CN113121709B

CN113121709B - Preparation method and application of modified starch

Info

Publication number: CN113121709B
Application number: CN201911394767.6A
Authority: CN
Inventors: 陈琼; 邱碧霞; 李绪发; 杨旭腾
Original assignee: Sirio Pharma Co Ltd
Current assignee: Sirio Pharma Co Ltd
Priority date: 2019-12-30
Filing date: 2019-12-30
Publication date: 2022-08-26
Anticipated expiration: 2039-12-30
Also published as: CN113121709A

Abstract

The invention relates to a preparation method and application of modified starch, belonging to the technical field of modification of natural high polymer materials. Discloses a continuous preparation process for strengthening starch composite modification by using a magnetic field and application thereof. The method is characterized in that the natural starch is subjected to magnetic immobilized enzyme enzymolysis, etherification and crosslinking reaction under the action of a magnetic field, and then is dehydrated, washed and dried to obtain the starch. The preparation process can recycle amylase, reduce energy consumption, and improve production efficiency. The obtained modified starch has the characteristics of low gelatinization temperature and peak viscosity, good film forming property, high gelling speed and good freeze-thaw stability, and can be used as a capsule wall material in the fields of foods, medicines and dietary health care products.

Description

Preparation method and application of modified starch

Technical Field

The invention belongs to the technical field of modification of natural high polymer materials, and particularly relates to a preparation method of modified starch and application of the modified starch in soft capsules.

Background

The soft capsule has the characteristics of high bioavailability, convenience for swallowing and human body absorption, good stability of functional substances, capability of covering the uncomfortable taste of the medicine, convenience for storage and carrying, neat appearance and the like, and is widely applied to the dietary health care products and the pharmaceutical industry. However, in order to effectively avoid the spread of mad cow disease and the occurrence of toxic capsule events and meet the consumption demands of people with special religious beliefs and vegetarians, non-gelatin plant soft capsules are gradually the research focus in recent years. Starch is a plant polysaccharide environment-friendly material widely existing in nature, has wide sources, rich content, renewable resources and relatively low price, and is widely used in the fields of food and restaurant, paper production, textile manufacturing, medicine and health care product development and the like. Because the particle structure and the phase change property of the starch are complex and cannot meet the production process of the traditional soft capsule, a starch modification technology is usually adopted to obtain a proper novel plant soft capsule shell material. On the basis of the inherent characteristics of the natural starch, the starch is modified by physical, chemical and biological methods, i.e. new functional groups are introduced to starch molecules or the size and the particle properties of the starch molecules are changed, so that the natural characteristics of the starch can be improved, the application range of the starch is expanded, and the starch is more suitable for the requirements of various industrial applications. The modified starch has stable physical and chemical properties, and the taste, tissue state, processing performance and tolerance of the product are improved obviously. The gelling capacity, film-forming property, transparency, oral disintegrating capacity and mechanical property of the soft capsule are obviously improved compared with the original starch, and the cost of the modified starch is far lower than that of animal gelatin, so that the modified starch becomes the first choice of the raw material for preparing the novel soft capsule.

Common modified starch mainly comprises pregelatinized starch, acidolysis starch, oxidized starch, dextrin, cross-linked starch, esterified starch, etherified starch, graft copolymer starch and the like. After the modified starch is modified by physical, chemical and biological means, the gelatinization temperature, hot viscosity and stability, freeze-thaw stability, gelling capacity, film forming property, transparency and the like of the modified starch are changed to different degrees. The development of modified starch suitable for soft capsules requires reasonable screening of a suitable modification method, so that the characteristics of gelation, film formation, disintegration and the like of the starch are adjusted, and the modified starch is suitable for the production requirements of the soft capsules. Chinese patent CN 104262493A discloses a preparation method and application of medicinal pregelatinized hydroxypropyl starch. The method comprises the steps of firstly carrying out acidolysis on natural starch, and then carrying out hydroxypropylation and pre-gelatinization treatment, so that the solubility and freeze-thaw stability of the obtained starch in cold water are greatly improved, and the starch can be used for preparing capsules and tablets. However, the preparation method of the modified starch has high dosage of the acidifying reagent, the part of the dispersion medium of the etherification reaction is an organic reagent with carcinogenic toxicity, the residue of hazardous substances can cause the problem of product safety, and the patent content does not clearly indicate whether the starch can be suitable for the production of soft capsules. Chinese patent CN 103893771A discloses a film-forming composition for producing starch material soft capsules and a preparation method thereof. The preparation method comprises taking 20-95% hydroxypropyl starch as main matrix, and adding 0-25% adjuvants (gel, softening agent and film forming agent) for improving soft capsule properties. However, the production cost is high because it still needs to be used in combination with natural plant polysaccharides or microbial exopolysaccharides as gelling agents. U.S. Pat. No. 4, 2013/0189522, 1(Film forming composition for soft capsules) discloses a plant soft capsule using acid-hydrolyzed waxy corn starch as the main raw material. The soft capsule shell has high mechanical strength, strong disintegrating ability, and good product stability during storage, but 8-30% carrageenan is still required to be added as gelling agent, and the maximum acidolysis temperature can reach 160 deg.C during preparation of the starch, and the energy consumption for production is high. U.S. Pat. No. 4, 2018/0221486, 1(Film-forming composition based on stable materials and objects obtained from the same general knowledge) uses hydroxypropyl starch with amylose content of 25-45% to partially replace gelatin, and prepares a starch/gelatin compound soft capsule with low production cost and high product transparency. However, the product does not completely break free of the use of gelatin and the health risks associated with animal-derived ingredients in soft gelatin capsules remain. U.S. Pat. No. 5, 2013/0302309, 1(Non-animal soft capsule shell compounding with modified dissolution and shell hardness) discloses a plant soft capsule prepared by using a compound of cross-linked starch and hydroxypropyl starch as main raw materials, and carrageenan gel, arabic gum and enzyme preparation in specific proportions as auxiliary materials. The addition of gum arabic and an enzyme preparation, although improving the disintegration ability and ductility of the gum shell, also causes the product production process to be complicated and increases the product cost.

