WO2019194328A1

WO2019194328A1 - Polygonal pyramid-shaped water-soluble microbead scrub particles

Info

Publication number: WO2019194328A1
Application number: PCT/KR2018/003879
Authority: WO
Inventors: 한규범
Original assignee: 주식회사 파이안에스테틱스
Priority date: 2018-04-03
Filing date: 2018-04-03
Publication date: 2019-10-10
Also published as: KR20200128402A; JP2021525112A

Abstract

The present invention relates to polygonal pyramid-shaped water-soluble microbead scrub particles, and a method for preparing same. More specifically, the present invention relates to water-soluble microbeads for imparting a cosmetic effect to the skin or for delivering a drug causing a therapeutic effect, through the stratum corneum, to the skin, and a method for preparing same.

Description

[Revision 11.05.2018 by Rule 26] Water-Soluble Fine Acicular Body Scrub Particles

The present invention relates to a water-soluble fine acicular scrub particle having a polygonal pyramid shape and a method for producing the same. More specifically, the present invention relates to a water-soluble micro needle and a method for producing the same for delivering a cosmetic effect to the skin or causing a therapeutic effect to penetrate the stratum corneum of the skin to the skin.

The method of applying an active substance such as a skin cosmetic ingredient or a drug to the skin, or applying a pack or patch containing the active substance to the skin and delivering it to the human body enables continuous drug delivery, painlessness, and ease of use. Has the advantage.

However, since the stratum corneum, 10 μm to 60 μm thick outside the skin, prevents the penetration of foreign substances into the body, the absorption rate of the active substance is very low. In particular, if the active substance is hydrophilic or has a high molecular weight, its absorption in the body is further lowered.

Therefore, administration methods using injection have been used to effectively deliver subcutaneous substances. However, since the diameter of a conventional injection needle is in the range of millimeters and its length is in the centimeter range, a significant pain occurs by stimulating a plurality of pain points present in the skin.

In addition, since the injection can be performed only in a hospital or a professional skin care institution, there is a disadvantage that it cannot be easily used at home.

In order to solve this drawback according to the prior art, microneedle having a diameter of several tens of micrometers to several hundreds of micrometers and a length of several tens of micrometers to several thousand micrometers has been developed.

Since the microneedle forms micropores in the stratum corneum of the skin, hydrophilic or high molecular weight substances can be easily absorbed into the skin or transferred through the skin to the body through the formed micropores.

In addition, the use of the conventional microneedle also increases the skin absorption rate and the body delivery rate of substances that are well absorbed even if applied to the skin.

Moreover, the short microneedle is painless because it does not penetrate into the dermal layer where the nerve is distributed. Even if the long microneedle penetrates to the dermal layer, the diameter is smaller and the length is shorter than that of the conventional needle, so that the number of stimulating points is small, so that the subject's pain is greatly reduced.

WO 02/47555 discloses a method for treating skin of a subject, comprising a head forming a convex head surface, and pins mounted to the head and protruding a predetermined distance from the head surface and spaced apart by a predetermined distance. An apparatus and a method for applying a skin-cosmetic substance after forming micropores in the stratum corneum using the apparatus are disclosed.

In addition, U.S. Patent No. 5,487,726 discloses a vaccine application system comprising applying a vaccine to the skin and forming micropores in the stratum corneum using a device having spikes on the skin to which the vaccine is applied. have.

However, according to WO 02/47555 and U.S. Patent No. 5,487,726, since the step of applying the drug and the step of forming fine pores in the stratum corneum of the skin are made separately, it causes inconvenience to the subject.

US Patent No. 6,603,998 discloses a method for delivering a skin care material by coating a skin care material on the surface of an electrode in the form of a microneedle and then applying it to the skin.

In addition, US Patent No. 6,132,755 discloses a system in which a drug storage container with micropins is applied to the skin so that the micropins pass through the stratum corneum and the drug is delivered to the skin through the micropins using a pump. have.

In addition, U.S. Patent Application Publication No. 2005/0251088 discloses a method of storing a drug in the pores of a porous needle, puncturing the pores of the skin stratum corneum, and delivering a skin cosmetic material stored in the pores of the needle.

In addition, U.S. Patent No. 3,964,482 discloses a drug delivery device in which the protrusion passes through the stratum corneum and the drug diffuses into the skin through the protrusion using a device having a protrusion connected to the drug reservoir.

However, according to Patent Nos. 6,603,998, 6,132,755 and 3,964,482, and US Published Patent Application No. 2005/0251088, there is a disadvantage that a separate device is required to deliver the skin cosmetic material to the skin.

