Nanoemulsion system for stabilizing curcumin based on interfacial cross-linking and preparation method thereof

Abstract

The present application relates to a kind of nanodroplet system based on interface crosslinking curcumin and its preparation method, by the crosslinking complexation between gallic acid ester, metal ion, curcumin to construct nanodroplet system.Gallic acid ester is polyphenol compound, contains a large number of phenolic hydroxyl in structure, has strong chelating metal ability, can be complexed with most of trivalent metal ions and divalent excessive metal ions, called metal phenolic network;Metal ions such as copper, iron and other metal ions form complex by electrostatic interaction with the beta diketone group in the structure of curcumin.Therefore, the nanodroplet system constructed by the present application can maintain the chemical stability and light stability of curcumin, and has wide prospect for improving the current food field curcumin low solubility, poor stability and other problems.

Description

Technical Field

[0001] This invention relates to the fields of food and pharmaceutical preparations, specifically to a nanoemulsion system based on interfacial cross-linking stabilized curcumin and its preparation method. Background Technology

[0002] Curcumin is a hydrophobic plant polyphenol with antioxidant, antibacterial, and anticancer activities. In the food industry, curcumin, as a natural pigment extracted and refined from plants, has advantages such as good coloring ability, safety, reliability, and no toxicity or side effects. It can be used as a flavoring agent, food preservative, natural colorant, and antioxidant in various food and beverages. However, it faces application challenges such as poor water solubility, chemical instability, photodegradation, rapid metabolic rate, and low bioavailability. Therefore, how to effectively improve the water solubility and environmental stability of curcumin is an urgent scientific problem to be solved.

[0003] Emulsion encapsulation is a simple and convenient method for preparing curcumin, and is often used to protect fat-soluble nutrients such as β-carotene, anthocyanins, and astaxanthin. Studies have shown that nanoemulsions are excellent carriers for hydrophobic curcumin (Araiza Calahorra et al. 2018; Hussain, Thu, Ng, Khan, & Katas, 2017). Current research on nanoemulsion delivery of curcumin mainly focuses on increasing its oral bioavailability, permeability, and resistance to metabolic processes during physiological transport (Zhang & McClements, 2016). Research on its color maintenance and other aspects related to food quality is relatively lacking. Maintaining the stability of curcumin in food and fully utilizing its color-enhancing function should be an urgent problem to be solved in current food research. Summary of the Invention

[0004] This invention provides a nanoemulsion system based on interfacial cross-linking to stabilize curcumin. The emulsion delivery system is constructed through the cross-linking and interaction between gallic esters, metal ions, and curcumin, thereby improving the problems of low solubility and poor stability of curcumin in the current food industry.

[0005] The present invention provides a solution to the above-mentioned technical problems as follows: a nanoemulsion system based on interfacial cross-linking stabilized curcumin, characterized in that the raw materials of the nanoemulsion system are composed of the following components in volume parts:

[0006] Curcumin-gallate-corn oil mixture 200-400 parts

[0007] 1600-1800 portions of buffer solution with pH 7-8

[0008] 8-15 parts of metal ion crosslinking agent.

[0009] The metal ion crosslinking agent is a salt containing metal ions, such as copper chloride or aluminum chloride.

[0010] More preferably, the raw materials of the nanoemulsion system are composed of the following components in parts by volume:

[0011] 200 parts curcumin-gallate-corn oil mixture

[0012] 1800 portions of buffer solution with pH = 7-8

[0013] 10 parts of metal ion crosslinking agent.

[0014] Preferably, in the curcumin-gallate-corn oil mixture, the curcumin concentration is 1 mg / mL; and the gallate concentration is 0.86-8.6 mg / mL.

[0015] Further preferably, in the curcumin-gallate-corn oil mixture, the concentration of curcumin is 1 mg / mL; and the concentration of gallate is 2.58 mg / mL.