With the continuous expansion and extension of the application field of the modified starch, the starch is endowed with more multiple characteristics in a composite modification mode, and the production process and performance requirements of the traditional soft capsule can be further met, so that the comprehensive quality of the plant soft capsule product is improved. At present, the composite modified starch used in the fields of paper making, food, textile, building, medicine and the like mainly comprises oxidized esterified starch, cross-linked esterified starch, etherified cross-linked starch, oxidized hydroxypropyl starch and the like. U.S. Pat. No. 4, 9339474, 2(Soft capsule based on stage and a method and device for the production of the same) discloses a plant Soft capsule which is produced by using hydroxypropyl crosslinked tapioca starch (model: Creamtex 75725, available from Cerestar) as the main raw material, keeping the proportion of granular starch above 50% by a specific technique and by using the inventive implementation device. The patent improves the production efficiency of the rubber by improving the concentration of starch, but the soft capsule encapsulation forming device is special and is not suitable for traditional soft capsule production equipment. Chinese patent CN 108559004 a discloses an acidolysis-etherification-esterification ternary composite modified starch suitable for preparing food gel soft sweets, jelly and medicinal hollow hard capsules, which is prepared by firstly acidifying starch with hydrochloric acid, then adding propylene oxide for hydroxypropylation reaction, and finally adding acetic anhydride or vinyl acetate for esterification reaction. Although the modified starch makes the processing process of the modified starch medicinal hollow hard capsule get rid of the dependence on the use of a gelling agent and an enhancer, the method for preparing the plant soft capsule by using the composite modified starch is not provided.

In a whole, the modified starch for the soft capsule still has the problems that the viscosity of the glue solution is too high, the forming speed of the wet glue skin is slow, the breaking strength and toughness are poor and other key indexes can not meet the production requirement of the soft capsule.

Disclosure of Invention

Aiming at key control indexes of soft capsule production such as peak viscosity of glue solution, gelation speed, breaking strength and toughness of wet glue skin in the production process of the soft capsule, the patent aims to develop a preparation process of composite modified starch suitable for soft capsule production through magnetic field reinforced starch enzymolysis, etherification and crosslinking composite continuous modification treatment. Meanwhile, the composite modified starch with good film forming property, high gelling speed, high breaking strength and good toughness and the plant soft capsule prepared by the modified starch are obtained.

The invention also aims to provide the modified starch obtained by the preparation method and the plant soft capsule prepared by the modified starch.

The purpose of the invention is realized by the following scheme:

a method for preparing modified starch comprises the following steps:

preparing starch into 25-45% starch milk by using water in a reaction system, adding a certain amount of magnetic immobilized enzyme, adjusting the temperature and pH value of a reaction solution, setting the magnetic field strength to be 2.0-6.0kA/m, and carrying out enzymolysis on the starch for 1-2 hours in a continuous circulating fluidized state by using nitrogen with the pressure controlled within the range of 0.5-1.2 MPa; setting the magnetic field intensity to be lower than 2.0kA/m, cooling to 20-28 ℃, adjusting the pH value to 10-12, adding a certain amount of propylene oxide, reacting for 0.5-1h, then heating to 36-40 ℃, and reacting for 18-22 h; then adding a cross-linking agent, and carrying out cross-linking reaction for 2-8 h; and neutralizing with acid, dehydrating, washing and drying to obtain the modified starch.

Further, the magnetic immobilized enzyme is magnetic immobilized medium-temperature alpha-amylase.

Further, the reaction temperature of the medium-temperature alpha-amylase is 40-70 ℃, preferably 50-65 ℃; the pH range is 5.0-7.0, preferably 5.5-6.5; the enzyme is used in an amount of 6-8U/g starch (dry basis).

Further, the modified starch has a hydroxypropyl content of 1.6-3.3g per 100g of starch (dry basis).

Further, the viscosity value of the 5% starch paste of the modified starch at 95 ℃ is 30-1000 BU.

Further, the natural starch is selected from tapioca starch, potato starch, corn starch, mung bean starch and pea starch.

Further, the cross-linking agent is selected from phosphorus oxychloride, sodium trimetaphosphate and sodium hexametaphosphate, and is preferably sodium trimetaphosphate.

Furthermore, the modified starch can be obtained according to the preparation process, and can completely replace the use of gelatin in the traditional soft capsule.

