KR102139336B1 - Soluble Microneedle device having improved absorbing rate of active agent and kit comprising thereof - Google Patents

Abstract

The present invention provides a soluble microneedle array and a sheet to which the microneedle array is attached, and the sheet provides a soluble microneedle device in which a plurality of holes are formed and a kit including the same. The present invention provides a microneedle system with improved absorption rate and improved absorption rate of a drug impregnated with a soluble microneedle.

Description

Soluble microneedle device having improved absorption rate of an active ingredient and a kit comprising the same{Soluble Microneedle device having improved absorbing rate of active agent and kit comprising thereof}

The present invention relates to a microneedle device having an improved skin absorption rate of an active ingredient or a microneedle kit comprising the same.

In order to improve the transdermal delivery efficiency of drugs that are difficult to be absorbed through the skin due to lack of skin affinity (lipid affinity) or too large in molecular weight (over 500 Dalton), the drug is impregnated with Soluble Microneedle to increase the skin delivery efficiency and I'm doing it.

Republic of Korea Patent Publication No. 10-2011-00653161 discloses a microneedle in which a microneedle is dissolved so that an active ingredient can be administered into the body.

However, since the microneedle penetrates directly into the skin and melts and is absorbed into the skin, the microneedle is made of water-soluble natural polymers (Carboxy methyl cellulose, Hyaluronic acid, Chitosan, Pulluran, etc.) with excellent biocompatibility. , There was a problem that the amount that can be absorbed and absorbed into the skin by penetrating and dissolving in the skin compared to the total microneedle disk content including the needle is 5% or less. In addition, there was a problem in that rapid delivery of drugs was difficult because the time required for the needle to dissolve by moisture in the skin after the needle penetrated the skin took several tens to several hours.

Therefore, the problem to be solved by the present invention is to provide a soluble microneedle device capable of effectively delivering an active ingredient into the skin. In particular, the present invention is to provide a microneedle device or microneedle system (e.g., a kit) capable of rapidly dissolving and delivering the active ingredient contained in the microneedle by improving the dissolution rate of the soluble microneedle.

In order to solve the above problems, the present invention provides a microneedle system that effectively delivers the drug impregnated in the microneedle into the skin.

The present invention includes a hole through which water can pass through an adhesive patch used for attaching a soluble microneedle impregnated with a drug to the skin, and after attaching a microneedle patch including a hole, Provided is a microneedle system that adheres to other moisture-containing adhesives.

Specifically, the present invention includes a soluble microneedle array and a sheet in which the microneedle array is attached to one surface, and the sheet provides a soluble microneedle device in which a plurality of holes are formed. The microneedle array includes a soluble microneedle and a microneedle disk in which the microneedle is aligned.

The microneedle system according to an embodiment of the present invention can effectively deliver the drug impregnated in the microneedle into the skin by dissolving the needle as well as the microneedle disc in a short time.

The microneedle array can perforate the skin by itself, and perforation can be applied to the skin in a form attached to a microneedle disk capable of aligning the microneedle according to the manufacturing method of the microneedle array.

The microneedle according to an embodiment of the present invention may be soluble in the skin, and to form a soluble microneedle, hyaluronic acid, sodium-carboxymethyl cellulose (Na-CMC, sodium carboxymethyl cellulose), vinyl Water-soluble polymers such as pyrrolidone-vinyl acetate copolymer, poly vinyl alcohol, and poly vinyl pyrrolidone; Sugars such as xylose, sucrose, maltose, lactose, and trehalose; Or mixtures of these can be used. In particular, considering the skin penetration strength of the microneedle and the dissolution rate in the skin comprehensively, hyaluronic acid, sodium-carboxymethyl cellulose (Na-CMC, sodium carboxymethyl cellulose), and saccharide (saccharide) ) (More preferably, a mixture of Trehalose) is more preferable, and even more preferably mixed with Glycerin described below.

Preferably, the microneedle according to the present invention may additionally include a plasticizer, a surfactant, a preservative, an anti-inflammatory agent, etc. in addition to the above-mentioned components.

As the plasticizer, for example, polyols such as ethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, and glycerin are solely used. It can be used as or mixed.

The drug that can be applied to the microneedle system of the present invention is not particularly limited, and any drug that can be applied to the soluble microneedle can be used.

A sheet may be attached to the microneedle array to bring the microneedle array into close contact with the skin.

