Amphiphilic cationized starch quaternary ammonium salt derivative as well as preparation method and application thereof

Abstract

The invention relates to the technical field of nano biology and medicine, and particularly discloses an amphipathic cationized starch quaternary ammonium salt derivative as well as a preparation method and application thereof, and the structural formula of the amphipathic cationized starch quaternary ammonium salt derivative is as shown in formula (1), wherein R is saturated fatty acid with different chain lengths, unsaturated fatty acid with different chain lengths, aromatic acid or heterocyclic acid, the value range of the average polymerization degree n is 5-12000, the reaction is efficient, the operation steps are simple and easy to implement, and needed equipment and raw materials are easy to obtain; researches show that the nano-micelle with an external hydrophilic-internal hydrophobic special core-shell structure, which is prepared from the amphiphilic cationized starch quaternary ammonium salt derivative, has good biocompatibility and relatively high entrapment capability, can obviously improve the water solubility and light stability of an entrapment compound, and is a nano-carrier material with good application value; the method can be widely applied to the fields of food and medicine.

Description

Technical Field

[0001] The present invention relates to the field of nano-biology and medicine technology, and specifically to an amphiphilic cationic starch quaternary ammonium salt derivative, a preparation method thereof, and an application thereof. Background Art

[0002] Starch is a high-molecular carbohydrate formed by connecting D-glucose through α-1,4 glycosidic bonds. Starch is mainly derived from crops such as corn, wheat, and potatoes, and is the main source of food supply for humans. Starch has the advantages of good biocompatibility, biodegradability, low cost, renewable, green and non-toxic. Therefore, it has great application potential in the fields of biopharmaceuticals, food, and daily chemical industry. Starch itself has a certain degree of hydrophobicity and cannot form a core-shell structure nano-micelle due to the lack of hydrophilic structures. Natural starch contains hydroxyl groups that can be used as chemical modification sites, and amphiphilic compounds can be obtained through efficient chemical modification means, and then prepared into nano-carriers. However, compared with other natural polysaccharides (such as hyaluronic acid and chitosan), natural starch itself has almost no obvious biological activity and only one hydroxyl modification group in its structure. Therefore, there has been less in-depth research on starch in the early stage, a small application range, and low application value. For this reason, an amphiphilic cationic starch quaternary ammonium salt derivative, a preparation method thereof, and an application thereof are provided. Summary of the Invention

[0003] The purpose of the present invention is to address the deficiencies of the prior art and provide an amphiphilic cationic starch quaternary ammonium salt derivative, a preparation method thereof, and an application thereof, so as to solve the problems raised in the above background art.

[0004] To achieve the above purpose, the present invention uses natural starch as a base material, and introduces hydrophilic groups (containing quaternary ammonium groups) and hydrophobic groups (saturated fatty acids with different chain lengths, unsaturated fatty acids with different chain lengths, aromatic acids, or heterocyclic acids) through quaternization and esterification reactions to synthesize amphiphilic compounds, and further prepares a special core-shell structure nano-micelle with hydrophilic outside and hydrophobic inside to expand its application prospects. The present invention provides the following technical solutions: An amphiphilic cationic starch quaternary ammonium salt derivative, and the structural formula of the amphiphilic cationic starch quaternary ammonium salt derivative is shown in formula (1), Formula (1), wherein R is a saturated fatty acid with different chain lengths, an unsaturated fatty acid with different chain lengths, an aromatic acid, or a heterocyclic acid, and the average degree of polymerization n ranges from 5 to 12000.