The invention provides a preparation method of modified starch and application thereof in the preparation of soft capsules, which is characterized by comprising the following steps:

preparing starch into 25-45% starch milk by using water in a reaction system, adding a certain amount of magnetic immobilized enzyme, setting the magnetic field intensity to be 2.0-6.0kA/m, adjusting the nitrogen pressure to be 0.5-1.2MPa, performing enzymolysis, hydroxypropylation and crosslinking reaction on the starch in a continuous circulating fluidized state, and neutralizing, washing, dehydrating and drying to obtain the modified starch for the soft capsules.

Furthermore, the preparation method of the modified starch is characterized in that the magnetic immobilized enzyme is mesophilic alpha-amylase. The reaction temperature of the magnetic immobilized moderate temperature alpha-amylase is 40-70 ℃, the pH range is 5.0-7.0, and the usage amount is 6-8U/g starch (dry basis).

Further, the modified starch is characterized by having a hydroxypropyl content of 1.6 to 3.3g per 100g of starch (dry basis) and a viscosity number of 30 to 1000BU at 95 ℃ for a 5% starch paste.

Further, the method for preparing the modified starch is characterized in that the starch is selected from potato starch, tapioca starch, corn starch, mung bean starch and pea starch.

Further, the preparation method of the modified starch is characterized in that the cross-linking agent is selected from phosphorus oxychloride, sodium trimetaphosphate and sodium hexametaphosphate.

The modified starch of the invention can be used for preparing plant soft capsules.

In one aspect, the present invention provides a method for preparing modified starch for soft capsule shells, comprising the steps of:

(1) an enzymolysis process, namely hydrolyzing starch by using alpha-amylase, preferably medium-temperature alpha-amylase, preferably magnetically immobilized alpha-amylase;

(2) in the etherification process, the starch subjected to enzymolysis is subjected to etherification treatment, preferably propylene oxide; and

(3) and in the cross-linking process, cross-linking agent is used for cross-linking the etherified starch.

In one embodiment, one or more, preferably all, of the above steps are carried out under magnetic field conditions to enhance and continue the enzymatic, etherification and crosslinking processes by magnetic field.

In one embodiment, the above processes (1) - (3) are performed in an environment filled with nitrogen.

In one embodiment, the cross-linking agent is added in an amount of 0.03% to 0.06% by mass of the starch and the propylene oxide is added in an amount of 5% to 10% by mass of the starch. For example, propylene oxide may be added in an amount of 6%, 7%, 8% or 9% by mass of the starch.

In one embodiment, the modified starch has a hydroxypropyl content of 0.8 to 3.3g per 100g of starch on a dry weight basis and a viscosity value of 30 to 1000BU for a 5% starch paste at 95 ℃, preferably 1.6 to 3.3g per 100g of starch, and a viscosity value of 30 to 1000BU for a 5% starch paste at 95 ℃.

In one embodiment, a method comprises:

(1) in the enzymolysis process, magnetically immobilized amylase and starch milk are reacted together for a first time period at the temperature of 40-70 ℃, the pH value of 5.0-7.0 and the magnetic field intensity of 2.0-6.0kA/m, so that the starch is subjected to enzymolysis in a continuous circulating fluidized state;

(2) setting a magnetic field strength lower than 2.0kA/m during the etherification and keeping the magnetic field strength in the whole preparation process, reducing the temperature to 20-28 ℃, adjusting the pH to 10-12, adding propylene oxide and reacting for a second time period, then heating to 36-40 ℃ and reacting for a third time period; and

(3) during crosslinking, a crosslinker is added and reacted for a fourth period of time.

In one embodiment, steps (1) - (3) are performed in an environment filled with nitrogen.

In one embodiment, the pressure of the nitrogen gas is from 0.5 to 1.2 MPa. For example, the pressure of nitrogen may be 0.8 MPa.

In one embodiment, the starch milk is present in an amount of 25-45%. For example, the content of starch milk may be 30%, 35% or 40%.

In one embodiment, the method of preparation further comprises the steps of: neutralizing, washing, dehydrating and drying.

In one embodiment, the enzymolysis temperature is 50-65 deg.C, enzymolysis pH is 5.5-6.5, magnetic field strength is 3.0-5.0kA/m, and magnetic field strength in crosslinking process is 1.0kA/m-1.8 kA/m. For example, the enzymatic hydrolysis temperature may be 55 ℃. The enzymatic pH may be 6. The magnetic field intensity in the enzymolysis process can be 4 kA/m. The magnetic field strength during crosslinking may be 1.2kA/m or 1.6 kA/m.

In one embodiment, the medium temperature alpha-amylase is used in an amount of 6-8U/g starch, e.g., 7U/g starch, on a dry weight basis.

In one embodiment, the first period of time is 1 to 2 hours. For example, the first period of time is 1.5 hours.

In one embodiment, the second period of time is from 0.5 to 1 hour. For example, the second period of time is 0.6, 0.8, or 0.9 hours.

In one embodiment, the third period of time is 18 to 22 hours. For example, the third period of time is 19, 20 or 21 hours.

In one embodiment, the fourth period of time is from 2 to 8 hours. For example, the fourth time period is 4, 5 or 7 hours.

In one embodiment, the starch is selected from the group consisting of potato starch, tapioca starch, corn starch, mung bean starch and pea starch.

In one embodiment, the crosslinking agent is selected from the group consisting of phosphorus oxychloride, sodium trimetaphosphate, and sodium hexametaphosphate.