The sheet may have tackiness on a surface contacting the skin. As used herein, "adhesiveness" refers to a sticky property, and the degree of sticking is not particularly limited, and is understood to be sticky if it sticks without falling off when the sheet touches a certain contact surface such as skin.

The sheet may be made of a flexible material in consideration of skin curvature and the like. For example, an acrylic or rubber adhesive having adhesiveness to a sheet having a material such as polyurethane, polyethylene, polyester, polypropylene, polyvinyl chloride, etc. Can be applied. The pressure-sensitive adhesive may be applied to a thickness of 1 to 100㎛, for example.

In another embodiment, the sheet may be a hydrocolloid (Hydrocolloid) adhesive. The hydrocolloid adhesive may be in a form in which hydrophilic hydrocolloid fine particles are dispersed in a hydrophobic polymer matrix by mixing a tackifier with a hydrophilic polymer and a hydrophobic polymer. The tackifier may include, for example, rosin ester, etc., and the tackifier generally used in the hydrocolloid adhesive in the industry may be included. In another embodiment, the hydrocolloid adhesive may be attached to the microneedle array in the form of lamination on a film of polyurethane, polyethylene, polypropylene, polyvinyl chloride or polyester material.

The shape of the sheet is not particularly limited, and the shape may be manufactured in consideration of the possibility of contact with the skin and the shape of the microneedle array.

The sheet may include a plurality of fine-sized holes, and may have a structure in which moisture (or liquid) can be transferred to the micro-needles along the holes. The number of holes is not limited, and may be appropriately selected in consideration of differences in solubility according to the material of the microneedle.

The hole may have a size of 0.01 to 10 mm in consideration of the liquid transfer, the contact area of the microneedle and moisture, and may preferably have a size of 0.05 to 8 mm, more preferably 1 to 5 mm. .

According to an embodiment of the present invention, the microneedle device may further include a moisture supply member capable of transferring moisture to the microneedle through a hole formed in the patch of the soluble microneedle device. That is, there is provided a soluble microneedle kit comprising a soluble microneedle device and a member that supplies moisture to the soluble microneedle device.

The member for supplying moisture to the soluble microneedle device included in the kit may be a non-woven fabric or a hydrogel mask containing a liquid. In another embodiment, without using a separate adhesive such as a non-woven fabric or hydrogel mask, a cosmetic composition such as essence or skin, toner, etc. may be applied over an adhesive patch comprising holes. The member to which the moisture is supplied may include all forms capable of storing and discharging moisture, for example, a moisture-containing sheet, a hydrogel sheet, a mask pack, a moisture gel, a moisture cream, skin, essence, and toner. can do.

In one embodiment of the present invention, a method of manufacturing a soluble microneedle and a porous microneedle patch comprising the same is provided.

The soluble microneedle may be manufactured by a molding method using a method for manufacturing a soluble microneedle generally known in the art.

The present invention can improve the transdermal delivery efficiency of the drug.

The microneedle system of the present invention improves the dissolution rate of the soluble microneedle so that the drug contained in the microneedle can be rapidly released.

The microneedle system of the present invention can increase the amount of drug that penetrates and dissolves into the skin and is absorbed.

The following drawings attached to this specification are intended to illustrate preferred embodiments of the present invention, and serve to further understand the technical idea of the present invention together with the contents of the above-described invention, so the present invention is limited to those described in those drawings. It should not be interpreted as limited.
1 is a view showing an example of a number of methods for manufacturing a microneedle according to the present invention. Soluble microneedles can be prepared by solution casting, and can be prepared by casting the solution into a mold, filling the micro mold with a vacuum and/or centrifuge and drying it. General synthetic and natural water-soluble polymers may be used as a material for forming the microneedle structure. An adhesive patch is used to attach the microneedle to the skin, and a plurality of holes are formed in the adhesive patch to have a structure in which moisture is transferred to the microneedles through the hole.
2 is a view showing an example of a porous adhesive patch. The microneedle disk may have a plurality of holes 23 in the sheet 20 having an adhesive property that can be attached to the skin.
3 exemplarily shows an embodiment of the microneedle device 1 of the present invention. One surface of the sheet 20 in which a plurality of holes 23 are formed may have adhesiveness. The adhesive face 21 is in contact with the microneedle array 10 including the microneedle 11 and the microneedle disk 12, and the adhesive face 21 can be attached to the skin.
4 shows a Franz diffusion cell for evaluating the release behavior of Niacinamide according to the present invention.
Figure 5 shows a graph comparing the skin penetration of Niacinamide over time after attaching a microneedle impregnated with Niacinamide, and attaching a water mask onto a porous microneedle patch.
6 is an experimental result showing the degree of wrinkle improvement after long-term use on the wrinkles around the eyes of the group treated with a microneedle impregnated with Niacinamide and a group with only a microneedle impregnated with Niacinamide.