[0005] A preparation method of an amphiphilic cationic starch quaternary ammonium salt derivative, characterized in that the specific steps are as follows: Step 1: React the activated starch with glycidyltrimethylammonium chloride to obtain a starch quaternary ammonium salt derivative, where the molar amount of glycidyltrimethylammonium chloride is 3.0 - 7.0 times that of the starch; Step 2: React the starch quaternary ammonium salt derivative obtained in Step 1 with N , N '-carbonyl starch-based diimidazole-activated saturated fatty acids with different chain lengths, unsaturated fatty acids with different chain lengths, aromatic acids, or heterocyclic acids to obtain the amphiphilic cationic starch quaternary ammonium salt derivative shown in formula (1); N , N The molar amount of '-carbonyl diimidazole is 1.0 - 4.0 times that of the saturated fatty acids with different chain lengths, unsaturated fatty acids with different chain lengths, aromatic acids, or heterocyclic acids; the molar amount of the saturated fatty acids with different chain lengths, unsaturated fatty acids with different chain lengths, aromatic acids, or heterocyclic acids is 1.0 - 4.0 times that of the starch quaternary ammonium salt derivative.

[0006] As a preferred technical solution of the present invention, the specific steps of Step 1 are as follows: Dissolve the starch in an isopropanol solution, heat and activate it at 55 - 85 °C for 3 - 8 h, and reserve the obtained solution; dissolve glycidyltrimethylammonium chloride in excess water, then drop it into the above solution, and continue to react at 40 - 80 °C for 12 - 60 h. After the reaction ends and cools to room temperature, precipitate with 400 - 1000 mL of absolute ethanol, precipitate, wash, and filter repeatedly, and finally cool and dry the obtained solid to obtain the starch quaternary ammonium salt derivative.

[0007] As a preferred technical solution of the present invention, the specific steps of Step 2 are as follows: Add N , N '-carbonyl diimidazole to dimethyl sulfoxide containing saturated fatty acids with different chain lengths, unsaturated fatty acids with different chain lengths, aromatic acids, or heterocyclic acids, mix well, and react at 40 - 80 °C for 12 - 60 h in a nitrogen atmosphere to obtain a standby solution A; at the same time, fully dissolve the obtained starch quaternary ammonium salt derivative in a dimethyl sulfoxide solution to obtain a standby solution B, then slowly add solution A to solution B, and react at 40 - 80 °C for 12 - 60 h in a nitrogen atmosphere. After the reaction ends, precipitate with 400 - 800 mL of acetone, filter, and dry to obtain the amphiphilic cationic starch quaternary ammonium salt derivative.

[0008] An application of an amphiphilic cationic starch quaternary ammonium salt derivative in the preparation of a drug carrier.

[0009] An application of an amphiphilic cationic starch quaternary ammonium salt derivative in the preparation of a food antioxidant.

[0010] Compared with the prior art, the beneficial effects of the present invention are: (1) The present invention prepares nano - micelles from amphiphilic cationic starch quaternary ammonium salt derivatives. The process is simple and efficient, the required equipment and raw materials are easily available, and the cost is relatively low. Moreover, the prepared nano - micelles are safe, non - toxic, and have good biocompatibility, making them suitable for the preparation of food antioxidants and drug carriers. (2) The nano - micelles prepared from amphiphilic cationic starch quaternary ammonium salt derivatives in the present invention have good encapsulation ability. (3) The nano - micelles prepared from amphiphilic cationic starch quaternary ammonium salt derivatives in the present invention have a positive net surface charge. Therefore, they can enter cells through endocytosis, enabling the encapsulated compounds to enter cells and better exert their biological activities, which has inherent advantages in material transfer. (4) The nano - micelles prepared from amphiphilic cationic starch quaternary ammonium salt derivatives in the present invention have a special core - shell structure, which can be used for the encapsulation and transport of hydrophobic food and drug substances. The external hydrophilic shell acts as a "gatekeeper", and the internal hydrophobic core acts as a "storage box". The prepared core - shell structure nano - micelles can effectively improve the solubility and stability of the encapsulated hydrophobic compounds, contribute to enhancing the biological activities of the encapsulated substances, and are a transport carrier with good application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 is the infrared spectrum of starch; Figure 2 is the infrared spectrum of the starch quaternary ammonium salt derivative provided by the embodiment of the present invention; the newly emerged characteristic absorption peak at 1479 cm −1 is the bending vibration characteristic absorption peak of the alkyl C - H bond on the newly formed quaternary ammonium salt group, proving the successful synthesis of the starch quaternary ammonium salt derivative.