In another aspect, the present invention provides a modified starch prepared by the method of the present invention. In one embodiment, the modified starch has a hydroxypropyl content of 0.8 to 3.3g per 100g of starch on a dry weight basis and a viscosity value of 30 to 1000BU for a 5% starch paste at 95 ℃, preferably 1.6 to 3.3g per 100g of starch, and a viscosity value of 30 to 1000BU for a 5% starch paste at 95 ℃.

In another aspect, the present invention provides a starch film-forming composition comprising a modified starch according to the present invention. In one embodiment, the starch film-forming composition further comprises glycerin. For example, the starch film-forming composition comprises 30-50 parts by weight of modified starch, 10-20 parts by weight of glycerol and 40-50 parts by weight of water.

In another aspect, the present invention provides the use of the modified starch of the invention for the preparation of a soft capsule shell.

The modified starch of the invention may have a variety of hydroxypropyl contents, for example from 0.8 to 3.3g/100g, for example 1.6g/100g, 2.0g/100g, 2.5g/100g, 3.0g/100g, 3.3g/100g starch (dry basis), or a 5% starch paste viscosity value at 95 ℃ of from 30 to 1000BU, for example 30BU, 60BU, 100BU, 500BU, 1000 BU. Surprisingly, the inventors have found that the use of a complex starch with a hydroxypropyl content and viscosity value within the above specified ranges can achieve better results in the preparation of soft capsule shells than commercial soft capsule starches of the prior art or complex starches outside this range, as determined from a comprehensive evaluation of soft capsule shells. Further, the inventors have found that certain starches typically further enhance the effect of the soft capsule shell, for example pea starch is slightly better than potato starch under the same conditions.

Compared with the prior patent contents, the invention has the following technical advantages and beneficial effects:

(1) the invention adopts a magnetic field to carry out coupling strengthening on starch enzymolysis, etherification and crosslinking reactions, adjusts the molecular weight of starch through medium-temperature alpha-amylase enzymolysis treatment, reduces the peak viscosity of the starch, increases the water retention and transparency of the starch and enhances the gel property of the starch; then, hydroxypropyl groups are introduced into starch molecules, and the obtained starch has low gelatinization temperature, weak retrogradation and good freeze-thaw stability; meanwhile, starch molecules are connected into a space network structure through a cross-linking reaction, so that the shearing resistance, the high temperature resistance and the bonding capability of the starch are improved.

(2) The invention realizes the simple, convenient and efficient recovery effect of the immobilized enzyme with higher yield by reasonably controlling the magnetic field intensity, so that the immobilized enzyme can be recycled, and the production cost is reduced. The contact area of the mixed reactants can be increased by the matching use of the steady magnetic field and the nitrogen, and the immobilized enzyme enzymolysis, etherification and crosslinking reaction of the natural starch can be safely and efficiently carried out, so that the overall reaction efficiency is improved.

(3) The modified starch prepared by the invention is applied to the preparation of soft capsules, and the breaking force of the formed wet rubber skin is between 82.27 and 255.51 g; the breaking distance is between-43 mm and-70 mm; the prepared soft capsule has disintegration time of 35-58min, can completely replace animal gelatin and vegetable gum for production and preparation of plant soft capsule, and reduces production cost.

(4) The inventor finds that the method of the invention can obtain the composite modified starch suitable for preparing soft capsule shells by increasing the hydroxypropyl content and reducing the viscosity value of the starch paste under the same conditions (such as time and raw materials) through magnetic field enhanced starch enzymolysis, etherification and crosslinking composite continuous modification treatment. The invention realizes the simple, convenient and efficient recovery effect of the immobilized enzyme with higher yield by reasonably controlling the magnetic field intensity, so that the immobilized enzyme can be recycled, and the production cost is reduced. The contact area of the mixed reactants can be increased by the matching use of the steady magnetic field and the nitrogen, and the immobilized enzyme enzymolysis, etherification and crosslinking reaction of the natural starch can be safely and efficiently carried out, so that the overall reaction efficiency is improved.

Detailed Description

In the present specification, "%" means mass% unless otherwise specified.

The objects, technical features and advantageous effects of the present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto.

The related preparation method of the immobilized enzyme comprises the following steps: adding 1.0-5.0 g of magnetic chitosan microspheres into 50-250 mL of 0.1-0.5 mol/L acetic acid-sodium acetate buffer solution for swelling for 2-5 hours, adding 100-500 mL of 1.0mg/mL medium-temperature alpha-amylase solution, oscillating on a constant-temperature oscillator at 20-40 ℃ and 100-250 r/min to allow the magnetic chitosan microspheres to adsorb the medium-temperature alpha-amylase, precipitating the magnetic chitosan microspheres under the action of a steady magnetic field after 6-16 hours, removing supernatant, and repeatedly washing the magnetic chitosan microspheres with 0.1-0.5 mol/L acetic acid-sodium acetate buffer solution until no protein is detected in the cleaning solution; obtaining the magnetic immobilized medium temperature alpha-amylase. The CAS accession number of the selected moderate temperature alpha-amylase is 9000-90-2, the EINECS accession number is 232-. The hydroxypropyl substitution degree is determined according to the national standard GB 29931-2013. The total phosphorus content of the starch and the derivatives thereof is determined by reference to national standard GB/T22427.11-2008/ISO 3949: 1982. the starch viscosity is measured by referring to the national standard GB/T22427.7-2008 and is used for characterizing the crosslinking degree and the enzymolysis degree.

