Nanoscale liposome vitamin C composition and preparation method thereof

Abstract

The invention discloses a nanoscale liposome vitamin C composition and a preparation method thereof. The liposome vitamin C composition is prepared from the following components in parts by weight: 10 to 70 parts of vitamin C, 10 to 70 parts of phosphatidylcholine, 5 to 20 parts of solubilizer, 1 to 5 parts of stabilizer and 0.1 to 1 part of nonionic surfactant. The liposome vitamin C is small in particle size and easy to absorb and utilize by a human body, the vesicle structure is relatively complete, the cost is low, and the liposome vitamin C is suitable for large-scale production.

Description

Technical Field

[0001] The invention relates to the technical field of food and health products, in particular to a nano-scale liposome vitamin C composition and a preparation method thereof. Background Art

[0002] Vitamin C is one of the essential nutrients for the human body and is also an antioxidant. However, it is easily oxidized, has poor fat solubility, poor stability, and its structure is destroyed in the stomach and intestines, which greatly reduces the absorption and utilization efficiency of vitamin C after it enters the human body, thus affecting the application of vitamin C. In order to improve the bioavailability of the nutrient vitamin C, many studies have been conducted at home and abroad, such as the production of calcium sodium salts of VC, synthetic vitamin C sulfate potassium, and vitamin C polyphosphate magnesium, but these methods will change the physical and chemical properties of VC and the process is complicated.

[0003] In view of this, a method is provided which does not change the physical and chemical properties of VC and can reduce VC oxidation and improve stability. Summary of the invention

[0004] The object of the present invention is to provide a nano-liposome vitamin C composition and a preparation method thereof, which is beneficial to reducing the oxidation of vitamin C and improving its stability.

[0005] The present invention is achieved in that:

[0006] In a first aspect, the present invention provides a nano-liposome vitamin C composition, comprising, by weight: 10-70 parts by weight of vitamin C, 10-70 parts by weight of phosphatidylcholine, 5-20 parts by weight of a solubilizer, 1-5 parts by weight of a stabilizer, and 0.1-1 parts by weight of a non-ionic surfactant.

[0007] In an optional embodiment, the purity of the phosphatidylcholine is 20%-80%;

[0008] And / or, the purity of the vitamin C is 90%-100%;

[0009] And / or, the solubilizing agent is hydroxypropyl-β-cyclodextrin;

[0010] And / or, the stabilizer is hydroxymethyl cellulose;

[0011] And / or, the nonionic surfactant is Tween-80.

[0012] In an optional embodiment, the composition comprises: 10wt%-70wt% of vitamin C, 10wt%-70wt% of phosphatidylcholine, 5wt%-20wt% of solubilizer, 1wt%-5wt% of stabilizer and 0.1wt%-1wt% of nonionic surfactant.

[0013] In a second aspect, the present invention provides a method for preparing the nano-liposome vitamin C composition according to any one of the aforementioned embodiments, comprising:

[0014] The raw material liquid of the composition containing vitamin C, phosphatidylcholine, a solubilizer, a stabilizer and a non-ionic surfactant is subjected to high pressure homogenization and freeze drying to obtain the nano-liposome vitamin C composition.

[0015] In an optional embodiment, the preparation of the composition raw material liquid includes: mixing the first mixed liquid, the second mixed liquid and a non-ionic surfactant to obtain the composition raw material liquid;

[0016] The first mixed solution is an ethanol aqueous solution of phosphatidylcholine, and the second mixed solution is a mixed aqueous solution of vitamin C, a solubilizer and a stabilizer.

[0017] In an optional embodiment, the high-pressure homogenization is performed at a temperature of 4°C-20°C, a pressure of 300 bar-1000 bar, and homogenization is performed 1-3 times.

[0018] In an optional embodiment, the freeze-drying temperature is less than -50°C;

[0019] And / or, the composition raw material liquid is first frozen before the freeze-drying.

[0020] In an optional embodiment, the liposomal vitamin C composition is in a granular form, and the average particle size of the particles is less than 400 nm, preferably less than 200 nm.

