KR20200128402A - Polygonal pyramid shaped water-soluble fine needle scrub particles - Google Patents

Abstract

The present invention relates to water-soluble fine needle-shaped scrub particles having a polygonal pyramid shape and a method for producing the same. More specifically, the present invention relates to a water-soluble fine acicular body for delivering a drug that imparts a cosmetic effect to the skin or causes a therapeutic effect to the skin through a stratum corneum layer, and a method of manufacturing the same.

Description

Polygonal pyramid shaped water-soluble fine needle scrub particles

The present invention relates to water-soluble fine needle-shaped scrub particles having a polygonal pyramid shape and a method for producing the same. More specifically, the present invention relates to a water-soluble fine acicular body for delivering a drug that imparts a cosmetic effect to the skin or causes a therapeutic effect to the skin through a stratum corneum layer, and a method of manufacturing the same.

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

However, since the stratum corneum layer of 10 μm to 60 μm thick at the outermost part of the skin prevents the penetration of foreign substances into the body, the absorption rate of the effective substance in the body is very low. In particular, when the active substance is hydrophilic or has a large molecular weight, its absorption rate in the body is further lowered.

Therefore, in order to effectively deliver an effective substance subcutaneously, an administration method using injection has been used. However, since the diameter of a conventional injection needle is in the range of millimeters and the length is in the range of centimeters, considerable pain occurs by stimulating a number of pain points existing in the skin.

In addition, since injection can be performed only in hospitals or specialized skin care institutions, there is a disadvantage that it cannot be easily used at home.

In order to solve the drawbacks according to the prior art, a microneedle having a diameter of several tens μm to several hundred μm and a length of several tens μm to thousands of μm has been developed.

Since these fine needles form fine pores in the stratum corneum of the skin, a material having a hydrophilic or high molecular weight can be easily absorbed into the skin or transferred to the body through the skin through the formed fine pores.

In addition, the use of conventional microneedles increases the skin absorption rate and intra-body delivery rate of substances that are well absorbed just by applying to the skin.

Moreover, since the short microneedles do not penetrate to the dermal layer where the nerves are distributed, there is no pain. Even if a long microneedle penetrates to the dermal layer, the number of painful points to be stimulated is small because the diameter is small and the length is shorter than that of a conventional needle, and thus the subject's pain is greatly reduced.

International Patent Publication No. WO 02/47555 describes a head that forms a convex head surface, and includes pins installed on the head and protruding from the head surface by a predetermined distance and spaced apart by a predetermined distance. Disclosed is an apparatus, and a method of applying a skin cosmetic material after forming micropores in a stratum corneum layer using the apparatus.

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

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

U.S. Patent No. 6,603,998 discloses a method of delivering a skin cosmetic substance by coating a skin cosmetic substance on the surface of an electrode in the form of a microneedle and then applying it to the skin.

In addition, U.S. Patent No. 6,132,755 discloses a system in which a drug storage container equipped with micropins is applied to the skin so that the micropins pass through the stratum corneum, and a 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, making the pores in the stratum corneum of the skin by the porous needle, and delivering the skin beauty material stored in the pores of the needle.

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

However, according to the Patent Nos. 6,603,998, 6,132,755 and 3,964,482, and U.S. Patent Application Publication No. 2005/0251088, there is a disadvantage in that a separate device is required to deliver the skin beauty substance to the skin.

Another way to make it easier for skin care ingredients to pass through the stratum corneum is to apply a skin care substance to the skin after using exfoliating cosmetics. Exfoliating cosmetics physically remove dead skin cells using a scrub that can remove dead skin cells.

However, there is a problem in that the skin care substance must be applied to the skin again after the scrub agent is washed off after use of the exfoliating cosmetic.

In addition, if it enters the eyes while using the scrub agent, it is not easy to remove the scrub agent, a foreign body sensation is felt, and the cornea may be damaged by rubbing the eye.

Korean Patent Registration No. 10-1206985 is a massage cosmetic that contains a large amount of sugar scrub that contains sugar scrub in a non-aqueous cosmetic that provides excellent skin moisturization, blood circulation, and skin impurities and dead skin removal, while excellent stability and spreadability over time. The composition is disclosed.

However, the sugar scrub of Korean Patent No. 10-1206985 generally has 8 or more sides, so the angle formed by each side is large, and the corner is blunt, so the scrub effect is not large.

In order to overcome the drawbacks of the prior art described above, the present inventors prepared a water-soluble fine acicular body in the shape of a polygonal pyramid and used a novel water-soluble fine acicular body (micro spicule) containing a skin cosmetic ingredient or drug as a scrub particle, The present invention was completed by confirming that the skin cosmetic ingredient or drug can easily and effectively pass through the stratum corneum.

The basic object of the present invention is to provide a scrub particle comprising water-soluble fine needle-shaped scrub particles having a polygonal pyramid shape and a water-soluble microspicule having a polygonal pyramid shape for absorbing skin care substances or drugs into the skin.