Example 1

The cassava starch is mixed with water into 25 mass percent starch milk in a reaction kettle, and the magnetically immobilized medium-temperature alpha-amylase with the dosage of 6U/g starch is added. Adjusting the reaction temperature to 40 ℃, adjusting the pH value to 5, setting the magnetic field strength to 2.0kA/m, and assisting nitrogen with the pressure of 0.5MPa to carry out enzymolysis on the starch for 2 hours in a continuous circulating fluidized state. Then adjusting the magnetic field intensity to 1.0kA/m, cooling to 28 ℃, and adjusting the pH to 10-12; adding propylene oxide with the mass fraction of 5% of starch, reacting for 0.5h, heating to 40 ℃, reacting for 18h, then adding sodium trimetaphosphate with the mass fraction of 0.06% of starch into starch milk, performing cross-linking reaction for 2h, and performing acid neutralization, dehydration, washing and drying to obtain the composite modified starch with the hydroxypropyl content of 1.6g/100g of starch (dry basis) and the viscosity value of 5% starch paste at 95 ℃ of 100 BU.

Example 2

Preparing potato starch into starch milk with the mass fraction of 35% by using water in a reaction kettle, and adding the magnetic immobilized medium-temperature alpha-amylase with the dosage of 7U/g starch. Adjusting the reaction temperature to 55 ℃, the pH value to 6, setting the magnetic field intensity to 4.0kA/m, adding nitrogen with the pressure of 0.8MPa to perform enzymolysis on the starch for 1.5h in a continuous circulating fluidized state, then adjusting the magnetic field intensity to 1.2kA/m, cooling to 24 ℃, and adjusting the pH value to 10-12; adding 7% of propylene oxide by mass of starch, reacting for 0.8h, heating to 38 ℃, reacting for 20h, then adding 0.06% of phosphorus oxychloride by mass of starch into starch milk, and after crosslinking reaction for 5h, carrying out acid neutralization, dehydration, washing and drying to obtain the composite modified starch with hydroxypropyl content of 2.5g/100g starch (dry basis) and viscosity value of 5% starch paste at 95 ℃ of 60 BU.

Example 3

Corn starch is mixed with water in a reaction kettle to form starch milk with the mass fraction of 45%, and magnetic immobilized medium-temperature alpha-amylase with the dosage of 8U/g starch is added. Adjusting the reaction temperature to 70 ℃, the pH value to 7, setting the magnetic field intensity to 6.0kA/m, adding nitrogen with the pressure of 1.2MPa to perform enzymolysis on the starch for 1 hour in a continuous circulating fluidized state, then adjusting the magnetic field intensity to 1.8kA/m, cooling to 20 ℃, and adjusting the pH value to 10-12; adding propylene oxide with the mass fraction of starch of 10 percent, reacting for 1h, heating to 36 ℃, reacting for 22h, then adding sodium hexametaphosphate with the mass fraction of 0.06 percent into starch milk, and after cross-linking reaction for 8h, carrying out acid neutralization, dehydration, washing and drying to obtain the composite modified starch with the hydroxypropyl content of 3.3g/100g starch (dry basis) and the viscosity value of 5 percent starch paste at 95 ℃ of 30 BU.

Example 4

The mung bean starch is mixed with water in a reaction kettle to form starch milk with the mass fraction of 25%, and magnetic immobilized medium-temperature alpha-amylase with the dosage of 6U/g starch is added. Adjusting the reaction temperature to 40 ℃, the pH value to 5, setting the magnetic field intensity to 2.0kA/m, assisting nitrogen with the pressure of 0.5MPa to perform enzymolysis on the starch for 2 hours in a continuous circulating fluidized state, then adjusting the magnetic field intensity to 1.0kA/m, cooling to 28 ℃, and adjusting the pH value to 10-12; adding propylene oxide with the mass fraction of starch of 5 percent, reacting for 0.5h, heating to 40 ℃, reacting for 18h, then adding sodium trimetaphosphate with the mass fraction of starch of 0.06 percent into starch milk, and after cross-linking reaction for 2h, carrying out acid neutralization, dehydration, washing and drying to obtain the composite modified starch with the hydroxypropyl content of 1.6g/100g starch (dry basis) and the viscosity value of 5 percent starch paste of 100BU at 95 ℃.

Example 5

Pea starch is prepared into starch milk with the mass fraction of 35% by water in a reaction kettle, and magnetic immobilized moderate-temperature alpha-amylase with the use amount of 7U/g starch is added. Adjusting the reaction temperature to 55 ℃, the pH value to 6, setting the magnetic field intensity to 4.0kA/m, adding nitrogen with the pressure of 0.8MPa to perform enzymolysis on the starch for 1.5h in a continuous circulating fluidized state, then adjusting the magnetic field intensity to 1.2kA/m, cooling to 24 ℃, and adjusting the pH value to 10-12; adding 7 mass percent of epoxypropane into the starch, reacting for 0.8h, heating to 38 ℃, reacting for 20h, then adding 0.06 mass percent of phosphorus oxychloride into the starch milk, and after crosslinking reaction for 5h, carrying out acid neutralization, dehydration, washing and drying to obtain the composite modified starch with hydroxypropyl content of 2.5g/100g of starch (dry basis) and viscosity value of 5 percent starch paste at 95 ℃ of 60 BU.

