KR20160123956A - Soluble micro-needle patch for skin volume augmentation - Google Patents

Abstract

Provided is a specific formulation for deriving effective drug efficacy of an adipocyte-differentiating component, especially anomalin. To this end, the adipocyte-differentiating component, especially anomalin, is contained in an intradermal biodegradable or soluble microneedle, and then injected into skin, thereby efficiently delivering the adipocyte-differentiating component into a subcutaneous fat layer, which is a target spot of the adipocyte-differentiating component. According to the present invention, the microneedle can be very effective for increasing skin volume and ameliorating wrinkles.

Description

(Soluble micro-needle patch for skin volume enhancement)

The present invention relates to a particular formulation or system for the efficient administration of adipocyte differentiation components.

The present invention also relates to certain formulations advantageous for efficient administration, stability, etc. of anomalins, one of the adipocyte differentiation components.

The basic structure of the skin is maintained by subcutaneous fat tissue, and this subcutaneous fat tissue plays a role in the volume and intensity of the skin. Therefore, increasing the volume of the adipose tissue may be a good solution to maintain the volume and elasticity of the skin, rather than the method of imparting elasticity to the dermis or epidermis in the skin layer which has been used previously.

Adipocyte differentiation refers to the conversion of adipose precursor cells into adipocytes through a number of external stimuli such as hormonal induction and complex gene expression regulatory processes. Korean Patent Laid-Open Publication No. 10-2011-0001407 discloses that it is possible to promote the production and accumulation of lipids through the differentiation of adipocytes, thereby improving wrinkles and elasticity of the skin. Recently, various materials for improving skin (wrinkles, elasticity, etc.) have been developed. In particular, materials for improving skin volume have been studied by promoting regeneration of adipose-derived stem cells and promoting differentiation into adipocytes.

Korean Patent Laid-Open Publication No. 10-2011-0001407 discloses a method for improving the skin condition such as wrinkles and elasticity through the differentiation of adipocytes, such as Rhizobia extract, Licorice extract, Wouin extract, Malt extract, Fruit extract, And it is known that anomalin, caspase extract, uroguanthus extract, pomegranate extract, Rhodiola extract, Ganghyeong extract, and ladybug extract have these effects in addition to the above components.

However, cosmetic preparations using such a mechanism have not been developed yet, and there is a problem in that the effects of the adipocyte differentiation component do not appear at a level that can be commercialized at the time of product development.

Korean Patent Publication No. 10-2011-0001407 (published on January 6, 2011) Korean Registered Patent No. 10-0793615 (2008. 1. 10. Announcement) International Patent Application Publication No. WO 02/064193 (published Aug. 22, 2002)

Therefore, the present invention is to develop a cosmetic product for efficiently administering the differentiation component of adipocyte, which is a component having an effect of improving skin volume and improving wrinkles.

Particularly, a specific object to be solved by the present invention is to develop cosmetics for efficient administration of anomalin, one of the differentiating components of adipocytes.

In order to solve the above problems, the present invention provides a cosmetic product for improving skin wrinkles or skin elasticity, comprising an adipocyte differentiation component as an active ingredient, wherein the cosmetic product is a biodegradable or skin- And a needle (microneedle).

The present inventors made various attempts to develop a cosmetic product containing an adipocyte differentiation component as an active ingredient. First, when applied using a conventional external composition for skin application, the adipocyte differentiation component enters the skin and functions to promote the differentiation of adipocytes so as to have a skin volume and wrinkle improving effect. Therefore, to be. That is, in order for the adipocyte differentiation component to exert its effect, the component must reach the subcutaneous fat layer located at the lower part of the epidermis layer and the dermal layer, but it is difficult for the adipocyte differentiation component to reach the subcutaneous fat layer through the composition for external application for skin. In addition, when the composition containing the adipocyte differentiation component is orally administered, the adipocyte differentiation component, which is an effective ingredient, must reach the subcutaneous fat layer after systemic circulation. In this case, there is a high possibility of causing adverse effects in other areas other than the desired subcutaneous fat layer The content ratio reaching the subcutaneous fat layer was very small and it was difficult to exert a great effect even in the case of a oral cosmetic preparation. In other words, the present inventors have studied various formulations of adipocyte differentiation component, but it has not been easy to exhibit a practical effect to commercialize the adipocyte differentiation component because it is a subcutaneous fat layer.

