WO2023106506A1 - Hydrogel composition for preparing transdermal patch comprising amphiphilic polymer adhesive, and transdermal patch using same - Google Patents

Abstract

The present invention relates to a hydrogel composition for preparing a transdermal patch comprising an amphiphilic polymer adhesive, and a transdermal patch prepared using same. An adhesive matrix hydrogel composition for preparing a transdermal patch comprising an amphiphilic polymer and an adhesive material and a transdermal adhesive patch prepared using same according to the present invention can effectively block pollutants such as germs while allowing the skin to breathe, and can transdermally deliver both water-soluble and oil-soluble active ingredients while stably containing same in a matrix.

Description

Hydrogel composition for preparing transdermal patch containing amphiphilic polymeric adhesive and transdermal patch using the same

The present invention relates to a hydrogel composition for preparing a transdermal patch containing an amphiphilic polymeric adhesive and a transdermal patch prepared using the hydrogel composition.

In general, skin-adhesive patches have been used to relieve pain in parts of the body, treat wounds, or protect the skin, and these methods have been used in medicine, beauty, Although it was used in various industrial fields, the scope of its application was very limited.

Patches for skin adhesion have been generally used as a form of treatment for medicinal action on skin tissues or joints, or to increase the motility of joints and muscles. The adhesive patch used for this purpose is formed by applying a drug on one side in contact with the skin, and the drug effect is transmitted through the skin or the physical force of the patch fixes joints and muscles to affect mobility. was formed

In addition, conventional commercially available skin adhesive patches do not have side effects caused by orally administered drugs and deliver drugs into the body through the skin, so that they maintain medicinal effects or are directly applied to the skin in the treatment of people with gastrointestinal disorders. combined with treatment. Typical examples of this include patches and smoking cessation patches.

Transdermal patches for transdermal delivery of cosmetic or pharmaceutical ingredients usually have an adhesive matrix containing active ingredients and a fabric structure, and the fabric layer protects the adhesive matrix layer and skin from the external environment and is included in the adhesive matrix layer. It helps the active ingredients to be delivered to the skin well. Therefore, it is important that the adhesive matrix layer not only maintain good adhesion to the skin, but also be able to deliver active ingredients toward the skin and maintain good bonding strength with the fabric layer. The fabric layer used in the transdermal patch is preferably made to allow the skin to breathe, but in this case, there is a disadvantage in that the skin cannot be protected from penetration of bacteria and the like.

In addition, as the adhesive composition included in the patch, oil-soluble adhesive compositions such as acrylic, rubber, and silicone are widely used. These oil-soluble adhesives cannot easily deliver active ingredients having water-soluble properties, and have a uniform and stable matrix layer with water-soluble components. has the disadvantage of not being able to achieve

Therefore, there is a need for a new patch that can solve the problems of the existing transdermal patch.

Accordingly, the inventors of the present invention were conducting research on a new patch formulation capable of delivering active ingredients transdermally while having a support layer capable of preventing bacterial invasion and maintaining stable binding capacity between the support layer and a matrix containing the active ingredient. , The present invention was completed after confirming that the use of an amphiphilic polymeric adhesive could solve all the disadvantages of existing transdermal patches.

Therefore, an object of the present invention is an adhesive matrix hydrogel composition for preparing a transdermal patch, including an amphiphilic polymer and an adhesive material, and an active ingredient, an adhesive matrix hydrogel layer comprising an amphiphilic polymer and an adhesive material, a primary support layer; and a second support layer to provide a transdermal patch.

In order to achieve the above object, the present invention provides a sequentially laminated transdermal patch comprising: an adhesive matrix hydrogel layer containing an active ingredient, an amphiphilic polymer and an adhesive material; a first support layer; and a second supporting layer.

In addition, the present invention comprises the steps of 1) preparing an adhesive matrix hydrogel containing an active ingredient, an amphiphilic polymer and an adhesive material; 2) laminating a first support layer on one side of the hydrogel prepared in step 1); and 3) coating or laminating a second support layer on the first support layer prepared in step 2); It provides a method for manufacturing a transdermal patch comprising a.