[0012] Figure 3 is the infrared spectrum of the amphiphilic cationic starch quaternary ammonium salt derivative provided by the embodiment of the present invention; compared with Figure 2 the starch quaternary ammonium salt derivative, the newly emerged 1737 cm −1 is the stretching vibration peak of the newly formed ester bond C = O; the characteristic absorption peak at 2853 cm −1 is the stretching vibration absorption peak of the alkyl C - H bond on the side chain of stearic acid, proving the amphiphilic cationic starch quaternary ammonium salt derivative.

[0013] Figure 4 is the morphology diagram of the nano - micelles prepared from the amphiphilic cationic starch quaternary ammonium salt derivative provided by the embodiment of the present invention; Figure 5 is the hemolysis experiment of the nano - micelles prepared from the amphiphilic cationic starch quaternary ammonium salt derivative provided by the embodiment of the present invention; Figure 6This is the water solubility experiment of α-tocopherol-loaded nanomicelles prepared from the amphiphilic cationic starch quaternary ammonium salt derivative provided by the embodiments of the present invention; Figure 7 This is the photo-stability experiment of α-tocopherol-loaded nanomicelles prepared from the amphiphilic cationic starch quaternary ammonium salt derivative provided by the embodiments of the present invention. Detailed implementation manners

[0014] The following elaborates on the preferred embodiments of the present invention with reference to the accompanying drawings, so that the advantages and features of the present invention can be more easily understood by those skilled in the art, thereby making a clearer and more definite definition of the protection scope of the present invention.

[0015] Please refer to Figure 1-4 , the present invention synthesizes an amphiphilic cationic starch quaternary ammonium salt derivative by introducing hydrophilic groups (containing quaternary ammonium groups) and hydrophobic groups (saturated fatty acids with different chain lengths, unsaturated fatty acids with different chain lengths, aromatic acids, or heterocyclic acids) through quaternization and esterification reactions. Both hydrophilic and hydrophobic groups exist in the structure, and they can self-assemble into nanomicelles. The present invention uses natural starch as the substrate to synthesize amphiphilic compounds, which is simple, easy to operate, and has mild conditions. The nanomicelles prepared from the amphiphilic cationic starch quaternary ammonium salt derivative have the characteristics of "safe and non-toxic", "good biocompatibility and biodegradability", and show the advantage of "high encapsulation" for hydrophobic compounds. They can effectively improve the physicochemical properties (solubility and photo-stability) of the encapsulated hydrophobic compounds and are a kind of nanocarrier with good application value.

[0016] Specifically: First, the activated starch reacts with glycidyltrimethylammonium chloride to obtain a starch quaternary ammonium salt derivative, and then reacts with N , N '-carbonyldiimidazole-activated saturated fatty acids with different chain lengths, unsaturated fatty acids with different chain lengths, aromatic acids, or heterocyclic acids to obtain the product shown in formula (1), the amphiphilic cationic starch quaternary ammonium salt derivative.

[0017] Formula (1) The core-shell structured nanomicelles prepared from the above-obtained amphiphilic cationic starch quaternary ammonium salt derivative are a kind of nanocarrier with good application value. The prepared nanocarrier can efficiently encapsulate hydrophobic food and drug substances, significantly improve the water solubility and photo-stability of the encapsulated compounds, and to a certain extent improve the biological activity and application value of the encapsulated compounds.

[0018] The synthesis route of the amphiphilic cationic starch quaternary ammonium salt derivative is as follows:

[0019] Wherein R is a saturated fatty acid with different chain lengths, an unsaturated fatty acid with different chain lengths, an aromatic acid or a heterocyclic acid, and the average degree of polymerization n ranges from 5 to 12,000.

