WO2022252818A1 - Hydrophilic compound-embedded nano microcapsule, and preparation method therefor and application thereof - Google Patents

Abstract

A hydrophilic compound-embedded nano microcapsule, and a preparation method therefor and an application thereof. In a hydrophilic compound nano microcapsule provided by the present invention, a protein and polysaccharide serve as wall materials; the wall materials and a hydrophilic compound are mixed in water to form a mixed solution; and the pH of the mixed solution is adjusted to 3.4-4.5 while the mixed solution is subjected to ultrasonic treatment, such that the hydrophilic compound nano microcapsule is obtained. According to the preparation method provided by the present invention, the hydrophilic compound accounts for 0.5-7% of the total weight of dry substances of the wall materials.

Description

A nano-microcapsule embedding a hydrophilic compound and its preparation method and application

cross reference

This application claims the priority of the Chinese patent application No. 202110625846.4 filed on June 4, 2021 with the patent title "A nano-microcapsule embedding a hydrophilic compound and its preparation method and application", the entire disclosure of which is incorporated by reference Incorporated into this article as a whole.

technical field

The invention relates to the technical field of hydrophilic compound embedding, and relates to a nano-microcapsule embedding a hydrophilic compound and its preparation method and application, in particular to a method and a product for embedding a hydrophilic compound in a protein and polysaccharide nano-microcapsule.

Background technique

Microencapsulation technology can achieve targeted delivery and precise release of food and drug active substances, but hydrophilic compounds are easily diffused into the aqueous phase, which limits the embedding of hydrophilic compounds. There are a large number of reports on the entrapment of hydrophobic components, however, there is still a lack of effective methods for entrapment and delivery of hydrophilic compounds. At present, the embedding methods of hydrophilic compounds mainly include multilayer emulsions, liposomes, and hydrogels. These methods have technical problems such as thermal instability, low embedding efficiency, and non-edible materials.

Among the embedding materials of hydrophilic compounds, polysaccharides and proteins have attracted widespread attention because of their natural and safe characteristics. Commonly used natural polysaccharides include sodium alginate, chitosan, gum arabic, etc. Natural proteins include whey protein, bovine serum protein, casein, etc. Some scholars use sodium alginate gel beads to embed hydrophilic drugs (doxorubicin hydrochloride), and add sodium alginate and hydrophilic compounds to the mixed solution of calcium chloride and chitosan to achieve hydrophilicity. The layer-by-layer self-assembly of compounds, however, the large particle size (about 100 μm) limits its application. There are also some scholars who use ultrasonic emulsion method to prepare microcapsules for the delivery of hydrophilic compounds, but the highest yield is 38.2%, and the highest embedding rate is 54.6%.

Caffeine is a central nervous system excitatory substance, which has extensive excitatory effects on the central nervous system, can enhance the excitement of the cerebral cortex and cortical motor areas, and is soluble in water and ethanol. Caffeine is widely found in tea, coffee, cocoa and other plants. Small doses of caffeine have the functions of anti-oxidation, protection of cardiovascular vessels, diuresis, reduction of fatigue, and improvement of work efficiency. After the human body ingests caffeine, it reaches the peak blood concentration in about 40-50 minutes, so multiple doses are required to produce sustained beneficial effects. However, large doses of caffeine may lead to adverse reactions, such as nervousness, palpitations, anxiety, tremors, muscle twitching, sleep disorders and other symptoms. The effect of caffeine can be delayed or prolonged by means of microcapsules, so as to achieve a sustained stimulating effect.

Contents of the invention

In the prior art, when preparing nanocapsules for embedding hydrophilic compounds, the commonly used embedding methods mainly include methods such as multilayer emulsions, liposomes, and hydrogels. These methods have thermal instability, low embedding efficiency, and Technical issues such as non-food grade materials. The present invention finds for the first time that under the appropriate ratio of wall material and core material, combined with continuous ultrasonic and acidification treatment, the core material (hydrophilic compound) can be successfully embedded in the wall material composed of polysaccharides and proteins, forming a durable Nanocapsules with core-shell or core-shell-shell structures that embed hydrophilic compounds.