The adhesive matrix hydrogel composition for preparing a transdermal patch comprising an amphiphilic polymer and an adhesive material of the present invention and the transdermal adhesive patch prepared using the same can effectively block contaminants such as bacteria while enabling skin respiration, and can effectively block water-soluble and fat-soluble active ingredients. All can be stably contained in a matrix and delivered transdermally.

1 is a schematic diagram showing the structure of a transdermal patch prepared according to the present invention.

Figure 2 is a view showing the results of confirming the pores and porous structure of the breathable polyurethane layer of the present invention.

3 is a schematic diagram showing a comparison between the structure of a conventional transdermal patch and the structure of a transdermal patch according to the present invention.

The present invention relates to an adhesive matrix hydrogel composition for preparing a transdermal patch, including an amphiphilic polymer and an adhesive material, and a transdermal patch prepared including the same.

The transdermal patch of the present invention is prepared by including an amphiphilic polymer and an adhesive material to enable skin respiration while effectively blocking contaminants such as bacteria, and can stably contain both water-soluble and oil-soluble active ingredients in a matrix for transdermal delivery. .

Hereinafter, the present invention will be described in detail.

In the present invention, the amphiphilic polymer refers to polymers and copolymers having both a hydrophilic functional group and a hydrophobic functional group, and may include biocompatible and biodegradable amphiphilic polymers (copolymers) used in the art without limitation. In the present invention, an amphiphilic polymer is included in the adhesive matrix hydrogel composition for preparing a transdermal patch so that an appropriate fabric binding force can be formed with the primary support layer and the secondary support layer formed on one side of the adhesive matrix layer, and hydrophilic active ingredients and lipophilic The thickening effect and dispersion stability and formulation stability of the active ingredient were sought. In the present invention, the amphiphilic polymer may include all biocompatible amphiphilic polymers without limitation, such as low-saponification polyvinyl alcohol, polyacrylamidomethylpropanesulfonic acid (Poly(AMPS)), and polyvinylpyrrolidone. , polyvinylpyrrolidone / vinyl acetate copolymer and polyvinylpyrrolidone / may be at least one selected from the group consisting of acrylic acid alkyl copolymer, and in a preferred embodiment of the present invention, polyacrylamidomethylpropanesulfonic acid (AMPS)) was used, but is not limited thereto.

When the amphiphilic polymer of the present invention is included in the adhesive matrix hydrogel composition for preparing a transdermal patch, it may be included in an amount of 1 to 40% by weight, preferably 2 to 20% by weight, more preferably 2 to 10% by weight, and even more, in the total composition. Preferably it may be included in 3 to 7% by weight.

In the present invention, the adhesive material may be water-soluble acrylic acid, and the adhesive material may be included to improve the adhesive strength, which is a disadvantage of the hydrogel. In addition, the inclusion of an adhesive material can improve the liquid resistance of the fabric. In a preferred embodiment of the present invention, polyacrylic acid is preferably used as an adhesive material. The adhesive material may be included in an amount of 2 to 20% by weight, more preferably 2 to 10% by weight, and more preferably 3 to 7% by weight, based on the total composition.

The present invention relates to a hydrogel composition containing both an amphiphilic polymer and an adhesive material, wherein the amphiphilic polymer and adhesive material may be included in the composition in a weight ratio of 1:1 to 1:2, preferably 1:1 may be included in a weight ratio of

The adhesive matrix hydrogel composition for preparing a transdermal patch of the present invention may include an amphiphilic polymer, an adhesive material, and a gel-forming polysaccharide polymer, preferably 1 to 40% by weight of the amphiphilic polymer, 2 to 20% by weight of the adhesive material, and 0.05 to 10% by weight of the polysaccharide polymer may be included.

The gel-forming polysaccharide polymer refers to a water-soluble polysaccharide polymer that forms a hydrogel matrix structure, and refers to a gelling agent that is dissolved by temperature control in an aqueous phase and forms a gel by a helical structure when cooled.

In the present invention, the gel-forming polysaccharide polymer is preferably carrageenan gum, locust bean gum, xanthan gum, agar, algin, guar gum, mannan, agar, chitosan, gellan gum, starch, pectin, karaya gum, tamarind gum and tara It may be one or more types selected from the group consisting of gums, and two or more types may be mixed and used. The gel-forming polysaccharide polymer of the present invention may be included in the adhesive matrix hydrogel composition for preparing a transdermal patch in an amount of 0.05 to 10% by weight, preferably 0.5 to 2% by weight.

