CN113083176B - A kind of preparation method and application of hollow proanthocyanidin wall material microcapsules - Google Patents

Abstract

The invention discloses a preparation method and application of hollow proanthocyanidin wall material microcapsules. Proanthocyanidin is a plant polyphenolic compound with good antibacterial, antioxidant and anticancer activities. Proanthocyanidins are widely found in the bark of darker fruit plants. However, proanthocyanidins have no fixed three-dimensional shape and are easily soluble in polar solvents, so ordinary proanthocyanidins are limited in embedding applications. The hollow proanthocyanidin microcapsules of the present invention use ZIF-8 as a sacrificial template, and use proanthocyanidin as an etchant to etch ZIF-8, and finally obtain hollow proanthocyanidin wall material microcapsules with a particle size of about 200 nanometers. The cedarwood essential oil was embedded in the hollow proanthocyanidin wall material microcapsules, and finally the cedarwood essential oil slow-release microcapsules with a loading capacity of about 26% were obtained. The invention successfully constructs a hollow microcapsule with proanthocyanidin as the wall material, which can be used in the field of embedding of oxidatively degenerated medicines or essential oils.

Description

A kind of preparation method and application of hollow proanthocyanidin wall material microcapsules

technical field

The invention belongs to the field of material preparation, and relates to a method for preparing hollow proanthocyanidin wall material microcapsules and its application, in particular to a method for preparing hollow microcapsules with proanthocyanidin as wall material and the prepared hollow microcapsules used in medicine or Applications in the field of essential oil embedding.

Background technique

Proanthocyanidins are condensed tannins with various pharmacological properties that widely exist on the surface and body of plants. For example, proanthocyanidins have good antioxidant properties, antibacterial properties, anti-cancer properties and other properties. Proanthocyanidins are the final products of flavonoid biosynthetic pathways, oligomers or polymers composed of monomeric flavan-3-ols, and are abundant in agricultural wastes and food processing wastes.

At present, the research on the application of proanthocyanidins is still limited to the above-mentioned properties of proanthocyanidins themselves. In the industry, proanthocyanidins are widely used as microcapsule core materials for embedding to highlight the effectiveness of proanthocyanidins as core materials. People such as Zhang Wanping used chitosan to embed proanthocyanidins in the field of cosmetics; people such as Wang Fang used maltodextrin and gum arabic to embed oligomeric proanthocyanidins in the field of health food; people such as Tan Mingqian used gelatin-sodium alginate to embed procyanidins. It is expected to be applied in the food field. To sum up, the current proanthocyanidins are all embedded as microcapsule core materials, aiming to exert some functions of proanthocyanidins in different fields. However, there is currently no case of developing proanthocyanidins as a microcapsule wall material. The present invention obtains hollow proanthocyanidin microcapsules by sacrificing the template, and uses proanthocyanidin as the microcapsule wall material. Because of its own antibacterial and anti-oxidation properties, it has a very broad application prospect in the field of core material protection and is expected to be applied to medicine development. , loading essential oils and other fields. In addition, proanthocyanidins, as a natural polyphenol whose color changes with the pH value of the environment, appear red under acidic conditions and blue under alkaline conditions. After the food is spoiled, its PH value tends to be acidic, so using proanthocyanidins as active food packaging also has a good prospect for visually judging whether the food is spoiled.

Contents of the invention

The object of the present invention is to provide a preparation method and application of hollow proanthocyanidin wall material microcapsules; the method can be completed in normal temperature aqueous solution. In order to obtain hollow proanthocyanidin wall material microcapsules with different particle sizes, the size of the hollow proanthocyanidin wall material microcapsules can be indirectly controlled by controlling the particle size of the sacrificial template ZIF-8.

To achieve the above object, the present invention provides the following technical solutions:

In the first aspect, the present invention relates to a method for preparing hollow proanthocyanidin wall material microcapsules, using zeolite imidazole framework-8 (ZIF-8) as a hard template, using procyanidin as an etchant, and forming a proanthocyanidin after etching ZIF-8 Hollow microcapsules for the wall material.

As an embodiment of the present invention, in the aqueous solution of hexadecyltrimethylammonium bromide as end-capping agent, the reaction duration of zinc nitrate hexahydrate 2-methylimidazole is controlled, and ZIF- 8 pellets.

