KR20220127509A - Process for preparing eco-friendly and stabilized complex coacervate particles - Google Patents

Abstract

The present invention relates to a method for producing eco-friendly and stabilized complex coacervate particles, and more specifically, to a method for producing eco-friendly and stabilized complex coacervate particles (HA-Ball) in which a natural extract is used as an acid/base regulator, and hyaluronic acid (HA), silica, block polymers, and the like are used as cross-linking agents and stabilizers in producing complex coacervate particles encapsulating a core material in a coacervate shell. According to the present invention, the method for producing eco-friendly and stabilized novel coacervate particles is implemented by replacing a chemical acid/base regulator and a cross-linking agent used in a conventional to prepare complex coacervate particles with natural product-based raw materials. In addition, the method for producing complex coacervate particles is implemented by using hyaluronic acid (HA) as a novel stabilizer such that coacervate can be stabilized or the strength of coacervate can be increased through matrix formation or linker connection.

Description

Method for preparing eco-friendly and stabilized complex coacervate particles {Process for preparing eco-friendly and stabilized complex coacervate particles}

The present invention relates to a method for producing environmentally friendly and stabilized composite coacervate particles, and more specifically, in producing composite coacervate particles encapsulating a core material in a coacervate shell, a natural extract is used as an acid/base regulator, and a crosslinking agent and stability It relates to a method for manufacturing eco-friendly and stabilized complex coacervate particles (HA-Ball) using hyaluronic acid (HA), silica, block polymer, etc.

Coacervation is the precipitation of polymers dissolved in aqueous solution through intermolecular forces, specifically electrostatic attraction, electrostatic bonding, hydrogen bonding, cation-π interaction, hydrophobic interaction, and attractive van der Waals forces in aqueous solution. It refers to the droplets that are formed by This reaction occurs spontaneously with low interfacial energy. Conditions that affect coacervation include the pH and ionic strength of the solution, temperature, the type of polyelectrolyte, the concentration of the polymer, the molecular weight and three-dimensional structure of the polymer, and the mixing ratio of the two oppositely charged polymers. When the prepared coacervation solution is left to stand for a long time, droplets can be obtained by phase separation. The low interfacial energy of complex coacervates allows them to encapsulate a variety of substances, including dyes, particles, fragrances, and cells.

Microencapsulation is the process of encapsulating a core material into small droplets in a protective coating. This process is carried out to aid in storage and to handle or control the release of the encapsulated material. Many techniques exist for forming microcapsules. As one technique, complex coacervation is known. Coacervation is the process of separating an aqueous colloid into two liquid phases, one of which is condensed into relatively colloids and the other is diluted to relatively colloids. When only a single type of colloidal material is present, the process is referred to as simple coacervation. However, when a mixture of two (oppositely charged) colloids is present, the process is referred to as complex coacervation. When complex coacervation occurs, the colloid must be ionized or capable of being ionized, and the conditions for coacervation require that the colloid be oppositely charged. Conditions for coacervation can be brought about by the selection of appropriately charged colloids. Alternatively, if an amphoteric colloid (eg protein, eg gelatin) is used, the pH of the colloidal mixture can be adjusted above or below the isoelectric point to impart a suitable charge to the amphiphilic colloid.

Complex coacervate can also be produced by electrostatic bonding of cationic polymer and anionic polymer, and by forming a coacervate shell that adsorbs on the surface of the core material and coats it, it is possible to make composite coacervate particles encapsulating the core material in the coacervate shell. have.

Since the coacervate technology is a spontaneous reaction, it is easy to manufacture without additional equipment or energy, but it requires the use of acids, base modifiers, and crosslinking agents to produce stable particles. However, there is a problem that the acid, base modifier or crosslinking agent is not environmentally friendly because it is a chemical substance.

Accordingly, as a result of intensive research efforts in order to overcome the problems of the prior art, the present inventors have completed an eco-friendly and stabilized novel coacervate particle manufacturing method by replacing an acid, a base regulator or a crosslinking agent with a natural product-based raw material.

US 10-2020-0116870 A US 10-1810540 B

Accordingly, the main object of the present invention is to provide a method for preparing complex coacervate particles that is more environmentally friendly and stabilized than conventional methods.

Another object of the present invention is to provide an environmentally friendly and stabilized complex coacervate particles prepared by the above manufacturing method.