Example 6

Cassava starch is prepared into starch milk with the mass fraction of 45% by using water in a reaction kettle, and magnetic immobilized medium-temperature alpha-amylase with the using amount of 8U/g starch is added. Adjusting the reaction temperature to 70 ℃, the pH value to 7, setting the magnetic field intensity to 6.0kA/m, adding nitrogen with the pressure of 1.2MPa to perform enzymolysis on the starch for 1 hour in a continuous circulating fluidized state, then adjusting the magnetic field intensity to 1.8kA/m, cooling to 20 ℃, and adjusting the pH value to 10-12; adding propylene oxide with the mass fraction of starch of 10 percent, reacting for 1h, heating to 36 ℃, reacting for 22h, then adding sodium trimetaphosphate with the mass fraction of starch of 0.06 percent into starch milk, and after cross-linking reaction for 8h, carrying out acid neutralization, dehydration, washing and drying to obtain the composite modified starch with the hydroxypropyl content of 3.3g/100g starch (dry basis) and the viscosity value of 5 percent starch paste at 95 ℃ of 30 BU.

Example 7

The cassava starch is prepared into starch milk with the mass fraction of 30% by using water in a reaction kettle, and the magnetic immobilized medium-temperature alpha-amylase with the use amount of 8U/g starch is added. Adjusting the reaction temperature to 70 ℃, the pH value to 7, setting the magnetic field strength to 6.0kA/m, assisting nitrogen with the pressure of 1.2MPa to perform enzymolysis on the starch for 1 hour in a continuous circulating fluidized state, then adjusting the magnetic field strength to 1.8kA/m, cooling to 22 ℃, and adjusting the pH value to 10-12; adding propylene oxide with the mass fraction of 6% of starch, reacting for 0.6h, heating to 37 ℃, reacting for 19h, then adding sodium trimetaphosphate with the mass fraction of 0.03% of starch into the starch milk, and after cross-linking reaction for 4h, carrying out acid neutralization, dehydration, washing and drying to obtain the composite modified starch with the hydroxypropyl content of 2.0g/100g of starch (dry basis) and the viscosity value of 5% starch paste of 1000BU at 95 ℃.

Example 8

Preparing potato starch into starch milk with the mass fraction of 40% by using water in a reaction kettle, and adding the magnetic immobilized medium-temperature alpha-amylase with the dosage of 7U/g starch. Adjusting the reaction temperature to 60 ℃, the pH value to 6.5, setting the magnetic field intensity to 5.0kA/m, assisting with nitrogen with the pressure of 0.8MPa to perform enzymolysis on the starch for 1.5h in a continuous circulating fluidized state, then adjusting the magnetic field intensity to 1.6kA/m, cooling to 24 ℃, and adjusting the pH value to 10-12; adding propylene oxide with the mass fraction of 8.5% of starch, reacting for 0.9h, heating to 39 ℃, reacting for 21h, adding sodium hexametaphosphate with the mass fraction of 0.03% of starch into starch milk, performing crosslinking reaction for 7h, and performing acid neutralization, dehydration, washing and drying to obtain the composite modified starch with the hydroxypropyl content of 3.0g/100g of starch (dry basis) and the viscosity value of 5% starch paste at 95 ℃ of 500 BU.

Comparative example 1

The method comprises the steps of preparing cassava starch into 25% starch milk by mass percent with water in a reaction kettle, adjusting the reaction temperature to 40 ℃, adjusting the pH value to 5, adding 6U/g of magnetically immobilized medium-temperature alpha-amylase of the starch, and performing enzymolysis on the starch for 2 hours in a continuous circulating fluidized state by nitrogen with the pressure of 0.5 MPa. Raising the temperature to 80 ℃, and maintaining for 2min for enzyme deactivation. Then cooling to 28 ℃, and adjusting the pH value to 10-12; adding propylene oxide with the mass fraction of starch of 5 percent, reacting for 0.5h, heating to 40 ℃, reacting for 18h, then adding sodium trimetaphosphate with the mass fraction of starch of 0.06 percent into starch milk, and after cross-linking reaction for 2h, carrying out acid neutralization, dehydration, washing and drying to obtain the composite modified starch with the hydroxypropyl content of 0.8g/100g starch (dry basis) and the viscosity value of 5 percent starch paste at 95 ℃ of 1500 BU.

Comparative example 2

The cassava starch is mixed with water into starch milk with the mass fraction of 45% in a reaction kettle, and the magnetic immobilized medium-temperature alpha-amylase with the use amount of 8U/g starch is added. Adjusting the reaction temperature to 70 ℃, the pH value to 7, setting the magnetic field intensity to 6.0kA/m, adding nitrogen with the pressure of 1.2MPa to perform enzymolysis on the starch for 1 hour in a continuous circulating fluidized state, then adjusting the magnetic field intensity to 1.8kA/m, cooling to 20 ℃, and adjusting the pH value to 10-12; adding propylene oxide with the mass fraction of starch being 12%, reacting for 1h, heating to 36 ℃, reacting for 22h, then adding sodium trimetaphosphate with the mass fraction of starch being 0.06% into starch milk, performing crosslinking reaction for 8h, and performing acid neutralization, dehydration, washing and drying to obtain the composite modified starch with the hydroxypropyl content being 3.6g/100g starch (dry basis) and the viscosity value of 5% starch paste being 30BU at 95 ℃.

