KR100493449B1 - A surface coating method of nanoparticle for cosmetic material - Google Patents

Abstract

The present invention relates to a surface coating method of nanoparticles used as a cosmetic material, and more particularly has an emulsification effect as a coating agent in the process of producing an emulsified nanoparticle containing a biodegradable polymer having a certain molecular weight and an active skin component. By coating the surface of the nanoparticles by adding a skin accelerator having excellent skin absorbency and skin affinity, it improves the skin absorbency and skin affinity of the nanoparticles and can be used as a cosmetic additive in the surface coating method of the nanoparticles. It is about.

Description

A surface coating method of nanoparticle for cosmetic material

The present invention relates to a surface coating method of nanoparticles used as a cosmetic material, and more particularly to emulsification in an aqueous solution as a coating agent in the process of preparing a nanoparticle containing a biodegradable polymer and a skin active ingredient having a certain molecular weight. By coating the surface of the nanoparticles by adding a skin accelerator having excellent skin absorption and skin affinity while improving the skin absorption and skin affinity of the nanoparticles, the surface coating method of the nanoparticles which can be usefully used as a cosmetic additive It is about.

Material technology using microcapsule or nanoparticle manufacturing technology is applied in various fields such as medicine, cosmetics, plastics, paints. In particular, the application of microcapsules to pharmaceuticals, cosmetics, household goods is used as an additive or a main raw material of the product for high functionalization and high efficiency, such as sustaining the effect of the product or improving skin absorption. As a practical example, there are application examples of UV ray blocking creams, sun-tanning creams, cleansing creams, skin pigment removers, emollients and deodorants in the cosmetic field, and antistatic agents, softeners, and antibacterial deodorants in the household goods field. Application products have been produced for various purposes in fragrance and fragrance release agents.

The microcapsule technology has a side that cannot partially maximize the effect depending on the application. For example, in the case of cosmetics, in the process of absorbing vitamin C, a skin active ingredient, into the skin, the existing microcapsule (liposome) is large in size and thus has low skin absorption rate and lacks control of release of microcapsules, thereby providing long-term effects. It is known to have a number of disadvantages. As another example, in the case of an antibacterial deodorant or a perfume, the particle size is large and the emission control effect is low.

Therefore, in order to solve the above problems, the size of the existing microcapsules is reduced to nanoparticles, and a coating agent is applied to the surface of the nanoparticles to impart skin absorbency and skin affinity. In the case of cosmetics, nanoparticles loaded with skin-active substances can be easily located in areas where skin absorption occurs, such as pores and sweat glands, thereby increasing the skin absorption and increasing the adhesion of the skin. That will have the advantage.

As described above, various methods have been introduced as well-known techniques related to methods of manufacturing nanoparticles, coating nanoparticles, and the like, and applying the same. Coletica, US Pat. No. 6,303,150 (October 16, 2001) discloses a method for making nanoparticles by crosslinking proteins with acrylic groups. US Patent No. 6,379,683 to L'Oreal (2002.4.30) describes a method for incorporating a fat-soluble skin active ingredient in a fat-soluble dendrimer of a polyester having a hydroxyl group in the composition of cosmetics and skin attachment compositions. have. U.S. Patent No. 6,197,349 (2001.3.6) to Westonsen discloses a process for producing particles of 30 to 500 nm comprising a stabilizer in a supercooled state (supercritical phase) of a water insoluble material. . Ryde, U.S. Patent No. 6,375,986 (2002.4.23), prepared nanoparticles containing insoluble active ingredients, polymer surface stabilizers, and dioctyl sodium sulfosuccinate to increase dispersibility between particles. Disclosed is a technique to make. Jacob, US Pat. No. 6,368,586 (2002.4.9), is a means of increasing the adhesion of nanoparticles to mucous membranes in the manufacture of polymeric nanoparticles and their application to drug carriers and diagnostic reagents. A method of coating a polyvalent cation of a component to easily bind to the negative charge of mucosal cells to increase adhesion is disclosed. Ribier's U.S. Patent No. 6,066,328 (2000.5.23) is intended for application in cosmetics or skin coatings and contains oily particles inside the O / W emulsified phase, and lamellar crystals as surface active agents on the particle surface. The present invention relates to a method for producing a particle having a particle size of 500 nm or less by coating an oligo lamellae to have a hydrophilic or ionic surface.

