Multilayer modified vitamin C liposome and preparation method thereof

Abstract

The invention discloses a multi-layer modified vitamin C liposome and a preparation method thereof. The liposome comprises a vitamin C core material positioned on the inner layer and a wall material positioned on the outer layer of the vitamin C core material, the wall material is prepared from the following raw materials in parts by weight: 12 to 16 parts of phospholipid, 1 to 2 parts of chitosan, 0.1 to 0.5 part of sodium alginate, 0.2 to 1.7 parts of calcium chloride and 22 to 27 parts of Arabic gum; the mass ratio of the vitamin C core material to the wall material is (1-1.5): 1. The vitamin C liposome provided by the invention not only can effectively prevent content leakage, but also can solve the problem that vitamin C is easy to oxidize. According to the preparation method provided by the invention, by optimizing the adding sequence of the raw materials, the stable liposome is formed, and the oxidability of the vitamin C is effectively improved.

Description

Technical Field

[0001] The invention belongs to the technical field of food processing, and in particular relates to a multilayer modified vitamin C liposome and a preparation method thereof. Background Art

[0002] Vitamin C has strong antioxidant and anti-aging effects, and is the water-soluble vitamin that the human body needs the most. It has the functions of enhancing human immunity, preventing and treating iron deficiency anemia and scurvy, and is a very important substance in the human metabolism process. However, the human body lacks the last key enzyme in the vitamin C biosynthesis metabolic pathway and cannot synthesize the vitamin C required for human metabolism. The only way to meet the body's needs is to take in exogenous vitamin C by eating fruits and vegetables.

[0003] Vitamin C has a strong reducing property and is easily oxidized under the conditions of oxygen, moisture, high temperature and heavy metals. It is extremely unstable in aqueous solution, especially in neutral or alkaline solution. This may cause its utilization rate to decrease significantly, so its application is limited. Therefore, it can be used as a small amount of active substance in medicine, food, cosmetics, etc. So far, this vitamin C is taken in the form of tablets, capsules, powders, and liquids, but is not effectively absorbed by the human body.

[0004] At present, the prior art publicly uses lecithin and cholesterol as wall materials, and adopts a variety of organic solvents and emulsifiers to assist, and vitamin C is embedded. Although the stability of vitamin C can be improved, it is effectively prevented from being decomposed by reacting with external environments such as water, oxygen, heat and light, but the phospholipids of liposomes are easily hydrolyzed, causing the structure of liposomes to change from lamellar to micellar, and the lipid membrane permeability increases, and the package leaks, and the removal of organic solvents and other processes are not suitable for amplification production, and these instabilities limit its wide application. For example, there is a public patent that uses chitosan-sodium alginate as outer layer modification, but its vesicle interior is still an aqueous solution, which is easy to leak, and the organic reagent (Tween 80) used in the operation process limits its use field, and the precision instrument used in the preparation process cannot be applied to large-scale production. There is also a public patent that uses calcium chloride and sodium alginate to cross-link to form gel spheres, and then the gel spheres are processed, and the wall material stability of this means is weak, and the preparation efficiency is low, which is not suitable for terminal product application and large-scale mass production. Summary of the invention

[0005] The purpose of the present invention is to provide a multilayer modified vitamin C liposome and a preparation method to solve the deficiencies of the prior art.

[0006] The purpose of the present invention is achieved by the following technical solutions:

[0007] A multilayer modified vitamin C liposome, comprising a vitamin C core material located in an inner layer and a wall material located in an outer layer of the vitamin C core material;

[0008] The wall material is prepared from the following raw materials in parts by weight:

[0009] 12-16 parts of phospholipids, 1-2 parts of chitosan, 0.1-0.5 parts of sodium alginate, 0.2-1.7 parts of calcium chloride, 22-27 parts of gum arabic;

[0010] The mass ratio of the vitamin C core material to the wall material is (1-1.5):1.

[0011] Preferably, the phospholipids are composed of sunflower phospholipids and egg phospholipids in a mass ratio of (1.5-2.5):1.

[0012] Preferably, the purity of phosphatidylcholine in the sunflower lecithin is 50%.

[0013] Preferably, the gum arabic is gum arabic rich in AGP, wherein the mass percentage of AGP is ≥35%.

[0014] The method for preparing the multilayer modified vitamin C liposome as described above comprises the following steps:

[0015] S1. Preparation of phospholipid wall material solution: Take a formulated amount of phospholipid and add it to the first solvent to fully dissolve;

[0016] S2. Preparation of initial liposomes: Take the formulated amount of vitamin C, calcium chloride and gum arabic and add them to the second solvent to fully dissolve, then slowly add the solution of step S1 and mix thoroughly;

[0017] S3. The solution of step S2 and the chitosan solution are thoroughly mixed, and then sheared at high speed to form uniform liposome droplets;

[0018] S4. The liposome droplets of step S3 and the sodium alginate solution are fully mixed, and then dried to obtain multilayer modified vitamin C liposomes.