[0020] The specific steps are as follows: Step 1: React the activated starch with glycidyltrimethylammonium chloride to obtain a starch quaternary ammonium salt derivative, and the molar amount of glycidyltrimethylammonium chloride is 3.0 - 7.0 times the molar amount of starch; Dissolve the starch in an isopropanol solution, heat and activate it at 55 - 85 °C for 3 - 8 h, and keep the obtained solution for later use; dissolve glycidyltrimethylammonium chloride in excess water, then drop it into the above solution, and continue to react at 40 - 80 °C for 12 - 60 h. After the reaction ends and cools to room temperature, precipitate with 400 - 1000 mL of absolute ethanol, precipitate, wash, and filter by suction repeatedly. Finally, cool and dry the obtained solid to obtain the starch quaternary ammonium salt derivative; Step 2: React the starch quaternary ammonium salt derivative obtained in Step 1 with N , N '-carbonyldiimidazole-activated saturated fatty acids or unsaturated fatty acids or aromatic acids or heterocyclic acids with different chain lengths to obtain the amphiphilic cationic starch quaternary ammonium salt derivative shown in formula (1); N , N The molar amount of '-carbonyldiimidazole is 1.0 - 4.0 times the molar amount of saturated fatty acids or unsaturated fatty acids or aromatic acids or heterocyclic acids with different chain lengths; the molar amount of saturated fatty acids or unsaturated fatty acids or aromatic acids or heterocyclic acids with different chain lengths is 1.0 - 4.0 times the molar amount of the starch quaternary ammonium salt derivative; Add N , N '-carbonyldiimidazole to dimethyl sulfoxide containing saturated fatty acids or unsaturated fatty acids or aromatic acids or heterocyclic acids with different chain lengths, mix well, and react at 40 - 80 °C for 12 - 60 h in a nitrogen atmosphere to obtain the standby solution A; at the same time, fully dissolve the obtained starch quaternary ammonium salt derivative in a dimethyl sulfoxide solution to obtain the standby solution B, then slowly add solution A to solution B, and react at 40 - 80 °C for 12 - 60 h in a nitrogen atmosphere. After the reaction ends, precipitate with 400 - 800 mL of acetone, filter by suction, and dry to obtain the amphiphilic cationic starch quaternary ammonium salt derivative.

[0021] Example 1: In this example, the target compound amphiphilic cationic starch quaternary ammonium salt derivative was synthesized according to the above synthesis route; the specific steps are as follows: 1) Preparation of starch quaternary ammonium salt derivative: Accurately weigh 8.10 g (50 mmol) of starch and place it in a 250 mL round-bottom flask. Add 40 mL of isopropanol solution to dissolve it completely, and then heat it to 55 °C for activation for 3 h for later use. At the same time, accurately weigh 22.744 g (150 mmol) of glycidyltrimethylammonium chloride and place it in another round-bottom flask. Add 30 mL of deionized water to dissolve it completely, and then add it to the above solution. React in a water bath at 60 °C for 24 h. After the reaction is completed, precipitate with 400 mL of absolute ethanol, wash, filter by suction, and freeze-dry to obtain 13.44 g of starch quaternary ammonium salt derivative for later use.

[0022] 2) Preparation of amphiphilic cationic starch quaternary ammonium salt derivative: Accurately weigh 1.42 g (5 mmol) of stearic acid and place it in a 100 mL round-bottom flask containing 10 mL of dimethyl sulfoxide. Dissolve it completely in a water bath at 60 °C, and then add 0.82 g (5 mmol) N , N '-carbonyldiimidazole and activate it in a water bath at 60 °C for 12 h to obtain solution A. At the same time, weigh 1.57 g (5 mmol) of starch quaternary ammonium salt derivative and place it in another round-bottom flask. Add 20 mL of dimethyl sulfoxide to dissolve it completely to obtain solution B. Then add solution A to solution B and react at 60 °C for 12 h under nitrogen protection. After the reaction is completed and cooled to room temperature, dissolve and precipitate repeatedly with 450 mL of acetone, filter by suction, and dry to obtain 1.88 g of amphiphilic cationic starch quaternary ammonium salt derivative.