According to one aspect of the present invention, there is provided a method for preparing an environmentally friendly and stabilized complex coacervate particle comprising the steps of:

(a) preparing a core material to be encapsulated in coacervate particles;

(b) homogenizing the cationic polymer and the anionic polymer in an aqueous phase to prepare a coacervate emulsion;

(c) adding the core material of step (a) to the coacervate emulsion of step (b);

(d) adding an acidic natural product or a basic natural product for pH adjustment; and

(e) adding high molecular weight hyaluronic acid and low molecular weight hyaluronic acid as a stabilizer for stabilizing the coacervate particles; and

(f) recovering the coacervate particles after washing the precipitate separated from the result of step (e).

In the present invention, the core material of step (a) may include any material that can be encapsulated in the coacervate shell, and both water-soluble materials or fat-soluble/poorly-soluble materials are possible. As a water-soluble substance, it is a substance that cannot be dissolved in a simple aqueous phase, has a strong odor, or has poor stability due to factors such as light, heat, pH, salt, etc. You can choose. As fat-soluble substances, common oils include dimethicone, hydrogenated C6-14 olefin polymer, diphenylsiloxy phenyl trimethicone, mineral oil, caprylic/capric triglyceride, C18-21 alkane, etc. The above oils may be included, and as the vegetable oil, one or more types may be selected from meadowfoam seed oil, sunflower seed oil, camellia oil, olive oil, grape seed oil, and fermented camellia oil. As a poorly soluble substance, it is not soluble in water and has a property of lowering stability due to factors such as light, heat, pH and salt. Vitamin A, vitamin E, coenzyme Q10, Esculin, lucinol, ceramide, TECA, phytosterol, One or more types can be selected from routines, etc.

In the present invention, preferably, the core material of step (a) provides a method for producing complex coacervate particles, characterized in that the pharmaceutical or cosmetic active material. In an embodiment of the present invention, as a cosmetic active material, cholesteryl liquid crystal, which is a component of skin intercellular lipid, has excellent skin moisturizing effect and has excellent visual aesthetic effect due to optical specificity, was used as a core material.

In the present invention, the cationic polymer of step (b) may be any cationic polymer that is cationically charged and capable of electrostatically bonding with an anionic polymer to form a complex coacervate, but preferably, a cationic polymer. The sexual polymer is at least one selected from the group consisting of agar, xanthan, gelatin, tylcellulose, polyacrylate, carboxyvinyl polymer, polyamide, polyvinyl alcohol, polyvinylpyrrolidone, albumin, chitosan, or polylysine. It provides a method for producing complex coacervate particles comprising

In the present invention, the anionic polymer of step (b) may be any anionic polymer capable of being anionically charged and electrostatically binding with the cationic polymer to form a complex coacervate, but preferably, arabic At least one selected from the group consisting of gum, carboxymethyl cellulose, gelatin, gellan, carboxyvinyl polymer, low methoxyl pectin, xanthan gum, sodium carboxymethyl guar gum, sodium hyaluronate, alginate, dextran sulfate, alginic acid, or carrageenan It provides a method for producing complex coacervate particles, characterized in that.

In the present invention, the acidic natural product or basic natural product in step (d) may be any natural product capable of adjusting the pH by being acidic or basic, but preferably, the acidic natural product is an amino acid complex, lemon extract, lemon fermented vinegar , aloe vera extract, AHA / BHA complex, or a natural product selected from vitamin extract, and the basic natural product is avocado extract, celery extract, broccoli extract, yellow lotus extract, yellow white extract, resurrected plant water, snail mucus extract, black pearl extract, or menthol extract It provides a method for producing complex coacervate particles, characterized in that the selected natural product.

In the present invention, as the stabilizer in step (e), the high molecular weight hyaluronic acid has an average molecular weight of 500,000 to 3,000,000 daltons, and the low molecular weight hyaluronic acid has an average molecular weight of 500 to 50,000 daltons. It provides a method for producing complex coacervate particles. . In the present invention, the weight ratio of the high molecular weight hyaluronic acid to the low molecular weight hyaluronic acid is preferably 1:1 to 5:1, and most preferably 2:1. As the ratio of the polymeric hyaluronic acid increases, the composite coacervate particles are hardened and may be more helpful for stabilization, but if it is 10:1 or more, the composite coacervate particles may be hardened too much and the physical properties may deteriorate.

