JP2021525112A - Pyramid-shaped water-soluble fine needle-shaped scrub particles - Google Patents

Abstract

The present invention relates to pyramidal-shaped water-soluble fine needle-shaped scrub particles and a method for producing the same. More specifically, the present invention relates to a water-soluble spicule for transmitting a drug having a cosmetic effect or a therapeutic effect to the skin by opening the stratum corneum of the skin and a method for producing the same. be. [Selection diagram] Fig. 1

Description

The present invention relates to pyramidal-shaped water-soluble fine needle-shaped scrub particles and a method for producing the same. More specifically, the present invention relates to a water-soluble spicule for transmitting a drug that imparts a cosmetic effect or a therapeutic effect to the skin by opening the stratum corneum of the skin and a method for producing the same. be.

A method of applying an active substance such as a skin cosmetological ingredient or a drug to the skin, or applying a pack or patch containing the active substance to the skin and transmitting it to the human body enables continuous drug transmission. It has the advantage of being painless and easy to use.

However, since the stratum corneum having a thickness of 10 μm to 60 μm, which is the outermost part of the skin, prevents the permeation of external substances into the body, the absorption rate of the effective substance in the body is very low. In particular, if the active substance is hydrophilic or has a large molecular weight, its absorption rate in the body will be even lower.

Therefore, in order to effectively transfer the active substance subcutaneously, an administration method using injection is used. However, since the diameter of a conventional injection needle is in the millimeter range and its length is in the centimeter range, it stimulates a large number of pain points existing on the skin and causes considerable pain.

In addition, injection can be performed only at hospitals and specialized skin management institutions, so it has the disadvantage that it cannot be easily used at home.

In order to solve such disadvantages of the prior art, microneedles having a diameter of several tens of μm to several hundreds of μm and a length of several tens of μm to several thousand μm have been developed.

Since such fine needles form micropores in the stratum corneum of the skin, they are either hydrophilic through the formed micropores, or substances having a large molecular weight are easily absorbed by the skin, or through the skin. It can be transmitted to the body.

In addition, if a conventional fine needle is used, the skin absorption rate and the internal transmission rate of substances that are well absorbed even when applied to the skin are increased.

In addition, short needles do not penetrate into the dermis layer, where nerves are distributed, so they are painless. Even if a long fine needle penetrates into the dermis layer, the diameter is smaller and the length is shorter than that of a conventional needle, so that the number of pain points to be stimulated is small, and therefore the pain of the subject is greatly reduced.

International Publication Patent No. WO02 / 47555 describes a head forming a bulging head surface and a pin provided on the head that protrudes by a predetermined distance from the head surface and is separated by a predetermined distance. Disclosed includes an apparatus for treating the skin of a subject, and a method for applying a skin cosmetological substance after forming micropores in the stratum corneum of the skin using the apparatus.

In addition, US Registered Patent No. 5,487,726 is a step of applying a vaccine to the skin and a step of forming micropores in the stratum corneum of the skin by using a device in which a spike is attached to the skin to which the vaccine is applied. The vaccine application system including the above is disclosed.

However, according to International Publication Patent No. WO02 / 47555 and US Registered Patent No. 5,487,726, the step of applying the drug to the skin and the step of forming micropores in the stratum corneum of the skin are separated. Gives inconvenience to the person.

US Registered Patent No. 6,603,998 discloses a method of transmitting a skin cosmetic substance by coating the surface of an electrode in the form of a fine needle with a skin cosmetic substance and then applying the skin cosmetic substance to the skin.

In addition, US Registered Patent No. 6,132,755 applies a drug storage container provided with micropins to the skin, the micropins pass through the stratum corneum of the skin, and the micropins are passed through the micropins using a pump. Discloses the system by which the drug is transmitted to the skin.

Further, in US Publication No. 2005/0251088, a drug is stored in the voids of the porous needles, the porous needles make micropores in the stratum corneum of the skin, and a skin cosmetological substance stored in the voids of the needles is used. It discloses a method of communication.

Also, US Registered Patent No. 3,964,482 uses a device with a protrusion connected to a drug storage container, the protrusion passing through the stratum corneum of the skin and the drug through the protrusion. Discloses a drug transmission device that diffuses the drug into the skin.

However, according to Registered Patents Nos. 6,603,998, 6,132,755, and 3,964,482, and US Patent Application No. 2005/0251088, the skin cosmetological substance is applied to the skin. It has the disadvantage of requiring a separate device to communicate to.