Specifically, in order to solve the problems of thermal instability of the system, low embedding rate, and non-edible grade materials in the prior art, the present invention provides a specific solution as follows:

In the first aspect, the present invention provides a method for preparing nano-microcapsules embedding hydrophilic compounds, using protein and polysaccharide as wall materials, mixing the wall materials and the hydrophilic compounds in water to form a mixed solution, and ultrasonically During the process of treating the mixed solution, the pH of the mixed solution is adjusted to 3.4-4.5, and the nano-microcapsules with the core-shell structure capable of embedding the hydrophilic compound are obtained.

The preparation method provided by the present invention adopts food-grade wall materials and physical treatment methods, which effectively reduces the difficulty of process treatment. The present invention changes the pH of the mixed solution while ultrasonicating, so that polysaccharides and proteins used as wall materials form dense nano-microcapsules The core-shell structure effectively entraps hydrophilic compounds dispersed in water. The nano-microcapsules obtained by the preparation method provided by the invention can be used in fine processing fields such as food, medicine and health products.

In the preparation method provided by the present invention, the concentration of the protein is 0.3-10%, and the concentration of the polysaccharide is 0.3-10% in terms of mass volume percentage; the ultrasonic treatment is 100-750W ultrasonic 1- 5min.

In the preparation method provided by the present invention, the polysaccharide is carrageenan and/or chondroitin sulfate; the concentration of the polysaccharide is 1-3%.

In the preparation method provided by the present invention, the protein is whey protein, bovine serum albumin, casein and/or egg white protein; the protein is whey protein; and the concentration of the protein is 1-3%.

When the preparation method provided by the present invention is used to prepare the hydrophilic compound nano-microcapsules, the hydrophilic compound accounts for 0.5-7% of the total weight of the dry matter of the wall material. During the ultrasonic treatment process, the concentration of 1-3 % protein solution, can form core-shell-shell self-assembled hydrophilic compound nanocapsules.

In the preparation method provided by the present invention, the hydrophilic compound is caffeine, coffee extract, anthocyanin, polysaccharide, oligopeptide, polypeptide, phycocyanin, cyclic nucleotide, cyclic adenosine monophosphate and/or terpene acids.

In the second aspect, the present invention provides a nano-microcapsule that can be used to embed hydrophilic compounds, which is prepared by the above-mentioned preparation method.

In a third aspect, the present invention provides a hydrophilic compound nanocapsule prepared by the above-mentioned method. The nanocapsule has a particle size of 100-500 nm and exhibits a core-shell structure or a core-shell-shell structure.

According to the understanding of those skilled in the art, the present invention also claims the application of the above-mentioned preparation method or the above-mentioned nano-microcapsules in the production of functional foods, functional health products or targeted therapeutic drugs.

Specifically, after sterilizing and filling the solution containing the above-mentioned nano-microcapsules, a beverage containing hydrophilic compound nano-microcapsules is obtained;

Or spray-dry the solution containing the above-mentioned nano-microcapsules, the inlet air temperature: 160-190° C., the outlet temperature: 70-90° C., collect the tower bottom product, and obtain the powder of the hydrophilic compound nano-microcapsules.

As a specific embodiment of the present invention, the present invention also claims a method for preparing caffeine nanocapsules, wherein whey protein, chondroitin sulfate and caffeine are mixed in water to form a mixed solution, and the whey protein or The concentration of chondroitin sulfate is 0.3-3%; the caffeine accounts for 0.5-7% of the total weight of protein and polysaccharide dry matter; while the mixed solution is ultrasonically treated at 100-750W for 1-5min, the pH of the mixed solution is adjusted For 4, obtain caffeine nano-microcapsules.

In the preparation of caffeine nano-microcapsules, whey protein and chondroitin sulfate form a cavity under ultrasonic treatment, and in an acidic environment, whey protein and chondroitin sulfate are further cross-linked to form a nanocapsule shell. The cavity of the nanocapsule shell provides space for the entrapment of caffeine.