In the experimental example of the present invention, it was confirmed that the stabilization effect was higher when the high molecular weight and low molecular weight hyaluronic acid were used together, compared to the case where only the high molecular weight hyaluronic acid or the low molecular weight hyaluronic acid was used. Conventionally, hyaluronic acid (HA) is used as a kind of anionic polymer for making coacervate, but in the present invention, hyaluronic acid (HA) is used as a stabilizer for stabilizing coacervate.

In the present invention, preferably, the stabilizer of step (e) further comprises at least one stabilizer selected from silica or block copolymer in addition to high molecular weight and low molecular weight hyaluronic acid. to provide. In the present invention, the block copolymer is preferably a block copolymer having both hydrophilic/lipophilic groups, for example, a PEG-PCL copolymer or a PS-PCL copolymer may be used. In the experimental example of the present invention, it was confirmed that when silica and block copolymer were further included in addition to high molecular weight and low molecular weight hyaluronic acid, the stabilizing effect was higher than that containing only high molecular weight and low molecular weight hyaluronic acid. The stabilizer in step (e) stabilizes the coacervate or increases the strength through linker linkage or matrix formation.

According to another aspect of the present invention, the present invention provides a composite coacervate particle encapsulated in a core material produced by the method of the present invention.

In the present invention, the primary stabilizer, preferably silica or a block copolymer, is arranged like a linker between the coacervate shell and the core material, and the secondary stabilizer, which is a high molecular weight and low molecular weight hyaluronic acid, is outside the coacervation shell. It provides a composite coacervate particle characterized in that it is oriented on the side to form a matrix shell.

According to the present invention, it is possible to provide an eco-friendly and stabilized novel coacervate particle manufacturing method by replacing the chemical acid, base modifier, and crosslinking agent used to prepare the conventional composite coacervate particles with a natural product-based raw material. In addition, by using hyaluronic acid (HA) or the like as a new stabilizer, it is possible to provide a method for preparing complex coacervate particles that stabilizes the coacervate or increases the strength through matrix formation or linker linking.

1 is a schematic diagram showing the structure and manufacturing method of the composite coacervate particles of the present invention.
Figure 2 is a photograph of a comparative experiment on the stability of the composite coacervate particles according to the Examples and Comparative Examples of the present invention at 25 ℃ after 3 months (Figure 2a is Example 1-3, Figure 2b is Comparative Example 1-4)

Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention and should not be construed as limiting the scope of the present invention by these examples.

Examples and Comparative Examples: Preparation of Composite Coacervate Particles

(a) preparing the active material to be encapsulated in the coacervate particles

Cholesteryl chloride (CC), cholesteryl stearate (CS), and cholesteryl benzoate (CB) in the ratios shown in Table 1 below were homogeneously mixed at high temperature (70-80 degrees) using AZI MIXER. A cholesteric liquid crystal composition exhibiting various colors was prepared by mixing.

Content (g)
Raw material name liquid crystal 1 liquid crystal 2 liquid crystal 3 liquid crystal 4 Cholesteryl Chloride (CC) 3.0 2.5 2.0 3.5 Cholesteryl Stearate (CS) 6.0 4.0 3.0 5.0 Cholesteryl Benzoate (CB) 1.5 4.0 5.0 2.0

(b) homogenizing the cationic polymer and the anionic polymer in an aqueous phase to prepare a coacervate emulsion;

Agar as a cationic polymer was put in purified water to make a 5% solution, and carrageenan as an anionic polymer was added to purified water to make a 5% solution, and then the two solutions were homogenized with AZI MIXER at 500 rpm for 30 minutes to prepare a coacervate emulsion.

(c) adding the liquid crystal raw material of step (a) to the coacervate emulsion of step (b);

A cholesteryl liquid crystal (CLC) made of liquid crystal 1 among the cholesterol liquid crystal composition prepared in (a) was placed in the aqueous emulsion of step (b) and encapsulated in coacervate particles using AZI MIXER.

(d) adding an acidic or basic natural product to adjust pH;

Coacervation can be induced by using lemon extract as an acidic natural product and by adjusting the pH to 7 to 9 using revitalizing water as a basic natural product.