Another way to make the skin cosmetic ingredients more easily pass through the stratum corneum is to apply the skin exfoliant to the skin after using the exfoliating cosmetic. Exfoliating cosmetics mainly remove exfoliation physically using a scrub agent that can exfoliate.

However, after using the exfoliating cosmetics, there is a problem that the skin beauty material must be applied to the skin again after washing off the scrub agent.

In addition, if the eye gets into the eye while using the scrub agent, the removal of the scrub agent is not easy, and a foreign body may be felt, and the cornea may be damaged by rubbing the eyes.

Republic of Korea Patent Registration No. 10-1206985 is a massage cosmetics containing a large amount of sugar scrub excellent in use and excellent in moisturizing, blood circulation, skin waste and exfoliation, excellent stability and spread over time by containing sugar scrub in non-aqueous cosmetics The composition is disclosed.

However, the sugar scrub of the Republic of Korea Patent No. 10-1206985 generally has a disadvantage that the scrub effect is not large because the angle formed by each side is larger than 8 sides, the edges are also blunt.

In order to overcome the shortcomings of the above-mentioned prior arts, the present inventors have prepared a polypyramidal water-soluble fine acicular body and using a novel water-soluble fine acicular body (micro spicule) containing a skin cosmetic ingredient or drug as a scrub particle, The present invention has been completed by confirming that skin cosmetic ingredients or drugs can be easily and effectively passed through the stratum corneum.

A basic object of the present invention is to provide a scrub particle composed of a polypyramidal water-soluble fine acicular scrub particles and a polypyramidal-shaped water-soluble microspicule for absorbing skin cosmetic materials or drugs.

Still another object of the present invention is the method comprising the steps of: (i) filling the engraved mold with a mixed solution of a skin cosmetic material or drug and a biocompatible material and water; (ii) drying the mixed solution to obtain micro spicules; And (iii) separating the micro spicules from the engraved mold, to provide a polypyramidal water-soluble fine acicular body for absorbing a skin cosmetic material or drug into the skin.

The basic object of the present invention described above is achieved by providing microspicules for absorbing skin cosmetic substances or drugs into the skin.

As used herein, the term "polypyramidal water-soluble micro-spicule" refers to a microstructure in the form of a tetrahedron or polygonal pyramid (see FIG. 1). In addition, the polygonal pyramid refers to a polyhedron consisting of triangles in which one side is a polygon (referred to as a bottom) and all other faces meet at a vertex.

In this specification, each side of the micro spicule may be flat, uneven or hollow. In addition, there may be a defect such as a part of the corners or vertices of the micro spicule.

The micro spicule of the present invention may be a biocompatible material such as polysaccharide, polyvinyl alcohol, carboxyvinyl polymer, chitosan, hyaluronic acid, cellulose polymer or salt. The biocompatible material refers to a material that is harmless to the human body and can be dissolved, decomposed or swelled in a body fluid or water.

A depression may be formed in one or more surfaces of the micro spicule, and the depth of the depression may be within 1/2 of the height of the micro spicule.

The micro spicule of the present invention further includes a skin beauty substance or drug, so that the skin beauty substance or drug can be effectively absorbed into the skin.

As shown in FIG. 2, the skin beauty substance 2 included in the micro spicule 1 is applied on the skin 10 and patted or rubbed by hand, and the vertices and edges of the polyhedron are fine on the keratin 11. Form a hole or remove part of the dead skin.

When the skin-care substance passes through the micropores 13 or thinned stratum corneum, which is formed in the stratum corneum, which is the largest physical barrier in the skin tissue, the skin-derived substance is rich in the epidermis and dermis 12 layer rich in moisture and relatively low in cell density. Since the skin-care substance diffuses relatively easily, the skin absorption of the skin-care substance increases.

In order for such an action to occur, the vertices or corners of the micro spicule of the present invention must have a sharp angle, so that the polyhedron or more of the cube may not be suitable for the present invention.

In addition, if the micro spicule does not dissolve in the skin and maintains its shape, there is inconvenience that the user must wash. Furthermore, if the micro spicules are embedded in the stratum corneum, the micro spicules block most of the micropores, so that the skin absorbency of the skin-care substance is improved less.

Therefore, it is preferable that the micro spicule which effectively absorbs skin-derived substances or drugs into the skin is easily dissolved, decomposed or swelled in body fluids or water.

When the skin care substance 2 is included in the micro spicule 1, the skin care substance should be made of a component that does not dissolve the micro spicule.

Since the thickness of the skin stratum corneum is 10 μm to 60 μm and the skin is elastic, the micro-spicules are preferably tetrahedral or polygonal pyramidal in order to form micropores in the stratum corneum, and the base and height of the tetrahedron or polypyramid are respectively It is preferable that it is 50 micrometers-500 micrometers.