[0023] Example 2: In this example, the target compound amphiphilic cationic starch quaternary ammonium salt derivative was synthesized according to the above synthetic route; the specific steps are as follows: 1) Preparation of starch quaternary ammonium salt derivative: Accurately weigh 8.10 g (50 mmol) of starch and place it in a 250 mL round-bottom flask. Add 40 mL of isopropanol solution to dissolve it completely, and then heat it to 65 °C for activation for 4 h for later use. At the same time, accurately weigh 26.535 g (175 mmol) of glycidyltrimethylammonium chloride and place it in another round-bottom flask. Add 45 mL of deionized water to dissolve it completely, and then add it to the above solution. React in a water bath at 70 °C for 48 h. After the reaction is completed, precipitate with 600 mL of absolute ethanol, wash, filter by suction, and freeze-dry to obtain 14.56 g of starch quaternary ammonium salt derivative for later use.

[0024] 2) Preparation of amphiphilic cationic starch quaternary ammonium salt derivative: Accurately weigh 1.706 g (6 mmol) of stearic acid and place it in a 100 mL round-bottom flask containing 15 mL of dimethyl sulfoxide. Dissolve it completely in a water bath at 60 °C, and then add 1.31 g (8 mmol)N , N '-Carbonyldiimidazole was activated in a 75 °C water bath for 24 h to obtain solution A; meanwhile, 1.57 g (5 mmol) of starch quaternary ammonium salt derivative was weighed and placed in another round-bottom flask, and 20 mL of dimethyl sulfoxide was added and fully dissolved to obtain solution B. Then, solution A was added to solution B, and the reaction was carried out at 75 °C for 24 h under nitrogen protection. After the reaction was completed and cooled to room temperature, it was repeatedly dissolved, precipitated, filtered, and dried with 600 mL of acetone to obtain 2.56 g of amphiphilic cationic starch quaternary ammonium salt derivative.

[0025] Example 3: The target compound amphiphilic cationic starch quaternary ammonium salt derivative was synthesized according to the above synthetic route in this example; the specific steps are as follows: 1) Preparation of starch quaternary ammonium salt derivative: Accurately weigh 8.10 g (50 mmol) of starch and place it in a 250 mL round-bottom flask, add 40 mL of isopropanol solution and fully dissolve it, and then heat it to 75 °C for activation for 5 h and set aside; meanwhile, accurately weigh 30.326 g (200 mmol) of glycidyltrimethylammonium chloride and place it in another round-bottom flask, add 60 mL of deionized water and fully dissolve it, and then add it to the above solution and react in an 80 °C water bath for 60 h. After the reaction is completed, it is precipitated, washed, filtered, and freeze-dried with 1000 mL of absolute ethanol to obtain 18.33 g of starch quaternary ammonium salt derivative for standby.

[0026] 2) Preparation of amphiphilic cationic starch quaternary ammonium salt derivative: Accurately weigh 2.133 g (7.5 mmol) of stearic acid and place it in a round-bottom flask containing 25 mL of dimethyl sulfoxide and 100 mL, and fully dissolve it in a 60 °C water bath. Then add 2.456 g (15 mmol) N , N '-Carbonyldiimidazole was activated in an 80 °C water bath for 48 h to obtain solution A; meanwhile, 1.57 g (5 mmol) of starch quaternary ammonium salt derivative was weighed and placed in another round-bottom flask, and 20 mL of dimethyl sulfoxide was added and fully dissolved to obtain solution B. Then, solution A was added to solution B, and the reaction was carried out at 80 °C for 48 h under nitrogen protection. After the reaction was completed and cooled to room temperature, it was repeatedly dissolved, precipitated, filtered, and dried with 800 mL of acetone to obtain 4.08 g of amphiphilic cationic starch quaternary ammonium salt derivative.

[0027] Application Example 1: Prepare nanomicelles with amphiphilic cationic starch quaternary ammonium salt derivative; (1) Prepare nanomicelles by the ultrasonic method; Weigh 20 mg of the amphiphilic cationic starch quaternary ammonium salt derivative synthesized in Example 1 and dissolve it in 20 mL of deionized water. Ultrasonicate for 5 min to disperse it evenly, and then place it under a probe sonicator (135 W, 2 s on, 1 s off) and sonicate for 20 min to obtain core-shell structured nanomicelles.

