KR101114659B1 - Nanoparticle stabilizing the oil soluble active ingredients by using biodegradable polymers and the process for preparing the same - Google Patents

Abstract

The present invention relates to nanoparticles stabilized with at least one oil-soluble active ingredient using a biodegradable polymer and a method for preparing the same. More specifically, the nanoparticles stabilized in the oil-soluble active ingredient according to the present invention comprises the steps of: (1) dissolving the oil-soluble active ingredient and the biodegradable polymer in a volatile organic solvent mixed with water; (2) dispersing and stirring the solution in water to form nanoparticles; And (3) removing the volatile organic solvent in the nanoparticle solution by evaporation. Nanoparticles prepared by the above steps are two kinds By using the above biodegradable polymers, the particle size can be freely controlled while maintaining the same concentration of the polymer encapsulating agent, and the stability of the formulation can be stabilized by maintaining the concentration of the useful active ingredient in the cosmetic formulation without crystallization. can do.

Biodegradable Polymer * Nanoparticles * Active Ingredients * Stabilization

Description

Nanoparticle stabilizing the oil soluble active ingredients by using biodegradable polymers and the process for preparing the same}

1 is a transmission electron micrograph of the nanoparticles prepared in Example 2 of the present invention.

Figure 2 is an optical microscope picture of Formulation Example 2 (a) and Comparative Formulation Example 2 (b) of the present invention.

The present invention relates to nanoparticles stabilized with at least one oil-soluble active ingredient using a biodegradable polymer and a method for preparing the same. More specifically, the nanoparticles stabilized in the oil-soluble active ingredient according to the present invention comprises the steps of: (1) dissolving the oil-soluble active ingredient and the biodegradable polymer in a volatile organic solvent mixed with water; (2) dispersing and stirring the solution in water to form nanoparticles; And (3) removing the volatile organic solvent in the nanoparticle solution by evaporation.

Recently, active ingredients used in cosmetics are related to whitening and aging, and water-soluble substances such as L-ascorbic acid and EGCG can be used as ingredients of cosmetics. However, in most cases they are present in a hydrophobic form, insoluble in water, and are very crystalline. In this case, dissolved in ethanol or 1,3-butylene glycol (butylene glycol) may be used in addition to cosmetics, but in most cases recrystallization is formed in the formulation. When micro or mm crystals precipitate in the formulation, the active ingredient cannot be absorbed into the skin, so the efficacy of the active ingredient cannot be expected. In addition, crystallization can have a significant detrimental effect on appearance as well as stability of the formulation. In addition, since most active substances are easily oxidized in the formulation, it may cause problems of discoloration and malodor.

Therefore, in order to maximize the stabilization and efficacy of the oil-soluble active ingredient, by allowing the active ingredient to be protected through an external substance, it is possible to prevent crystallization of the oil-soluble active ingredient and to prevent rapid oxidation in the cosmetic formulation. The most known method of protecting the active ingredient through an external material is encapsulation, which may be microcapsulation or nanocapsulation depending on the size of the encapsulated particles.

In general, microencapsulation is mostly used to protect the useful materials by using an insoluble external material, and a polymer is used as the external material to be encapsulated. Encapsulation methods include spraying, solvent evaporation, and co-diffusion methods depending on the purpose of use. In general, the particle size is between several microns and hundreds of microns, and the shape of the particle varies greatly depending on the method of manufacture.

Meanwhile, among the nanoencapsulation methods, the most widely known methods so far are the solvent evaporation method and the solvent displacement method. The solvent evaporation method dissolves a substance encapsulated in a volatile organic solvent and an oil-soluble substance in water, disperses the solution in an aqueous solution containing an anti-agglomerating agent to form particles, and distills the volatile organic solvent to prepare particles. will be. At this time, the size of the particles largely depends on the stirring speed at the time of dispersion, when using a common agitator (agitator) is formed a number of micron units, when using a high-speed stirring homogenizer (hundreds of nanometers) Particles form. However, in general, to obtain particles of several tens of nanometers, a high pressure homogenizer should be used, and when using this, particles having a size of 100 nanometers or less can be obtained. When the solvent evaporation method is used, the organic solvent should use a highly volatile solvent, and specific examples thereof include methylene chloride and ethyl acetate.