As an embodiment of the present invention, the control reaction time length is 20～120min, and the ZIF-8 particle of 50-200 nanometers is synthesized

As one embodiment of the present invention, described synthesis comprises the following steps:

S1. Cetyltrimethylammonium bromide aqueous solution and 2-methylimidazole aqueous solution are mixed uniformly to form solution D;

S2. After mixing the zinc nitrate aqueous solution and the solution D, stirring evenly, standing at 22-28° C. to form a solution E; centrifuging, washing and drying to obtain the ZIF-8 particles.

As an embodiment of the present invention, the mass concentration of the cetyltrimethylammonium bromide aqueous solution is 0.10%-0.25%, the mass concentration of the 2-methylimidazole aqueous solution is 4.5%-10%; the nitric acid The zinc aqueous solution is prepared by dissolving 500mg-1000mg of zinc nitrate hexahydrate in 100ml of water.

As an implementation example of the present invention, the mass concentration of the cetyltrimethylammonium bromide aqueous solution is 0.18%, and the mass concentration of the 2-methylimidazole aqueous solution is 4.5%-10%; the zinc nitrate aqueous solution is Prepared by dissolving 700mg of zinc nitrate hexahydrate in 100ml of water.

As an embodiment of the present invention, the zinc nitrate aqueous solution, the 2-methylimidazole aqueous solution and the cetyltrimethylammonium bromide aqueous solution are mixed in a volume ratio of 1-1.5:1-1.5:0.04-0.75. As an implementation example, an aqueous solution of zinc nitrate, an aqueous solution of 2-methylimidazole, and an aqueous solution of cetyltrimethylammonium bromide are mixed at a volume ratio of 1:1:0.045.

As an embodiment of the present invention, in step S2, the standing time is 20-120 minutes. Among them, the average particle diameter of ZIF-8 particles synthesized by standing for 20～30min is 50 nanometers; the average particle diameter of ZIF-8 particles synthesized by standing for 50±10min is 100 nm; The particle size is 200 nm.

As an embodiment of the present invention, in step S2, the centrifugation, washing, and drying are specifically: centrifuging at 9000-13000rpm for 5-20 minutes to collect the precipitate and washing with anhydrous methanol for 2-5 times and centrifuging, and finally The precipitate was vacuum dried at 45-60°C for 10-24 hours.

As an implementation example of the present invention, in step S2, the centrifugation, washing, and drying are specifically: centrifuging at 10,000 rpm for 10 minutes to collect the precipitate, washing with anhydrous methanol three times and centrifuging, and finally vacuuming the precipitate at 60°C Let dry for 12 hours.

As an embodiment of the present invention, proanthocyanidin etching ZIF-8 comprises the following steps:

a. Uniformly disperse ZIF-8 particles in deionized water to form dispersion A;

b. uniformly dispersing the proanthocyanidins in deionized water to form dispersion B;

c. Mix the dispersion A and dispersion B, and stir at 500-1000rpm at 22-28°C for 0.5-12 hours; the mass content of dispersion A in the mixed solution is 1%-15%, and the mass content of dispersion B is The content is 85-99%; the hollow proanthocyanidin wall material microcapsules can be obtained after centrifugation, washing and drying.

As an implementation example of the present invention, when the ZIF-8 particle average particle diameter is 50 nanometers, the stirring time is 30-40 minutes in the step c; when the ZIF-8 particle average particle diameter is 100 nanometers, the stirring time is 2 in the step c -3 hours; when the average particle size of ZIF-8 particles is 200 nanometers, the stirring time in step c is 8-12 hours.

As an embodiment of the present invention, the mass concentration of ZIF-8 particles in the dispersion A is 4%-20%; the mass concentration of proanthocyanidins in the dispersion B is 1%-10%.

As an implementation example of the present invention, the mass concentration of ZIF-8 particles (average particle diameter is 200nm) in the dispersion liquid A is 5%-20%, and the mass concentration of proanthocyanidins in the dispersion liquid B is 1%-10% %.

As an embodiment of the present invention, in step c, the average particle diameter of ZIF-8 particles is 200-300 nanometers; the stirring time is 8-12 hours.