Yet another way to allow skin cosmetological ingredients to pass through the stratum corneum more easily is
After using exfoliating cosmetics, a skin cosmetological substance is applied to the skin. Exfoliating cosmetics mainly use a scrubbing agent that can remove dead skin cells to physically remove dead skin cells.

However, there is a problem that after using the exfoliating cosmetics, the scrubbing agent must be washed off and then the skin beauty substance must be reapplied to the skin.

In addition, if the scrubbing agent gets into the eyes during use, it is not easy to remove the scrubbing agent, and a foreign body feeling is felt, and the cornea may be damaged by rubbing the eyes.

The Republic of Korea Registered Patent No. 10-1206985 is excellent in skin moisturizing, blood circulation promotion, skin waste and exfoliation by containing sugar scrub in non-aqueous cosmetics, but has good stability and diffusivity over time, and has a feeling of use. Discloses a massage cosmetic composition containing a large amount of excellent sugar scrub.

However, the sugar scrub of the above-mentioned Republic of Korea Registered Patent No. 10-1206985 generally has eight or more faces, each face has a large angle, and the edges are blunted, so that the scrubbing effect is not great. There is.

In order to overcome the disadvantages of the above-mentioned prior arts and the like, the present inventors have produced a water-soluble fine needle-like body having a stratum corneum shape, and a novel water-soluble fine needle-like body (microspicule) containing a skin cosmetological ingredient or a drug. ) As scrubbing particles, the present invention has been completed by confirming that a skin cosmetological ingredient or a drug can be easily and effectively passed through the stratum corneum.

A basic object of the present invention is a scrub particle composed of a pyramidal-shaped water-soluble fine needle-shaped scicule particle and a pyramid-shaped water-soluble fine needle-shaped body (microspire) for absorbing a skin cosmetic substance or a drug into the skin. Is to provide.

Yet another object of the present invention is (i) a step of filling an engraved mold with a mixed solution of a skin cosmetic substance or drug, a biocompatible substance, and water, and (ii) drying the mixed solution. Production of a prismatic water-soluble spicule for the absorption of a skin cosmetic substance or drug into the skin, comprising the step of obtaining a microspicule and (iii) the step of separating the microspicule from the engraved mold. To provide a method.

The basic object of the present invention described above is achieved by providing a microspicule for allowing a skin cosmetological substance or drug to be absorbed by the skin.

As used herein, the term "pyramid-shaped water-soluble microspicule" refers to a tetrahedral or pyramidal-shaped microstructure (see FIG. 1). Further, the pyramid is a polyhedron composed of a triangle whose one surface is a polygon (referred to as a bottom surface) and whose all other surfaces meet at the vertices.

In the present specification, each surface of the microspicule may be flat, uneven, or hollow. In addition, there may be defects such as a part of the edge or apex of the microspicule being cracked.

The microspicules of the present invention can be biocompatible substances such as polysaccharides, polyvinyl alcohols, carboxyvinyl polymers, chitosan, hyaluronic acid, cellulose polymers, or salts. The biocompatible substance refers to a substance that is harmless to the human body and can be dissolved, decomposed, or swollen in body fluids or water.

A depression can be formed on one or more surfaces of the microspicule, and the depth of the depression can be within 1/2 of the height of the microspicule.
The microspicules of the present invention further comprise a skin cosmetic substance or drug, allowing the skin cosmetic substance or drug to be effectively absorbed by the skin.

As shown in FIG. 2, when the skin beauty substance 2 contained in the microspicule 1 is applied onto the skin 10 and tapped or rubbed by hand, the vertices and edges of the polyhedron form micropores in the stratum corneum 11. Or remove some of the dead skin cells.

If the skin cosmetic substance passes through the micropores 13 formed in the stratum corneum, which is the largest physical barrier of the skin tissue, or the thinned stratum corneum, the skin is rich in water and the cell density is high. Since the skin cosmetic substance is relatively easily diffused in the relatively low epidermis and dermis 12 layers, the degree of skin absorption of the skin cosmetic substance is increased.

A polyhedron of hexahedrons or more may not be suitable for the present invention because the vertices and edges of the microspicules of the present invention must have sharp angles in order for such an action to occur.

In addition, if the microspicule is not dissolved in the skin and continues to maintain its shape, there is the inconvenience that the user has to wash it. Further, when the microspicule is inserted into the stratum corneum, the microspicule prevents most of the micropores, so that the improvement in the absorption of the skin cosmetological substance into the skin is reduced.

Therefore, microspicules that effectively absorb skin cosmetological substances or drugs into the skin are preferably easily dissolved, decomposed, or swollen in body fluids or water.