(e) adding a stabilizer to harden the coacervate particles;

In the present invention, high molecular weight HA (Mw 1.8~0.6Mda) and low molecular weight HA (Mw 0.5~10.1Kda and silica, PEG-PCL block copolymer were used as stabilizers. As a positive control, GA, which is widely known as a crosslinking agent for curing coacervates (Glutaraldehyde) was used The names and contents of raw materials used in Examples and Comparative Examples are shown in Table 2 below.

Content (g)
Raw material name Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 cholesteric liquid crystal One One One One One One One baby 0.5 0.5 0.5 0.5 0.5 0.5 0.5 carrageenan 0.7 0.7 0.7 0.7 0.7 0.7 0.7 lemon extract 3 3 3 3 3 3 3 resurrection candle 5 5 5 5 5 5 5 low molecular weight HA One One One - One - - polymer HA 2 2 5 2 - - - PEG-PCL block copolymer - 0.5 0.5 0.5 0.5 0.5 - Silica - 0.3 0.3 0.3 0.3 0.3 - GA - - - - - - 3

(f) recovering the coacervate particles after washing the precipitate separated from the emulsion;

It is washed with purified water to remove unreacted substances in coacervation and to obtain coacervate particles (HA-Ball) (repeat 3 times)

A schematic diagram of the structure and manufacturing method of the composite coacervate particles (HA-Ball) of the present invention prepared according to the above example is shown in FIG. 1 .

Experimental Example 1: Stability test of composite coacervate particles

조건에서 제조 직후, 1개월 경과후, 3개월 경과후로 나누어 관찰했다. 평가는 입자 안정도에 따라 X: 입자 터짐, △: 약간 변함, ○: 입자 안정, ●: 입자 경화로 표시하였다. In order to compare the stability of the composite coacervate particles prepared according to the Examples and Comparative Examples, the state of the particles dispersed in purified water was

Under the conditions, observations were made immediately after production, after 1 month, and after 3 months. The evaluation was expressed as X: particle burst, △: slightly changed, ○: particle stability, ●: particle hardening, depending on particle stability.

of particles
appearance Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 immediately after manufacturing ○ ○ ○ X X X ○ 1 month passed ○ ○ ○ X X X ○ 3 months passed △ ○ ● X X X ○

As shown in the table above, in Examples 1 to 3 (HA-Ball) using a polymer and a low molecular weight HA as a stabilizer according to the present invention, the particles did not burst and the stability was maintained until after 3 months. However, in Comparative Examples 1 to 3, in which only high molecular weight or low molecular weight HA was used as a stabilizer, or neither was used, the particles burst immediately after preparation, and thus stability was not maintained. When only high molecular weight and low molecular weight HA were used as stabilizers (Example 1), the particles showed a slight change after 3 months, but they were much more stable than when only high molecular weight or low molecular weight HA was used or neither was used (Comparative Examples 1 to 3). showed up When the polymer HA content was high (Example 3), the particles were hardened after 3 months, but the particles did not burst as in Comparative Examples 1 to 3. When all of the polymer and low molecular weight HA, silica, and block copolymer were included as stabilizers (Example 2), the particles were most stably maintained until 3 months elapsed.

High molecular weight and low molecular weight HA increase stability by forming a matrix shell on the outermost part of the composite coacervate particle (HA-Ball). Silica and the block copolymer act as a stabilizer to lower the interfacial energy by arranging like a linker between the CLC in the core and the coacervation shell. As in Example 2, when the primary stabilizer (silica, block copolymer, etc.) and the secondary stabilizer (high/low molecular weight HA) are together, HA-Ball is most stable. When only the 1st or 2nd stabilizer is added, the particles are well realized in the initial months, but as the additional months pass, the HA-Ball particles may change or break.

2 is a photograph of a comparative experiment of the stability of composite coacervate particles according to Examples and Comparative Examples at 25° C. after 3 months (Examples 1-3 and Comparative Examples 1-4 in that order) Examples 1-3 and In Comparative Example 4, the stability of the particles was maintained, but in Comparative Examples 1-3, the stability was not maintained because the particles burst.

Cosmetics of various formulation examples were prepared using the complex coacervate particles (HA-Ball) of Example 2.