The skin cosmetic material that may be included in the micro spicule of the present invention may be an antioxidant, a growth factor, a wrinkle improving material, or a cell culture or a culture medium.

The antioxidant may be vitamin C, the growth factor may be epidermal growth factor (EGF) or fibroblast growth factor (FGF), the cell culture or culture medium is a culture or culture medium of stem cells Can be.

In addition, the drug that may be included in the micro spicule of the present invention may be insulin or growth hormone.

The tetrahedral or polygonal pyramid-shaped micro spicules 1 may be filled and used together with the skin care material 2 on the patch 20, which may be attached to the skin, as shown in FIG. 3. In this manner, the microchannels are formed only in the stratum corneum of the portion to which the skin-care substance is to be delivered, and the microchannels are not formed in the keratin, such as a finger or the palm.

The tetrahedral or polygonal pyramid-shaped micro spicule (1) can be used in combination with the skin-care substance (2), as disclosed in U.S. Patent No. 6,132,755 or U.S. Patent Publication No. 2005/0251088, etc. Skin beauty ingredients or vaccines, epidermal growth factor, growth hormone, and insulin, which are effective in preventing skin aging, wrinkle improvement, and skin tone improvement, may be directly filled and delivered into the skin.

Another object of the present invention described above is (i) filling the engraved mold with a mixed solution of a skin cosmetic material or drug and a biocompatible material and water; (ii) drying the mixed solution to obtain micro spicules; And (iii) separating the micro spicules from the engraved mold, to provide a method for producing micro spicules for absorbing a skin cosmetic material or drug into the skin.

In one embodiment of the present invention, the tetrahedral or polygonal pyramid-shaped micro spicules 1, as shown in Fig. 5, and the solution 31 containing the components (biocompatible materials) constituting the micro spicules and Filling the engraved mold 32 with a mixed solution of water (Fig. 5-a), drying the mixed solution to obtain micro spicules (Fig. 5-b), and engraving the micro spicules with the engraved mold It can be prepared by a method comprising the step of separating from (Fig. 5-c).

In the method of the present invention, the skin cosmetic material can be selected from antioxidants, growth factors, wrinkle improving materials and cell cultures or culture media.

The growth factor contained in the recombinant growth factor or the stem cell culture filtrate is a protein, and when the protein is added to the cosmetic composition because it is unstable due to changes in the physical or chemical environment, and particularly prone to hydrolysis in the presence of water. Maintaining biological activity is not easy

In order to protect the amide bonds of proteins that are susceptible to hydrolysis, and to maintain the activity of various peptides for a long period of time during storage distribution and use, lyophilization with a composition containing a sugar such as mannitol or the like for stabilization, or after purification with high purity Methods have been attempted to stabilize biological activity using additives in the liquid phase. However, these techniques are not easy to apply to cosmetics.

In particular, epidermal growth factor (Epidermal Growth Factor, rh-oligopeptide-1 or sh-oligopeptide-1) is stored and stored for a long time due to the decrease in biological activity due to physical and chemical changes at room temperature and even in cold storage. There are several problems in formulating for time-consuming commercialization.

European Patent Publication No. 205,051 is a composition of skin and ophthalmic creams for preventing the decrease of the activity of EGF epithelial cell growth factor EGF and 1 to 10% surfactant, 5 to 45% fat and 0.3 to 0.8% preservative A composition is disclosed.

EP 267,015 and US Pat. No. 4,717,717 disclose EGF containing stabilizing compositions in which EGF is added a water soluble cellulose polymer. European Patent Publication No. 398,619 also discloses an EGF-containing stabilizing composition in which metal cations such as zinc are added to EGF.

Korean Patent Publication No. 10-1996-0013439 consists of phenol, polyethylene glycol, fatty acid salt, surfactant, sucrose, fatty acid ester, sodium sulfate, amino acid, taurine, mannitol, gelatin, whibronectin, hyaluronic acid and organic acid buffer solution Stable EGF compositions containing one or more substances selected from the group are disclosed.

In addition, as a patent for stabilizing EGF, Korean Patent No. 10-0570358 discloses a nano vector composition containing epidermal growth factor and selenium and a cosmetic using the same, and Korean Patent No. 10-0752990 discloses a nano Disclosed is a composition for preventing or treating skin diseases, including liposomes and natural extracts.

Even with these conventional techniques, it is not easy to maintain the activity of epithelial growth factor in the cosmetics, which are room temperature distribution conditions, non-sterile conditions, aqueous conditions. In particular, when the epidermal growth factor is added to the cosmetic at a very low concentration, which is acceptable in the cosmetic, it is almost impossible to maintain EGF activity for the period of storage, distribution and use.