However, the known techniques as described above may contain a solvent or the like that causes skin irritation when the skin is attached to a particle size of 100 nm or more when used as a material for cosmetics. The technique of coating the skin-friendly material on the nanoparticles can be expected to prevent the self-aggregation of the particles in the aqueous solution and to suppress the trouble of the skin when the skin is applied, but there is a problem in the existing invention. Therefore, the present invention focuses on the preparation of nanoparticles having high skin absorption rate, improving skin affinity and excellent release control by coating a skin-friendly material on particles having a particle size of 100 nm or less.

In order to solve the above problems, the present inventors have applied a coating agent in an emulsified process to prepare nanoparticles containing a low molecular weight biodegradable polymer and a skin active ingredient using a spontaneous emulsification solvent diffusion method. When the surface of the nanoparticles is coated by adding a skin accelerator having excellent skin absorption and skin affinity, the skin accelerator is surrounded on the surface of the nanoparticles, and the nanoparticles thus made increase the skin absorbency and skin affinity when applied to the skin. Effects can be seen to complete the present invention.

Accordingly, an object of the present invention is to provide a surface coating method of nanoparticles for obtaining nanoparticles which can be usefully used as a cosmetic additive by coating a skin accelerator having excellent skin absorbency and skin affinity to nanoparticles.

The present invention provides a surface of the nanoparticles by adding a skin accelerator containing an alkyl group having 8 to 16 carbon atoms as a coating agent in an emulsifying process for preparing a nanoparticle by containing a biodegradable polymer having a molecular weight of 2,000 to 20,000 and an oil-soluble skin active ingredient. Its characteristics are the method of coating.

Referring to the present invention in more detail as follows.

The present invention is a coating of a material having excellent skin affinity and skin absorption on the surface of the nanoparticles containing the biodegradable low molecular weight polymer and the skin active ingredient, the nanoparticles do not cause side effects to the skin when the nanoparticles are applied to the skin It is characterized by constructing coating conditions that can easily pass through the micro glands of the skin's glands or pores (known as about 120 nm).

Surface coating method of the nanoparticles according to the present invention that can be usefully used as a cosmetic additive by improving the skin absorption and skin affinity as described above are as follows.

The method for preparing nanoparticles in the present invention may be prepared using a spontaneous emulsification solvent diffusion (SESD) method which is a generally known technique. That is, a skin active ingredient and a biodegradable polymer having a molecular weight of 2,000 to 20,000 are dissolved in a solvent. It is preferable that a skin active ingredient contains 0.1-1% (w / v) of a total solution here, More preferably, 0.5-0.7% (w / v) is good. If the content of the skin active ingredient is less than 0.1% (w / v), the loading amount of the skin active ingredient into the nanoparticles is reduced and inefficient. If the content of the skin active ingredient exceeds 1% (w / v), the particle size is 100 nm or more. There is a growing problem. The content of the biodegradable polymer is preferably 1 to 10% (w / v) of the total solution, more preferably 5% (w / v). If the content of the polymer is less than 1% (w / v), the yield of the nanoparticles is reduced and economically disadvantageous, and if the content exceeds 10% (w / v), there is a disadvantage in that the size of the particles increases. In addition, it is preferable to use an organic solvent such as dichloromethane, alcohol, acetone, etc. as a solvent for dissolving the polymer and the skin active ingredient, and the amount of the solvent is in the range of 90 to 99% (w / v).

The skin active ingredient may be selected from among vitamin A and its derivatives, vitamin E and its derivatives, vitamin C derivatives, arbutin, collagen and chondroitin extract as having fat-soluble properties. The present invention using the skin active ingredients as described above nanoparticles are less than 120 nm of pores of the skin is easy to absorb the active ingredient into the skin, after being absorbed slowly release the cosmetic ingredients from the particles can sustain the cosmetic effect It can be used as a cosmetic additive because it can expect high efficiency cosmetic effect.