The beneficial effects of the present invention are at least:

(1) The nano-microcapsules of hydrophilic compounds prepared by the present invention adopt food-grade materials as wall materials, and the protein and polysaccharides used as wall materials are highly safe and have good edible value;

(2) The hydrophilic compound nano-microcapsules prepared by the present invention have a particle diameter of 100-500nm and have good dispersibility;

(3) By adopting the preparation method provided by the present invention, hydrophilic compounds such as caffeine can be effectively embedded to form a core-shell structure, and further a core-shell-shell structure can be formed;

(4) The preparation method provided by the present invention has a wide range of applications and can be used for anthocyanins, polysaccharides, functional oligosaccharides (oligosaccharides), polypeptides, proteins, cyclic nucleotides, cyclic adenosine monophosphate, terpene Preparation of nano-microcapsules of water-soluble compounds such as enoic acid compounds.

Description of drawings

Fig. 1 is a scanning electron microscope image (left) and a transmission electron microscope image (right) of hydrophilic compound nanocapsules in Example 1 of the present invention.

Figure 2 is an effect diagram of the hydrophilic compound nanocapsules prepared in the present invention.

Detailed ways

The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention. Without departing from the spirit and essence of the present invention, any modifications or replacements made to the methods, steps or conditions of the present invention belong to the protection scope of the present invention.

If not specified, the experimental materials, reagents, instruments, etc. used in the examples of the present invention are commercially available; if not specified, all technical means in the examples of the present invention are conventional means well known to those skilled in the art.

Example 1

The present embodiment provides the preparation method of caffeine nano-microcapsules, the steps are as follows:

(1) Preparation of nano-microcapsules

The protein, polysaccharide and caffeine are dissolved in water, wherein the concentration of protein is 0.8%, the concentration of polysaccharide is 1.2%, and the content of caffeine accounts for 1% of the total weight of protein and polysaccharide dry matter.

The polysaccharide is chondroitin sulfate; the protein is whey protein; and the caffeine is the extract of coffee.

Immerse the ultrasonic probe in the mixed solution or use an ultrasonic device to sonicate the mixed solution at 500W for 3 minutes;

During the ultrasonic process, the pH of the system is adjusted to 3.5 by using 1% citric acid solution to obtain nanometer microcapsules.

(2) Layer by layer self-assembled nano-microcapsules

In order to further enhance the slow-release effect of nano-microcapsules, protein solution can be added during the continuous ultrasonication of the above solution to form core-shell-shell self-assembled nano-microcapsules. The electron microscope scanning image of the prepared nano-microcapsules is shown in Fig. 1. The caffeine mixed solution prepared in this embodiment is shown in FIG. 2 .

The finally obtained core-shell-shell structure nano-microcapsule embedding rate was 81.5%, and the core-shell structure nano-microcapsule embedding rate was 70.2%.

Example 2

The present embodiment provides the preparation method of caffeine nano-microcapsules, the steps are as follows:

(1) Preparation of nano-microcapsules

The protein, polysaccharide and caffeine are dissolved in water, wherein the concentration of protein is 0.3%, the concentration of polysaccharide is 0.5%, and the content of caffeine accounts for 1% of the total weight of protein and polysaccharide dry matter.

The polysaccharide is chondroitin sulfate; the protein is whey protein.

Immerse the ultrasonic probe in the mixed solution or use an ultrasonic device to sonicate the mixed solution at 100W for 3 minutes;

During the ultrasonic process, the pH of the system is adjusted to 3.5 by using 1% citric acid solution to obtain nanometer microcapsules.

(2) Layer by layer self-assembled nano-microcapsules

In order to further enhance the slow-release effect of the nano-microcapsules, the protein solution can be added during the continuous ultrasonication of the above solution to form core-shell-shell self-assembled nano-microcapsules.

The embedding rate of the finally obtained nano-microcapsules with the core-shell-shell structure was 66.8%, and the embedding rate of the nano-microcapsules with the core-shell structure was 60.3%.

Example 3

The present embodiment provides the preparation method of caffeine nano-microcapsules, the steps are as follows:

(1) Preparation of nano-microcapsules

The protein, polysaccharide and caffeine are dissolved in water, wherein the concentration of protein is 2%, the concentration of polysaccharide is 3%, and the content of caffeine accounts for 0.5% of the total weight of protein and polysaccharide dry matter.