[0016] Preferably, the gallic ester is one or a mixture of any of the following: propyl gallate, lauryl gallate, octyl gallate, and octadecyl gallate.

[0017] Further preferably, the gallic acid ester is octyl gallate.

[0018] Preferably, the metal ions in the metal ion crosslinking agent include Fe. 2+ Mg 2+ Al 3+ Cu 2+ Mg 2+ Ca 2+ Zn 2+ One or any combination of several of them.

[0019] Further preferably, the metal ions in the metal ion crosslinking agent include Cu. 2+ .

[0020] The preparation method of the nanoemulsion system based on interfacial crosslinking stabilized curcumin, as described above, includes the following steps:

[0021] 1) Under the stirring condition of 60℃ water bath, add curcumin to the oil to dissolve, then add gallic acid ester to dissolve, to obtain a curcumin-gallic acid ester-corn oil mixture;

[0022] 2) Mix the curcumin-gallate-corn oil mixture with a pH=7-8 buffer solution to obtain an oil-water mixture;

[0023] 3) Set the ultrasonic disruptor power to 80W. During the cyclic ultrasonic process, add a metal ion crosslinking agent to the oil-water mixture. After ultrasonication, a nanoemulsion system is obtained.

[0024] Preferably, in step 2), the volume percentage of the curcumin-gallate-corn oil mixture in the oil-water mixture is 10%-20%. More preferably, the volume percentage of the curcumin-gallate-corn oil mixture in the oil-water mixture is 10%.

[0025] Preferably, in step 3), the concentration of metal ions in the metal ion crosslinking agent is 24 mM.

[0026] Preferably, in step 3), the volume ratio of the metal ion crosslinking agent to the oil-water mixture is 0.25%-0.75%. More preferably, the volume ratio of the metal ion crosslinking agent to the oil-water mixture is 0.5%.

[0027] The working principle of this invention is as follows: Gallic esters are polyphenolic compounds containing a large number of phenolic hydroxyl groups, exhibiting a strong ability to chelate metals. They can complex with most trivalent metal ions and divalent transition metal ions. Copper, iron, and other metal ions can form complexes with the β-diketone groups in curcumin through electrostatic interactions, resulting in complexes with excellent stability and good optical properties. An emulsion delivery system is constructed through the cross-linking and complexation among gallic esters, metal ions, and curcumin, thereby improving the problems of low solubility and poor stability of curcumin in the current food industry.

[0028] The beneficial effects of this invention are:

[0029] (1) This invention proposes an interfacial crosslinking technology based on hydroxyl-metal ion-β-diketone groups, which improves the problems of low solubility and poor stability of curcumin in the current food industry;

[0030] (2) This invention can not only expand the application pathways and fields of curcumin, but also provide theoretical basis and research direction for other hydrophobic nutrients, and has guiding significance for the development of corresponding encapsulation processes.

[0031] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it in accordance with the contents of the specification, the preferred embodiments of the present invention are described in detail below. Detailed Implementation

[0032] The principles and features of the present invention are described below with reference to examples. The examples are only used to explain the present invention and are not intended to limit the scope of the present invention.

[0033] Example 1

[0034] This embodiment provides a basic emulsion formed from a mixture of curcumin-gallate-corn oil and a buffer solution with pH=7-8. The preparation steps are as follows:

[0035] 1) Curcumin was dissolved in corn oil under stirring in a 60°C water bath. Then, propyl gallate was added, and the water bath temperature was maintained at 60°C until the curcumin-gallate-corn oil mixture was completely dissolved, resulting in a curcumin-gallate-corn oil mixture. The concentration of curcumin was 1 mg / mL, and the mass concentration of gallate was 8.6 mg / mL.

[0036] 2) Using a 3-propanesulfonic acid buffer solution with pH=7.6 as the aqueous phase, and a curcumin-gallate-corn oil mixture as the oil phase, the oil phase and the aqueous phase were mixed evenly with a total volume of 20 mL, wherein the oil phase accounted for 10% of the volume, and the base emulsion was obtained under ultrasonic disruption at 80 W.