On the other hand, although gel-forming polysaccharide polymers form a matrix hydrogel structure, they alone have limitations in their ability to adhere to the skin, and their limitations are that they cannot maintain adhesion to the skin for a long time because they do not effectively maintain the bond with the fabric layer. there is. In addition, due to the water separation phenomenon after gel formation, the active ingredients included in the matrix hydrogel layer are separated to the surface of the hydrogel, so that uniform and constant delivery of the active ingredients to the skin cannot be achieved.

However, in order to solve the above problems, the present invention prepared an adhesive matrix hydrogel including an amphiphilic polymer and an adhesive material, and the transdermal patch prepared using the same has excellent bonding strength between the fabric and the matrix hydrogel, and the yield rate , It was confirmed that the stability of the lipophilic active ingredient in the matrix, the active ingredient's ability to penetrate the skin, adhesive strength, and liquid resistance were all excellent.

The adhesive matrix hydrogel composition for preparing a transdermal patch of the present invention may further include a moisturizer, a preservative, and an active ingredient.

The moisturizer may include any moisturizer used in the art without limitation, and a suitable moisturizer may be selected and included according to the water-solubility or oil-solubility characteristics of the active ingredient contained therein. For example, the moisturizer of the present invention is not limited thereto, but may include polyhydric alcohols, silicone oils, natural vegetable oils, natural mineral oils, fatty acid alkyl esters, and other natural extracts and oils having a moisturizing function, and preferred examples include glycerin , diglycerol, ethylene glycol, 1,3-butylene glycol, propylene glycol, dipropylene glycol, sorbitol, xylitol, saccharide isomer, glutamate, glycogen, molasses, glycosaminoglycan, biosaccharide gum, glue Carmine salt, glucuronate, isopropyl adipate, dioctyl adipate, hexadecyl dioctanoate, ethyl oleate, diglyceride oleate, triglyceride oleate, decyl oleate, cesyl octanoate, caprylic/capryl glyceride, Caprylic acid diglyceride, caprylic acid triglyceride, capric acid diglyceride, capric acid triglyceride, dioctyl succinate, sucrose fatty acid ester, buttal stearate, octyl stearate, octyl hydroxystearate, diethyl sebacate, triacetin, palmitic acid isopropyl, octyl palmitate, sorbitan monopalmitate, isopropyl myristate, octyldodecyl myristate, hexyl laurylate, linol diglyceride, hyaluronic acid, and the like. When a moisturizer is included in the adhesive matrix hydrogel composition of the present invention, it may be included in 1 to 60% by weight in the hydrogel composition, and when the active ingredient is water-soluble, the hydrophilic moisturizer is 1 to 60% by weight in the composition, preferably. 1 to 30% by weight, more preferably 5 to 15% by weight. When the active ingredient is oil-soluble, a lipophilic moisturizer may be further included in order to compensate for insufficient moisturizing power with the hydrophilic moisturizer alone and to increase emulsion stability. In this case, 5 to 15% by weight of the hydrophilic moisturizer and 15 to 30% by weight of the lipophilic moisturizer may be included in the composition. In one embodiment of the present invention, glycerin was used as a hydrophilic moisturizer and caprylic/capryl glyceride was used as a lipophilic moisturizer.

In the present invention, the preservative is a biocompatible component capable of preventing deterioration of the active ingredient contained therein, and ingredients known in the art may be used without limitation, and in one embodiment of the present invention, 1,2-hexanediol was used .

In the present invention, the active ingredient can be used interchangeably with pharmacologically active ingredients and active ingredients, and refers to ingredients intended to be delivered and administered transdermally by being included in the adhesive matrix hydrogel composition of the transdermal patch. Since the present invention includes an amphiphilic adhesive polymer, it can include both water-soluble and oil-soluble active ingredients without limitation, and any material that can be transdermally delivered can be included without limitation. For example, as pharmacologically active ingredients, substances having skin beauty functions such as skin whitening, wrinkle improvement, UV protection, skin elasticity, skin moisturizing, antioxidant, antibacterial, dead skin cell improvement, and sebum relief, vitamins A, C, E, D and their derivatives, Arbutin, ceramide, niacinamide, azelaic acid, tretinoin, coenzyme Q10, adenosine, oil-soluble licorice extract, gamma aminobutyric acid, madecassic acid, alpha-bisabolol, idebenone, polyethoxylated retinamide, retinol , retinyl palmitate, collagen, peptide, elastin, mulberry extract, moth extract, bottle extract, squalane, salicylic acid, methyl salicylate, and at least one selected from the group consisting of hyaluronic acid extract, inflammation relief having medical efficacy, A transdermal patch for cosmetic or medical use may be prepared including materials having effects such as antibiotics, wound healing, pain relief, atopy improvement, athlete's foot treatment, and the like.