[0021] The present invention has the following beneficial effects:

[0022] The nano-liposome vitamin C composition of the present application is easy to be absorbed and utilized by the human body, has a small particle size, a complete structure and a low cost, and is suitable for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0024] Figure 1 It is the particle size analysis diagram of Examples 1, 4, and 5;

[0025] Figure 2 It is the particle size analysis diagram of comparative examples 1, 2 and 3;

[0026] Figure 3 TEM images of Examples 1, 4 and 5;

[0027] Figure 4 It is the transmission electron microscope image of comparative examples 1, 2 and 3;

[0028] Figure 5 This is a picture of the liposome powder obtained in Example 1. DETAILED DESCRIPTION

[0029] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0030] As a dietary supplement, VC products have too many additives, often accounting for more than 50% of the total, which will increase the metabolic burden on the human body. When VC is combined with common foods, the content of active ingredients is low, which cannot achieve the purpose of health care. In addition, VC is easily soluble in water and easily oxidized by heat. After being taken by the human body, it is easily diluted by saliva and has poor bioavailability. Liposome encapsulation technology usually has problems such as organic solvent residues and high energy consumption, which restricts the industrial production of liposome vitamins.

[0031] By using liposome encapsulation technology to fuse vitamin C with liposomes, its solubility, photosensitivity, heat sensitivity and processing adaptability can be changed, so that vitamin C can maintain its original biological activity and chemical properties in a microscopic state and be released when needed. Therefore, if vitamin C is encapsulated in liposomes, its bioavailability can be improved and its application range can be expanded.

[0032] Liposomal vitamin C is a dietary supplement that uses liposome technology to enhance the delivery of nutrients to the body. Liposomes are tiny spherical vesicles composed of a lipid bilayer that can encapsulate vitamins, thereby improving the absorption and bioavailability of vitamin C. Compared with traditional supplements, liposomal vitamin C can more effectively deliver nutrients to cells that need them, avoiding excretion as waste. It has the characteristics of targeted efficiency, controlled sustained release, and safety and non-toxicity. In water, the hydrophilic head of the phospholipid molecule is inserted into the water, and the hydrophobic tail of the liposome extends into the air. After stirring, a spherical liposome with a double layer of lipid molecules is formed, with a diameter ranging from 25 to 1000nm. By taking advantage of the fact that liposomes can fuse with cell membranes, drugs can be delivered into cells.

[0033] In view of this, the present invention provides a nano-liposome vitamin C composition, which comprises, by weight: 10-70 parts by weight of vitamin C, 10-70 parts by weight of phosphatidylcholine, 5-20 parts by weight of solubilizer, 1-5 parts by weight of stabilizer and 0.1-1 part by weight of non-ionic surfactant.

[0034] Phosphatidylcholine, as a liposome, has a phospholipid bilayer structure and is a natural artificial membrane that plays a role of wrapping. In the present application system, compared with other liposomes, phosphatidylcholine can better coat vitamin C, which is beneficial to improving the integrity of the liposome vitamin C structure. In some embodiments, the source of phosphatidylcholine can be soy lecithin or sunflower lecithin.

[0035] Solubilizers can improve the solubility of liposomal vitamin C, which is beneficial to expand its scope of use.

[0036] Non-ionic surfactants can make water-soluble vitamins and fat-soluble components phosphatidylcholine mix better together to form an emulsion. During the preparation process, each component can be evenly dispersed in the solution, which is beneficial to improve the stability of liposome vitamin C.

[0037] The liposome vitamin C composition of the present application is easily absorbed and utilized by the human body, has a relatively complete vesicle structure and is low in cost, and is suitable for large-scale production.

[0038] In an optional embodiment, the purity of the phosphatidylcholine is 20%-80%. The improvement of the purity of phosphatidylcholine is beneficial to improving the integrity of the liposome vitamin C structure.

[0039] In an optional embodiment, the purity of the vitamin C is 90%-100%. Improving the purity of vitamin C is beneficial to increasing the proportion of vitamin C in the liposome vitamin C composition, which is beneficial to increasing the effective dosage.

[0040] In an optional embodiment, the solubilizer is hydroxypropyl-β-cyclodextrin, which can improve the solubility and stability of liposome vitamin C and reduce the aggregation of liposome vitamin C particles.

[0041] In an optional embodiment, the stabilizer is hydroxymethyl cellulose, which can make the liposome vitamin C more stable and increase the dispersibility of the liposome in water.

[0042] In an optional embodiment, the nonionic surfactant is Tween-80.

[0043] In an optional embodiment, the composition comprises: 10wt%-70wt% of vitamin C, 10wt%-70wt% of phosphatidylcholine, 5wt%-20wt% of solubilizer, 1wt%-5wt% of stabilizer and 0.1wt%-1wt% of nonionic surfactant.

[0044] The content of vitamin C in the liposome vitamin C composition can reach 70%, which is beneficial to increase the effective dosage and reduce auxiliary materials at the same time. The auxiliary materials are easily metabolized by the human body, which is beneficial to reduce the metabolic burden of the human body.