[0037] Example 2

[0038] This embodiment provides a basic emulsion formed from a mixture of curcumin-gallate-corn oil and a buffer solution with pH=7-8. The preparation steps are basically the same as those in Example 1, except that in step 1), propyl gallate is replaced with lauryl gallate.

[0039] Example 3

[0040] This embodiment provides a basic emulsion formed from a mixture of curcumin-gallate-corn oil and a buffer solution with pH=7-8. The preparation steps are basically the same as those in Example 1, except that in step 1), propyl gallate is replaced with octyl gallate.

[0041] Example 4

[0042] This embodiment provides a basic emulsion formed from a mixture of curcumin-gallate-corn oil and a buffer solution with pH=7-8. The preparation steps are basically the same as those in Example 1, except that in step 1), propyl gallate is replaced with octadecyl gallate.

[0043] The particle size and average potential of the base emulsions provided in Test Examples 1-4 are shown in Table 1.

[0044] Table 1. Effect of gallic acid ester type on the stability of the base emulsion

[0045]

[0046] The smaller the particle size of the emulsion and the higher the potential, the more stable the emulsion system and the better the solubility of curcumin. A PDI ≥ 0.5 indicates a wide molecular weight distribution and an unstable solution. Conversely, a PDI < 0.5 indicates a uniform molecular weight distribution and a stable solution.

[0047] The particle size of the base emulsion is maintained at the nanoscale. When the emulsifier is lauryl gallate and octadecyl gallate, the whole system is unstable (PDI > 0.5). When the emulsifier is propyl gallate, the particle size of the system is too large. Taking all factors into consideration, octyl gallate is selected as the best emulsifier.

[0048] Example 5

[0049] This embodiment provides a basic emulsion formed from a mixture of curcumin-gallate-corn oil and a buffer solution with pH=7-8. The preparation steps are basically the same as those in Example 3, except that in step 2), the volume ratio of oil is 15%.

[0050] Example 6

[0051] This embodiment provides a basic emulsion formed from a mixture of curcumin-gallate-corn oil and a buffer solution with pH=7-8. The preparation steps are basically the same as those in Example 3, except that in step 2), the volume ratio of oil is 20%.

[0052] The particle size and average potential of the base emulsions provided in Examples 3, 5, and 6 are shown in Table 2.

[0053] Table 2. Effect of oil phase content on the stability of the base emulsion

[0054]

[0055] As shown in Table 2, the emulsion system is relatively stable when the total volume of the curcumin-gallate-corn oil mixture is 10%.

[0056] Example 7

[0057] This embodiment provides a nanoemulsion system based on interfacial cross-linking stabilized curcumin, and the specific steps are as follows:

[0058] 1) Under stirring conditions in a 60℃ water bath, curcumin was dissolved in 2 mL of corn oil, and then octyl gallate was added. The water bath temperature was maintained at 60℃ until the curcumin-gallate-corn oil mixture was completely dissolved, resulting in a curcumin-gallate-corn oil mixture. The concentration of curcumin was 1 mg / mL, and the mass concentration of octyl gallate was 8.6 mg / mL.

[0059] 2) Using a 3-propanesulfonic acid buffer solution with pH=7.6 as the aqueous phase, the curcumin-gallate-corn oil mixture was mixed evenly with 18 mL of the aqueous phase to obtain an oil-water mixture.

[0060] 3) Under ultrasonic disruption at 80W, after 5 minutes of ultrasonication, Fe was added to the system. 2+A 24 mM, 100 μL ferrous sulfate solution was used as a metal ion crosslinking agent, and the mixture was sonicated for another 2 minutes to obtain a nanoemulsion system.