Meanwhile, the solvent replacement method dissolves a substance encapsulated in a volatile organic solvent mixed with water and an oil-soluble substance, disperses the solution in an aqueous solution containing an anti-agglomerating agent to form particles, and distills the volatile organic solvent to prepare particles. It is. Since this method uses a volatile organic solvent mixed with water, particles are formed by the difference in the solubility of the encapsulating material and the useful material in the cosolvent of water and the organic solvent. Therefore, water-soluble surfactants and other surfactants for preventing aggregation need. These include poly (ethylene oxide) -b-poly (propylene oxide) -b-poly (ethylene oxide) (Poly (ethylene oxide) -b-Poly (propylene oxide) -b-Poly (ethylene oxide); (PEO- b-PPO-b-PEO)) polymers having a high PEO content (eg, BASF F68), polyvinyl alcohol (PVA), etc. among the triblock polymers. A hydrophobic surfactant is used to stabilize the encapsulated oil-soluble active substance, which can prevent oxidization of the active substance from external water and oxygen by forming a lamellar phase on the capsule outer wall of the hydrophobic portion of the hydrophobic surfactant. (Korean Patent No. 2000-0048452; US2003-0224046). Such hydrophobic surfactants include high PPO polymers (e.g. Unichema Synpersonic L121) among PEO-b-PPO-b-PEO triblock polymers, silicon-based polymers grafted with PEO (e.g., DC5329 from Dow Corning) There is this. Factors affecting the size of the particles produced by the solvent replacement method is the ratio of the organic solvent and water, the concentration of the encapsulating agent and sparingly soluble active ingredient used in the organic solvent used, the amount of hydrophobic surfactant, It depends on the amount of hydrophilic surfactant and the stirring speed, and generally the size of particles obtained through these components and methods is between 100 and 300 nm.

Conventionally, when encapsulating an active ingredient, the purpose of preventing and stabilizing crystallization of the active ingredient is a microencapsulation method, which is a system well suited to the above two purposes, and is still used. However, as cosmetics are expected to have a direct effect on the skin in recent years, the encapsulating agent that stabilizes the active ingredient needs to be designed to have a practical effect. Recently, the development of encapsulation of the active ingredient through nanoparticles It is actively underway. In fact, considering that the human skin gap is between several tens to 100 nanometers, it is obvious that the particles are manufactured in nanometer size, so that the active ingredient is more likely to be delivered than the microparticles through the skin gap. In addition, when the prepared nanoparticles penetrate the skin, the encapsulating agent used in consideration of the safety of the body should be excellent in biocompatibility and biodegradability, and such encapsulating agents include polycaprolactone and poly (d, l-lac). Poly (d, l-lactide), Poly (L-lactide), poly (alkylene-succinate), poly (alkylene) Adipate) (poly (alkylene adipate)) and the like.

Solvent evaporation method of nanoencapsulation method can control the size of tens to hundreds of nanometers when manufacturing nanoparticles through high pressure emulsifier, but it requires special equipment such as high pressure emulsifier and it is impossible to remove organic solvent effectively after particle manufacturing. There is a problem that can occur precipitation and aggregation phenomenon during storage. In addition, the solvent substitution method is the concentration of the encapsulant used to have the greatest influence on the particle size, the low concentration of the encapsulant may not effectively encapsulate the useful active ingredient may cause crystallization of the useful active ingredient. In addition, when the concentration of the oil-soluble active ingredient and the encapsulating agent is low, it is necessary to use an excessive amount of the solution in which the active ingredient is encapsulated in the cosmetic formulation.