[0019] Preferably, in step S1, the first solvent consists of ethanol and water, and the volume percentage of the ethanol is 5-10%.

[0020] Preferably, the dissolving temperature in step S1 is 40-60°C.

[0021] Preferably, the second solvent in step S2 is water, and the solvents of the chitosan solution in step S3 and the sodium alginate solution in step S4 are both water.

[0022] Preferably, the shear rate in step S3 is 6000-8000 r / min, and the shear time is 2-5 min.

[0023] Preferably, step S4 adopts spray drying, and the spray drying parameters are:

[0024] Inlet air temperature 160~200℃, outlet air temperature 80~120℃, atomizer cooling temperature 70~90℃, atomizer frequency 160~200Hz.

[0025] Compared with the prior art, the vitamin C liposomes provided in the present application have better application effects, can effectively prevent leakage of contents, and can solve the problem of easy oxidation of vitamin C. The preparation method provided optimizes the order of adding raw materials, forms stable liposomes through cross-linking of inner phospholipids and middle chitosan, combination of middle chitosan and outer sodium alginate, and cross-linking of inner calcium chloride and outer sodium alginate, and effectively improves the oxidizability of vitamin C. DETAILED DESCRIPTION

[0026] The present invention provides a multilayer modified vitamin C liposome, comprising a vitamin C core material located in an inner layer and a wall material located on the surface of the vitamin C core material; the wall material is prepared from the following raw materials in parts by weight:

[0027] 12-16 parts of complex phospholipids, 1-2 parts of chitosan, 0.1-0.5 parts of sodium alginate, 0.2-1.7 parts of calcium chloride, 22-27 parts of gum arabic;

[0028] The mass ratio of vitamin C to wall material is (1-1.5):1.

[0029] This application adopts liposome technology, uses natural or synthetic polymer materials as wall materials, modifies the surface of liposomes, forms a complete and continuous protective film on the surface of vitamin C, improves the stability of liposomes in the environment, delays the decomposition of vitamin C, and improves the biological activity of vitamin C. Chitosan is a biocompatible cationic polysaccharide with good water solubility and mucosal adhesion. The surface modification of chitosan can improve the stability of liposomes and achieve the effect of controlled release. Sodium alginate is a non-toxic, inert, hydrophilic molecule that is conducive to the storage and delivery of active proteins, drugs, and cells. Chitosan and sodium alginate can form cation-anion complexes and self-assemble layer by layer to wrap around the outer surface of liposomes, which can not only improve the stability of vitamin C, but also effectively isolate vitamin C from contact with substances such as air.

[0030] Sodium alginate and calcium chloride can form hydrogel. On the basis of the phospholipid bilayer membrane formed by liposomes, hydrogel is formed on the outside. The multi-layer modification further isolates vitamin C from the outside world.

[0031] Gum arabic is a typical natural plant hydrophilic colloid with good emulsifying properties and good film-forming properties. On the basis of increasing the emulsifying effect, it also forms an external film, further prolonging the oxidation time and prolonging the flavor quality.

[0032] At the same time, phospholipids have good emulsifying properties and are the main component of cell membranes. They have high biocompatibility and can promote the absorption rate of vitamin C in the intestines, solving problems such as vitamin C being easily oxidized and having low bioavailability.

[0033] In addition, the liposomes only introduce a trace amount of food processing aids during the preparation process, which can be quickly removed during the continuous production of the product. The processing process is highly safe and does not cause any impact on the environment.

[0034] Therefore, compared with the prior art, the vitamin C liposomes provided in the present application have better application effects, not only can they effectively prevent leakage of contents, but also can solve the problem of easy oxidation of vitamin C.

[0035] According to research, the composite phospholipid has a higher encapsulation rate, lower leakage and better stability than a single phospholipid. Preferably, the phospholipid is composed of sunflower phospholipid and lecithin in a mass ratio of (1.5-2.5):1, and more preferably, it is composed of sunflower phospholipid and lecithin in a mass ratio of 2:1. Further preferably, the sunflower phospholipid is sunflower phospholipid PC50, that is, sunflower phospholipid with a phosphatidylcholine purity of 50%. Preferably, gum arabic is gum arabic rich in AGP (arabinogalactan protein), wherein the minimum AGP mass percentage is 35%.