[0061] Example 8

[0062] This embodiment provides a nanoemulsion system based on interfacial crosslinking to stabilize curcumin. The specific steps are basically the same as in Example 7, except that in step 3), the metal ion of the metal ion crosslinking agent is Ca. 2+ The metal ion crosslinking agent is anhydrous calcium chloride solution.

[0063] Example 9

[0064] This embodiment provides a nanoemulsion system based on interfacial crosslinking to stabilize curcumin. The specific steps are basically the same as in Example 7, except that in step 3), the metal ion of the metal ion crosslinking agent is Mg. 2+ The metal ion crosslinking agent is anhydrous magnesium chloride solution.

[0065] Example 10

[0066] This embodiment provides a nanoemulsion system based on interfacial crosslinking to stabilize curcumin. The specific steps are basically the same as in Example 7, except that in step 3), the metal ion of the metal ion crosslinking agent is Zn. 2+ The metal ion crosslinking agent is zinc sulfate heptahydrate solution.

[0067] Example 11

[0068] This embodiment provides a nanoemulsion system based on interfacial crosslinking to stabilize curcumin. The specific steps are basically the same as in Example 7, except that in step 3), the metal ion of the metal ion crosslinking agent is Cu. 2+ The metal ion crosslinking agent is a copper chloride solution.

[0069] Example 12

[0070] This embodiment provides a nanoemulsion system based on interfacial crosslinking to stabilize curcumin. The specific steps are basically the same as in Example 7, except that in step 3), the metal ion of the metal ion crosslinking agent is Al. 3+ The metal ion crosslinking agent is magnesium chloride solution.

[0071] The particle size and average potential of the nanoemulsion systems provided in Examples 7-12 were tested, and the results are shown in Table 3.

[0072] Table 3. Effect of metal ion type on nanoemulsion system of metal ion crosslinking agent

[0073]

[0074] It can be seen that the type of metal ion has a significant impact on the nanoemulsion system, but overall, the addition of Cu to the system... 2+ The particle size and PDI are relatively small, and the system is relatively homogeneous.

[0075] Example 13

[0076] This embodiment provides a nanoemulsion system based on interfacial cross-linking stabilized curcumin, and the specific steps are as follows:

[0077] 1) Under stirring conditions in a 60℃ water bath, curcumin was dissolved in 2 mL of corn oil, and then octyl gallate was added. The water bath temperature was maintained at 60℃ until the curcumin-gallate-corn oil mixture was completely dissolved, resulting in a curcumin-gallate-corn oil mixture. The concentration of curcumin was 1 mg / mL, and the mass concentration of octyl gallate was 0.86 mg / mL.

[0078] 2) Using a 3-propanesulfonic acid buffer solution with pH=7.6 as the aqueous phase, the curcumin-gallate-corn oil mixture was mixed evenly with 18 mL of the aqueous phase to obtain an oil-water mixture.

[0079] 3) Under ultrasonic disruption at 80W, after 5 minutes of ultrasonication, Cu was added to the system. 2+ A nanoemulsion system was prepared by adding a metal ion crosslinking agent with a concentration of 24 mM and a volume of 100 μL and then sonicating for another 2 min.

[0080] Example 14

[0081] This embodiment provides a nanoemulsion system based on interfacial cross-linking to stabilize curcumin. The specific steps are basically the same as those in Example 13, except that in step 1), the mass concentration of octyl gallate is 1.72 mg / mL.

[0082] Example 15

[0083] This embodiment provides a nanoemulsion system based on interfacial cross-linking to stabilize curcumin. The specific steps are basically the same as those in Example 13, except that in step 1), the mass concentration of octyl gallate is 2.58 mg / mL.

[0084] Example 16

[0085] This embodiment provides a nanoemulsion system based on interfacial cross-linking to stabilize curcumin. The specific steps are basically the same as those in Example 13, except that in step 1), the mass concentration of octyl gallate is 3.44 mg / mL.

[0086] The particle size and average potential of the nanoemulsion systems provided in Examples 13-16 were tested, and the results are shown in Table 4.