Therefore, the present inventors have a high concentration of encapsulating agent and oil-soluble active ingredient in the water phase, and easy to control the particles, In addition, the useful active ingredient contained in the prepared nanoparticles can be effectively stabilized, so as to study the nanoparticles containing the active ingredient did not affect the physical properties when added into the formulation, as a result of using two or more biodegradable polymers In the preparation of nanoparticles, the present inventors found that not only the size of the nanoparticles can be freely controlled, but also the oil-soluble active ingredient can be stabilized in the formulation, thereby completing the present invention.

Accordingly, an object of the present invention is to provide a nanoparticle stabilized oil-soluble active ingredient using a biodegradable polymer.

In addition, another object of the present invention to provide a method for producing the nanoparticles.

In order to achieve the above object, the nanoparticles stabilized in the oil-soluble active ingredient according to the present invention comprises the steps of: (1) dissolving the oil-soluble active ingredient and biodegradable polymer in a volatile organic solvent mixed with water; (2) dispersing and stirring the solution in water to form nanoparticles; And (3) removing the volatile organic solvent in the nanoparticle solution by evaporation.

Hereinafter, the present invention will be described in more detail.

The nanoparticles stabilized in the oil-soluble active ingredient according to the present invention have a problem that it is not easy to control the size of the particles while maintaining the concentration of the polymer encapsulating agent in the case of nano-particles of the oil-soluble active ingredient by the conventional method. By using a polymer of a single component and a polymer block copolymer of a heterogeneous component as a polymer encapsulating agent together, the size of the particles can be freely controlled while maintaining the same concentration of the encapsulating agent.

The polymer encapsulating agent maintains a high concentration, the high concentration means 10 to 40% by weight relative to the total weight of the nanoparticle solution, the corresponding concentration of the active ingredient is 1 to 2% by weight relative to the total weight of the nanoparticle solution. .

Nanoparticles according to the present invention are prepared in the following steps (1) to (3):

(1) dissolving the oil-soluble active ingredient and the biodegradable polymer in a volatile organic solvent mixed with water; (2) dispersing and stirring the solution in water to form nanoparticles; And (3) removing the volatile organic solvent in the nanoparticle solution by evaporation.

First, in order to include the oil-soluble active ingredient in the biodegradable polymer particles, the active ingredient must be dissolved in a volatile organic solvent mixed with water.

Volatile organic solvents mixed with water include methanol, ethanol, acetone, and THF (tetrahydrofuran), and acetonitrile and 1,4-dioxane as needed. Low volatility organic solvents such as) can also be used.

The oil-soluble active ingredient used in the present invention is specifically retinol, retinyl acetate, retinyl palmitate, tocopherol, tocopheryl acetate, tocopheryl linoleate, tocopheryl nicotinate, linoleic acid, coenzyme Q-10, Resveratrol ((E) -5- [2- (4-hydroxyphenyl ethenyl)]-1,3-benzene diol 3,4,5-trihydroxy stilbene), lipoic acid, licorice extract, thymol trimethoxycinnamate ( Thymol Trimethoxycinnamate, Curcumin, Tetrahydrocurcumin, Oleanolic acid, Ursolic acid, Betulin, Betulinic acid, Diosmetin , Quercetin, and lycopene. The content of the active ingredient is contained in an amount of 1 to 2% by weight based on the total weight of the nanoparticle solution.

In the present invention, the polymer used to encapsulate the oil-soluble active ingredient uses a polymer block copolymer including a single component polymer and a heterologous component having biodegradability and biocompatibility. Specifically, polymers having a single component include polycaprolactone, poly (D, L-lactide), poly (L-lactide), and poly (L-lactide). ) And so on.