[0036] According to research, the use of gum arabic rich in AGP has a larger molecular weight than ordinary gum arabic (the mass percentage of AGP in ordinary gum arabic is generally about 10%), which improves the stability of the emulsion and has a better film-forming effect.

[0037] The present application also provides a method for preparing the multilayer modified vitamin C liposome as described above, comprising the following steps:

[0038] S1. Preparation of phospholipid wall material solution: Take a formula amount of composite phospholipid and add it to a first solvent to fully dissolve it; the first solvent is preferably a mixed reagent of ethanol and water, and the volume percentage of ethanol in the mixed reagent is 5-10%. Adding a small amount of ethanol can promote the dissolution of phospholipids, and ethanol can be quickly removed in subsequent production. In order to further promote the dissolution of phospholipids, heating and magnetic stirring can be used, and the temperature is preferably 40-60°C.

[0039] S2. Preparation of initial liposomes: Take the formulated amount of vitamin C, calcium chloride and gum arabic and add them to the second solvent to fully dissolve them, then slowly add the solution of step S1 and mix them thoroughly.

[0040] S3. The solution of step S2 and the chitosan solution are fully mixed, and then sheared at high speed to form uniform liposome droplets; preferably, the shear rate is 6000-8000 r / min, and the shear time is 2-5 min.

[0041] S4. The liposome droplets of step S3 and the sodium alginate solution are fully mixed, and then dried to obtain multilayer modified vitamin C liposomes.

[0042] Preferably, the above solution is prepared with a total solid content of 30-40% by mass.

[0043] Preferably, the second solvent in step S2 is water, and the solvents of the chitosan solution in step S3 and the sodium alginate solution in step S4 are both water. By using water as the solvent, raw materials such as chitosan and sodium alginate can be well dissolved, and it is safe and pollution-free.

[0044] Preferably, step S4 uses spray drying. Compared with other methods, spray drying has a fast drying speed, uniform particle distribution, and less loss of active ingredients. The spray drying parameters are:

[0045] Inlet air temperature 160~200℃, outlet air temperature 80~120℃, atomizer cooling temperature 70~90℃, atomizer frequency 160~200Hz.

[0046] In the preparation process of vitamin C liposomes of the present application, a wet coating method is adopted. First, vitamin C, calcium chloride and gum arabic are mixed and reacted. Gum arabic as an emulsifier can first improve the binding property of hydrophilic vitamin C with subsequent phospholipids and help film formation. Calcium chloride is added first as a cross-linking agent so that sodium alginate can enter the cavity through the phospholipid embedding layer and form a gel with it, which is more conducive to the overall stability; then it is added to the phospholipid solution to form a phospholipid bilayer membrane on the surface of vitamin C to wrap it in the first layer; chitosan is then added, and chitosan can cross-link with the charge on the surface of the phospholipid to prevent chitosan from falling off; sodium alginate is added last, and the negatively charged carboxyl groups on the sodium alginate combine with the protonated amino groups on the chitosan through electrostatic action to form a polyelectrolyte complex, forming a second protective layer, and sodium alginate is cross-linked with the inner layer of calcium chloride to form a gel, which further improves the stability of vitamin C.

[0047] Therefore, the present application optimizes the order of adding raw materials, forms stable liposomes through cross-linking of inner phospholipids and middle chitosan, combination of middle chitosan and outer sodium alginate, and cross-linking of inner calcium chloride and outer sodium alginate, and effectively improves the oxidizability of vitamin C.

[0048] Experimental Example 1 Effect of different phospholipids on vitamin C retention rate

[0049] Under the same production conditions, different mass ratios of sunflower lecithin PC50 and lecithin were used to test the vitamin C retention rate of the spray-dried product. The results are shown in Table 1:

[0050] Table 1

[0051]

[0052] As can be seen from Table 1, different proportions of composite lecithin have a great influence on the retention rate of vitamin C. The results show that when the ratio of sunflower lecithin PC50 and lecithin is 2:1, the emulsification effect and film-forming effect are the best. Therefore, the composite lecithin used in the present invention is preferably sunflower lecithin PC50: lecithin = 2:1, in terms of mass ratio.

[0053] Experimental Example 2 Effects of different types of gum arabic on vitamin C encapsulation rate and retention rate

[0054] Under the same production conditions, different types of gum arabic were used for experiments (the AGP content of ordinary gum arabic was 10%, and the AGP content of AGP-rich gum arabic was 35%), and the vitamin C encapsulation rate and retention rate of the spray-dried products were tested. The results are shown in Table 2:

[0055] Table 2

[0056]

[0057] The results showed that the embedding rate and vitamin C retention rate of gum arabic rich in AGP were better than those of ordinary gum arabic.