[0028] (2) Characterize the prepared nanomicelles; Characterize the nanomicelles obtained in step (1) above by dynamic light scattering (DLS). Take 2 mL of the nanomicelles prepared in step (1) above and place them in a cuvette, and measure the particle size, zeta potential, and PDI values in a Litesizer 500 nanoparticle size analyzer; Experimental results: The characterization of the nanomicelles prepared from the amphiphilic cationic starch quaternary ammonium salt derivative synthesized in Example 1 of the present invention is shown in Table 1. The particle size of the nanomicelles prepared from the amphiphilic cationic starch quaternary ammonium salt derivative in the present invention is 257.32 ± 6.77, and the PDI is 24.23 ± 1.78, less than 30, indicating that the prepared nanomicelles are evenly distributed; the zeta potential is +39.97 ± 0.13, which is positive. A higher zeta potential indicates that the prepared nanomicelles have good stability. At the same time, because of the introduction of quaternary cations, the net charge on its surface is positive. Since the phospholipid bilayer of the cell membrane is negatively charged, it also indicates that the prepared nanomicelles can better enter the cell to exert their biological activity.

[0029] Table 1: Test results of particle size, PDI, and zeta potential of the nanomicelles prepared in Example 1 Experimental group name Particle size (nm) PDI Potential (mV) Nanomicelles 257.32±6.77 24.23±1.78 +39.97±0.13 (3) Observe the appearance morphology of the prepared nanomicelles; Observe the appearance morphology of the prepared nanomicelles by transmission electron microscopy (TEM). Specific steps: Drop 200 µL of nanomicelles onto a copper grid, stain with 2% phosphotungstic acid for 20 min, air-dry at room temperature, and observe the morphology and take pictures under TEM.

[0030] Experimental results: The morphology diagram of the nanomicelles prepared from the amphiphilic cationic starch quaternary ammonium salt derivative synthesized in Example 1 of the present invention is shown in Figure 4. The hydrophilic groups (quaternary ammonium groups) are distributed in the aqueous phase, and the hydrophobic groups (stearic acid) avoid the aqueous phase and self-assemble into spherical nanoparticles.

[0031] (4) Evaluate the safety of the prepared nanomicelles; The steps are as follows: First, take 5 mL of blood from healthy rabbits. After centrifuging at 2500 rpm for 3 min, discard the supernatant plasma, add physiological saline containing EDTA and mix well, then centrifuge again under the same conditions. Repeat this operation three times until the supernatant is colorless, and add physiological saline to obtain a 2% erythrocyte suspension. Using physiological saline as a solvent, prepare the prepared nanomicelles into 2.0, 1.5, 1.0, 0.5 mg / mL. At the same time, set distilled water and physiological saline as the positive and negative control groups respectively. Place all the test tubes with added reagents in a constant temperature water bath at 37 °C for 1 h, then centrifuge the samples at 4500 rpm for 10 min. After centrifugation, take the supernatant and measure the absorbance at 541 nm using an ultraviolet spectrophotometer. Calculate according to the following formula: Hemolysis rate = (A 样品 - A 阴 ) / (A 阳 - A 阴 ) × 100% Among them, A 样品 , A 阳 , A 阴 represent the absorbance values of the test sample, distilled water, and physiological saline groups respectively.

[0032] Experimental results: The safety evaluation of the nanomicelles prepared from the amphiphilic cationic starch quaternary ammonium salt derivative synthesized in Example 1 of the present invention is as Figure 5 shown. The hemolysis rates of the nanomicelles are all lower than 5%, indicating that the prepared nanomicelles have no obvious interference on red blood cells and have good blood safety within the tested concentration range.