On the other hand, the heterogeneous described herein means "different", "not the same", and the polymer block copolymer of the heterogeneous component is poly (caprolactone) -b-poly (ethylene oxide) (Poly (caprolactone) -b- Poly (ethylene oxide)), poly (D, L-lactide) -b-poly (ethylene oxide) (Poly (D, L-lactide) -b-Poly (ethylene oxide)), poly (L-lactide) -b-poly (ethylene oxide) (Poly (L-lactide) -b-Poly (ethylene oxde)), poly (ethylene oxide) -b-poly (caprolactone) -b-poly (ethylene oxide) (Poly (ethylene oxide) -b- Poly (caprolactone) -b-Poly (ethylene oxide)), poly (ethylene oxide) -b-poly (D, L-lactide) -poly (ethylene oxide) -b -Poly (D, L-lactide)-Poly (ethylene oxide)), poly (ethylene oxide) -b-poly (L-lactide) -b-poly (ethylene oxide) -b-Poly (L-lactide) -b-Poly (ethylene oxide)).

The number average molecular weight of the above-mentioned polymer is 10,000 to 100,000, preferably 50,000 or less in the case of a single component polymer. Moreover, in the case of the block copolymer which has a heterogeneous polymer, it is 5,000-50,000, Preferably it is 10,000-20,000. When preparing nanoparticles using the polymer, a biodegradable polymer of at least one single component and at least one block copolymer must be included, and the ratio of the polymer having a single component to the block copolymer is 100: 1 to 1: 100. This is preferred.

Nanoparticles according to the present invention is the particle size is determined according to the ratio of the polymer and the block copolymer having a single component used, the size of the particles can be produced up to 30 ~ 300nm. The size of such nanoparticles can vary depending on the type of oil-soluble active ingredient used.

Nanoparticles stabilized in the oil-soluble active ingredient according to the present invention may be contained in the cosmetic composition in an amount of 5 to 10% by weight based on the total weight of the composition, wherein the viscosity of the formulation, the surfactant to minimize the change in the characteristics of the formulation And an anti-agglomeration agent.

The formulation of the cosmetic composition containing the nanoparticles according to the present invention is not particularly limited, but skin, latex, cream, lotion, essence, pack, gel, powder, makeup base, foundation, lotion, ointment, patch, essence, cleansing Formulations such as foams, cleansing creams, cleansing water, body lotions, body creams, body oils, body essences, body cleansers, soaps, sprays and the like.

Hereinafter, although an Example and a test example are given and this invention is demonstrated in detail, this invention is not limited only to these examples.

Example 1: Nanoparticles Containing Two or More Biodegradable Polymers

Polycaprolactone with a number average molecular weight of 10,000 g / mol and poly (caprolactone) -b-poly (ethylene oxide) with 14,000 g / mol are 100: 1, 3: 1, 1: 1, 1: 3, The solution was completely dissolved in 200 ml of acetone at a weight ratio of 1: 100 at room temperature. Each solution was added to 300 ml of purified water, and then stirred for about 2-3 minutes in a stirrer, and residual acetone was removed at a temperature of about room temperature or about 40 ° C to prepare biodegradable polymer nanoparticles.

Example 2: Retinol Stabilized Nanoparticles Using Two or More Biodegradable Polymers

Polycarprolactone with a number average molecular weight of 10,000 g / mol, poly (caprolactone) -b-poly (ethylene oxide) and a retinol / Tween 20 mixture (1: 1 composition, BASF Retinol 50C) containing pure retinol The solution was completely dissolved by stirring in 200 ml of acetone at room temperature in a weight ratio of 5: 5: 1, 15: 5: 1, 25: 5: 1, 10: 10: 1, 15: 15: 1. Next, each solution was added to 300 ml of purified water and stirred for about 2-3 minutes in a stirrer, and then distilled acetone and water at room temperature or about 40 ° C. to prepare nanoparticles containing 1% by weight of retinol. .

Example 3: Thymol Trimethoxycinnamate Stabilized Nanoparticles Using Two or More Biodegradable Polymers

A number average molecular weight of 10,000 g / mol polycaprolactone, 14,000 g / mol polycaprolactone-b-poly (ethylene oxide), and thymol trimethoxycinnamate are 7: 3: 1, 14: 6: 1, 20 It was completely dissolved in 200 ml of acetone at a weight ratio of 10: 1 at room temperature. Then, each solution was added to 300 ml of purified water, stirred for 2-3 minutes in a stirrer, and distilled residual acetone and water at a temperature of about room temperature or about 40 ° C to contain 2% by weight of thymol trimethoxycinnamate. Nanoparticles were prepared.