Comparative example 3

The cassava starch is mixed with water into starch milk with the mass fraction of 45% in a reaction kettle, and the magnetic immobilized medium-temperature alpha-amylase with the use amount of 8U/g starch is added. Adjusting the reaction temperature to 70 ℃, the pH value to 7, setting the magnetic field intensity to 6.0kA/m, adding nitrogen with the pressure of 1.2MPa to perform enzymolysis on the starch for 1 hour in a continuous circulating fluidized state, then adjusting the magnetic field intensity to 1.8kA/m, cooling to 20 ℃, and adjusting the pH value to 10-12; adding propylene oxide with the mass fraction of starch being 12%, reacting for 1h, heating to 36 ℃, reacting for 22h, then adding sodium trimetaphosphate with the mass fraction of starch being 0.09% into starch milk, performing crosslinking reaction for 8h, and performing acid neutralization, dehydration, washing and drying to obtain the composite modified starch with the hydroxypropyl content being 3.6g/100g starch (dry basis) and the viscosity value of 5% starch paste being 10BU at 95 ℃.

Example 1A composite modified starch was prepared having a hydroxypropyl content of 1.6g per 100g of starch (dry basis) and a viscosity number of 100BU at 95 ℃ for a 5% starch paste. Comparative example 1A composite modified starch was prepared having a hydroxypropyl content of 0.8g per 100g of starch (dry basis) and a viscosity number of 1500BU at 95 ℃ for a 5% starch paste. As can be seen from the comparison of example 1 with comparative example 1, the modified starch prepared in example 1 has an increased hydroxypropyl content and a significantly reduced viscosity value over the same period of time. Therefore, the increase of the magnetic field in the preparation process can greatly improve the hydroxypropyl content of the synthesized starch, and simultaneously reduce the viscosity of the starch to a greater extent, thereby realizing simple and efficient synthesis and obtaining the modified starch which is more suitable for preparing soft capsules.

Examples 1a-8a, comparative examples 1a-3a, comparative example 4

Examples 1a to 8a and comparative examples 1a to 3a correspond to modified starches prepared in examples 1 to 8 and comparative examples 1 to 3, respectively, and comparative example 4 to a modified starch for commercial soft capsules (StarchGel) ^TM Lake nan Er kang pharmaceutical products GmbH), 40 parts of modified starch, 16 parts of glycerol, 44 parts of deionized water, pasting for 1h at 95 ℃, vacuum degassing, keeping the temperature of a glue solution at 85 ℃ for 1h, and preparing the modified starch soft capsule by adopting the traditional soft capsule production process (ingredients-glue melting-pelleting-drying). The formed wet capsule skin is taken out to test the breaking force and the breaking distance in the pelleting process, the dried soft capsule is taken out to test the disintegration time, and the test results are shown in tables 2-3.

And conveying the glue solution into a glue solution box of a soft capsule production line, and controlling the thickness of the rubber on the rotary drum to be 0.7-0.8mm to form the soft capsule rubber with uniform thickness. Cutting the rubber into a rectangular rubber strip with the thickness of 1 multiplied by 10cm, fixing and clamping two ends of the rubber strip by using an A/SPR probe, and then testing the tensile strength and elasticity of the rubber by using a physical property tester, wherein the testing method comprises the following steps: the speed before the test is 1.5mm/s, the test speed is 1mm/s, the speed after the test is 10mm/s and the induction force is 5 g; target mode: the distance is 100 mm; the triggering type is as follows: and (4) automatic. Measurement indexes are as follows: breaking force (g), breaking distance (mm). Each sample was assayed in duplicate six times. Each sample is parallelly measured for six times, and the average value is calculated to obtain the rubber breaking force and the breaking distance.

And then pressing the capsule content and the glue solution into soft capsules in a soft capsule machine, and transferring the soft capsules into a drying cage for shaping for 2 hours. Placing the shaped soft capsule in a drying tray, and drying until the water content of the capsule shell is 8-10%.

The prepared soft capsule is tested for disintegration time limit by adopting an appendix method of four parts of the 2015 edition of Chinese pharmacopoeia, a lifting disintegration tester, water as a medium, the temperature of 37 +/-1 ℃, and a baffle plate. The disintegration standard is that all the capsule shells for testing are disintegrated and dissolved or crushed within 60min under the specified conditions, and all the capsule shells except the crushed capsule shells are passed through a screen. If a small amount of the waste water cannot pass through the screen, but the waste water is softened or light and floats upwards without hard core, the waste water is treated according to the regulations.

The soft capsule sample produced by the starch composition is taken for crack adhesion degree detection, a small opening is cut at a non-crack position from the capsule, the content is extruded and emptied, then a ring containing two cracks is cut from the middle part and kept vertical to the crack, the ring is placed on a glass slide, the two cracks are vertical to the glass slide, the thickness of the two cracks and the thickness of the capsule shell are respectively measured under a microscope, and the ratio (P) of the minimum crack thickness to the capsule shell thickness is respectively calculated.