Another object of the present invention is (i) filling a mixed solution of a skin beauty substance or drug, a biocompatible substance, and water into an engraved mold; (ii) drying the mixed solution to obtain micro spicules; And (iii) separating the micro spicules from the engraved mold, to provide a method of manufacturing a water-soluble fine acicular body having a polygonal pyramid shape for absorbing skin beauty substances or drugs into the skin.

The basic object of the present invention described above is achieved by providing a microsphere for absorbing a skin cosmetic substance or drug into the skin.

In the present specification, the term "water-soluble micro-spicule in the shape of a polygonal pyramid" refers to a micro-structure in the form of a tetrahedron or a polygonal pyramid (see FIG. 1). In addition, the polygonal pyramid refers to a polyhedron consisting of one side of a polygon (referred to as a base) and a triangular tooth where all other sides meet at a vertex.

In the present specification, each surface of the micro spicules may be flat, may have irregularities, and may be hollow. In addition, there may be defects such as cracking of a part of the corner or vertex of the microspicules.

The micro spicules 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 body fluids or water.

A depression may be formed on one or more surfaces of the microspicules, and the depth of the depressions may be within 1/2 of the height of the microspicules.

The micro spicules of the present invention further include a skin cosmetic substance or drug, so that the skin cosmetic substance or drug can be effectively absorbed into the skin.

When the skin care material 2 contained in the micro spicules 1 is applied onto the skin 10 and rubbed with hands, as shown in FIG. 2, the vertices or corners of the polyhedron are finely formed on the keratin 11 Make holes or remove some of the dead skin cells.

When the skin care material passes through the fine pores 13 formed in the stratum corneum, the largest physical barrier among skin tissues, or through the thinned stratum corneum, the epidermis and dermis 12 layers, which are rich in moisture and have relatively low cell density, are Since the skin care material is relatively easily diffused, the skin absorption of the skin care material is increased.

In order for such an action to occur, since the vertices or corners of the microspicules of the present invention must have a sharp angle, a polyhedron having a hexahedron or larger may not be suitable for the present invention.

In addition, if the micro spicules do not dissolve in the skin and continue to maintain their shape, there is an inconvenience that the user must wash. Moreover, when the micro-spiculs are embedded in the stratum corneum, the micro-spiculs block most of the micropores, so that the skin absorbency of the skin care material is less improved.

Therefore, it is preferable that the micro spicules that effectively absorb skin care substances or drugs into the skin are easily dissolved, decomposed, or swelled in body fluids or water.

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

Since the skin stratum corneum has a thickness of 10 μm to 60 μm and the skin has elasticity, in order to form micropores in the stratum corneum, the micro spicules are preferably in the shape of a tetrahedron or polygonal pyramid, and the base and height of the tetrahedron or polygonal pyramid are respectively It is preferably 50 μm to 500 μm.

Skin beauty substances that may be included in the micro spicules of the present invention may be antioxidants, growth factors, wrinkle improvement substances, or cell culture or culture medium.

The antioxidant may be vitamin C, the growth factor may be epithelial cell growth factor (EGF) or fibroblast growth factor (FGF), and the cell culture or culture medium is a stem cell culture or culture medium. I can.

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

The tetrahedral or polygonal pyramid-shaped microspiculs 1 may be used by being filled with a skin care material 2 on a patch 20 that can be attached to the skin, as shown in FIG. 3. In this method, there is an advantage in that microchannels are formed only in the stratum corneum of a region to which the skin care material is to be delivered, and microchannels are not formed in the stratum corneum such as fingers or palms.

The tetrahedral or polygonal pyramid-shaped micro-spicul (1) can be used by mixing with the skin care material (2), and as disclosed in US Patent No. 6,132,755 or US Patent Publication No. 2005/0251088, the inside of a microneedle Skin care ingredients or vaccines, epidermal growth factors, growth hormones, and insulin, which are effective in preventing skin aging, improving wrinkles, and improving skin tone, can be directly filled and delivered into the skin.

Another object of the present invention as described above is (i) filling a mixed solution of a skin beauty substance or drug, a biocompatible substance, and water into an engraved mold; (ii) drying the mixed solution to obtain micro spicules; And (iii) separating the micro spicules from the engraved mold, to provide a method of manufacturing micro spicules for absorbing skin beauty substances or drugs into the skin.

In one embodiment of the present invention, the tetrahedral or polygonal pyramid-shaped micro spicules 1 are, as shown in FIG. 5, a solution 31 containing a component (biocompatible material) forming a micro spicule and Filling the mixed solution of water into the engraved mold 32 (Fig. 5-a), the step of drying the mixed solution to obtain micro-spicules (Fig. 5-b), and the micro-spicules into 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 may be selected from antioxidants, growth factors, anti-wrinkle substances, and cell cultures or culture media.

Recombinant growth factors or growth factors included in the stem cell culture filtrate are proteins, and these proteins are unstable according to changes in physical or chemical environments, especially in the presence of water, because they are easily hydrolyzed, so when added to a cosmetic composition It is not easy to maintain biological activity

In order to protect the amide bonds of proteins that are likely to be hydrolyzed and maintain the activity of various peptides for a long period of time during storage, distribution and use, stabilization is achieved by lyophilization with a composition containing sugars such as mannitol, or after purification with high purity. Methods of stabilizing biological activity using additives in the liquid phase have been tried. However, these techniques are not easy to apply to cosmetics.