[0045] The present invention also provides a method for preparing the nano-liposome vitamin C composition according to any one of the above embodiments, comprising:

[0046] The raw material liquid of the composition containing vitamin C, phosphatidylcholine, a solubilizer, a stabilizer and a non-ionic surfactant is subjected to high pressure homogenization and freeze drying to obtain the liposome vitamin C composition.

[0047] The liposome vitamin C composition produced by the spray drying process has the disadvantages of high viscosity and poor fluidity, which restricts the application range of liposome vitamins, and many liposome vitamins have large particle sizes, uneven particle sizes, incomplete liposome structures, etc., which greatly reduce the utilization efficiency of liposome vitamins and affect human body absorption. In the embodiment of the present application, by selecting a suitable film-forming wall material and embedding vitamin C by a high-pressure homogenization-freeze drying method, the obtained liposome vitamin C particle size reaches nanometer level, which is beneficial to human body absorption. At the same time, the freeze drying method is adopted, the preparation method is simple, no toxic and harmful solvents are required, vitamins and other nutrients will not be destroyed, and the obtained liposome powder has good fluidity and stable structure, which is suitable for making raw materials for finished products such as tablets and capsules.

[0048] In an optional embodiment, the preparation of the composition raw material liquid includes: mixing the first mixed liquid, the second mixed liquid and a non-ionic surfactant to obtain the composition raw material liquid;

[0049] The first mixed solution is an ethanol aqueous solution of phosphatidylcholine, and the second mixed solution is a mixed aqueous solution of vitamin C, a solubilizer and a stabilizer.

[0050] Specifically, in this embodiment, the nonionic surfactant can be mixed with the second mixed liquid first and then with the first mixed liquid, or the first mixed liquid and the second mixed liquid can be mixed before adding the nonionic surfactant, or the first mixed liquid, the second mixed liquid and the nonionic surfactant can be mixed at the same time. Specifically, when the first mixed liquid and the second mixed liquid are mixed, the second mixed liquid can be slowly poured into the first mixed liquid and stirred at 100-800 rpm for 10-60 min.

[0051] However, it should be noted that due to the large difference in solubility between phosphatidylcholine and vitamin C, the two need to be prepared in solution separately and then mixed. If the raw materials are directly added to the solvent at the same time, the stirring and dissolving time will be too long and the vitamin C will be easily oxidized and degraded.

[0052] In an optional embodiment, the volume ratio of ethanol to water in the first mixed solution is (10-15): (85-90), and the mass fraction of phosphatidylcholine is 23%-27%.

[0053] Specifically, when preparing the first mixed solution, phosphatidylcholine can be added to the ethanol aqueous solution and stirred at 100-800 rpm for 10-60 min.

[0054] In an optional embodiment, the mass ratio of vitamin C to water in the second mixed solution is 1:(5-15). Specifically, when preparing the second mixed solution, vitamin C, a solubilizer and a stabilizer can be added to water and stirred at 100-800 rpm for 10-60 min.

[0055] In an optional embodiment, the high-pressure homogenization is performed at a temperature of 4°C-20°C, a pressure of 300 bar-1000 bar, and homogenization is performed 1-3 times.

[0056] Increasing the homogenization pressure and times is beneficial to reducing the particle size of liposome vitamin C particles and improving the uniformity of the particle size.

[0057] In an optional embodiment, the freeze-drying temperature is less than -50°C;

[0058] And / or, the composition raw material liquid is first frozen before the freeze-drying.

[0059] In an optional embodiment, the liposomal vitamin C composition is in a granular form, and the average particle size of the particles is less than 400 nm, preferably less than 200 nm.

[0060] The features and performance of the present invention are further described in detail below in conjunction with the embodiments.

[0061] Example 1

[0062] This embodiment provides a liposome vitamin C composition, which includes 60 parts of sunflower-derived phosphatidylcholine PC 20 (i.e., phosphatidylcholine with a purity of 20wt%), 30 parts of vitamin C (purity ≥97%), 7 parts of hydroxypropyl-β-cyclodextrin, 3 parts of hydroxymethylcellulose, and 100ul of Tween-80, each part being 1g.