[0058] Experimental Example 3 Screening of wall materials

[0059] The different wall material compositions directly affect the quality of the product, whether it is the oxidative stability of the product or the sensory changes. Only by controlling the wall material composition within a certain range can high-quality products be obtained. Therefore, this experiment screened and obtained suitable wall materials by analyzing different wall materials and proportions. In this experiment, the composite lecithin used sunflower lecithin PC50 and lecithin with a mass ratio of 2:1, and the arabic gum used arabic gum with an AGP content of 35%. The types and amounts of each raw material in the wall material (by weight) are shown in Table 3:

[0060] Table 3

[0061]

[0062] The physicochemical indicators of the vitamin C liposomes prepared by the above formula are shown in Table 4. The vitamin C content (solid content) of each product is ≥50%, and the bulk density is ≥0.7 g / cm 3, the angle of repose ≤40θ°, which can meet the requirements of powders and tablets.

[0063] Table 4

[0064]

[0065] The vitamin C liposomes were subjected to an accelerated test in a constant temperature accelerated test chamber (temperature 37° C., humidity 76%). The vitamin C content and color change were detected after being placed for different days. The results are shown in Table 5.

[0066] Table 5

[0067]

[0068] As can be seen from Table 5, the liposomes (serial numbers 1 to 4) obtained by using the wall materials of the raw material types and amounts of the present application can effectively prevent the loss and oxidation of vitamin C compared with the comparative examples (serial numbers 5 to 8), which proves that the technical solution of the present invention has the effect of improving the stability of vitamin C.

[0069] Example 1

[0070] This embodiment provides a multilayer modified vitamin C liposome, including vitamin C located in the inner layer and a wall material located on the surface of the vitamin C; the mass ratio of vitamin C to the wall material is 1.38:1.

[0071] The wall material is prepared from the following raw materials in parts by weight:

[0072] 13 parts of phospholipids, 2 parts of chitosan, 0.5 parts of sodium alginate, 1.5 parts of calcium chloride, and 25 parts of gum arabic.

[0073] The composite lecithin uses sunflower lecithin PC50 and lecithin in a mass ratio of 2:1, and the gum arabic uses gum arabic rich in AGP, with an AGP content of 35%.

[0074] The liposome preparation method is as follows:

[0075] S1. Preparation of phospholipid wall material solution: Take the formulated amount of phospholipid, add it to an ethanol aqueous solution (ethanol volume percentage is 6.5%), and fully dissolve it in a magnetic stirrer at 50°C;

[0076] S2. Preparation of initial liposomes: Take the formulated amount of vitamin C, calcium chloride and gum arabic and add them to water to fully dissolve, then slowly add the solution of step S1 and mix thoroughly to form an initial vitamin C liposome;

[0077] S3. The solution of step S2 and the aqueous solution containing chitosan are fully mixed and sheared at a speed of 7000r / min for 3min so that the wall material is completely coated on the surface of vitamin C to form a relatively uniform liposome droplets;

[0078] S4. The liposome liquid droplets of step S3 were added to the sodium alginate aqueous solution, stirred for 1 hour for sufficient reaction, and then spray-dried to obtain multilayer modified vitamin C liposomes; the spray-drying parameters were:

[0079] Inlet air temperature 180℃, outlet air temperature 100℃, atomizer cooling temperature 80℃, atomizer frequency 180Hz.

[0080] Example 2

[0081] This embodiment provides a multilayer modified vitamin C liposome, including vitamin C located in the inner layer and a wall material located on the surface of the vitamin C; the mass ratio of vitamin C to the wall material is 1.46:1.

[0082] The wall material is prepared from the following raw materials in parts by weight:

[0083] 14 parts of phospholipids, 1 part of chitosan, 0.5 parts of sodium alginate, 0.2 parts of calcium chloride, and 25 parts of gum arabic.

[0084] The liposome preparation method is as follows:

[0085] S1. Preparation of phospholipid wall material solution: Take the formulated amount of phospholipid, add it to an ethanol aqueous solution (ethanol volume percentage is 5%), and fully dissolve it in a magnetic stirrer at 45°C;

[0086] S2. Preparation of initial liposomes: the same method as in Example 1;

[0087] S3. The solution of step S2 and the aqueous solution containing chitosan are fully mixed and sheared at a speed of 6000r / min for 2min to completely coat the surface of vitamin C with the wall material to form relatively uniform liposome droplets;

[0088] S4. The liposome liquid droplets of step S3 were added to the sodium alginate aqueous solution, stirred for 1 hour for sufficient reaction, and then spray-dried to obtain multilayer modified vitamin C liposomes; the spray-drying parameters were:

[0089] Inlet air temperature 180℃, outlet air temperature 100℃, atomizer cooling temperature 80℃, atomizer frequency 180Hz.