TABLE 1 comprehensive evaluation criteria for each index

Table 2 test results of each index of examples and comparative examples

TABLE 3 comprehensive scoring results for each index of examples and comparative examples

Note: in the actual production and processing process, the breaking force of the wet rubber of the starch soft capsule is a better result (the thickness of the rubber is 0.8mm) within the range of 120-260g, and in the range, the larger the breaking force is, the better the effect is; the fracture distance is within-40 to-80 mm, the better result is obtained (the thickness of the rubber is 0.8mm), and in the range, the larger the absolute value of the fracture distance is, the better the effect is; the starch soft capsule has the better result of the disintegration time of less than 60min, and the shorter the time, the better the effect. The ratio of the thickness of the seam to the thickness of the capsule shell is preferably not less than 30%, and the higher the ratio, the stronger the adhesion. Compared with the prior art, the soft capsule prepared from the composite modified starch is obviously superior to the prior art in the aspect that the thickness of a crack accounts for the thickness of a capsule shell, and the soft capsule is firmer in pelleting forming adhesion, difficult to leak oil and more suitable for industrial production.

Unexpectedly, the inventors have found that the continuous denaturation treatment of the present invention by magnetic field enhanced starch enzymolysis, etherification and crosslinking, compared to comparative example 1, enables to obtain a complex modified starch suitable for the preparation of soft capsule shells by increasing the hydroxypropyl content and decreasing the viscosity value of the starch paste under equivalent conditions (e.g. time and raw materials). The invention realizes the simple, convenient and efficient recovery effect of the immobilized enzyme with higher yield by reasonably controlling the magnetic field intensity, so that the immobilized enzyme can be recycled, and the production cost is reduced. The contact area of the mixed reactants can be increased by the matching use of the steady magnetic field and the nitrogen, and the immobilized enzyme enzymolysis, etherification and crosslinking reaction of the natural starch can be safely and efficiently carried out, so that the overall reaction efficiency is improved.

The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims

1. A method for preparing modified starch for soft capsule shells, comprising the following processes:

(1) carrying out enzymolysis on starch by using magnetic immobilized medium-temperature alpha-amylase;

(2) etherification process, etherification of the enzymatically hydrolyzed starch with propylene oxide and

(3) crosslinking, namely crosslinking the etherified starch by using a crosslinking agent;

the processes (1) to (3) are carried out under the condition of a magnetic field, so that the enzymolysis process, the etherification process and the cross-linking process are enhanced by the magnetic field and the processes are continuous;

the processes (1) to (3) are carried out in an atmosphere filled with nitrogen gas;

wherein the addition amount of the cross-linking agent is 0.03-0.06% of the mass of the starch, and the addition amount of the propylene oxide is 5-10% of the mass of the starch;

the modified starch has a hydroxypropyl content of 0.8-3.3g per 100g of starch on a dry weight basis and a 5% starch paste viscosity value of 30-1000BU at 95 ℃; the cross-linking agent is selected from one or more of phosphorus oxychloride, sodium trimetaphosphate and sodium hexametaphosphate;

wherein the method comprises:

(1) in the enzymolysis process, under the temperature of 40-70 ℃, the pH value of 5.0-7.0 and the magnetic field intensity of 2.0-6.0kA/m, the magnetically immobilized medium-temperature alpha-amylase and starch milk react together for a first time period, so that the starch is subjected to enzymolysis in a continuous circulating fluidized state;

(2) setting the magnetic field intensity to be lower than 2.0kA/m and keeping the magnetic field intensity in the whole preparation process during the etherification, reducing the temperature to 20-28 ℃, adjusting the pH to 10-12, adding propylene oxide and reacting for a second time period, then heating to 36-40 ℃ and reacting for a third time period; and

(3) during the crosslinking process, adding a crosslinking agent and reacting for a fourth time period, wherein the magnetic field intensity of the crosslinking process is 1.0kA/m-1.8 kA/m.

2. The method according to claim 1, characterized in that the modified starch has a hydroxypropyl content of 1.6-3.3g per 100g of starch on a dry weight basis and a viscosity value of 30-1000BU for a 5% starch paste at 95 ℃.

3. The method according to claim 1, characterized in that the pressure of the nitrogen is 0.5-1.2 MPa.

4. Method according to claim 1, characterized in that the content of starch milk is 25-45%.

5. The method of claim 1, further comprising the steps of: neutralizing, washing, dehydrating and drying.

6. The method of claim 1, wherein in the enzymolysis process, the enzymolysis temperature is 50-65 ℃, the enzymolysis pH is 5.5-6.5, and the magnetic field strength is 3.0-5.0 kA/m.

7. The method according to claim 1, wherein the quantity of magnetically immobilized moderate alpha-amylase used is 6-8U/g starch on a dry weight basis.

8. The method of claim 1, wherein the first period of time is 1-2 hours; the second time period is 0.5-1 hour; the third time period is 18-22 hours; and the fourth period of time is 2-8 hours.

9. A method according to any one of claims 1-8, characterised in that the starch is selected from one or more of potato starch, tapioca starch, corn starch, mung bean starch and pea starch.

10. A modified starch prepared according to the method of any one of claims 1-9.

11. Starch film-forming composition characterized in that it comprises a modified starch according to claim 10.

12. The starch film-forming composition according to claim 11, further comprising glycerol.

13. Use of a modified starch according to claim 10 for the preparation of a soft capsule shell.