[0063] The preparation method of the above-mentioned liposome vitamin C composition comprises:

[0064] ① Accurately weigh 60 g of phosphatidylcholine PC20 and dissolve it in 15% ethanol aqueous solution, the mass ratio of phosphatidylcholine PC to ethanol aqueous solution is 1:3, and stir the solution at 500 rpm for 15 min to obtain a lipid solution;

[0065] ②, weigh 30g of vitamin C, 7g of hydroxypropyl-β-cyclodextrin, and 3g of hydroxymethyl cellulose and dissolve them in aqueous solution, with the mass ratio of solute to solvent being 1:10. After mixing evenly, add 100ul of Tween-80;

[0066] ③. Slowly pour ② into ①, stirring while adding, and continue stirring at 500 rpm for 30 min to obtain a mixed liposome solution;

[0067] ④. Set the parameters of high-pressure homogenization: pressure 600 bar, temperature 10°C. After homogenization three times, a uniform liposome solution is obtained, which is placed in a -20°C freezer for pre-freezing; finally, the solution is placed in a -55°C freeze dryer and dried for 20 hours, then crushed and sieved to obtain liposome vitamin C powder.

[0068] The liposome vitamin C composition prepared in this embodiment is an off-white powder. Figure 5 As shown, the moisture content is less than 3%.

[0069] Example 2

[0070] The difference between this embodiment and embodiment 1 is that the liposome vitamin C composition includes 70 g vitamin C, 20 g PC20, 5 g hydroxypropyl-β-cyclodextrin, 5 g hydroxymethylcellulose and 100 ul Tween-80.

[0071] Example 3

[0072] The difference between this embodiment and embodiment 1 is that the liposome vitamin C composition includes 10 g vitamin C, 70 g PC20, 15 g hydroxypropyl-β-cyclodextrin, 5 g hydroxymethylcellulose and 100 ul Tween-80.

[0073] Example 4

[0074] The difference between this embodiment and embodiment 1 is that the pressure set for high-pressure homogenization is 300 bar, and homogenization is performed once.

[0075] Example 5

[0076] The difference between this embodiment and embodiment 1 is that the pressure set for high-pressure homogenization is 1000 bar, and homogenization is performed once.

[0077] Example 6

[0078] The difference between this embodiment and embodiment 1 is that hydroxypropyl-β-cyclodextrin is replaced by β-cyclodextrin of equal mass.

[0079] Comparative Example 1

[0080] The difference between this comparative example and Example 1 is that the liposome vitamin C composition includes 85g vitamin C, 5g PC20, 10g hydroxymethylcellulose and 100ul Tween-80.

[0081] Comparative Example 2

[0082] The difference between this comparative example and Example 1 is that the liposomes include 5g of vitamin C, 90g of PC20, 2g of hydroxypropyl-β-cyclodextrin, 3g of hydroxymethylcellulose and 100ul of Tween-80.

[0083] Comparative Example 3

[0084] The difference between this comparative example and Example 1 is that high pressure homogenization is not performed.

[0085] Comparative Example 4

[0086] The difference between this comparative example and Example 1 is that lecithin is used instead of phosphatidylcholine.

[0087] Comparative Example 5

[0088] This comparative example provides a liposome vitamin C composition prepared by spray drying. The difference from Example 1 is that the drying method is different. Freeze drying is replaced by spray drying. The specific parameters include: spray drying temperature of 120°C, flow rate of 10mL / min, and air outlet temperature of 90°C.

[0089] Experimental Example 1: Particle Size Analysis

[0090] The nanoparticle size and Zeta potential analyzer is an accurate, fast and convenient instrument for nano and submicron particle size analysis and testing. Compared with the traditional light scattering method based on frequency shift technology, the sensitivity can be increased by 1000 times. The particle size distribution of the liposomes obtained in each embodiment and comparative example was measured using this instrument. The results are shown in Table 1. Some of the results are shown in Table 1. Figure 1 , Figure 2 shown.

[0091] Experimental Example 2: Liquidity Analysis

[0092] The angle of repose method is one of the commonly used methods for measuring the fluidity of powders. The angle of repose refers to the maximum angle formed by the free slope of the powder stacking layer and the horizontal plane. The smaller the angle of repose, the better the fluidity of the powder. The results of measuring the fluidity of the liposomes in the above-mentioned embodiments and comparative examples using the angle of repose method are shown in Table 1.

[0093] Experimental Example 3: Stability Analysis

[0094] The stability was determined by an accelerated test. The vitamin C content of the sample was measured after it was kept under a certain environment (high temperature and high humidity, 40°C, RH70%) for one month. The results of the accelerated test for the stability of the liposomes of the above embodiments and comparative examples are shown in Table 1.