[0087] Table 4. Effect of gallate concentration on nanoemulsion liquids

[0088]

[0089] The concentration of octyl gallate has a certain impact on the stability of the nanoemulsion system. It can be clearly seen that when the concentration is 2.58 mg / mL, the particle size and PDI are smaller, and the system is more stable.

[0090] Example 17

[0091] This embodiment provides a nanoemulsion system based on interfacial cross-linking stabilized curcumin, and the specific steps are as follows:

[0092] 1) Under stirring conditions in a 60℃ water bath, curcumin was dissolved in 2 mL of corn oil, and then octyl gallate was added. The water bath temperature was maintained at 60℃ until the curcumin-gallate-corn oil mixture was completely dissolved, resulting in a curcumin-gallate-corn oil mixture. The concentration of curcumin was 1 mg / mL, and the concentration of octyl gallate was 2.58 mg / mL.

[0093] 2) Using a 3-propanesulfonic acid buffer solution with pH=7.6 as the aqueous phase, the curcumin-gallate-corn oil mixture was mixed evenly with 18 mL of the aqueous phase to obtain an oil-water mixture.

[0094] 3) Under ultrasonic disruption at 80W, after 5 minutes of ultrasonication, Cu was added to the system. 2+ A nanoemulsion system was prepared by adding a metal ion crosslinking agent with a concentration of 24 mM and a volume of 80 μL and then sonicating for another 2 min.

[0095] Example 18

[0096] This embodiment provides a nanoemulsion system based on interfacial crosslinking to stabilize curcumin. The specific steps are basically the same as those in Example 17, except that in step 3), the amount of metal ion crosslinking agent added is 100uL.

[0097] Example 19

[0098] This embodiment provides a nanoemulsion system based on interfacial crosslinking to stabilize curcumin. The specific steps are basically the same as those in Example 17, except that in step 3), the amount of metal ion crosslinking agent added is 150uL.

[0099] The particle size and average potential of the nanoemulsion systems provided in Examples 17-19 were tested, and the results are shown in Table 5.

[0100] Table 5. Effect of metal ion crosslinking agent dosage on nanoemulsion system

[0101]

[0102] It can be seen that the nanoemulsion system is most stable when the amount of metal crosslinking agent added is 100uL.

[0103] Comparative Example 1

[0104] This comparative example provides a basic emulsion, the preparation steps of which are as follows: under the stirring condition of a water bath at 60°C, curcumin is dissolved in corn oil to obtain an oil phase, wherein the curcumin concentration is 1 mg / mL; 3-propanesulfonic acid buffer solution with pH=7.6 is used as the aqueous phase, and 2 mL of the oil phase and 18 mL of the aqueous phase are mixed evenly to obtain an oil-water mixture; the basic emulsion is obtained by cyclic sonication under ultrasonic disruption at 80 W.

[0105] The photodegradation stability of Examples 18 and 3, and Comparative Example 1, was compared, and the preparation conditions are summarized in Table 6:

[0106] Table 6. Preparation conditions for the experimental group and each control group

[0107]

[0108]

[0109] The emulsions prepared in the above examples and comparative examples were irradiated under ultraviolet light for 100 min. The total curcumin content was measured every 20 min, and the retention rate (EE) of curcumin in the emulsion was calculated. The results are shown in Table 7.

[0110] The emulsion retention rate is calculated using the following formula: EE% = C1 / C0 × 100%

[0111] (C1: Curcumin concentration in the emulsion; C0: Initial curcumin concentration in the emulsion)

[0112] Table 7 Curcumin content of the examples and comparative examples

[0113] Time (t) Comparative Example 1 Example 3 Example 18 20min 94.3％ 95.6％ 97.8％ 40min 84.1％ 91.2％ 96.3％ 60min 81.5％ 88.1％ 95.35％ 80min 76.8％ 87.3％ 93.7％ 100min 68.0％ 83.4％ 93.5％