The adhesive matrix hydrogel composition for preparing a transdermal patch of the present invention may include 1 to 40% by weight of the amphiphilic polymer, 2 to 20% by weight of an adhesive material, 0.05 to 10% by weight of a gel-forming polysaccharide polymer, and 1 to 60% by weight of a moisturizer. there is; More specifically, when the active ingredient is water-soluble, 1 to 40% by weight of an amphiphilic polymer, 2 to 20% by weight of an adhesive material, 0.05 to 10% by weight of a gel-forming polysaccharide polymer, 5 to 15% by weight of a hydrophilic humectant; If the active ingredient is oil-soluble, 1 to 40% by weight of an amphiphilic polymer, 2 to 20% by weight of an adhesive material, 0.05 to 10% by weight of a gel-forming polysaccharide polymer, 5 to 15% by weight of a hydrophilic humectant, and 15 to 30% by weight of a lipophilic humectant can include

The adhesive matrix hydrogel composition for preparing a transdermal patch of the present invention may further include a skin penetration enhancer for promoting skin penetration of other active ingredients, such as N-cyclohexyl-2-pyrrolidone (N-cyclohexyl-2 -pyrrolidone), 1-butyl-3-dodecyl-2-pyrrolidone, 1,5-dimethyl-2-pyrrolidone 2-pyrrolidone), 1-ethyl-2-pyrrolidone, 1-hexyl-4-methyloxycarbonyl-2-pyrrolidone ), 1-hexyl-2-pyrrolidone, 1-(2-hydroxyethyl)pyrrolidone, 3-hydroxy-N -Methyl-2-pyrrolidone (3-hydroxy-N-methyl-2-pyrrolidone), 1-lauryl-4-methyloxycarbonyl-2-pyrrolidone (1-lauryl-4-methyloxycarbonyl-2- pyrrolidone), N-methyl-2-pyrrolidone, N-caprylyl-2-pyrrolidone, N-dodecyl-2-pyrroly Money (N-dodecyl-2-pyrrolidone), glycerol lauryl alcohol, oleyl alcohol, isopropyl myristrate, sorbitan mono-oleate, Propylene monolaurate, propylene mono-oleate, oleylmacrogolglyceride, oleic acid, lauroylmacrogoglyceride, linoleoyl Macrogoglyceride (linoleoylmacrogoglyceride), Propylene glycol caprylate/caprate, Sorbitan monostearate mono-oleate, Glycerol monolaurate, Propylene glycol Propylene glycol monolaurate, propylene glycol monocaprylate, sorbitan monolaurate, lauryl lactate, caprylic/capric triglyceride /capric triglyceride), corn oil PEG-8 ester, corn oil PEG-6 ester, or at least one selected from the group consisting of triacetin may be optionally included.

The adhesive matrix hydrogel composition for preparing a transdermal patch of the present invention may also include preservatives, fragrances, pH adjusting agents, gel strength adjusting agents, auxiliary thickeners, auxiliary tackifiers, skin irritation relievers, pigments, petals, flowers, branches, extracts, etc., if necessary. Other additives such as may be further included.

The present invention relates to a transdermal patch comprising the adhesive matrix hydrogel layer.

More specifically, the present invention is a sequentially laminated transdermal patch comprising: an adhesive matrix hydrogel layer containing an active ingredient, an amphiphilic polymer and an adhesive material; a first support layer; and a second supporting layer.

The adhesive matrix hydrogel layer is a layer attached to the skin surface, and is prepared by sequentially stacking a first support layer and a second support layer on the opposite side other than the skin adhesion side. shown in

The adhesive matrix hydrogel layer of the transdermal patch is equally applicable to the description of the hydrogel layer described above.

