KR102110571B1 - Manufacturing method of transdermal patch comprising effective ingredients - Google Patents

Abstract

The present invention relates to a method for manufacturing a patch carrying an active component. More specifically, the present invention relates to a method for manufacturing a patch carrying an active component, which is composed of: a release control adhesive layer being in contact with the skin; an active component carrying layer formed on the upper part of the adhesive layer; and a support layer formed on the upper part of the active component carrying layer. The present invention can eliminate side effects in an existing method of administration such as an injection or oral administration.

Description

Manufacturing method of patch containing active ingredient {MANUFACTURING METHOD OF TRANSDERMAL PATCH COMPRISING EFFECTIVE INGREDIENTS}

The present invention relates to a method for manufacturing a patch carrying an active ingredient, more specifically, a release-adhesive adhesive layer contacting the skin, an active ingredient supporting layer formed on the adhesive layer, and a support layer formed on the active ingredient supporting layer It relates to a method of manufacturing a patch carrying an active ingredient consisting of.

Drug Delivery System (DDS) refers to a series of technologies that deliver drugs to target sites such as cells and tissues to control drug absorption and release, thereby reducing side effects of drugs and maximizing efficacy.

In the case of a typical injection therapy, the administration method is cumbersome and may cause pain depending on the patient, and there is a problem in that there is a limitation in control in addition to the method of temporarily injecting the drug. A representative drug delivery system that can conveniently apply drugs in addition to injection therapy is a transdermal delivery system using a patch, etc. In particular, research has been continuously conducted to efficiently and safely administer active ingredients such as drugs.

However, there are still difficulties in allowing the patch, etc. to stably adhere to the skin for a long period of time, and there are limitations in allowing the effective ingredient to be efficiently penetrated into the skin, and various studies have been conducted to overcome this.

For example, Korean Patent Publication No. 10-2019-0123642 discloses a patch formed with a multi-layered microneedle having excellent skin permeability, and Korean Patent Publication No. 10-2019-0118701 discloses adhesion of an anion-generating material to a skin. Disclosed for the body patch, there was a limitation that the manufacturing process was too complex or insufficient effect.

Republic of Korea Publication No. 10-2019-0123642 Republic of Korea Publication No. 10-2019-0118701

In order to solve the above-mentioned problems, the present invention aims to provide a method of manufacturing a transdermal patch carrying an active ingredient having a simple manufacturing process and excellent skin adhesion and long-term active ingredient transmittance.

In order to achieve the above object, the present invention is a release-adhesive pressure-sensitive adhesive layer contacting the skin, an active ingredient-carrying layer formed on the adhesive layer, and an active ingredient-supporting patch formed on the active ingredient-carrying layer. In the manufacturing method, preparing an active ingredient supporting layer solution by mixing 20 to 40 parts by weight of an active ingredient, 50 to 60 parts by weight of a polymer solvent for forming a matrix, and 2 to 10 parts by weight of a skin penetration promoter; After applying the active ingredient supporting layer solution on a support layer, drying at 40 ~ 80 ℃ to form an active ingredient supporting layer; And laminating a release control adhesive layer on the dried active ingredient-carrying layer.

At this time, the manufacturing method may further include the step of forming a release liner layer on the release control adhesive layer.

In addition, the release control adhesive layer is hydroxyl cellulose (hydroxyethylcellulose), ethylcellulose polymers (ethylcellulose polymers), polyvinyl pidolidone (PVP), polyethylene oxide (PEO), polyethylene glycol (PEG), polyacrylic acid (PAA), It is preferable to include at least one water-soluble polymer selected from the group consisting of hydroxylpropylcellulose (HPC).

The patch containing the active ingredient prepared according to the present invention has excellent long-term skin adhesion and active ingredient permeability, and optimally utilizes the effects of the active ingredients while eliminating side effects of concern in the conventional administration method such as injection method or oral administration method. can do.

In addition, since it does not undergo the initial pass effect of the liver, it is possible to increase the bioavailability of the ingredient, and it is not affected by the gastrointestinal liver such as acidity, food, enzymes, bacteria, etc. It is possible to control the absorption duration and speed of the ingredient, and the effect lasts for a long time with one use It is possible.

Hereinafter, the present invention will be described in detail with reference to examples of the present invention. These examples are only provided by way of example to illustrate the present invention in more detail, it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples. .

In addition, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention belongs, and in case of conflict, the present specification including definitions. The description will take precedence.