Formulation Example 1: Preparation of lotion containing HA-Ball composition

A lotion was prepared by a conventional method with the composition described in the table below.

ingredient content(%) HA-Ball 0.5 Carbomer 0.05 tromethamine q.s Glycerin 3 BG 4 PEG-60 Hydrogenated Castor Oil 0.3 EDTA 0.02 preservatives, fragrances q.s Purified water To 100

Formulation Example 2: Preparation of Essence Containing HA-Ball Composition

Essence was prepared in a conventional manner with the composition described in the table below.

ingredient content(%) HA-Ball One Hydroxyethyl acrylate/sodium acryloyldimethyltaurate copolymer 0.2 Glycerin 7 BG 5 allantoin 0.1 betaine 0.2 Polyglyceryl-10 Stearate 0.1 EDTA 0.02 preservatives, fragrances q.s Purified water To 100

Formulation Example 3: Preparation of nutritional cream containing HA-Ball composition

Nutrient cream was prepared in a conventional manner with the composition described in the table below.

ingredient content(%) HA-Ball 0.5 Ammonium Acryloyl Dimethyl Taurate/Vpicopolymer 0.3 Glycerin 5 BG 7 squalane 2 Caprylic/Capric Triglycerides 3 Sorbitan Stearate One cetearyl alcohol One Polysorbate 60 0.5 EDTA 0.02 preservatives, fragrances q.s Purified water To 100

Although the present invention has been described with reference to the above embodiments, it will be understood that these are merely exemplary, and that various modifications and equivalent other embodiments are possible therefrom by those skilled in the art to which the present invention pertains. . Therefore, the true technical protection scope of the present invention should be determined by the technical matters of the appended claims.

Claims (8)

A method for producing environmentally friendly and stabilized complex coacervate particles comprising the steps of:
(a) preparing a core material to be encapsulated in coacervate particles;
(b) homogenizing the cationic polymer and the anionic polymer in an aqueous phase to prepare a coacervate emulsion;
(c) adding the core material of step (a) to the coacervate emulsion of step (b);
(d) adding an acidic natural product or a basic natural product for pH adjustment; and
(e) adding high molecular weight hyaluronic acid and low molecular weight hyaluronic acid as a stabilizer for stabilizing the coacervate particles; and
(f) recovering the coacervate particles after washing the precipitate separated from the result of step (e). According to claim 1, wherein the cationic polymer of step (b) is agar, xanthan, gelatin, tylcellulose, polyacrylate, carboxyvinyl polymer, polyamide, polyvinyl alcohol, polyvinylpyrrolidone, albumin, chitosan, or at least one selected from the group consisting of polylysine. According to claim 1, wherein the anionic polymer of step (b) is gum arabic, carboxymethyl cellulose, gelatin, gellan, carboxyvinyl polymer, low methoxyl pectin, xanthan gum, sodium carboxymethyl guar gum, sodium hyaluronate, alginate , dextran sulfate, alginic acid, or a method for producing complex coacervate particles, characterized in that at least one selected from the group consisting of carrageenan. The natural product according to claim 1, wherein the acidic natural product in step (d) is a natural product selected from amino acid complex, lemon extract, lemon fermented vinegar, aloe vera extract, AHA/BHA complex, or vitamin extract, and the basic natural product is avocado extract, celery extract , broccoli extract, hwangyeon lotus extract, hwangbaek extract, resurrection chosu, snail mucus extract, black pearl extract, or a method for producing complex coacervate particles, characterized in that the natural product selected from menthol extract. The method of claim 1, wherein the high molecular weight hyaluronic acid as the stabilizer in step (e) has an average molecular weight of 500,000 to 3,000,000 daltons, and the low molecular weight hyaluronic acid has an average molecular weight of 500 to 50,000 daltons. The method of claim 1, wherein the stabilizer in step (e) further comprises one or more stabilizers selected from silica or block copolymers in addition to high molecular weight and low molecular weight hyaluronic acid. The complex coacervate particle encapsulated in the core material prepared by the method of any one of claims 1 to 6. The method according to claim 7, wherein the primary stabilizer of silica or block copolymer is arranged like a linker between the coacervate shell and the core material, and the secondary stabilizer of high molecular weight and low molecular weight hyaluronic acid is oriented outside the coacervation shell. Composite coacervate particles, characterized in that they form a matrix shell.

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