[0033] (5) Determination of the encapsulation efficiency and drug loading of the nanomicelles prepared from the amphiphilic cationic starch quaternary ammonium salt derivative synthesized in Example 1; Specific steps: Weigh 20 mg of the amphiphilic cationic starch quaternary ammonium salt derivative synthesized in Example 1 and dissolve it in 20 mL of deionized water. Ultrasonic for 5 min to disperse it evenly, then place it under the conditions of a probe sonicator (135 W, 2 s on, 1 s off) and sonicate for 20 min. While sonicating, dropwise add 75 μL (80 mg / mL) of α-tocopherol solution. After sonication, centrifuge the obtained solution at 12000 rpm for 30 min, take the supernatant and measure the absorbance at 283 nm by ultraviolet spectrophotometry, and calculate the encapsulation efficiency and drug loading of the drug-loaded nanomicelles according to the following formula.

[0034] Encapsulation efficiency = (total amount of drug - free drug) / total amount of drug × 100% Drug loading = (total amount of drug - free drug) / (carrier + total amount of drug) × 100% Table 2: Determination results of the encapsulation efficiency and drug loading of the nanomicelles prepared in Example 1 Experimental results: The encapsulation ability of the amphiphilic cationic starch quaternary ammonium salt derivative synthesized in Example 1 of the present invention for preparing nano - micelles is shown in Table 2. The encapsulation efficiency and drug loading amount are 71.48% ± 0.071 and 17.66% ± 0.014 respectively, indicating that the prepared core - shell spherical - like nano - micelles have good encapsulation ability for hydrophobic α - tocopherol.

[0035] (6)Analysis of the water solubility of the prepared α - tocopherol - loaded nano - micelles; Specific steps: Different amounts of α - tocopherol (1, 2, 3, 4, 5 mg) were respectively dropped into an aqueous solution (control group) and a nano - micelle solution (experimental group). The control group was sonicated for 12 h, and the experimental group was centrifuged at 12000 rpm for 30 min. The supernatant was discarded and the solid was left. After freeze - drying, α - tocopherol - loaded nano - micelles with different ratios were obtained. The absorbance of each group of samples at 283 nm was measured by ultraviolet spectrophotometry to evaluate the water solubility of different amounts of α - tocopherol in water and nano - micelles.

[0036] Experimental results: The water solubility results of different amounts of α - tocopherol in the aqueous solution and nano - micelles are as Figure 6 shown. The solubility of α - tocopherol in water is very low, and there is no increasing trend in the absorbance at 283 nm with the increase of the amount of α - tocopherol. Compared with the absorbance of α - tocopherol in water, the absorbance of α - tocopherol in the nano - micelles prepared in (1) above is significantly increased, that is, it shows that the solubility of α - tocopherol in the nano - micelles is significantly increased, and with the increase of the feeding ratio of α - tocopherol: blank nano - micelles, the absorbance at 283 nm also increases significantly. This is mainly because the hydrophobic core inside the prepared nano - micelles can combine with α - tocopherol, thus effectively improving the solubility of α - tocopherol.

[0037] (7)Analysis of the photostability of the prepared α - tocopherol - loaded nano - micelles; Specific steps: Free α - tocopherol and α - tocopherol - loaded nano - micelles were irradiated under ultraviolet light (254 nm) at a distance of 5 cm. Samples were collected at predetermined time intervals (1, 2, 4, 6, 8, and 10 h), and the content of the remaining α - tocopherol was measured by ultraviolet spectrophotometry. The photostability of the α - tocopherol - loaded nano - micelles was evaluated by calculating the ratio of the amount of the remaining α - tocopherol at different times to the total amount of the encapsulated α - tocopherol.

[0038] Experimental results: The photostability results of free α - tocopherol and α - tocopherol - loaded nano - micelles are as Figure 7 shown. Free α - tocopherol rapidly degraded under ultraviolet light at 254 nm, and only 19.09% of α - tocopherol remained after 10 h, and the half - life (t 1 / 2The time was 3.03 h, which indicates that α-tocopherol is very sensitive to ultraviolet light. Compared with free α-tocopherol, 67.24% of α-tocopherol remained after irradiation for the same time under the same conditions for the nano micelles loaded with free α-tocopherol prepared in the present invention, which is 3.5 times higher than the remaining amount of free α-tocopherol. This shows that the nano micelles with a special hydrophilic outer-hydrophobic inner core-shell structure prepared from amphiphilic cationic starch quaternary ammonium salt derivatives in the present invention contribute to improving the photo-stability of α-tocopherol. Therefore, the nano carrier prepared from amphiphilic cationic starch quaternary ammonium salt derivatives in the present invention has great application prospects in the fields of food and medicine.