Therefore, the amphiphilic polymer included in the adhesive matrix hydrogel of the present invention is a preferred embodiment of low-saponification polyvinyl alcohol, polyacrylamidomethylpropanesulfonic acid (Poly (AMPS)), polyvinylpyrrolidone, polyvinylpyrroly It may be at least one selected from the group consisting of money/vinyl acetate copolymer and polyvinylpyrrolidone/alkyl acrylate copolymer.

When the amphiphilic polymer of the present invention is included in the adhesive matrix hydrogel composition for preparing a transdermal patch, it may be included in an amount of 1 to 40% by weight, preferably 2 to 20% by weight, more preferably 2 to 10% by weight, based on the total composition. , More preferably, it may be included in 3 to 7% by weight.

In the present invention, the adhesive material may be water-soluble acrylic acid, and the adhesive material may be included to improve the adhesive strength, which is a disadvantage of the hydrogel. In addition, the inclusion of an adhesive material can improve the liquid resistance of the fabric. In a preferred embodiment of the present invention, polyacrylic acid is preferably used as an adhesive material. The adhesive material may be included in an amount of 2 to 20% by weight, preferably 2 to 10% by weight, more preferably 3 to 7% by weight, based on the total composition.

The adhesive matrix hydrogel of the transdermal patch of the present invention contains an adhesive substance and an amphiphilic polymer, thereby stably maintaining the active ingredient, promoting the delivery of the active ingredient, and preventing contamination from external substances. And proper adhesion with the secondary support layer can be maintained.

The support layer of the present invention can be used interchangeably with a backing membrane, and a material that is non-absorbable to active ingredients and has flexibility for skin adhesion can be used.

The primary support layer may be referred to as a fabric layer, and preferably may be at least one selected from the group consisting of cotton, nonwoven fabric, rayon, and cellulose.

The secondary support layer may be a film or coating layer having porosity, and it is preferable to provide air permeability to the transdermal patch and to prevent skin infection by bacteria or external contaminants. The secondary support layer of the present invention may be a support layer made of polyurethane, polyethylene phthalate or polyethylene, and the primary support layer and the secondary support layer may be laminated, or a secondary support layer may be coated on the first support layer.

The thickness of the secondary support layer of the present invention may be preferably formed to a thickness of 10 to 40 μm, preferably 10 to 30 μm, more preferably 20 to 30 μm. In addition, the secondary support layer is characterized by having porosity, and has air permeability, but may be manufactured by forming air bubbles for the purpose of blocking external contaminants. The formed pores may have a diameter of 0.01 to 0.5 μm or less, more preferably 0.1 to 0.3 μm.

Such a porous secondary support layer may have a moisture permeability of 90 to 150 g/m ² *h. The secondary support layer of the present invention may be characterized in that it has a more improved moisture permeability index compared to the moisture permeability of general patch fabrics.

The transdermal patch of the present invention may be used for cosmetic or medical purposes depending on the type of active ingredient included in the matrix hydrogel layer. The types of active ingredients that can be included in the patch of the present invention are the same as described above.

In addition, the present invention relates to a method for manufacturing a transdermal patch, and specifically, 1) preparing an adhesive matrix hydrogel containing an active ingredient, an amphiphilic polymer, and an adhesive material; 2) laminating a first support layer on one side of the hydrogel prepared in step 1); and 3) coating or laminating a second support layer on the first support layer prepared in step 2); It provides a method for manufacturing a transdermal patch comprising a.

That is, the transdermal patch of the present invention can be prepared by forming a support layer on a matrix layer containing an active ingredient. At this time, the matrix layer may be formed on the peeling layer, and the peeling layer may use a release liner or a laminate thereof commonly used in the field of patch preparation for transdermal absorption. For example, but not limited thereto, films such as polyethylene, polyester, polyvinyl chloride, and polyvinylidene chloride coated with silicone resin or fluorine resin, paper, or laminates thereof may be used.

The secondary support layer of the present invention may be characterized by having porosity, and a method known in the art may be used without limitation as long as it can impart porosity to a polyurethane, polyethylene phthalate or polyethylene film, preferably air. It can be prepared to have porosity by forming bubbles.

Hereinafter, the present invention will be described in detail by experimental examples and examples. However, the following examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following examples.