As an embodiment of the present invention, in step c, the centrifugation, washing, and drying specifically include: centrifuging at 9000-13000rpm for 5-20 minutes to collect the precipitate, washing with deionized water for 2-5 times and centrifuging again, and finally Dry the precipitate under vacuum at 45-60° C. for 10-20 hours.

As an implementation example of the present invention, the centrifugation, washing, and drying specifically include: centrifuging at 10,000 rpm for 10 minutes to collect the precipitate, washing with deionized water three times and centrifuging again, and finally vacuum drying the precipitate at 45°C for 12 Hour.

In the second aspect, the present invention relates to a hollow proanthocyanidin wall material microcapsule prepared by the above preparation method.

In a third aspect, the present invention relates to an application of the above-mentioned hollow proanthocyanidin wall material microcapsules in drug embedding or essential oil embedding.

The present invention aims to obtain hollow proanthocyanidin wall material microcapsules at relatively low cost, so the above-mentioned proanthocyanidin is not a particularly high-purity proanthocyanidin monomer, but a proanthocyanidin oligomer or polymer. Proanthocyanidins with high purity are more expensive, which limits their application scenarios.

Compared with the prior art, the present invention has the following beneficial effects:

1) The present invention uses ZIF-8 prepared by a safe and easy method as a sacrificial template, and uses proanthocyanidins as an etchant to etch ZIF-8;

2) In the aqueous solution system, due to the collision adsorption of proanthocyanidins and ZIF-8, the two are combined in the aqueous solution; and the H ⁺ dissociated from the proanthocyanidins in the aqueous solution fully dissociates ZIF-8, and after fully reacting and washing, only the hollow Proanthocyanidin microcapsules exist in the system;

3) Because proanthocyanidins themselves have excellent antibacterial and antioxidant properties, on the one hand, hollow proanthocyanidin wall material microcapsules can alleviate the release of core material to a certain extent; Oxidative deterioration; therefore, it has a good prospect in the field of drug embedding or essential oil embedding.

Description of drawings

Other characteristics, objects and advantages of the present invention will become more apparent by reading the detailed description of non-limiting embodiments made with reference to the following drawings:

Fig. 1 is the scanning electron micrograph of the ZIF-8 nanoparticles of different reaction times in embodiment 1;

Fig. 2 is the transmission electron microscope figure of experiment four hollow proanthocyanidin wall materials in embodiment 2;

Fig. 3 is the transmission electron microscope figure of experiment five hollow proanthocyanidin wall materials in embodiment 2;

Fig. 4 is the transmission electron microscope figure of experimental six hollow proanthocyanidin wall materials in embodiment 2;

Fig. 5 is the transmission electron micrograph of experiment seven hollow proanthocyanidin wall materials in embodiment 2;

Fig. 6 is the transmission electron microscope picture of hollow proanthocyanidin wall material in embodiment 2;

Fig. 7 is the thermal gravimetric analysis diagram of cedarwood essential oil microcapsules in embodiment 3.

Detailed ways

The present invention will be described in detail below in conjunction with examples. The following examples will help those skilled in the art to further understand the present invention, but do not limit the present invention in any form. It should be noted that those skilled in the art can make some adjustments and improvements without departing from the concept of the present invention. These all belong to the protection scope of the present invention.

Proanthocyanidin is a plant polyphenolic compound with good antibacterial, antioxidant and anticancer activities. Proanthocyanidins are widely found in the bark of darker fruit plants. However, proanthocyanidins have no fixed three-dimensional shape and are easily soluble in polar solvents, so ordinary proanthocyanidins are limited in embedding applications. The hollow proanthocyanidin microcapsules of the present invention use ZIF-8 as a sacrificial template, and use proanthocyanidin as an etchant to etch the ZIF-8, and finally obtain hollow proanthocyanidin wall material microcapsules with a particle size of about 200 nanometers. The cedarwood essential oil was embedded in the hollow proanthocyanidin wall material microcapsules, and finally the cedarwood essential oil slow-release microcapsules with a loading capacity of about 26% were obtained. The invention aims to construct a hollow microcapsule with proanthocyanidin as the wall material, which can be used in the field of embedding of oxidatively degenerated medicines or essential oils. See the following examples for specific examples:

Example 1

The specific examples of the preparation of ZIF-8 particles are as follows:

1) Dissolve zinc nitrate hexahydrate (Zn(NO ₃ ) ₂ 6H ₂ O) in 100mL deionized water to form solution A,

2) Dissolving 2-methylimidazole (C ₄ H ₆ N ₂ ) in 100 mL deionized water to form solution B;

3) dissolving cetyltrimethylammonium bromide in 10mL deionized water to form solution C;

4) Fully stir and mix the above solution B and solution C; then mix with solution A and stir evenly (10 minutes), then let it stand at room temperature for different periods of time, collect the precipitate at 10000rpm for 10 minutes and wash it with anhydrous methanol three times And, finally, the precipitate was vacuum-dried at 6° C. for 12 hours to obtain ZIF-8 crystals; wherein, solution A, solution B and solution C were mixed at a volume ratio of 1:1:0.045.

The experimental parameters and test results are summarized as follows:

According to experiments 1 to 3, under the experimental conditions, the particle size of ZIF-8 particles is closely related to the crystal growth time. When the reaction time was 20 minutes, the size of the ZIF-8 crystal particles was about 50 nanometers, also known as nanocrystals; when the reaction time was 50 minutes, the ZIF-8 crystal particle size was about 100 nanometers; When the time is 120 minutes, the ZIF-8 crystal particles are about 200 nanometers (as shown in FIG. 1 ).

Example 2

Using ZIF-8 as a hard template and using proanthocyanidins as an etchant to etch ZIF-8, the specific examples of preparing hollow proanthocyanidin microcapsules are as follows:

1) Uniformly disperse 0.05g of ZIF-8 particles in 1mL of deionized water under the action of ultrasound for 10 minutes to form turbid solution A;

2) Uniformly disperse 1 g of proanthocyanidins into 99 mL of deionized water under the action of ultrasound to form turbid liquid B;

3) Mix the above-mentioned turbid solution A and turbid solution B rapidly, and stir at room temperature at 25° C. at 800 rpm for different periods of time, and obtain hollow proanthocyanidin wall material microcapsules by centrifugal washing and drying; the centrifugal washing and drying is specifically: The precipitate was collected by centrifugation at 10000 rpm for 10 minutes, washed three times with deionized water and centrifuged, and finally the precipitate was vacuum-dried at 45° C. for 12 hours.

The experimental parameters and test results are summarized as follows:

parameter ZIF-8 (mg) Proanthocyanidins (g) Total solution volume (mL) Reaction time (h) Experiment four (50nm)50 1 100 0.5 Experiment five (100nm)50 1 100 2 Experiment six (200nm)50 1 100 5 Experiment seven (200nm)50 0.1 100 8 Experiment eight (200nm)50 1 100 8

According to experiments 4 to 7, the etching of ZIF-8 by proanthocyanidins is a process related to sample concentration and time. When the template particles are small, the concentration of the etchant is required to be low, and the etching time can be completed in a short time, such as the results of Experiment 4 (FIG. 2) and Experiment 5 (FIG. 3). When the template particles are large, the etchant concentration is too low (Experiment 7, Figure 5) and the etching time is not enough (Experiment 6, Figure 4) will affect the etching result, that is, the etching is not complete, thus obtaining the core-shell structure. Finally, through Experiment 8, we obtained hollow proanthocyanidin wall material microcapsules with a particle size of about 200 nanometers, and the thickness of the microcapsule wall is about 20-30 nanometers (as shown in Figure 6).

The present invention also attempts to etch with small molecule polyphenols such as quercetin, but it cannot etch ZIF-8.

Example 3

The specific examples of preparing cedarwood essential oil microcapsules by using hollow proanthocyanidins as wall materials are as follows:

1) Uniformly disperse cedarwood essential oil into absolute ethanol under the action of ultrasound to form solution A;

2) Add the hollow proanthocyanidin wall material microcapsule particles into solution A and ultrasonicate for 10 minutes at a room temperature of about 25°C;

3) Stir and embed the above mixed solution at 600rpm for 3 hours;

4) Cedarwood essential oil microcapsules were obtained by centrifugation, washing with absolute ethanol and freeze-drying for 24 hours.