[0039] The above embodiments only express the implementation modes of the present invention, and the description thereof is relatively specific and detailed, but it should not be construed as a limitation on the scope of the invention. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention.

Claims

1. An amphiphilic cationic starch quaternary ammonium salt derivative, characterized in that: The structural formula of the amphiphilic cationic starch quaternary ammonium salt derivative is shown in formula (1), Formula (1), wherein R is a saturated fatty acid with different chain lengths, an unsaturated fatty acid with different chain lengths, an aromatic acid or a heterocyclic acid, and the average degree of polymerization n ranges from 5 to 12000.

2. A preparation method of the amphiphilic cationic starch quaternary ammonium salt derivative as described in claim 1, characterized in that: The specific steps are as follows: Step 1: React the activated starch with glycidyltrimethylammonium chloride to obtain a starch quaternary ammonium salt derivative, and the molar amount of glycidyltrimethylammonium chloride is 3.0 - 7.0 times the molar amount of starch; Step 2: React the starch quaternary ammonium salt derivative obtained in Step 1 with N , N '-carbonyl starch-based diimidazole-activated saturated fatty acids with different chain lengths, unsaturated fatty acids with different chain lengths, aromatic acids or heterocyclic acids to obtain the amphiphilic cationic starch quaternary ammonium salt derivative shown in formula (1); N , N The molar amount of '-carbonyldiimidazole is 1.0 - 4.0 times the molar amount of saturated fatty acids with different chain lengths or unsaturated fatty acids with different chain lengths or aromatic acids or heterocyclic acids; the molar amount of saturated fatty acids with different chain lengths or unsaturated fatty acids with different chain lengths or aromatic acids or heterocyclic acids is 1.0 - 4.0 times the molar amount of the starch quaternary ammonium salt derivative.

3. The preparation method of the amphiphilic cationic starch quaternary ammonium salt derivative according to claim 2, characterized in that: The specific steps of Step 1 are as follows: Dissolve the starch in an isopropanol solution, heat and activate it at 55 - 85 °C for 3 - 8 h, and reserve the obtained solution; dissolve glycidyltrimethylammonium chloride in excess water, then drop it into the above solution, and continue to react at 40 - 80 °C for 12 - 60 h. After the reaction is completed and cooled to room temperature, precipitate with 400 - 1000 mL of absolute ethanol repeatedly, wash, filter by suction, and finally cool and dry the obtained solid to obtain the starch quaternary ammonium salt derivative.

4. The preparation method of the amphiphilic cationic starch quaternary ammonium salt derivative according to claim 2, wherein: The specific steps of Step 2 are as follows: Add N , N '-carbonyldiimidazole into dimethyl sulfoxide containing saturated fatty acids with different chain lengths, unsaturated fatty acids with different chain lengths, aromatic acids or heterocyclic acids, mix well, and react at 40-80 °C for 12-60 h in a nitrogen atmosphere to obtain a standby solution A; at the same time, fully dissolve the obtained starch quaternary ammonium salt derivative in a dimethyl sulfoxide solution to obtain a standby solution B, then slowly add solution A to solution B, and react at 40-80 °C for 12-60 h in a nitrogen atmosphere. After the reaction is completed, precipitate with 400-800 mL of acetone, filter by suction, and dry to obtain an amphiphilic cationic starch quaternary ammonium salt derivative.

5. Use of an amphiphilic cationic starch quaternary ammonium salt derivative as described in claim 1 in the preparation of a drug carrier.

6. Use of an amphiphilic cationic starch quaternary ammonium salt derivative as described in claim 1 in the preparation of a food antioxidant.

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