The polysaccharide is chondroitin sulfate; the protein is bovine serum albumin.

Immerse the ultrasonic probe in the mixed solution or use an ultrasonic device to sonicate the mixed solution at 750W for 4 minutes;

During the ultrasonic process, the pH of the system is adjusted to 4.5 by using 1% citric acid solution to obtain nanometer microcapsules.

(2) Layer by layer self-assembled nano-microcapsules

In order to further enhance the slow-release effect of the nano-microcapsules, the protein solution can be continuously added during the continuous ultrasonication of the above solution to form core-shell-shell self-assembled nano-microcapsules.

The embedding rate of the finally obtained nano-microcapsules with core-shell-shell structure was 89.5%, and the embedding rate of nano-microcapsules with core-shell structure was 79.2%.

Embodiment 4 Anthocyanin nano-microcapsules, phycocyanin nano-microcapsules

This example provides anthocyanins and phycocyanin as core materials to prepare nano-microcapsules. The preparation of the solution and the preparation of the nano-microcapsules in this example are the same as in Example 1, except that the core materials used in this example are anthocyanins and phycocyanin.

The mixed solution of anthocyanin and phycocyanin prepared in this example is shown in FIG. 2 . It can be seen from Figure 2 that the three core materials are all in a uniform and stable state, and Figure 2 confirms that the present invention is used as a general system to realize the embedding of hydrophilic compounds in food or medicine. This example proves that the preparation method provided by the present invention has universal applicability in preparing nano-microcapsules for embedding hydrophilic compounds. The preparation method provided by the present invention can be used to prepare anthocyanins, polysaccharides, phycocyanin, functional oligosaccharides (oligosaccharides), polypeptides, proteins, cyclic nucleotides, cyclic adenosine monophosphate, Nanocapsules of water-soluble compounds such as terpene acids.

Embodiment 5 Nano-microcapsule product

After the solution of the nano-microcapsules prepared in Example 1 is sterilized and canned, the beverage in which protein and polysaccharide nano-microcapsules are embedded with caffeine is obtained; the solution containing the nano-microcapsules is spray-dried, and the air inlet temperature is 180 °C, outlet temperature: 80 °C, and finally collect the bottom product to obtain caffeine nanocapsule powder.

Comparative example 1 Different wall materials

This comparative example adopts gum arabic and whey protein as wall materials, adopts the same method as embodiment 2 to prepare caffeine nano-microcapsules, finds that the nano-microcapsules that successfully embed caffeine cannot be obtained, and the test shows that gum arabic cannot be mixed with whey The protein forms the shell of the nanocapsules in which the caffeine is embedded.

Comparative example 2 The ratio of different core materials and wall materials

This comparative example provides a preparation method of caffeine nano-microcapsules, the preparation method provided by this comparative example is the same as that of Example 1, the difference is that the concentration of protein in the mixed solution of this comparative example is 2.7%, and the concentration of polysaccharide is 0.3% %, the content of caffeine accounts for 8% of the total weight of protein and polysaccharide dry matter. The whole system cannot maintain uniformity and stability, and a large amount of precipitation occurs.

Comparative Example 3 Different ultrasonic frequencies

This comparative example provides a preparation method of caffeine nano-microcapsules. The preparation method provided by this comparative example is the same as that of Example 1. The difference is that in this comparative example, after the solutions are mixed, the ultrasonic probe is immersed in the mixed solution or ultrasonically device, ultrasonically process the mixed solution for 3 minutes under the condition of 800W.

The finally obtained core-shell-shell structure nano-microcapsule embedding rate is 52.6%, and the core-shell structure nano-microcapsule embedding rate is 46.1%. This comparative example proves that ultrasonic treatment with too high power may cause microcapsule rupture, which is not conducive to the formation of caffeine nano-microcapsules.

Comparative example 4

This comparative example provides a preparation method of caffeine nano-microcapsules. The preparation method provided by this comparative example is the same as that of Example 1. The difference is that in this comparative example, after the solution is mixed, it is stirred magnetically for 3 minutes, and the pH is adjusted during magnetic stirring. value. Experiments cannot obtain nano-microcapsules with core-shell-shell or core-shell structure. This comparative example confirms that ultrasound produces cavitation, forming a spherical structure of nano-microcapsules.