Experimental Example 1. Preparation of an amphiphilic polymer-containing adhesive matrix hydrogel composition

An adhesive matrix hydrogel composition containing an amphiphilic polymer was prepared in order to prepare an adhesive matrix having fabric binding force and skin adhesion without complex ionic bonds while forming a hydrogel like the existing temperature-sensitive water-soluble hydrogel composition.

The composition of the adhesive matrix hydrogel composition containing the amphiphilic polymer of the present invention is shown in Table 1 below.

ingredient	function	Example 1	Example 2
Carrageenan Gum	Gel-forming polysaccharide polymer	0.5
Locust Bean Gum	Gel-forming polysaccharide polymer	0.5	0.5
xanthan gum	Gel-forming polysaccharide polymer		0.5
glycerin	hydrophilic moisturizer	10.0	20.0
1,2-hexanediol	antiseptic	2.0	2.0
Poly(AMPS)	Tackifying Amphiphilic Polymer	5.0	5.0
Niacinamide	Skin whitening functional ingredient (water soluble)	2.0
methyl salicylate	Anti-inflammatory pain relief ingredient (usefulness)		0.5
Caprylic/caprylicglycerides	Oils (lipophilic humectants)		20.0
polyacrylic acid	tackifier	5.0	5.0
Purified water	solvent	To 100	To 100
Sum		100	100

As described in Table 1, the present invention is a parenteral parent in order to stably retain active ingredients and deliver them transdermally while maintaining good bonding strength with a polyurethane laminated fabric layer having bacterial penetration protection and air permeability when preparing a patch. An adhesive matrix hydrogel composition containing Poly(AMPS) (poly(2-acrylamido-2-methyl-1-propanesulfonic acid)) as a medium adhesive polymer and polyacrylic acid as a tackifier was prepared.

By including Poly(AMPS) as an amphiphilic adhesive polymer and polyacrylic acid as a tackifier, unlike the oil-soluble adhesive matrix layer, it is possible to keep the skin moisturized and at the same time easily dissolve and disperse water-soluble active ingredients in the matrix layer. , Bonding strength with non-polar polyurethane fabrics can be increased as the bonding strength with fabric is increased.

Experimental Example 2. Preparation of Patch Formulation Containing Adhesive Matrix Hydrogel Composition Containing Amphiphilic Polymer

A transdermal patch for skin attachment including the adhesive matrix hydrogel layer prepared in Experimental Example 1 was prepared. A patch was prepared so that an adhesive matrix hydrogel containing an active ingredient, a nonwoven fabric or fabric, and an air permeable polyurethane film layer were formed from the skin attachment surface, and the shape of the prepared patch is shown in FIG. 1 .

Among the transdermal patches of the present invention, the air permeable polyurethane film layer located at the outermost layer from the skin adhesive surface was prepared by forming air bubbles to have porosity, and was prepared to have a thickness of 27 μm and a porous diameter of 0.2 μm or less. Such a polyurethane film layer having small porosity can effectively block bacteria or external contaminants. Figure 2 shows the results of confirming the cross-section of the polyurethane film layer of the patch of the present invention with porosity formed through air bubbles and the cross-section of the fabric used for general hydrogel patches or oil-soluble adhesive matrices with an optical microscope.

As shown in FIG. 2, it was confirmed that air permeable pores were formed in the porous polyurethane film layer of the present invention.

More specifically, the air permeability of the porous polyurethane film fabric of the present invention was confirmed through a water vapor transmission measurement method (water vapor transmission test method KS K0594: 2021 of textiles), and the results are shown in Table 2.

fabric type	Fabric thickness/weight	Porous particles (micrometer)	After 1 hour (g)	After 2 hours (g)	Moisture permeation (g)	area (equal)	Permeability (g/m 2 *h)
Porous Polyurethane Film	27㎛	0.05~0.14	326.47	326.06	0.41	0.0038465	106.59
Non-woven	50g	Several to several tens of μm	328.5	326.63	1.74	0.0038465	452.36

As can be seen in Table 2, the porous polyurethane film of the present invention has sufficient air permeability and at the same time has a very small pore size of 0.05 to 0.14㎛, ultrafine dust having a particle size of about 2.5㎛ It was confirmed that it can effectively block various bacteria.