In addition, the biodegradable polymer having a molecular weight of 2,000 to 20,000 includes poly (lactic acid) (PLA), poly (lactide-co-glycolide), and PLGA. Natural derivatives such as ethyl cellulose (Ethyl cellulose, EC), butyl cellulose (Buthyl cellulose, BC) and hydroxylpropyl methyl cellulose phthalate (Hydroxyl propyl methyl cellulose phthalate (HPMCP)) may be used. At this time, when the molecular weight of the biodegradable polymer is less than 2,000 to form nanoparticles, the aggregation of the molecular car body is difficult to reduce the yield and also the problem that the skin active ingredient is not loaded, when the size exceeds 20,000, the particle size is more than 100 nm There is a growing problem. When the nanoparticles are prepared using the biodegradable polymer as described above, the present invention serves as a basic medium for forming hydrophobic particles in an emulsion solution and also serves as a receptor for holding a hydrophobic fat-soluble active ingredient in solution. In addition, this polymer is biodegradable after being absorbed into the skin, and is decomposed by hydrolysis in the skin, thereby slowly releasing active ingredients, thereby providing a long-term cosmetic effect, and ultimately do not accumulate in vivo, making it useful as a cosmetic additive. Can be used.

In particular, the present invention is characterized by coating the surface of the nanoparticles by replacing the emulsion solution using the skin accelerator as an emulsion solution in the process of preparing the nanoparticles using the skin active ingredient and biodegradable polymer as described above. have.

That is, among the surfactants containing alkyl groups having 8 to 16 carbon atoms for the purpose of improving skin absorption and skin affinity, those containing lauryl ether or alkyl group containing polyethylene oxide (PEO) Used as an accelerator to replace the emulsion solution to coat the surface of the nanoparticles. These skin accelerators used as coatings are lauryl ether-based isopropyl myristate, polyoxyethylene 4 lauryl ether (Brij 30 ™), sodium lauryl sulfate, propylene glycol monolau Propyleneglycolmonolaurate, Monolaurin, Monostearin, Monoearin, Monooolein, Monomyristin, Lauryl alcohol or Polyoxyethylene 9 lauryl ether (POE9LE) Polyoxyethylene-based polyoxyethylene 2 lauryl ether (Brij 92 ™), Pluronic, Sorbitan monopalmitate or Sorbitan trioleate Etc. can be used. It is preferable to contain 1-8% (w / v) of such skin accelerators in an aqueous emulsion solution, More preferably, it is preferable to contain 2-4% (w / v). If the skin accelerator content is less than 1% (w / v), the loading of the skin active ingredient is reduced, and if the skin accelerator is more than 8% (w / v), there is a problem that the size of the particles increases. The present invention prevents sedimentation and increase in particle size due to self-aggregation even after nanoparticles are formed using the skin accelerator as described above, and has excellent affinity with the skin even after application to the skin, resulting in very little skin trouble. It can also be used as a cosmetic additive by promoting the absorption of the skin.

The mechanism in which the skin accelerator is coated on the nanoparticles is emulsified with strong agitation (1200 rpm) while the solution containing the hydrophobic polymer and the active ingredient of the skin is dropped into the aqueous solution of the skin accelerator, which is an emulsion solution. As the solvent is removed by evaporation or diffusion into an aqueous solution, solidification of the hydrophobic polymer and the skin active ingredient proceeds. The hydrophobic solidified nanoparticles are surrounded by the skin accelerator which is an emulsifier at the interface of the aqueous solution, the hydrophobic portion of the skin accelerator penetrates into the solidified nanoparticles and is immobilized, and the hydrophilic portion of the skin accelerator is oriented toward the emulsion solution. Ultimately, when the polymer nanoparticles are manufactured, the skin accelerator remains coated on the surface of the nanoparticles.

In addition, the size of the nanoparticles of the present invention produced by the above method is in the range of 60 to 100 nm.