The patch containing the active ingredient of the present invention is composed of a release-adhesive adhesive layer that comes into contact with the skin, an active ingredient supporting layer formed on the adhesive layer, and a support layer formed on the active ingredient supporting layer.

The patch on which the active ingredient is supported comprises preparing 20 to 40 parts by weight of the active ingredient, 50 to 60 parts by weight of a polymer solvent for forming a matrix, and 2 to 10 parts by weight of a skin permeation promoter to prepare an active ingredient supporting layer solution; After applying the active ingredient supporting layer solution on a support layer, drying at 40 ~ 80 ℃ to form an active ingredient supporting layer; And laminating a release control adhesive layer on the dried active ingredient-carrying layer. Hereinafter, each step will be described in detail.

First, the active ingredient-carrying layer of the present invention comprises an active ingredient, a polymer solvent for forming a matrix, and a skin permeation accelerator, and the active ingredient and skin permeation accelerator are completely dissolved in a polymer solvent for forming the matrix. exist.

As the active ingredient, various active ingredients beneficial to the human body, such as natural extracts, pharmaceutical ingredients, and mineral ingredients, may be used. The active ingredient 20 to 40 parts by weight is mixed with 50 to 60 parts by weight of a polymer solvent for forming a matrix and 2 to 10 parts by weight of a skin penetration accelerator to form an active ingredient supporting layer solution.

The polymer solvent for forming the matrix is used to form a matrix of the active ingredient-carrying layer, and is preferably a group consisting of polydimethyloxane, acrylate, methacrylate, polyisobutylene, and styrene-isoprene-styrene One or more of them are used. In addition, the polymer solvent for forming the matrix is preferably included 50 to 60 parts by weight in the total weight of the active ingredient-carrying layer solution. If it exceeds this, the active ingredient may not penetrate well, and if it is less, it is difficult to exert a sufficient supporting function.

The skin penetration promoting agent is used to control the permeation rate at which the active ingredient is carried out, preferably N-cyclohexyl-2-pyrrolidone, 1-butyl-3-dodecyl- 2-pyrrolidone (1-butyl-3-dodecyl-2-pyrrolidone), 1,5-dimethyl-2-pyrrolidone, 1-ethyl-2-pyrrolidone Don (1-ethyl-2-pyrrolidone), 1-hexyl-4-methyloxycarbonyl-2-pyrrolidone, 1-hexyl-2-pyrrolidone (1 -hexyl-2-pyrrolidone), 1- (2-hydroxyethyl) pyrrolidone (1- (2-hydroxyethyl) pyrrolidone), 3-hydroxy-N-methyl-2-pyrrolidone (3-hydroxy- N-methyl-2-pyrrolidone), N-methyl-2-pyrrolidone, N-caprylyl-2-pyrrolidone, glycerol Glycerol lauryl alcohol, oleyl alcohol, isopropyl myristrate, sorbitan mono-oleate, propylene mono Propylene monolaurate, propylene mono-oleate, oleyl macrogolglyceride, oleic acid, lauroyl macrogoglyceride, linoleoyl Macrole glycerides (linoleoyl macrogoglyceride), propylene glycol caprylate / caprate, sorbitan monostearate mono-oleate, glycerol monolaurate, Propylene glycol monolaurate, propylene glycol monocaprylate, sorbitan monolaurate, lauryl lactate, caprylic / capric triglyceride Seride (caprylic / capric triglyceride), corn oil PEG-8 ester, corn oil PEG-6 ester, triacetin One or more of the group is used, more preferably one of the group consisting of glycerol monooleate, glycerol monolaurate, propylene glycol monolaurate, propylene glycol monocaprylate, sorbitan monolaurate Or more can be used.

In addition, the skin penetration promoting agent is preferably 2 to 10 parts by weight based on the total weight of the active ingredient-carrying layer solution in order to minimize skin side effects.

When the active ingredient supporting layer solution is prepared, it is applied onto a support layer, and then dried at 40 to 80 ° C. to form an active ingredient supporting layer. The support layer serves as an external protective film, and various materials generally used for transdermal patches may be used, but in one embodiment, polyester, polyolefin film, polyurethane, polyvinyl acetate, polyvinylidene chloride, polyethylene, At least one material selected from the group consisting of ethylene vinyl acetate, polyethylene terephthalate, polyacrylonitrile, polyethylene terephthalate, polybutylene terephthalate, nylon, rayon, nonwoven fabric, acrylic, silk, cotton, aluminum sheet and polyamide. Can be used. The form of the material constituting the support may be a sheet, a film, a fiber, a fabric, a knitted fabric, a nonwoven fabric, or the like, and may be a permeable or impermeable material including a laminate made of a combination of two or more polymers using a porous membrane.