[0095] Table 1

[0096]

[0097]

[0098] From Table 1, Figure 1 It can be seen that the average particle size of the liposome vitamin C powder obtained in Example 1 is 145nm, and the average particle size of the liposome vitamin C powder obtained in Examples 2 and 3 is also below 400nm; the homogenization pressure in Example 4 is relatively low, and the liposome particle size obtained is relatively large, and the homogenization pressure in Example 5 is relatively large, and the liposome particle size obtained is relatively small. The smaller the particle size, the more conducive to human absorption, thereby improving bioavailability, but the energy consumption caused by the high pressure homogenization pressure is also large. Similarly, it can be seen from the comparative example that if the PC content is too little or too high, the hydroxypropyl-β-cyclodextrin is less, and the high-pressure homogenizer is not used, liposomes with uniform particle size will not be obtained, and the particle size is relatively large. The liposome vitamin C product obtained by spray drying is sticky, has poor fluidity, and has a yield of only 50%, which limits the use of spray drying, while the repose angle of the freeze-dried sample is between 30 and 40°, and has good fluidity, which can effectively prevent the product from getting damp and agglomerating, and extend the shelf life of food. From the test results of the accelerated experiment, it can be seen that the liposome vitamin C content obtained by freeze drying remains stable and the loss rate of vitamin C is reduced.

[0099] Experimental Example 4: Structural Analysis

[0100] The structure of liposomes was observed by transmission electron microscopy. Figure 3 and Figure 4 As shown by Figure 3 It can be seen that the liposomes obtained in Examples 1, 4 and 5 are small vesicles with stable structure and are evenly dispersed. Figure 4 It can be concluded that the liposomes obtained when the PC content is too little or too high, the hydroxypropyl-β-cyclodextrin is too little, or the high-pressure homogenizer is not used are not uniform, or the vesicle structure is incomplete and the structural stability is poor.

[0101] In summary, the liposome vitamin C prepared by using specific raw materials in a specific ratio in the present application can reach the nanometer level and has a stable structure, is easy to be absorbed and utilized by the human body, improves the bioavailability of vitamin C, and has a low cost. The liposome powder obtained by high-pressure homogenization-freeze drying has good fluidity, low viscosity, and is not easy to agglomerate, and is suitable for large-scale production.

[0102] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A nano-liposome vitamin C composition, characterized in that: The components include, by weight: 10-70 parts by weight of vitamin C, 10-70 parts by weight of phosphatidylcholine, 5-20 parts by weight of solubilizer, 1-5 parts by weight of stabilizer and 0.1-1 part by weight of nonionic surfactant.

2. The nano-liposome vitamin C composition according to claim 1, characterized in that: The purity of the phosphatidylcholine is 20%-80%; And / or, the purity of the vitamin C is 90%-100%; And / or, the solubilizing agent is hydroxypropyl-β-cyclodextrin; And / or, the stabilizer is hydroxymethyl cellulose; And / or, the nonionic surfactant is Tween-80.

3. The nano-liposome vitamin C composition according to claim 1, characterized in that: include: Vitamin C 10wt%-70wt%, phosphatidylcholine 10wt%-70wt%, solubilizer 5wt%-20wt%, stabilizer 1wt%-5wt% and non-ionic surfactant 0.1wt%-1wt%.

4. A method for preparing the nano-liposome vitamin C composition according to any one of claims 1 to 3, characterized in that: include: The raw material liquid of the composition containing vitamin C, phosphatidylcholine, a solubilizer, a stabilizer and a non-ionic surfactant is subjected to high pressure homogenization and freeze drying to obtain the liposome vitamin C composition.

5. The method for preparing the nano-liposome vitamin C composition according to claim 4, characterized in that: The preparation of the composition raw material liquid comprises: mixing the first mixed liquid, the second mixed liquid and a non-ionic surfactant to obtain the composition raw material liquid; The first mixed solution is an ethanol aqueous solution of phosphatidylcholine, and the second mixed solution is a mixed aqueous solution of vitamin C, a solubilizer and a stabilizer.

6. The method for preparing the nano-liposome vitamin C composition according to claim 4, characterized in that: The high pressure homogenization temperature is 4°C-20°C, the pressure is 300bar-1000bar, and the homogenization is performed 1-3 times.

7. The method for preparing the nano-liposome vitamin C composition according to claim 4, characterized in that: The freeze-drying temperature is less than -50°C; And / or, the composition raw material liquid is first frozen before the freeze-drying.

8. The method for preparing the nano-liposome vitamin C composition according to claim 4, characterized in that: The liposome vitamin C composition is in the form of particles, and the average particle size of the particles is less than 400 nm, preferably less than 200 nm.

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