Accordingly, the inventors of the present invention confirmed that the above-mentioned problem can be solved by introducing a micro needle (microneedle) patch system as a subcutaneous fat layer administration of an adipocyte differentiation component, particularly an anomalin, .

In addition, the present inventors have found that an adipocyte differentiation component, particularly an anomaline, is useful for applying a micro needle system in the course of manufacturing a conventional microneedle patch and maintaining stability even in a soluble microneedle during storage. Thereby completing the invention.

Examples of the adipocyte differentiation component according to the present invention include anomalin, rhizosphere extract, licorice extract, wiin extract, malt extract, mugwort extract, ogumi extract, Puerariae radix extract, caspase extract, An extract, and a leaf extract may be used.

In particular, most of the ingredients except anomalin are plant extracts. Since these extracts contain various effective ingredients, transdermal administration is difficult and it is not easy to reach the subcutaneous fat layer after systemic circulation after oral administration. In this respect, the introduction of a micro-needle patch system for administration of the adipocyte differentiation component is very useful.

The extracts according to the present invention can be produced, for example, by the method disclosed in Korean Patent Laid-Open Publication No. 10-2011-0001407, but the present invention is not limited to the method for producing such extracts.

The length of the microneedles according to the present invention is not limited to a specific size. However, for the purpose of the present invention targeting the subcutaneous fat layer, the upper and lower lengths of the microneedles are preferably 150 to 2000 micrometers, more preferably 250 to 1000 micrometers.

The present invention is also directed to a method for producing a micro-needle, wherein when the adipocyte differentiation component is anomalin, not only the stability of the micro-needle (micro needle) is secured during the manufacturing process, but also the storage stability in a specific micro- . In fact, many candidate drugs were degraded or changed in activity during the production of microneedles and decomposition occurred rapidly during storage, but there was no such problem in the case of anomalin, one of the adipocyte differentiation components.

In order to achieve the desired effect of the present invention, the material forming the microneedles is biodegraded or dissolved in the skin to dissolve or collapse the microneedles when applying the skin of the microneedles, It is preferred that the differentiating component be released.

The adipocyte differentiation component according to the present invention may be impregnated in a form dispersed in the microneedle or may be contained in a form coated on the outer surface of the microneedle. When impregnated in a dispersed form, there is an adipocyte differentiation component between the biodegradable or skin-soluble substances forming the microneedles.

Such microneedles can be produced, for example, by using materials described in Korean Patent Publication No. 10-0793615, International Patent Application Publication No. WO 02/064193, Korean Patent Laid-Open Publication No. 10-2011-0065361, .

More specifically, in order to administer the subcutaneous fat layer of the differentiating adipocyte according to the present invention, it is preferable that the microneedle is made of a substance that dissolves in the skin rather than the biodegradable polymer. Examples of such a microneedle include hyaluronic acid, Sodium carboxymethyl cellulose, vinyl pyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, polyvinyl pyrrolidone, saccharide, or a mixture thereof may be used . The sugar may be xylose, sucrose, maltose, lactose, trehalose or a mixture thereof.

Considering the skin permeation intensity and the dissolution rate in the skin of the microneedles in the microneedle forming materials comprehensively and considering the stability of the anomalin and the compatibility with the anomalin in general, As a material for forming needles, hyaluronic acid, sodium carboxymethylcellulose and a mixture of sugars are preferable, and in such a mixture, the sugar is more preferably trehalose.

In the present invention, the anomaline may be included in an amount of 0.001 to 10% by weight, preferably 0.01 to 5% by weight, more preferably 0.1 to 1% by weight, based on the total weight of the micro- % Can be included. If it is contained in an amount of less than 0.001% by weight, the effective effect may not be exhibited. If it is contained in an amount exceeding 10% by weight, the physical properties and durability of the fine needle may be deteriorated.

Preferably, the microneedle according to the present invention may further include a plasticizer, a surfactant, a preservative, an anti-inflammatory agent, and the like in addition to the above-mentioned microneedle structure forming material.