Example 4: Tetrahydrocucumin Stabilized Nanoparticles Using Two or More Biodegradable Polymers

Number average molecular weight 10,000 g / mol of polycaprolactone, 14,000 g / mol of polycaprolactone-b-poly (ethylene oxide), and tetrahydrocurcumin in 7: 3: 1, 14: 6: 1 weight ratio in 200 ml of acetone at room temperature Stir at to dissolve completely. Next, each solution was added to 300 ml of purified water, followed by stirring for 2-3 minutes in a stirrer, followed by distillation of residual acetone and water at a temperature of about room temperature or about 40 ° C. to obtain 2% by weight of tetrahydrocurcumin nanoparticles. Prepared.

Comparative Example 1: Preparation of Retinol Nanoparticles Containing Only a Single-Component Biodegradable Polymer

Polycaprolactone with a number average molecular weight of 10,000 g / mol, dimethyl ethylene oxide silicon (Dow Corning DC5329) as a hydrophobic surfactant, and a retinol / Tween 20 mixture (1: 1 composition, BASF Retinol 50C) based on pure retinol content 3 It completely dissolved by stirring in 200 ml of acetone at room temperature in the ratio of 3: 3 and 7: 3: 1. Then, each solution was added to 300 ml of 0.2 wt% polyethylene oxide-b-polypropylene oxide-b-polyethylene oxide copolymer (BASF F68) solution, and then stirred for about 2-3 minutes in a stirrer, followed by room temperature or 40 ° C. Residual acetone and water were distilled at a temperature of about 1% by weight to prepare a nanoparticle containing retinol.

Comparative Example 2: Preparation of Retinol Nanoparticles Containing Only Biodegradable Polymers Composed of Heterogeneous Copolymers

Polycaprolactone-b-poly (ethylene oxide) with a number average molecular weight of 14,000 g / mol was mixed with a retinol / Tween 20 mixture (1: 1 composition, BASF Retinol 50C) at a weight ratio of 10: 1 and 20: 1 based on the pure retinol content. The solution was dissolved completely in acetone at room temperature. Next, each solution was added to 300 ml of purified water and stirred for about 2-3 minutes in a stirrer, and then distilled acetone and water at room temperature or about 40 ° C. to prepare nanoparticles containing 1% by weight of retinol. .

[Test Example 1] Characterization of the prepared nanoparticles

The capsule form of the nanoparticles prepared in Example 2 was observed by transmission scanning microscope, and the particle size of the nanoparticles prepared in Examples 1 to 4 using dynamic light scattering (Zetasizer 3000HSa Malvern Instruments) Measured. The results are shown in FIG. 1 and Table 1 below.

Example Composition (PCL: PCL-b-PEO: active ingredient) Particle size (nm) One 100: 1: 0 252 3: 1: 0 203 1: 1: 0 150 1: 3: 0 101 1: 100: 0 55 2 5: 5: 1 98 15: 5: 1 130 25: 5: 1 180 10: 10: 1 115 15: 15: 1 140 3 7: 3: 1 130 14: 6: 1 180 20: 10: 1 220 4 7: 3: 1 146 14: 6: 1 250

As shown in FIG. 1, polycaprolactone having a hydrophobicity and polycaprolactone, which is part of a block copolymer, form a particle together with retinol to form particles. It can be seen that the poly (ethylene oxide), which is part of the block copolymer, is present in the form of a tail so that it can be safely present. Therefore, inferring each component as a result of the above results, retinol and polycaprolactone become constituents inside the nanoparticles to form a core portion, and polycaprolactone stabilizes retinol to prevent crystallization of retinol. And it is thought that the retinol oxidation from water and oxygen is effectively blocked, and the poly (ethylene oxide) portion, which is part of the block copolymer, is hydrophilic, and thus, it is considered that the nanoparticle plays a stable role in the aqueous phase.