When the skin beauty substance 2 is contained in the microspicule 1, the skin beauty substance must consist of a component that does not dissolve the microspicule.

Since the thickness of the stratum corneum of the skin is 10 μm to 60 μm and the skin is elastic, the microspicule is preferably tetrahedral or pyramidal in order to form micropores in the stratum corneum. Alternatively, the bottom surface and the height of the pyramid are preferably 50 μm to 500 μm, respectively.

The skin cosmetic substances that can be contained in the microspicules of the present invention can be antioxidants, growth factors, wrinkle improving substances, or cell cultures, or culture media.

The antioxidant can be vitamin C, the growth factor can be epidermal growth factor (EGF) or fibroblast growth factor (FGF), and the cell culture or culture medium can be a culture of stem cells. Alternatively, it can be a culture medium.

Also, the drug that can be included in the microspicules of the present invention can be insulin or growth hormone.

As shown in FIG. 3, the tetrahedral or pyramidal microspicule 1 can be used by being packed together with a skin cosmetological substance 2 on a patch 20 that can be attached to the skin. Such a method has an advantage that fine channels are formed only in the stratum corneum of the site where the skin cosmetic substance is to be transmitted, and fine channels are not formed in the stratum corneum such as fingers and palms.

As disclosed in US Registered Patent No. 6,132,755, US Published Patent No. 2005/0251088, etc., the tetrahedral or prismatic microspiral 1 can be used in combination with the skin cosmetic substance 2. In addition, the inside of the fine needle is directly filled with skin cosmetic ingredients or vaccines, skin growth factors, growth hormones, insulin, etc. that have effects such as skin aging prevention, wrinkle improvement, and skin tone improvement, and are transmitted into the skin. You can also.

Yet another object of the invention described above is (i) a step of filling an engraved mold with a mixed solution of a skin cosmetic substance or drug, a biocompatible substance, and water, and (ii) drying the mixed solution. To provide a method for producing a microspicule for allowing a skin cosmetic substance or drug to be absorbed into the skin, comprising the step of obtaining the microspicule and (iii) separating the microspicule from the engraved mold. Is.

In one embodiment of the present invention, the tetrahedral or pyramidal microspicule 1 is a mixed solution of water and a solution 31 containing a microspicule component (biocompatible substance), as shown in FIG. To the engraved mold 32 (FIG. 5-a), to dry the mixed solution to obtain microspicules (FIG. 5-b), and to separate the microspicules from the engraved mold. It can be produced by a method including (Fig. 5-c).

In the methods of the invention, the skin cosmetics can be selected from antioxidants, growth factors, wrinkle improvers, and cell cultures or culture media.

Recombinant growth factors, growth factors contained in stem cell culture filtrate, etc. are proteins, and such proteins are unstable due to changes in the physical or chemical environment, and are hydrolyzed especially in the presence of water. It is not easy to maintain biological activity when added to cosmetic compositions due to its tendency to grow.

In order to protect the amide bond of easily hydrolyzable proteins and maintain the activity of various peptides for a long period of time during storage, distribution and use, freeze-dry with a composition containing a saccharide such as mannitol. Attempts have been made to stabilize the biological activity by using an additive in a liquid state after purification to a high degree of purity. However, such techniques and the like are not easy to apply to cosmetics.

In particular, epidermal growth factor (Epidermal Growth Factor, rh-oligopeptide-1 or sh-oligopeptide-1) undergoes physical and chemical changes not only at room temperature but also in a refrigerated storage state during long-term storage. Since the biological activity is reduced, there are various problems in formulation for commercialization, which requires a long storage and distribution period.

European Patent Publication Nos. 205,051 describes EGF and 1-10% surfactants, 5-45 as a composition of skin and ophthalmic creams to prevent such diminished activity of epidermal growth factor (EGF). A composition consisting of% fat and 0.3-0.8% preservative is disclosed.

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

Republic of Korea Patent Publication No. 10-1996-0013439 describes 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 solution. Discloses a stable EGF composition containing one or more substances selected from the group composed of.

In addition, as a patent for stabilizing EGF, Korean Registered Patent No. 10-0570358 discloses a nanovector composition containing epidermal growth factor and selenium and a cosmetic using the same, and is registered in the Republic of Korea. Patent No. 10-0752990 discloses a composition for preventing or treating skin diseases, which comprises nanoliposomes and natural extracts.