Examples of such plasticizers include polyols such as ethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, and glycerin, Or may be used in combination. In particular, glycerin was more preferable in terms of stability to anomalins and compatibility with anomalins.

The present invention not only provides the microneedle itself containing an adipocyte differentiation component, but also a microneedle patch with a plurality of such microneedles. The size of the patch is not limited to a specific size, but can be appropriately adjusted depending on the amount of the adipocyte differentiation component to be absorbed into the skin or the attachment site.

The present invention also provides a method for improving skin wrinkles and skin elasticity, which comprises applying an adipocyte differentiation component according to the present invention, in particular, a microneedle comprising an anomaline as an active ingredient, to the skin. For example, as a method of applying or using such a microneedle, a microneedle device such as a roller having a microneedle according to the present invention is used to form a predetermined number or more holes in the skin, May remain in the skin.

The present invention provides a skin volume enhancing cosmetic comprising, as an active ingredient, ingredients that promote differentiation into adipocytes. The present invention relates to a method for producing an oily organs, which is permeated into the skin by the microneedles by applying the adipocyte differentiation component to the skin by impregnating the microneedles with biodegradability or intracutaneous solubility, more preferably by intramuscular microneedles and the microneedles are biodegraded The active ingredient can be efficiently delivered to the desired subcutaneous fat layer while being dissolved by moisture in the skin.

BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate exemplary embodiments of the invention and, together with the description of the invention, It should not be construed as limited.
BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a view showing one example of various methods for producing microneedles (microneedles) according to the present invention. Fig. The dissolvable microneedles can be prepared by a solution casting method. The solution in which the microneedle forming material is dissolved is cast in a mold, the microneedle is filled with the solution by vacuum and / or centrifugation Followed by drying. Various materials well known to those skilled in the art can be used as the material for forming the microneedle (micro needle) structure, and general biocompatible synthetic polymers, natural water-soluble polymers, biodegradable polymers, etc. can be used have.
Figure 2 shows a Franz diffusion cell for evaluating the anomalous release behavior of the micro needle according to the present invention.
FIG. 3 is a graph showing an anomalous release evaluation result, which was evaluated using a Franz diffusion cell equipped with pig skin.
FIG. 4 shows experimental results showing the degree of wrinkle improvement of the anomaline-containing cream used as a comparative example and the anomaline-containing micro-needle patch according to the present invention.

Hereinafter, embodiments of the present invention will be described in detail to facilitate understanding of the present invention. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following embodiments. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art.

≪ Preparation of soluble fine needle patch >

According to the following Table 1, microneedle patches were prepared using methods well known to those of ordinary skill in the art. In the present specification, the contents of the compositions are expressed as weight% unless otherwise specified.

Anomalin MN oligo-HA 6 Na-CMC 6 Trehalose 10 Glycerin 5 HCO-40 0.2 Anomalin-DPG solution (10%) 1.5 water To 100

More specifically, an anomaline-impregnated soluble microneedle patch was prepared as follows. Hyaluronic acid (Hyaluronic acid), Na-CMC (sodium carboxymethyl cellulose) and trehalose were dissolved in purified water and glycerin, HCO-40 and anomalin 10%, DPG (Dipropylene glycol) 90 %) Was added thereto to prepare a solution in which an anomalin was dispersed. The prepared anomalin dispersion solution was cast in a silicon microneedle mold and then centrifuged at 3000 rpm for 10 minutes to fill the micro mold with the anomalous dispersion.

After filling the solution, it was dried in a drying oven (70 ° C) for 3 hours, and the micro-needles produced using the adhesive film were separated from the silicon mold.