On the other hand, as can be seen from Table 1, it was observed from the results of Example 1 that the size of the nanoparticles freely changed depending on the amount and proportion of the single-component polymer and the block copolymer containing at least one monomer. In addition, in the preparation of nanoparticles containing an active ingredient (Examples 2 to 4), the size of the particles was observed to be freely controlled according to the concentration of the polymer, the amount and ratio of the single component and the block copolymer as in the case of Example 1. Could. In general, when the nanoparticles of oil-soluble active substances, especially active substances having high crystallinity, a high proportion of encapsulating agent should be added, particles of the active ingredient which cannot be encapsulated with only a single component encapsulating agent, anti-agglomerating agent and surfactant can be freely particled. Size control was enabled (see Test Example 4 below).

Formulation Examples 1-2 and Comparative Formulation Examples 1-2

Formulation Examples 1 and 2 and Comparative Formulation Examples 1 and 2 having water-in-oil (O / W) formulations were prepared in the compositions of Table 2 below.

Component (Content; Weight%) Formulation Example 1 Formulation Example 2 Comparative Formulation Example 1 Comparative Formulation Example 2 glycerin 3 3 3 3 1,3-butylene glycol 5 5 5 7 Nanoparticles solution prepared in Example 2: 25: 5: 1 ratio 7.5 - - - Nanoparticles solution prepared in Example 3 14: 6: 1 ratio - 10 - - Cetyl alcohol 4 4 4 4 Retinol / Tween 20 mixture (50:50) - - 0.15 - Thymoltrimethoxycinnamate (100%) - - - 0.2 Cyclomethicone 3 3 3 3 antiseptic Quantity Quantity Quantity Quantity Thickener 0.1-0.2 0.1-0.2 0.1-0.2 0.1-0.2 Purified water To 100 To 100 To 100 To 100

Test Example 2 Analysis of Stability of Active Ingredients in Formulations

In order to confirm the stability of the retinol collected in the nanoparticles using the biodegradable polymer prepared in Example 2, after storing the Formulation Example 1 and Comparative Formulation Example 1 in a container at 25 ℃ and 40 ℃ for a certain time, The amount of the remaining active ingredients was measured using liquid chromatography. The results are shown in Table 3 below.

Storage temperature (℃) Initial concentration retention rate (%) 1 day later after 2 weeks 4 weeks later 8 weeks later Formulation Example 1 25 100 100 99 95 40 100 90-95 90 75-80 Comparative Formulation Example 1 25 100 50 30 10 40 100 45 10 3

As can be seen in Table 3 below, in the case of Formulation Example 1, the retinol concentration was maintained at 95% or more at 4 ° C and 8 weeks at 25 ° C and 90% at 40 ° C and 4 weeks. On the other hand, in the case of Comparative Formulation Example 1 contained only pure retinol does not contain an encapsulant, it was confirmed that the titer drops rapidly.

[Test Example 3] Observation of crystallization of the active ingredient in the formulation

In order to confirm the formulation stability of the active ingredients collected in the nanoparticles using the biodegradable polymer prepared in Example 3, after storing the Formulation Example 2 and Comparative Formulation Example 2 in a container at low temperature and 40 ℃ for 3 months Taking the light microscope (Olympus BX50) was used to observe the crystallization of the active ingredients. The results are shown in FIG. 2.

From the results of FIG. 2, the soluble thymol trimethoxycinnamate, which is an oil-soluble active ingredient, was immediately produced in Comparative Formulation Example 2 prepared by dissolving in a solvent such as alcohol and 1,3-butylene glycol without using nanocapsules (FIG. 2A). The morphological and acicular thymol trimethoxycinnamate crystals were not observed after 3 months at 40 ° C. in Formulation Example 2 (FIG. 2B) using biodegradable nanocapsules, which were observed at low temperatures. Could.

