bean gum and 5% propylene glycol at a mass ratio of 10% of the mass of the hydroxypropyl high-amylose corn starch, stirring at 80°C for 1h, standing at 50°C for 30min, dipping in glue to prepare embryos, placing capsule shells in a 45°C oven to dry for 2.5h, shelling, cutting and fitting, to obtain composite plant hollow capsules.

[0095] Example 2-3

[0096] A preparation method of a composite plant hollow capsule, the preparation method comprising: adding hydroxypropyl high-amylose corn starch and linseed gum obtained in Example 1-3 in a mass ratio of 3:1 into a round-bottom flask, reacting at 80°C for 3h, then adding locust bean gum and 5% propylene glycol which are 10% by mass of the hydroxypropyl high-amylose corn starch, stirring at 80°C for 1h, standing at 50°C for 30min, dipping in glue to prepare embryos, placing capsule shells in a 45°C oven to dry for 2.5h, shelling, cutting and fitting, to obtain composite plant hollow capsules.

[0097] Embodiment 2-4

[0098] A preparation method of a composite plant hollow capsule, the preparation method comprising: adding hydroxypropyl high-amylose corn starch and linseed gum obtained in Example 1-4 in a mass ratio of 2:1 into a round-bottom flask, reacting at 80°C for 2.5 hours, then adding locust bean gum and 4% propylene glycol at a mass ratio of 7% of the mass of the hydroxypropyl high-amylose corn starch, stirring at 80°C for 1 hour, standing at 50°C for 30 minutes, dipping in glue to prepare embryos, placing capsule shells in a 45°C oven to dry for 2.5 hours, shelling, cutting and fitting, to obtain composite plant hollow capsules.

[0099] The detection method for capsule wall thickness, light transmittance and moisture content is as follows: take 3 plant capsules, measure the thickness of the plant capsule wall and capsule top, and take the average value of the results; take 3 plant capsules, and use a UV-visible spectrophotometer to measure the light transmittance of the plant capsules at 400nm and 800nm; weigh 3 plant capsules, separate the cap and body, dry them at 105℃ for 6h, weigh them again, and take the ratio of the weight difference before and after drying to the original weight as the moisture content. The results are shown in Table 2.

[0100] The test method for capsule friability is as follows: at room temperature, 50 empty capsules are placed in a desiccator with a saturated solution of magnesium nitrate at the bottom for one day. After taking out the capsules, they are placed upright in a glass tube. Then, a weight is allowed to fall freely on the bottom of the glass tube to check the breakage of the capsules. According to relevant regulations, the total number of broken capsules shall not exceed 5. The results are shown in Table 3.

[0101] The test method for the capsule disintegration time limit is: the capsule disintegration time limit is tested according to the relevant provisions of the Pharmacopoeia of the People's Republic of China. The results are shown in Table 3.

[0102] Capsule stability detection method: Place the starch-based empty capsules and the capsules filled with 0.25g of 5-aminosalicylic acid or amoxicillin in a suitable container, check them in an oven at 60°C for 10 days, take appropriate empty capsules and capsules on the 0th, 5th and 10th days, and observe the appearance, color, gloss and other properties of the capsule shell; Place the starch-based empty capsules and the capsules filled with 0.25g of 5-aminosalicylic acid or amoxicillin in a suitable container, place them at 25°C and 90±5% relative humidity for 10 days, take appropriate empty capsules and capsules on the 0th, 5th and 10th days, and observe the appearance, color, gloss and other properties of the capsule shell. The tightness is tested according to the requirements of the YBX-2000-2007 determination method. Friability: Tested according to the requirements of the YBX-2000-2007 determination method. The results are shown in Table 4.

[0103] Capsule characterization test method: The surface and cross section of the capsule were observed using a scanning electron microscope (SEM). Figure 1 ; X-ray diffractometer (XRD) was used to detect the microstructure of the capsule. Figure 2 .

[0104] Table 2 Wall thickness and light transmittance of composite plant hollow capsules obtained from Examples 2-1 to 2-4

[0105]

[0106] Table 3 Friability and disintegration time of composite plant hollow capsules obtained from Examples 2-1 to 2-4

[0107] sample friability Disintegration time / min Example 2-1 50 capsules without cracks 4.5 Example 2-2 50 capsules without cracks 4.5 Example 2-3 50 capsules without cracks 4.0 Embodiment 2-4 50 capsules without cracks 4.5

[0108] Table 4 Comparison of stability test of composite plant hollow capsules and gelatin capsules in Example 2-1

[0109]

[0110] It can be seen from Table 1 and Table 2 that when the viscosity is low, the capsule wall is thinner, and when the viscosity is slightly higher, the capsule wall thickens, indicating that the viscosity is directly related to the capsule wall thickness; it can also be seen that compared with the gelatin hollow capsules, the composite plant hollow capsules obtained in Examples 2-1 to 2-4 have higher transmittance at 400nm and 800nm ​​and lower water content, indicating that the hydroxypropyl high-amylose corn starch has good compatibility with other ingredients and can be filled with highly hygroscopic drugs.

[0111] As can be seen from Table 3, none of the 50 test capsules of Examples 2-1 to 2-4 broke, and their disintegration times were all less than 5 minutes. The results showed that the four composite plant hollow capsules prepared in Example 2 all met the relevant provisions of the Pharmacopoeia of the People's Republic of China.