As described above, the nanoparticles according to the method of the present invention coat the surface of the nanoparticles by adding a skin accelerator having excellent skin absorptivity and skin affinity to the emulsion phase process of preparing the nanoparticles using the biodegradable polymer and the skin active ingredient. As a result, skin active ingredients such as vitamin A, vitamin E, vitamin C and vitamin derivatives, arbutin, collagen and chondroitin extract, which have excellent beauty effects such as skin whitening and anti-aging, are absorbed into the skin through nanoparticles. After being absorbed by the biodegradability of the nanoparticles in the skin slowly release it can be useful as a cosmetic additive to act for a long time. The nanoparticles prepared by the method according to the present invention may be applied to lotions, creams, gels or patches as examples applied to the final product.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited by Examples.

Example 1

0.5 g of polymer (PLGA, Mw 20,000) was dissolved in 9.45 ml of solvent (dichloromethane) with warming at about 25 ° C., and the dissolved solution was cooled to about 10 ° C., and then 0.05 g of skin active ingredient (Vitamin E ) Was added to prepare a polymer mixed solution. The coating solution was dissolved in 100 ml of 3 g of skin accelerator (Lutrol 75) in distilled water, passed through a 0.2 micron membrane to remove insoluble impurities, and then heated to 30 ° C. and mounted on a homo mixer. Stirred at rpm. Then, the polymer mixed solution was transferred to a syringe, added to the coating solution at a rate of 1 ml / min, and stirred at 1200 rpm. After stirring for 5 minutes, the stirring speed of the homomixer was reduced to 400 rpm and stirred for an additional 2 hours to remove dichloromethane in the polymer. The resulting nanoparticle solution was passed through a 0.2 micron membrane to remove large particles, and then purified using a 400,000 molecular weight ultrafiltration membrane and adding 1000 ml of distilled water to obtain a final nanoparticle solution. The nanoparticle solution was lyophilized to obtain powdery final nanoparticles.

The electron microscope (SEM; scanning electron microscope and TEM; transmission electron microscope) photograph of the nanoparticles thus obtained is shown in FIG. 1, and the particle size, loading rate of the skin active ingredient, and coating rate were measured as follows. Table 1 shows.

1. Particle size (nm)

Particle size was obtained by Gaussian distribution using a particle analyzer (electrophoretic light scattering spectrometer, Otsuka Electronics, CO, LTD) and measured by the number average calculation method.

2. Coating rate (%): The ratio of the weight difference of the finally produced total particles to the amount of the polymer initially introduced under the same conditions without loading of the skin active ingredient was calculated as the coating rate.

3. Loading rate of skin active ingredient (%): The prepared nanoparticles were dissolved in acetone solvent and the solution was calibrated with uv-spectrometa to calculate the loading rate in the amount remaining in the particles with respect to the initially added amount.

Examples 2 to 8

Next, nanoparticles were prepared in the same manner and in the same manner as in Example 1, using the ingredients shown in Table 1 below.

The particle size of the prepared nanoparticles, the loading rate of the skin active ingredient, the coating rate were measured in the same manner as in Example 1, and the results are shown in Table 1 below.

Polymer Skin active ingredients Skin accelerator menstruum Particle Size (nm) Coating rate (%) Loading rate (%) Example 1 PLGA ¹ Vitamin E Root Roll 75 Dichloromethane 77 22 35 Example 2 PLGA ¹ Vitamin E Bridge 30 Ethanol / Acetone (1/1) 85 25 31 Example 3 PLGA ¹ Vitamin A Polyoxyethylene 9 Lauryl Ether Ethanol / Acetone (1/1) 65 13 25 Example 4 PLGA ¹ Chondrichin Propylene Glycol Monolaurate Ethanol / Acetone (1/1) 76 17 24 Example 5 PLGA ¹ Arbutin Sorbitan trioleate Ethanol / Acetone (1/1) 70 15 25 Example 6 BC ² Vitamin E Root Roll 75 Ethanol / Acetone (1/1) 98 24 36 Example 7 EC ³ Vitamin E Root Roll Ethanol / Acetone (1/1) 94 20 38 Example 8 HPMCP ⁴ Vitamin E Root Roll Ethanol / Acetone (1/1) 95 21 29  1.PLGA: Poly (lactide-co-glycolide), Mw 20,000 2. BC: Buthyl cellulose, Mw 15,000 3. EC: Ethyl cellulose, Mw 12,000 4.HPMCP: Hydroxyl propyl methyl cellulose phthalate, Mw 20,000