From the results of Test Examples 2 and 3, when the active ingredient is collected in the nanoparticles using the biodegradable polymer prepared in the present invention, the size of the nanoparticles not realized in the prior art can be freely adjusted as desired. It was confirmed that the stabilization of the unstable active ingredients can be realized to the level of advanced technology, and also the crystal precipitation of the active ingredients can be prevented. The reason why nanoparticles can be used to effectively stabilize unstable active ingredients is that unlike conventional microparticles, nanoparticles enclose the active ingredients tightly without voids in the particles, effectively blocking the passage of air and water into the particles. It is believed to be due to. In addition, the solubility parameters of the polycaprolactone main chains having the hydrophobicity and the active ingredient are similar, so that the polymer chain and the active ingredient molecules in the particles do not easily form crystals when the nanoparticles are formed.

[Test Example 4] Observation of the size and stability of the formulation of the retinol nanoparticles using only a single component biodegradable polymer and polymer copolymer

In order to compare the sizes of the retinol nanoparticles prepared in Example 2 and the retinol nanoparticles prepared in Comparative Examples 1 and 2, the size of the particles prepared in Comparative Examples 1 and 2 was measured using a dynamic light scattering apparatus. It is shown in Table 4 below.

Comparative example Furtherance Particle size (nm) PCL DC5329 PCL-b-PEO Retinol One 3 3 - One 270 7 3 - One Particle aggregation 2 - - 10 One 50 - - 20 One 65

As shown in Table 4, when the particles were prepared using only a biodegradable polymer of a single polycaprolactone component and a hydrophobic surfactant, coagulation occurred when a large amount of polycaprolactone was used. In the case of using only a biodegradable polymer made of a copolymer of the component, even though a large amount of polymer was used, particles were formed. However, in the case of Example 2 (see Table 1 above), the size of the particles increased significantly depending on the amount used. I could observe that I did not.

In addition, using the nanoparticles prepared in Comparative Examples 1 and 2 were added (7.5% by weight) of the same amount of retinol particles as Comparative Formulation Example 1 and observed the retinol concentration stability for 4 weeks at 40 ℃, Comparative Example In the case of PCL: DC5329: Retinol 3: 3: 1 of 1, 80% stability was observed, and in the case of Comparative Example 2, both nanoparticles prepared were observed to have 70% stability. The reason for the reason that the stability is about 10% less than that of Example 2 in the case of Comparative Example 1 is thought to be due to the fact that the amount of polycaprolactone used is not effectively blocked from retinol from oxygen and water, and also Comparative Example 2 In this case, polycaprolactone, which is a hydrophobic part of the copolymer of heterogeneous components, is bound to the hydrophilic polyethylene oxad, and thus, it is considered that the retinol does not effectively block oxygen and water because it does not form a dense center. On the other hand, in the case of Example 2, it is considered that the polycaprolactone of the single component densifies the central portion containing the retinol and can effectively maintain the retinol stability.

As described above, since the nanoparticles stabilized of the useful active ingredient using the biodegradable polymer of the present invention have a high proportion of encapsulating agent compared to the active material when the nanoparticles of the active material having high crystallinity must be added. It is possible to prepare nanoparticles by freely controlling the particle size of the active ingredient that cannot be encapsulated with only a single component, an anti-agglomerating agent and a surfactant. In addition, the prepared nanoparticles are a system that can prevent the precipitation of crystals in the formulation as well as stabilize the concentration of the active ingredients of the existing advanced technologies. In addition, since the particles do not use a separate surfactant, oil, and anti-agglomeration, it is a system that can minimize the denaturation and change of the formulation when added to the cosmetic formulation.

Therefore, the present invention not only prevents the determination of the oil-soluble active ingredient in the formulation, but also maintains the concentration of the active ingredient in the formulation and induces skin absorption enhancement of the active ingredient through free particle control to maintain the maximum efficacy of the oil-soluble active ingredient. It is expected to be able. In addition, since the material used to manufacture nanoparticles uses biodegradable and biocompatible materials, it may be widely used in the field of pharmaceuticals as well as functional cosmetics.