When the active ingredient-carrying layer is formed on the support layer, the release-controlled adhesive layer, which is a surface contacting the skin on the active ingredient-carrying layer, is laminated.

In addition, the release control adhesive layer is made of an adhesive component, preferably one or two or more selected from the group consisting of a functional group of -COOH, -OH or -NH2 is used as an acrylic adhesive, preferably, As a polyacrylate block copolymer, acrylic acid, 2-ethylhexyl acrylate, butyl acrylate, 2-hydroxyethyl acrylate, methyl methacrylate, methyl acrylate, glycidyl methacrylate, vinyl acetate, N-vinyl One or two or more pressure-sensitive adhesives may be mixed and used in the group consisting of -2 pyrrolidone, diacetone acrylamide, t-octyl acrylamide, and 2- (dimethyl aminoethyl) methacrylate. The content of the pressure-sensitive adhesive is preferably 80 to 95 parts by weight based on the total weight of the release-controlling adhesive layer.

The release control adhesive layer is characterized in that it comprises a water-soluble polymer to tightly contact the active ingredient-carrying layer and the skin, and to prevent the release of the agent from the skin due to excessive sweat release and to control the skin absorption of the active ingredient. The water-soluble polymer is preferably hydroxylcellulose (hydroxyethylcellulose), ethylcellulose polymers (ethylcellulose polymers), polyvinylpidolidone (PVP), polyethylene oxide (PEO), polyethylene glycol (PEG), polyacrylic acid (PAA), hydroxyl It is preferred that one or more of the groups consisting of roxylpropylcellulose (HPC) is used in combination. The water-soluble polymer is preferably within 1 to 10 parts by weight based on the total weight of the release-controlling adhesive layer.

On the other hand, the release-adjustable adhesive layer may further include mineral-coated micro-particles so as to broaden the surface area of the adhesive layer in contact with the skin and to effectively deliver active ingredients to the skin through pore formation. Suitable microparticle size is preferably in the range of 1 μm to 10 μm in diameter, and the content of the microparticles is preferably 1 to 10 parts by weight relative to the total weight of the release controlling adhesive layer.

As the core material on which the mineral coating is formed, various materials harmless to the human body may be used, but preferably, hydroxyapatite or beta-tricalcium phosphate (beta-TCP, β-TCP) in the form of particles may be used.

The mineral coating made on the core material consists of calcium, phosphate, carbonate or combinations thereof. The mineral coating may be made by various methods, but preferably, the core material may be formed by incubating the biomaterial for use (SBF) containing calcium ions, phosphate ions, and carbonate ions for several minutes to several hours.

In one embodiment, the bio-used solution may include 5mM to about 125mM calcium ion, 7mM to about 10mM calcium ion, 2mM to about 125mM phosphate ion, and about 4mM to about 100mM carbonate ion.

More preferably, it is preferable that the bio-used solution additionally includes a fluoride ion serving as a kind of dopant in order to further improve the delivery effect of the active ingredient. For example, the bio-used liquid may include 0.1 mM to 15 mM fluoride ions. Suitable fluoride ions can be provided by water-soluble fluoride salts, including, for example, alkali and ammonium fluoride salts.

On the other hand, the release control adhesive layer may further include mineral nanoparticles made of germanium, mackban stone, bentonite, illite, and combinations thereof to minimize skin irritation even during long-term adhesion and to deliver active ingredients such as minerals to the skin. . The size of the mineral nanoparticles is preferably in the range of 100 nm to 500 nm in diameter, and the content is preferably 1 to 10 parts by weight based on the total weight of the emission control adhesive layer.

A separate release liner layer may be formed on the surface of the release control adhesive layer formed as described above.

Hereinafter, the configuration of the present invention and its effects will be described in more detail through specific manufacturing examples and examples. However, the present examples are intended to illustrate the present invention in more detail, and the scope of the present invention is not limited to these examples.