In particular, epidermal growth factor (rh-oligopeptide-1 or sh-oligopeptide-1) is stored and distributed because its biological activity decreases due to physical and chemical changes during long-term storage, not only at room temperature but even in refrigerated storage conditions. There are various problems in formulation for commercialization that takes a period of time.

European Patent Publication No. 205,051 is a composition of skin and ophthalmic cream for preventing the decrease in the activity of the epithelial growth factor EGF. EGF and 1 to 10% surfactant, 5 to 45% fat, and 0.3 to 0.8% preservative It discloses a composition consisting of.

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

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

In addition, as a patent for stabilizing EGF, Korean Patent Registration No. 10-0570358 discloses a nano vector composition containing epithelial cell growth factor and selenium, and a cosmetic agent using the same, and Korean Patent No. 10-0752990 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 the epithelial cell growth factor in a cosmetic product in room temperature distribution conditions, non-sterile conditions, and aqueous conditions. In particular, when epithelial cell growth factors are added to cosmetics at a very low concentration allowed by cosmetics, it is almost impossible to maintain EGF activity during the period required for storage, distribution, and use.

In addition, because protein has a large molecular weight, it is difficult to see the effect because it does not penetrate the skin well even if added to a cosmetic product. Therefore, biocosmetics containing growth factors use a protein transduction domain (PTD). Peptide fusion technology is used, a liposome technology that helps skin penetration by wrapping a growth factor in lipids is applied, or a method combining a microneedle therapy system (MTS) is mainly used.

The antioxidant may be vitamin C, the growth factor may be epithelial cell growth factor (EGF) or fibroblast growth factor (FGF), and the cell culture or culture medium is a stem cell culture or culture medium. May be.

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

The biocompatible material may be selected from polysaccharides, polyvinyl alcohol, carboxyvinyl polymer, chitosan, hyaluronic acid, cellulose polymer or salt.

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

Using the micro spicules of the present invention, a large amount of skin care substances or drugs can be absorbed into the skin or delivered into the body through the skin more efficiently than in the prior art.

In addition, the micro spicules of the present invention can be manufactured very easily because they have an efficient shape and a simple structure.

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

Best mode for carrying out the 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 specific embodiments of the present invention, and is not intended to limit or limit the scope of the present invention to the contents described therein.

After exposing the pattern on a silicon wafer, a silicon embossed mold was manufactured by bulk-etching. After nickel-plating the silicone mold, heat at 220° C. was applied to a hot-press to melt polypropylene, and a pressure of 17 kg _f /cm ² was applied to engrave about 23,400 polygonal pyramids, and the length of the base and An intaglio plastic mold having a depth of 380 μm × 500 μm and 700 μm × 700 μm, respectively, with a size of 9 cm × 9 cm was prepared.

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 intaglio plastic mold. Thereafter, the plastic mold was dried at room temperature, and then the molded polygonal pyramid-shaped micro spicules were detached. The photographs of the micro acicular body obtained in the form of a polygonal pyramid are shown in FIGS. 1 to 3.

Mode for carrying out the invention

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

Example: Preparation of water-soluble fine needle scrub particles of the present invention containing epithelial cell growth factor or cell culture filtrate component

A mixed solution containing 2 g of hyaluronic acid, 4 g of water, and 200 ug of epithelial growth factor, or a mixed solution of 2 g of hyaluronic acid and 4 g of cell culture filtrate is a small hole in the shape of a pyramid with sharp corners. By loading and drying the formed plate, a sharply angled water-soluble scrub particle containing an epithelial cell growth factor or a cell culture filtrate component was prepared (see FIG. 2 or 3). The cell culture filtrate used in this example is a cell culture filtrate described in Korean Patent Application Publication No. 10-2010-0098298, contains a number of growth factors, and has excellent skin regeneration effect, so it is used as a raw material for cosmetics.

After applying the non-aqueous cosmetic composition containing the water-soluble fine needle-like scrub particles of the present invention to the skin and dissolving the scrub particles with an aqueous cosmetic such as a skin emulsion, the water-soluble fine needle-like scrub particles of the present invention Since the active ingredients of various peptide growth factors or cell culture filtrate contained penetrate deep into the skin into the stratum corneum, the water-soluble fine acicular particles of the present invention are used as cosmetic ingredients.

Claims (5)

Scrub particles composed of fine needles having a polygonal pyramid shape having a size of 0.01 mm to 2 mm, made of dilutealuronic acid having a molecular weight of 1,000 to 500,000 Daltons. The scrub particle according to claim 1, wherein the fine acicular body contains a polypeptide or a cell culture filtrate component. The scrub particle according to claim 1, wherein the fine acicular body contains both a polypeptide and a cell culture filtrate component. The scrub particle according to claim 2, wherein the content of the polypeptide is 0.0001% by weight to 1% by weight. The scrub particle of claim 2, wherein the content of the cell culture filtrate component is 0.0001% by weight to 10% by weight.

Images