[0090] Example 3

[0091] This embodiment provides a multilayer modified vitamin C liposome, including vitamin C located in the inner layer and a wall material located on the surface of the vitamin C; the mass ratio of vitamin C to the wall material is 1.38:1.

[0092] The wall material is prepared from the following raw materials in parts by weight:

[0093] 16 parts of phospholipids, 1 part of chitosan, 0.5 parts of sodium alginate, 1.5 parts of calcium chloride, and 23 parts of gum arabic.

[0094] The liposome preparation method is as follows:

[0095] S1. Preparation of phospholipid wall material solution: Take the formulated amount of phospholipid, add it to an ethanol aqueous solution (ethanol volume percentage is 8%), and fully dissolve it in a magnetic stirrer at 60°C;

[0096] S2. Preparation of initial liposomes: the same method as in Example 1;

[0097] S3. The solution of step S2 and the aqueous solution containing chitosan are fully mixed and sheared at a speed of 8000r / min for 5min to completely coat the surface of vitamin C with the wall material to form relatively uniform liposome droplets;

[0098] S4. The liposome liquid droplets of step S3 were added to the sodium alginate aqueous solution, stirred for 1 hour for sufficient reaction, and then spray-dried to obtain multilayer modified vitamin C liposomes; the spray-drying parameters were:

[0099] Inlet air temperature 190℃, outlet air temperature 110℃, atomizer cooling temperature 90℃, atomizer frequency 200Hz.

[0100] Although preferred embodiments of the present invention have been described, additional changes and modifications may be made to these embodiments by those skilled in the art once the basic inventive concepts are known. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention. Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A multi-layer modified vitamin C liposome, characterized in that: It includes a vitamin C core material located in an inner layer and a wall material located in an outer layer of the vitamin C core material; The wall material is prepared from the following raw materials in parts by weight: 12-16 parts of phospholipids, 1-2 parts of chitosan, 0.1-0.5 parts of sodium alginate, 0.2-1.7 parts of calcium chloride, 22-27 parts of gum arabic; The mass ratio of the vitamin C core material to the wall material is (1-1.5):

1.

2. The multi-layered modified vitamin C liposome according to claim 1, wherein The phospholipids are composed of sunflower phospholipids and egg phospholipids in a mass ratio of (1.5-2.5):

1.

3. The multi-layer modified vitamin C liposome according to claim 2, characterized in that The purity of the phosphatidylcholine in the sunflower lecithin is 50%.

4. The multi-layer modified vitamin C liposome according to claim 1, characterized in that The gum arabic is gum arabic rich in AGP, wherein the mass percentage of AGP is ≥35%.

5. The method for preparing the multi-layered modified vitamin C liposome according to any one of claims 1 to 4, characterized in that: The following steps are involved: S1. Preparation of phospholipid wall material solution: Take a formulated amount of phospholipid and add it to the first solvent to fully dissolve; S2. Preparation of initial liposomes: Take the formulated amount of vitamin C, calcium chloride and gum arabic and add them to the second solvent to fully dissolve, then slowly add the solution of step S1 and mix thoroughly; S3. The solution of step S2 and the chitosan solution are thoroughly mixed, and then sheared at high speed to form uniform liposome droplets; S4. The liposome droplets of step S3 and the sodium alginate solution are fully mixed, and then dried to obtain multilayer modified vitamin C liposomes.

6. The method for preparing multi-layer modified vitamin C liposomes according to claim 5, characterized in that: Step S1: The first solvent consists of ethanol and water, and the volume percentage of the ethanol is 5-10%.

7. The method for preparing multi-layer modified vitamin C liposomes according to claim 5, characterized in that: The dissolving temperature in step S1 is 40-60°C.

8. The method for preparing multi-layer modified vitamin C liposomes according to claim 5, characterized in that: The second solvent in step S2 is water, and the solvents of the chitosan solution in step S3 and the sodium alginate solution in step S4 are both water.

9. The method for preparing multi-layer modified vitamin C liposomes according to claim 5, characterized in that: The shear rate in step S3 is 6000-8000 r / min, and the shear time is 2-5 min.

10. The method for preparing multi-layer modified vitamin C liposomes according to claim 5, characterized in that: Step S4 adopts spray drying, and the spray drying parameters are: Inlet air temperature 160~200℃, outlet air temperature 80~120℃, atomizer cooling temperature 70~90℃, atomizer frequency 160~200Hz.

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