<Preparation of Oil-in-Water Cream of Comparative Example>

The emulsions of the type emulsified in water as described in Table 2 below were prepared by well known methods to those skilled in the art and used as comparative examples of the present invention. That is, in order to compare the skin permeation amount of the anomalin impregnated into the microneedles (patches), a comparative example was compared by impregnating cream ananomalins of the general emulsifier type.

ingredient Formulation Example C14-22 alcohol, C12-20 alkyl glucoside
(Mixture C14-22 alcohol: C12-20 alkyl glucoside = 80:20 weight ratio) 1.5 Glyceryl stearate, phage-100 stearate
(Mixture 50:50 weight ratio) 1.2 Glyceryl stearate 0.9 Cetearyl alcohol 1.5 Polyglyceryl-3 methyl glucoside distearate 1.5 Hydrogenated polydecene 4.5 Cyclohexasiloxane 3.5 Carbomer 0.2 Tromethamine 0.2 glycerin 3 Dipropylene glycol 5 1,2-hexanediol 2 Anomalin 0.5 Purified water Remaining amount (To 100)

<Evaluation of Anomaline Release Behavior>

Using an Franz diffusion cell, the anomalous content of porcine skin tissue and acceptor solution over time was measured using liquid chromatography techniques.

Pork skin was coated with an anomalic cream, or anomalin-impregnated micro-needle patches were applied to compare the skin permeation amount of anomalin over time. The results are shown in Fig.

The anomalin-containing cream had a penetration amount of about 1 μg or less through the skin. However, the anomalin impregnated in the micro needle was directly penetrated to the skin by the needle, and its permeation amount was 15 μg or more, The skin permeation rate was high.

&Lt; Wrinkle improvement effect &

Anomalin cream and anomalin impregnated microneedle patches were treated daily for 12 weeks on wrinkles, and the degree of wrinkle improvement was confirmed by silicone replica and wrinkle image analysis method. At this time, the test number of each sample was 20 (N = 20). The results are shown in Fig.

Showed an improvement of about 2 ~ 3 times better than that of the anomalin - impregnated microneedle. That is, it was confirmed that the anomaline effectively penetrated into the skin by the microneedles and the effect of improving wrinkles was high.

&Lt; Evaluation of Stability of Anomalins in Fine Needles >

A microneedle containing 0.5% by weight of an anomaline based on the total weight of the microneedles was prepared in the same manner as described in Table 1 above. The anomalous content was evaluated immediately after the preparation and the stability was evaluated for 3 months at the low temperature (0 ° C), the normal temperature (25 ° C) and the high temperature (40 ° C) for 3 months.

The content of anomalin was analyzed by the following method. An amount of microneedles was dissolved in a small amount of purified water, and an anomaline was extracted by adding an organic solvent. After appropriate dilution and filtration, anomalin content was analyzed using liquid chromatography.

The results of the analysis are shown in Table 3 below.

Content of ananomalin in MN (%) After manufacturing 0.51 After 3 months storage at 0 0.50 After 3 months and 25 days storage 0.49 After 3 months and 40 days storage 0.47

As shown in Table 3, it was confirmed that the anomaline could be stably present in the microneedles at 90% or more of the initial concentration.

Claims (8)

1. A cosmetic product for improving skin wrinkles or skin elasticity comprising an adipocyte differentiation component as an active ingredient,
Wherein the cosmetic comprises biodegradable or skin-soluble microneedle containing an adipocyte differentiation component. [3] The method of claim 1, wherein the adipocyte differentiation component is selected from the group consisting of anomalin, an extract of Rhododendrons, licorice extract, Uinta extract, malt extract, mugwort extract, , Ganghyeol extract, and lavender extract. &Lt; RTI ID = 0.0 &gt; 15. &lt; / RTI &gt; 3. The cosmetic product according to claim 2, wherein the fat cell differentiation component is anomaline. The method of claim 1, wherein the microneedle is selected from the group consisting of hyaluronic acid, sodium carboxymethyl cellulose, vinyl pyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, polyvinyl pyrrolidone (polyvinyl pyrrolidone), and a saccharide. 5. The cosmetic product according to claim 4, wherein the microneedles contain an anomaline as an adipocyte differentiation component and are produced using a mixture of hyaluronic acid, sodium carboxymethylcellulose and a saccharide as a microneedle forming material. 6. The cosmetic product according to claim 5, wherein the sugar is trehalose. A method for improving skin wrinkles or skin elasticity comprising applying a microneedle containing an adipocyte differentiation component as an active ingredient to the skin. 8. The method of claim 7, wherein the adipocyte differentiation component is an anomalous.

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