Even if such conventional techniques are used, it is not easy to maintain the activity of epidermal growth factor in cosmetics under room temperature distribution conditions, non-sterile conditions, and aqueous conditions. In particular, when epidermal growth factor is added to cosmetics at very low concentrations that are acceptable for cosmetics, it is almost impossible to maintain EGF activity during the period of storage, distribution and use. ..

In addition, since proteins have a large molecular weight, they may be added to cosmetics and do not penetrate the skin, and it is difficult to exert their effects. Biocosmetics containing growth factors are defined as protein transfer domain. Peptide fusion technology using PTD), liposome technology that wraps growth factors in lipids to aid skin penetration, and combined microneedle therapy system (MTS) Is mainly used.

The antioxidant can be vitamin C, the growth factor can be epidermal growth factor (EGF) or fibroblast growth factor (FGF), and the cell culture or culture medium can be a culture of stem cells. Alternatively, it can be a culture medium.

Also, the drug that can be included in the microspicules of the present invention can be insulin or growth hormone.

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

The mold is engraved in the form of a tetrahedron or pyramid, and the bottom surface and height of the engraved tetrahedron or pyramid can be 50 μm to 500 μm, respectively.

By using the microspicule of the present invention, a large amount of skin cosmetological substance or drug can be absorbed into the skin or transmitted into the body through the skin more efficiently than the prior art.
In addition, the microspicule of the present invention has an efficient form, has a simple structure, and can be manufactured extremely easily.

It is a perspective view with respect to the microspicule which concerns on this invention. This is an application example of microspicule according to one embodiment of the present invention. This is an application example of microspicule according to one embodiment of the present invention.

The best form 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 intended to specify and explain specific embodiments of the present invention, and the scope of rights of the present invention may be limited to the contents described therein. It is not intended to be a restrictive interpretation.

After exposing the pattern to a silicon wafer, bulk etching was performed to produce a silicon positive mold. After nickel-plating the silicon mold, heat of 220 ° C. was applied to a hot press to melt polypropylene, and _{a pressure of 17 kg f} / cm ² was applied to engrave approximately 23,400 pyramids. An inscribed plastic mold having a size of 9 cm × 9 cm was produced in which the length and depth of the bottom surface were 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 inscribed plastic mold. Then, the plastic mold was dried at room temperature, and then the molded pyramid-shaped microspicule was attached and detached. Photographs of the pyramidal-shaped microneedle spicules thus obtained are 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 description of the following examples or drawings is intended to specify and explain specific embodiments of the present invention, and the scope of rights of the present invention may be limited to the contents described therein. It is not intended to be a restrictive interpretation.

Example: Production of water-soluble fine needle spicule scrub particles of the present invention containing epidermal growth factor or cell culture filtrate component.

A small pyramid-shaped mixed solution containing 2 g of hyaluronic acid, 4 g of water, and 200 μg of epidermal growth factor, or a mixed solution of 2 g of hyaluronic acid and 4 g of cell culture filtrate. Water-soluble scrub particles in sharp, angular form containing epidermal growth factor or cell culture filtrate components were produced by loading onto a perforated plate and drying (see FIG. 2 or FIG. 3). The cell culture filtrate used in the present embodiment is the cell culture filtrate described in the Republic of Korea Patent Application Publication No. 10-2010-0998298, which contains a plurality of growth factors and has an excellent skin regeneration effect. It is used as a raw material for cosmetics.
Industrial applicability

The present invention is performed by applying a non-aqueous cosmetic composition containing the water-soluble fine needle-like scrub particles of the present invention to the skin and then dissolving the scrub particles using an aqueous cosmetic such as a skin emulsion. Since various peptide growth factors contained in the water-soluble fine needle-shaped scrub particles of the present invention or the active ingredient of the cell culture filtrate have the effect of deeply penetrating the inside of the stratum corneum, the water-soluble fine needle-shaped body of the present invention The particles are used as a raw material for cosmetics.

Claims (5)

Scrub particles made of hyaluronic acid having a molecular weight of 1,000 to 500,000 daltons and consisting of pyramidal-shaped fine needles having a size of 0.01 mm to 2 mm. The scrub particle according to claim 1, wherein the fine needle-like body contains a polypeptide or a cell culture filtrate component. The scrub particle according to claim 1, wherein the fine needle-like body contains both a polypeptide and a cell culture filtrate component. The scrub particle according to claim 2, wherein the polypeptide content is 0.0001% by weight to 1% by weight. The scrub particle according to claim 2, wherein the content of the cell culture filtrate component is 0.0001% by weight to 10% by weight.

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