The experimental parameters and test results are as follows:

According to the results of experiments 9 to 11, the mass ratio of proanthocyanidins to cypress essential oil is 1;1 when the optimum ratio of hollow proanthocyanidins to embed cypress essential oil is obtained through thermogravimetric analysis. The maximum loading obtained is shown in Fig. 7. It can be seen from the thermogravimetric diagram that the mass loss at 0-100°C comes from the volatilization of the remaining water in the system. The loss that begins to appear at 250°C is the transformation of proanthocyanidins. The mass loss around 350 °C comes from the transformation of ZIF-8. In principle, there are some light olefinic compounds in the essential oil system, and some of their boiling points are lower than 100°C. The loading of cypress essential oil obtained by thermogravimetric diagram is about 26% by weight, due to the low boiling point olefins Volatile, the actual loading of cypress essential oil should be higher than 26% mass fraction.

Using hollow proanthocyanidins as microcapsule wall material to embed drugs or essential oils has a good effect. Due to the antibacterial, anti-oxidation, anti-tumor cell growth and other characteristics of proanthocyanidins themselves, it can play multiple functions as a microcapsule wall material. Synergistic therapeutic effect of drugs or synergistic antibacterial effect with essential oils. Therefore, using hollow proanthocyanidins as the wall material of microcapsules has broad prospects in the field of medicine or essential oil embedding.

Specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art may make various changes or modifications within the scope of the claims, which do not affect the essence of the present invention.

Claims (7)

1. A preparation method for hollow proanthocyanidin wall material microcapsules, characterized in that, taking ZIF-8 as a hard template, taking proanthocyanidin as an etchant, forming hollow microcapsules with proanthocyanidin as a wall material after etching ZIF-8; Proanthocyanidin etching ZIF-8 comprises the following steps: a. Uniformly disperse ZIF-8 particles in deionized water to form dispersion A; b. uniformly dispersing the proanthocyanidins in deionized water to form dispersion B; c. Mix the dispersion A and dispersion B, and stir at 500-1000rpm at 22-28°C for 8-12 hours; the mass content of dispersion A in the mixed solution is 1%-15%, and the mass content of dispersion B is The content is 85-99%, and the average particle diameter of ZIF-8 particles is 200-300 nanometers; after centrifugation, washing and drying, the hollow proanthocyanidin wall material microcapsules are obtained; The mass concentration of ZIF-8 particles in the dispersion A is 4%-20%; the mass concentration of proanthocyanidins in the dispersion B is 1%-10%. 2. the preparation method of hollow proanthocyanidin wall material microcapsules according to claim 1, is characterized in that, the synthesis of ZIF-8 particle comprises the steps: S1. Cetyltrimethylammonium bromide aqueous solution and 2-methylimidazole aqueous solution are mixed uniformly to form solution D; S2. After mixing the zinc nitrate aqueous solution and the solution D, stirring evenly, standing at 22-28° C. to form a solution E; centrifuging, washing and drying to obtain the ZIF-8 particles. 3. the preparation method of hollow proanthocyanidin wall material microcapsules according to claim 2, is characterized in that, the mass concentration of described hexadecyltrimethylammonium bromide aqueous solution is 0.10%-0.25%, 2-methyl The mass concentration of the imidazole aqueous solution is 4.5%-10%. The zinc nitrate aqueous solution is prepared by dissolving 500mg-1000mg of zinc nitrate hexahydrate in 100ml of water. 4. the preparation method of hollow proanthocyanidin wall material microcapsules according to claim 3 is characterized in that, in the aqueous solution of cetyltrimethylammonium bromide as end-capping agent, control zinc nitrate hexahydrate and 2- The reaction time of methimazole is long, and ZIF-8 particles with different particle sizes are synthesized. 5. The method for preparing hollow proanthocyanidin wall material microcapsules according to claim 3, characterized in that, in step S2, the standing time is 20-120 minutes. 6. A hollow proanthocyanidin wall material microcapsule prepared according to any one of claims 1-5. 7. An application of the hollow proanthocyanidin wall material microcapsule according to claim 6 in drug embedding or essential oil embedding.

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