Hereinafter, examples and the like will be described in detail to help understanding of the present invention. However, the embodiments according to the present invention may be modified in various other forms, and the scope of the present invention should not be interpreted as being limited to the following examples. The embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

<Manufacture of soluble micro needle>

As shown in Table 1 below, a soluble microneedle was prepared.

Comparative example (% by weight) Oligo-HA 5 Na-CMC 10 Trehalose 10 Glycerin 5 HCO-40 0.2 PVP K-30 - Niacinamide 5 Water To 100

Oligo-HA (Hyaluronic acid), Na-CMC (Sodium carboxymethyl cellulose) and Trehalose were dissolved in purified water, and then Glycerin, HCO-40, and Niacinamide were added to prepare a solution. After casting the prepared solution in a silicone microneedle mold, centrifugation was performed at 3000 rpm for 10 minutes to fill the micro mold. After filling the solution, it was dried for 3 hours in a drying oven (70°C), and the microneedle was separated from the silicone mold using an adhesive film having a hole.

<Preparation of soluble microneedle and porous microneedle patch>

A soluble microneedle having the composition of Table 1 was prepared by the above method.

In order to attach the microneedle to the skin, an adhesive sheet was attached to the microneedle array. The adhesive sheet was prepared by coating an acrylic adhesive on a polyurethane film.

The adhesive sheet was manufactured so that about 2 holes having a size of about 2 mm were formed per unit area (1 cm ² ). A moisture mask was attached to the non-tacky side of the sheet.

<The behavior of drug niacinamide release>

The release of niacinamide from the microneedle prepared above was evaluated using a Franz diffusion cell equipped with pig skin (see FIG. 4). A PBS solution containing 30% by weight of DPG was used as an aqueous solution. That is, niacinamide content of pig skin tissue and acceptor solution over time was measured using a Franz diffusion cell using Liquid Chromatography. After attaching a microneedle impregnated with niacinamide to the pig skin, a water mask was attached to the porous microneedle patch, and the skin penetration of Niacinamide over time was compared. When only the microneedle was attached, the amount of Niacinamide permeated to the skin was lower than about 5%, but when the moisture mask was attached on the porous microneedle patch, the skin permeability of Niacinamide increased by more than 10 times to 50% or more.

Skin permeability (Penetration efficiency, %) was measured by the following method.

* Skin permeability = content in pig skin tissue + content in acceptor solution

<Wrinkle improvement effect>

The microneedle and moisture mask impregnated with Niacinamide were treated daily for 12 weeks on the wrinkles around the eyes, and the degree of wrinkle improvement was confirmed by a silicon replica and a wrinkle image analysis method. (N=20) The results are shown in FIG. 6.

Compared to the Niacinamide-impregnated Microneedle only, the moisture mask was applied on the porous Microneedle patch more than twice, which showed an excellent wrinkle improvement effect, which was effectively applied to the skin by the Niacinamide moisture mask attached on the Porous Microneedle patch. It was absorbed, and it was confirmed that the wrinkle improvement effect was high.

Claims (7)

Non-woven fabric or hydrogel mask containing moisture; And
Including a soluble microneedle device,
The soluble microneedle device
A soluble microneedle array impregnated with the drug; And
The microneedle array includes a sheet having a plurality of holes, attached to one surface,
Each of the plurality of holes has a size of 0.01 to 10 mm, and the moisture contained in the nonwoven fabric or hydrogel mask moves through the plurality of holes to promote dissolution of the soluble microneedle array. Soluble microneedle kit containing the non-woven fabric or hydrogel mask. The soluble microneedle kit of claim 1, wherein the soluble microneedle array comprises a microneedle and a microneedle disc. According to claim 1, One side of the sheet to which the microneedle array is attached has tackiness, and the soluble microneedle containing a non-woven fabric or hydrogel mask containing moisture, characterized in that the sticky side is attached to the skin. Kit. delete delete delete delete

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