[Examples and Comparative Examples]

Example 1

30 parts by weight of thistle extract, 30 parts by weight of ginger root extract, 15 parts by weight of pear extract, 15 parts by weight of taurine, 5 parts by weight of panthetin, and 5 parts by weight of choline were mixed to prepare an active ingredient to relieve hangover.

Thus, the prepared hangover-removing active ingredient 3g, a polymer solvent for forming a matrix, Eudragit E-100 6.6g, and isopropyl myristate 0.4g were mixed to prepare an active ingredient-carrying layer solution. In addition, 25 g of DT-9301 as an acrylic pressure sensitive adhesive having a solid content of 35 to 42% was used as a solution to be used in the release control pressure sensitive adhesive layer, and 0.3 g of polyvinyl pyrrolidone PVP (K90) was added to prepare a release control pressure sensitive adhesive layer.

The active ingredient-carrying layer solution was coated on a polyester film using a lab coater, and then dried completely at 50 ° C and 100 RPM for 5 minutes to form an active ingredient-carrying layer. In addition, the release-control adhesive layer was coated with a release-control adhesive layer solution on a PET release film, and then dried in a lab coater at 100 ° C. for 1300 RPM for 5 minutes to completely dry the solvent, after which the release film of the active ingredient supporting layer was released. Removed and laminated with the release control adhesive layer. Thus, a patch carrying an active ingredient according to the present invention was completed.

Example 2

A patch containing an active ingredient was prepared in the same manner as in Example 1, but 0.3 g of microparticles of beta-tricalcium phosphate (beta-TCP, β-TCP) coated with a mineral was added to the release controlling adhesive layer to obtain a release controlling adhesive layer. It was prepared. The microparticles were prepared by incubating β-TCP microparticles in mSBF (2 × calcium and phosphate concentrations in human serum) for 10 hours.

Example 2

In the same manner as in Example 2, a patch carrying an active ingredient was prepared, and 0.3 g of mineral nanoparticles composed of germanium, pulverite, bentonite, and illite were added to the release controlling adhesive layer to prepare a release controlling adhesive layer.

Comparative Example 1

A commercially available transdermal patch for relieving hangover was used as a comparative example.

[Experimental Example: Sensory test]

After 30 adult men and women were applied to the skins of Examples 1 to 3 and Comparative Examples to the skin, the results are shown in Table 1 below.

The evaluation was calculated using the general 5-point evaluation method, and the scores were divided into [5 points (very good), 4 points (excellent), 3 points (normal), 2 points (less), 1 point (very poor)]. Example 3 received the best evaluation.

Example 1 Example 2 Comparative Example 3 Comparative example Adhesion 4.2 4.5 4.5 4.0  Skin irritation 4.2 4.3 4.4 3.9 Effect persistence 4.0 4.1 4.2 4.0

 Although the present invention has been described in connection with a preferred embodiment as mentioned above, the technical spirit of the invention is not limited or limited thereto, and can be variously implemented by a person skilled in the art.

Claims (3)

In the release control adhesive layer in contact with the skin, in the manufacturing method of the patch containing the active ingredient consisting of a support layer formed on the active ingredient-carrying layer, the active ingredient-carrying layer formed on the adhesive layer,
Preparing an active ingredient supporting layer solution by mixing 20 to 40 parts by weight of an active ingredient, 50 to 60 parts by weight of a polymer solvent for forming a matrix, and 2 to 10 parts by weight of a skin penetration promoter; After applying the active ingredient supporting layer solution on a support layer, drying at 40 ~ 80 ℃ to form an active ingredient supporting layer; And laminating a release-controlling adhesive layer on the dried active ingredient-carrying layer.
The release control adhesive layer is hydroxyl cellulose (hydroxyethylcellulose), ethylcellulose polymers (ethylcellulose polymers), polyvinylpidolidone (PVP), polyethylene oxide (PEO), polyethylene glycol (PEG), polyacrylic acid (PAA), hydroxyl Contains any one or more water-soluble polymers selected from the group consisting of propyl cellulose (HPC), the content of the water-soluble polymer is 1 to 10 parts by weight based on the total weight of the release-adhesive adhesive layer,
The release-controlled adhesive layer contains 1-10 μm diameter mineral-coated microparticles, and the microparticles are hydroxyapatite or beta-tricalcium phosphate (beta-TCP, β-TCP), and the content of the microparticles Method for producing a patch carrying an active ingredient, characterized in that 1 to 10 parts by weight relative to the total weight of the silver release control adhesive layer. delete delete