[0112] As can be seen from Table 4, compared with the gelatin hollow capsules, the starch composite plant hollow capsules obtained in Example 2-1 have a slightly lower water content within 10 days at 60°C, and the tightness and brittleness do not change. The stability is good, and the storage conditions can be at room temperature. Moreover, it has good stability under a humidity of 90%±5%, without deformation, wrinkles, and gloss, indicating that the starch composite plant hollow capsules obtained in Example 2-1 are not too strict on storage conditions.

[0113] from Figure 1 It can be seen that the shell structure of the composite plant hollow capsule obtained in Example 2-1 is closely connected, indicating that the components of the capsule have good compatibility and strong mechanical properties.

[0114] from Figure 2 It can be seen that the XRD spectrum of the composite plant hollow capsule obtained in Example 2-1 is in a dispersed form, indicating that the composite plant hollow capsule is a typical amorphous structure.

[0115] In summary, the present invention adopts microwave heating combined with enzyme method to prepare porous starch, and the porous starch honeycomb structure fully exposes the hydroxyl group, and further applies pulse electric field and etherification cross-linking reaction to improve the degree and efficiency of hydroxypropyl substitution, and the finally obtained hydroxypropyl high-amylose starch has moderate viscosity. The composite plant hollow capsule prepared by the present invention has moderate wall thickness, high hardness, good compatibility between various components, strong mechanical properties, and disintegration time <5min, which meets the standard requirements of the "Pharmacopoeia of the People's Republic of China" and is a typical amorphous structure. It has the characteristics of low price, good quality, etc., and has good promotion prospects.

[0116] The above is an explanation of the embodiments of the present invention. By describing the disclosed embodiments, professionals in the field can implement or use the present invention, but it is not used to limit the present invention. It is impossible to fully reflect the various contents involved in the present invention in the above embodiments. Any equivalent changes or modifications made by any professional familiar with this technology without departing from the spirit or scope of the present invention are within the protection scope and disclosure scope of the present invention.

Claims

1. A method for preparing hydroxypropyl high-amylose starch, characterized in that: The following steps are involved: (1) heating a high-amylose starch solution with a microwave, adding a composite enzyme to the high-amylose starch solution for enzymolysis, inactivating the enzyme after enzymolysis, centrifuging, collecting a precipitate, and drying the precipitate to obtain porous starch, wherein the composite enzyme is α -Amylase and pullulanase are composed in a mass ratio of (4-6):1; (2) preparing the porous starch into starch milk, adjusting the pH of the starch milk to 8-10, and then adding a gelatinizer to the starch milk for gelatinization; (3) adding an etherifying agent to the gelatinized reaction system, and placing the reaction system in a pulsed electric field for etherification reaction, wherein the pH of the reaction system is controlled to be 8-10 during the etherification reaction; (4) After the etherification reaction is completed, a cross-linking agent is added to the reaction system to carry out a cross-linking reaction. After the cross-linking reaction is completed, the pH of the reaction solution is adjusted to 6-8, and then the reaction solution is filtered to collect the filtrate. The filtrate is dried to obtain hydroxypropyl high-amylose starch.

2. The method for preparing hydroxypropyl high amylose starch according to claim 1, characterized in that: The mass ratio of the high-amylose starch to the complex enzyme in step (1) is (80-100): (0.5-2).

3. The method for preparing hydroxypropyl high amylose starch according to claim 1, characterized in that: The pasting agent in step (2) is anhydrous sodium sulfate, the etherifying agent in step (3) is epichlorohydrin, and the cross-linking agent in step (4) is sodium trimetaphosphate solution.

4. The method for preparing hydroxypropyl high amylose starch according to claim 1, characterized in that: The microwave power in step (1) is 300-500W, and the microwave time is 25-40min.

5. The method for preparing hydroxypropyl high amylose starch according to claim 1, characterized in that: The electric field strength of the pulse electric field in step (4) is 20-30 kV / cm, the pulse width is 40-80 μs, the frequency is 500-1000 Hz, and the pulse reaction time is 30-60 min.

6. The method for preparing hydroxypropyl high amylose starch according to claim 1, characterized in that: The mass ratio of the gelatinizer to the high-amylose starch is (40-50):(1-2), the mass ratio of the etherifying agent to the high-amylose starch is (8-10):(1-2), the mass ratio of the cross-linking agent to the high-amylose starch is (8-10):(3-5), and the amylose content in the high-amylose starch is higher than 50%.

7. Use of the hydroxypropyl high-amylose starch prepared by the method of claims 1-7 in capsule preparation.

8. A method for preparing a composite plant hollow capsule, characterized in that: The preparation method comprises: mixing hydroxypropyl high-amylose starch and flaxseed gum prepared by any one of claims 1 to 6 in a mass ratio of (1-3):1, reacting at 50-80°C for 2-3h, then sequentially adding locust bean gum and propylene glycol, heating, heat preservation, and dipping in glue to prepare embryos to obtain capsule shells, and drying the capsule shells to obtain composite plant hollow capsules.

9. The method for preparing the composite plant hollow capsule according to claim 8, characterized in that: The mass of the locust bean gum is 5%-10% of the mass of the hydroxypropyl high-amylose starch, and the mass of the propylene glycol is 2%-5% of the mass of the hydroxypropyl high-amylose starch.

10. Composite plant hollow capsules prepared by the method according to any one of claims 8-9.

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