In addition, since the protein has a high molecular weight, even if it is added to the cosmetics, it does not penetrate the skin well, so it is difficult to see the effect. Using peptide fusion technology, liposome technology to help skin infiltrate growth factors with lipids, or methods that combine the microneedle therapy system (MTS) are mainly used.

The antioxidant may be vitamin C, the growth factor may be epidermal growth factor (EGF) or fibroblast growth factor (FGF), the cell culture or culture medium is a culture or culture medium of stem cells It may be.

The biocompatible material may be selected from polysaccharides, polyvinyl alcohols, carboxyvinyl polymers, chitosan, hyaluronic acid, cellulose polymers or salts.

The mold is in the form of a tetrahedron or polygonal pyramid, the base and the height of the engraved tetrahedron or polygonal pyramid may be 50 μm to 500 μm, respectively.

Using the micro spicules of the present invention, it is possible to absorb large amounts of skin-care substances or drugs into the skin or to deliver them through the skin more efficiently than the prior art.

In addition, the micro spicule of the present invention has an efficient form and its structure is simple and can be manufactured very easily.

1 is a perspective view of a micro spicule according to the present invention.

2 is an application example of a micro spicule according to one embodiment of the present invention.

3 is an application example of a micro spicule according to one embodiment of the present invention.

Hereinafter, the present invention will be described in more detail with reference to the following examples or drawings. However, the following description of the embodiments or drawings is only intended to specifically describe the specific embodiments of the present invention, it is not intended to limit or limit the scope of the present invention to the contents described therein.

After exposing the pattern on the silicon wafer, bulk etching was performed to fabricate a silicon embossed mold. After nickel-plating the silicon mold, a polypropylene was melted by applying a hot press at 220 ° C., and a pressure of 17 kg _f / cm ² was engraved to approximately 23,400 polygonal pyramids, Negative plastic molds of size 9 cm × 9 cm were fabricated with depths of 380 μm × 500 μm and 700 μm × 700 μm, respectively.

A mixed solution containing 2 g of hyaluronic acid, 4 g of water, and 200 μg (EGF) was applied to the recessed portion of the engraved plastic mold. Thereafter, the plastic mold was dried at room temperature, and then the molded micro spicule in the form of a polygonal pyramid was detached. The micro needle-shaped photograph of the polygonal pyramidal shape thus obtained is shown in FIGS. 1 to 3.

Hereinafter, the present invention will be described in more detail with reference to the following examples or drawings. However, the following description of the embodiments or drawings is only intended to specifically describe the specific embodiments of the present invention, it is not intended to limit or limit the scope of the present invention to only the specific details described therein.

EXAMPLES Preparation of Water Soluble Fine Acicular Scrub Particles of the Present Invention Containing Epithelial Growth Factor or Cell Culture Filtrate Components

A small hole in the shape of a pyramid with an angled corner is a mixed solution containing 2 g of hyaluronic acid, 4 g of water and 200 ug of epidermal growth factor, or a mixed solution of 2 g of hyaluronic acid and 4 g of cell culture filtrate. By loading and drying the formed plate, water-soluble scrub particles of sharply angled forms containing epidermal growth factor or cell culture filtrate components were prepared (see FIG. 2 or FIG. 3). The cell culture filtrate used in this embodiment is a cell culture filtrate described in Korean Patent Application Publication No. 10-2010-0098298, it contains a large number of growth factors, and has excellent skin regeneration effect and is used as a cosmetic raw material.

After applying the non-aqueous cosmetic composition containing the water-soluble fine acicular scrub particles of the present invention to the skin to dissolve the scrub particles using an aqueous cosmetic such as a skin emulsion, to the water-soluble fine acicular scrub particles of the present invention Since the effective ingredients of various peptide growth factors or cell culture filtrates contained are effective to penetrate deep into the stratum corneum, the water-soluble fine needle particles of the present invention are used as a cosmetic raw material.

Claims

A scrub particle composed of a polygonal pyramidal shaped needle having a size of 0.01 mm to 2 mm, which is made of a rare auronic acid having a molecular weight of 1,000 to 500,000 Daltons.

The scrub particle of claim 1, wherein the fine acicular body contains a polypeptide or a cell culture filtrate component.

The scrub particle of claim 1, wherein the fine acicular body contains both a polypeptide and a cell culture filtrate component.

The scrub particles of claim 2, wherein the polypeptide content is 0.0001% by weight to 1% by weight.

The scrub particles of claim 2, wherein the content of the cell culture filtrate component is 0.0001% by weight to 10% by weight.