[0114] In the emulsion system provided in Comparative Example 1, without the addition of emulsifiers and metal ions, curcumin showed the greatest degradation after 100 min of UV treatment, and the retention rate decreased with prolonged irradiation time. In the system of Example 5, the presence of octyl gallate allowed the phenolic hydroxyl groups on both sides to bind with the β-diketone groups in the curcumin structure, improving the stability of the system and thus protecting curcumin, resulting in an overall improved retention rate. In Example 18, the system contained both octyl gallate and Cu. 2+ Cu 2+When combined with curcumin in a certain proportion, the stability of curcumin is further improved under the action of hydroxyl-metal ion-β-diketone groups. In this system, the retention rate of curcumin after UV treatment is relatively large. After 100 min, 93.5% of curcumin is still remaining in the emulsion, indicating that the photostability of curcumin is improved to a certain extent.

[0115] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Those skilled in the art can readily implement the present invention according to the description and above. However, any modifications, alterations, or variations made by those skilled in the art without departing from the scope of the present invention, based on the disclosed technical content, are equivalent embodiments of the present invention. Furthermore, any modifications, alterations, or variations made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the present invention.

Claims

1. A nanoemulsion based on interfacial crosslinking stabilized curcumin, characterized in that, The raw materials of the nanoemulsion are composed of the following components in volume fraction: Curcumin-gallic acid ester-corn oil mixture 200-400 parts Buffer solution with pH=7-8 1600-1800 parts Metal ion crosslinking agent 8-15 parts In the curcumin-gallic acid ester-corn oil mixture, the concentration of curcumin is 1 mg / mL; the concentration of gallic acid ester is 1.72-8.6 mg / mL; and the concentration of metal ions in the metal ion crosslinking agent is 24 mM; The nanoemulsion is prepared by the following steps: 1) curcumin and gallic acid ester are sequentially added to corn oil to obtain a curcumin-gallic acid ester-corn oil mixture; 2) the curcumin-gallic acid ester-corn oil mixture is uniformly mixed with a buffer solution with pH=7-8 to obtain an oil-water mixture; 3) during the circulating ultrasonic process, the metal ion crosslinking agent is added to the oil-water mixture, and the nanoemulsion is obtained after ultrasonic treatment; The gallate ester is octyl gallate; the metal ion in the metal ion crosslinking agent is Cu 2＋ .

2. The nanoemulsion based on interfacially crosslinked stabilized curcumin according to claim 1, wherein, The raw materials of the nanoemulsion are composed of the following components in volume fraction: Curcumin-gallic acid ester-corn oil mixture 200-300 parts Buffer solution with pH=7-8 1700-1800 parts Metal ion crosslinking agent 10-15 parts.

3. The nanoemulsion based on interfacially crosslinked stabilized curcumin according to claim 1, wherein, The raw materials of the nanoemulsion are composed of the following components in volume fraction: Curcumin-gallic acid ester-corn oil mixture 200 parts Buffer solution with pH=7-8 1800 parts Metal ion crosslinking agent 10 parts.

4. A process for the preparation of the nanoemulsion based on the cross-linking of curcumin stabilized by interface according to claim 1, characterized in that, The steps include: 1) curcumin and gallic acid ester are sequentially added to corn oil to obtain a curcumin-gallic acid ester-corn oil mixture; 2) the curcumin-gallic acid ester-corn oil mixture is uniformly mixed with a buffer solution with pH=7-8 to obtain an oil-water mixture; 3) during the circulating ultrasonic process, the metal ion crosslinking agent is added to the oil-water mixture, and the nanoemulsion is obtained after ultrasonic treatment.

5. A process for the preparation of a stable curcumin nanoemulsion based on interfacial cross-linking as claimed in claim 4, wherein, In the step 2), the volume fraction of the curcumin-gallic acid ester-corn oil mixture in the oil-water mixture is 10%-20%.

Images