Although the present invention has been described in detail with general descriptions and specific embodiments above, it is obvious to those skilled in the art that some modifications or improvements can be made on the basis of the present invention. Therefore, the modifications or improvements made on the basis of not departing from the spirit of the present invention all belong to the protection scope of the present invention.

Industrial Applicability

The invention provides a nanometer microcapsule embedding a hydrophilic compound, a preparation method and application thereof. The hydrophilic compound nano-microcapsules provided by the present invention use protein and polysaccharide as the wall material, mix the wall material and the hydrophilic compound in water to form a mixed solution, and adjust the pH of the mixed solution to 3.4-4.5, obtaining hydrophilic compound nanocapsules. In the preparation method provided by the invention, the hydrophilic compound accounts for 0.5-7% of the total dry weight of the wall material. The hydrophilic compound nanocapsules provided by the present invention have good dispersibility, can effectively embed caffeine and other hydrophilic compounds, and form a core-shell structure. The hydrophilic compound nanocapsules provided by the present invention can further form a core-shell- The shell structure has good economic value and application prospect.

Claims (9)

1. A preparation method for nano-microcapsules embedding hydrophilic compounds, characterized in that protein and polysaccharides are used as wall materials, and the protein and polysaccharides are mixed with the hydrophilic compounds in water to form a mixed solution, and the mixed solution is Performing ultrasonic treatment, during the ultrasonic treatment of the mixed solution, adjusting the pH of the mixed solution to 3.4-4.5 to obtain nano-microcapsules with a core-shell structure embedding the hydrophilic compound;

   In terms of mass volume percentage, the concentration of the protein is 0.3-10%, the concentration of the polysaccharide is 0.3-10%; the hydrophilic compound accounts for 0.5-7% of the total weight of the dry matter of the wall material;

   The polysaccharide is carrageenan or chondroitin sulfate; the protein is whey protein, bovine serum albumin, casein or egg white protein;

   The hydrophilic compound is caffeine, coffee extract, anthocyanin, polysaccharide, oligopeptide, polypeptide, phycocyanin, cyclic nucleotide, cyclic adenosine monophosphate and/or terpene acid compound;

   The sonication is at 100-750W for 1-5min.
2. The preparation method according to claim 1, characterized in that the concentration of the polysaccharide is 1-3%; the concentration of the protein is 1-3%.
3. The preparation method according to claim 2, characterized in that the protein is whey protein.
4. According to the preparation method described in any one of claims 1-3, it is characterized in that, in the ultrasonic treatment process, continue to add the protein solution with a concentration of 1-3%, forming a core-shell-shell self-assembled hydrophilic compound nano Microcapsules.
5. A nano-microcapsule embedding a hydrophilic compound, characterized in that it is prepared by the preparation method described in any one of claims 1-4.
6. The nano-microcapsule for embedding a hydrophilic compound according to claim 5, characterized in that, the particle size of the nano-microcapsule is 100-500 nm, and presents a core-shell structure or a core-shell-shell structure.
7. Application of the preparation method described in any one of claims 1-4 or the nano-microcapsules described in any one of claims 5-6 in the production of functional food, functional health products or targeted therapeutic drugs.
8. Application according to claim 7, is characterized in that, after the solution containing the nano-microcapsules described in claim 6 is sterilized and canned, obtain the beverage containing the nano-microcapsules of hydrophilic compounds;

   Or spray-dry the solution containing the nanocapsules according to claim 6, the inlet air temperature: 160-190° C., the outlet temperature: 70-90° C., collect the tower bottom product, and obtain the powder of the hydrophilic compound nanocapsules.
9. A method for preparing caffeine nano-microcapsules, characterized in that whey protein, chondroitin sulfate and caffeine are mixed in water to form a mixed solution, and the concentrations of the whey protein and chondroitin sulfate are 1-3% ; the caffeine accounts for 0.5-7% of the total weight of protein and polysaccharide dry matter; the mixed solution is ultrasonically treated at 100-750W for 1-5 minutes, and the pH of the mixed solution is adjusted to 4 to obtain caffeine nanocapsules .

Images