Claims (13)

(1) dissolving the oil-soluble active ingredient and the biodegradable polymer in a volatile organic solvent mixed with water; (2) dispersing and stirring the solution in water to form nanoparticles; And (3) removing the volatile organic solvent in the nanoparticle solution through evaporation; The oil-soluble active ingredient is retinol, retinyl acetate, retinyl palmitate, tocopherol, tocopheryl acetate, tocopheryl linoleate, tocopheryl nicotinate, linoleic acid, coenzyme Q-10, resveratrol ((E ) -5- [2- (4-hydroxyphenyl ethenyl)]-1,3-benzene diol 3,4,5-trihydroxy stilbene), lipoic acid, licorice extract, thymol trimethoxycinnamate, curcumin ( Curcumin, Tetrahydrocurcumin, Oleanolic acid, Ursolic acid, Betulin, Betulinic acid, Diosmetin, Quercetin, And lycopene (Lycopene) is characterized in that at least one selected from the group consisting of The biodegradable polymer is composed of polycaprolactone, poly (D, L-lactide), and poly (L-lactide). Single component biodegradable polymer, characterized in that at least one selected from the group; And poly (caprolactone) -b-poly (ethylene oxide) (Poly (caprolactone) -b-Poly (ethylene oxide)), poly (D, L-lactide) -b-poly (ethylene oxide) (Poly (D , L-lactide) -b-Poly (ethylene oxide), poly (L-lactide) -b-poly (ethylene oxide), Poly (L-lactide) -b-Poly (ethylene oxde), poly (ethylene Oxide) -b-poly (caprolactone) -b-poly (ethylene oxide) (poly (ethylene oxide) -b-poly (caprolactone) -b-Poly (ethylene oxide)), poly (ethylene oxide) -b-poly (D, L-lactide) -poly (ethylene oxide) (Poly (ethylene oxide) -b-Poly (D, L-lactide) -Poly (ethylene oxide)), and poly (ethylene oxide) -b-poly ( Heterogeneous characterized in that at least one member selected from the group consisting of L-lactide) -b-poly (ethylene oxide) (Poly (ethylene oxide) -b-Poly (L-lactide) -b-Poly (ethylene oxide)) A method for producing nanoparticles having stabilized an oil-soluble active ingredient, comprising a block copolymer of ingredients. delete delete The method of claim 1, wherein the biodegradable polymer of the single component is a method for producing nanoparticles, characterized in that the polymer having a number average molecular weight of 10,000 ~ 100,000. delete The method of claim 1, wherein the block copolymer is a method for producing nanoparticles, characterized in that the polymer having a number average molecular weight of 5,000 ~ 50,000. The method of claim 1, wherein the ratio of the polymer having a single component and the block copolymer is 100: 1 to 1: 100. The organic solvent of claim 1, wherein the organic solvent is selected from methanol, ethanol, acetone, THF (tetrahydrofuran), acetonitrile, and 1,4-dioxane (dioxane). Method for producing nanoparticles. The method of claim 1, wherein the nanoparticles have a size of 30 to 300 nm. The method of claim 1, wherein the polymer contains 10 to 40% by weight based on the total weight of the nanoparticles. The polymer capsule according to any one of claims 1, 4 and 6 to 10, wherein the nanoparticles contain a polymer encapsulating agent at a concentration of 10 to 40% by weight based on the total weight of the nanoparticle solution. The size of the particles can be controlled by controlling the concentration of, the proportion of the single component and the block copolymer, the method of producing nanoparticles, characterized in that the particles do not aggregate in the water phase. A cosmetic composition comprising nanoparticles prepared by the method of any one of claims 1, 4 and 6 to 10. The cosmetic composition according to claim 12, wherein the nanoparticles are stably present in the cosmetic composition without precipitation of crystals while maintaining the concentration of the oil-soluble active ingredient at the same initial concentration.

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