As shown in Table 1, it can be seen that the nanoparticles of Examples 1 to 8 according to the present invention have a small particle size of 65 to 98 nm. Comparing Examples 1, 6, 7, and 8, the use of solvent as dichloromethane yielded smaller particles than the use of ethanol / acetone. Comparing the cases of Examples 2 to 5, the particle size did not show a significant relationship with the amount of the accelerator or the active ingredient. The coating rate and loading rate were relatively higher than those of the other skin accelerators when Lutrol was used. There was no significant difference between the types of polymers, but PLGA and EC showed a slight increase than HPMCP, which is thought to be due to the difference in hydrophobicity of the material.

Test Example

In order to observe skin absorption and release control using the nanoparticles of Example 1 according to the present invention, a comparative test for confirming skin absorption increase and release control of skin active ingredient through the skin of hairless mice is performed. It was performed in the following manner, and the results are shown in FIG.

First, the back skin of an 8-week-old hairless rat (female) is excised to remove the dermal layer by enzymatic treatment, and then the hairless mouse skin is fixed between the two diffusion cells prepared in advance, followed by 10% of nanoparticles in the donor cell. 5 ml of the particle solution was injected into a receptor cell into a disposable syringe with a phosphate buffer solution (pH 7.5) and 5 ml of a preservative 0.1% sodium azide solution. An emulsion solution was prepared and used in the same manner as in Example 1 except that no polymer (PLGA) was used as a control for the nanoparticle solution. The experiment time was a total of 170 hours. To investigate the effects of skin permeation and absorption, samples were collected over time, analyzed, and supplemented with fresh phosphate buffer solution by the amount collected. The solution in the cell was stirred continuously to minimize the difference in concentration in the cell.

As shown in Figure 2, the nanoparticle solution according to the present invention can be confirmed that the active ingredient is absorbed by the skin through the nanoparticles and after being absorbed by the biodegradation of the nanoparticles in the skin slowly release can act for a long time there was.

As described above, the nanoparticles according to the present invention have a skin accelerator coated on the surface of the nanoparticles having excellent skin absorbency and skin affinity to increase the skin absorbency and skin affinity, as well as small particle size, active skin components It can also control the release of can be useful as a cosmetic additive.

Figure 1 shows an electron microscope (SEM; scanning electron microscope and TEM; transmission electron microscope) of the nanoparticles according to Example 1 of the present invention.

Figure 2 is a graph showing the skin absorbance and release control in the nanoparticles and control mice in accordance with Example 1 of the present invention.

Claims (4)

In the process of preparing nanoparticles containing a biodegradable polymer having a molecular weight of 2,000 to 20,000 and a fat-soluble skin active ingredient by a spontaneous emulsified solvent diffusion (SESD) method, a surfactant selected from lauryl ether type and polyoxyethylene type is accelerated to the skin. It is prepared by coating the surface of the nanoparticles by adding zero, the surface coating method of the nanoparticles, characterized in that the particle size of the surface-coated nanoparticles is 60 ~ 100 nm. The surface of the nanoparticles according to claim 1, wherein the biodegradable polymer is selected from poly (lactic acid), poly (lactide-co-glycolide), ethyl cellulose, butyl cellulose and hydroxylpropylmethylcellulose phthalate. Coating method. The method of claim 1, wherein the skin active ingredient is selected from vitamin A, vitamin E, vitamin C, arbutin, collagen and chondroitin extract. The method of claim 1, wherein the skin accelerator is isopropyl myristate, polyoxyethylene 4 lauryl ether, sodium lauryl sulfate, Propyleneglycolmonolaurate, monolaurin Monolaurin, Monoostearin, Monooolein, Monomyristin, Lauryl alcohol, Lauryl alcohol, Polyoxyethylene 9 lauryl ether, Polyoxyethylene 2 lauryl ether, Fluoro Nickel (Pluronic), sorbitan monopalmitate (Sorbitan monopalmitate) and sorbitan trioleate (Sorbitan trioleate) characterized in that the surface coating method of nanoparticles.