3 shows a schematic diagram comparing the structure of a conventionally manufactured patch and the patch of the present invention.

As shown in FIG. 3, the transdermal patch for skin attachment of the present invention includes a nonwoven fabric or fabric due to its effective adhesive ability, along with the feature that the skin attachment surface is composed of an amphiphilic adhesive matrix, and a breathable polyurethane film layer thereon. It is characterized in that it additionally includes.

The structure of such a patch solves the problems that it is difficult to uniformly and stably contain water-soluble active ingredients that conventional patches containing an oil-soluble adhesive matrix made of acrylic, rubber, or silicone have, and that water-soluble skin moisturizing ingredients cannot be effectively delivered to the skin. can do. In addition, the transdermal patch, which used a water-soluble adhesive matrix using a polysaccharide polymer hydrogel or sodium polyacrylate, has a messy structure including only non-woven fabric or fabric, and thus solves the problem that bacterial infection cannot be prevented, and the water-soluble adhesive matrix It is possible to solve the problem that the adhesive strength with the air permeable polyurethane film layer is lowered due to the characteristics of.

Overall, the transdermal patch of the present invention includes a polyurethane layer having bacterial penetration protection and breathability characteristics in addition to conventional nonwoven fabrics or fabrics, and includes a water-soluble hydrogel adhesive layer containing an amphiphilic adhesive, so that skin respiration It is a patch formulation capable of simultaneously blocking contaminants having a microstructure such as bacteria and containing water-soluble active ingredients and oil-soluble active ingredients in the adhesive layer.

experimental example . Comparison of characteristics of patch formulations containing adhesive matrix hydrogel compositions containing amphiphilic polymers

A conventional cosmetic hydrogel patch and a medical pap hydrogel patch not containing the amphiphilic adhesive polymer Poly(AMPS) and polyacrylic acid were prepared as comparative examples, and the adhesive matrix hydrogel composition containing the amphiphilic polymer of the present invention was prepared. It was compared with the patch prepared with

The compositions of Examples and Comparative Examples 1 to 8 of the present invention are shown in Tables 3 and 4 below.

ingredient	function	Comparative Example 1	Comparative Example 2	Comparative Example 3	Comparative Example 4	Example 1	Example 2
Carrageenan Gum	Gel-forming polysaccharide polymer	1.5	1.5	1.5	1.5	0.5
Locust Bean Gum	Gel-forming polysaccharide polymer	1.5	1.5	1.1	1.1	0.5	0.5
xanthan gum	Gel-forming polysaccharide polymer			0.2	0.2		0.5
guar gum	Gel-forming polysaccharide polymer			0.2	0.2
potassium chloride	gel strength modifier	0.1	0.1	0.1	0.1
glycerin	hydrophilic moisturizer	10.0	10.0	10.0	10.0	10.0	20.0
1,2-hexanediol	antiseptic	2.0	2.0	2.0	2.0	2.0	2.0
Poly(AMPS)	Tackifying Amphiphilic Polymer					5.0	5.0
Niacinamide	Skin whitening functional ingredient (water soluble)	2.0		2.0		2.0
methyl salicylate	Anti-inflammatory analgesic ingredient (usefulness)		0.5		0.5		0.5
Caprylic/caprylicglycerides	Oils (lipophilic humectants)		10		10		20.0
polyacrylic acid	tackifier
Purified water	solvent	To 100	To 100	To 100	To 100	To 100	To 100
Sum		100	100	100	100	100	100
Hydrogel coated fabric 1	skin-adhesive layer	release film				release film
Hydrogel coated fabric 2	Matrix protective layer	release film				PU film non-woven fabric laminated fabric

Comparative Examples 1 to 4 in Table 3 correspond to transdermal patches made of an active ingredient-containing water-soluble adhesive matrix and without a separate fabric or polyurethane layer in FIG. 3 . Comparative Examples 1 to 4 are general cosmetic hydrogel compositions containing a polysaccharide polymer hydrogel, and in particular, Comparative Examples 2 and 4 are compositions containing an excess of oil in the same oil-soluble active ingredient, due to the presence of amphiphilic adhesive polymers. It was prepared to compare stability and compared with Example 2. Example 2 contains an excess of oil in the same oil-soluble active ingredient as Comparative Examples 2 and 4.

ingredient	function	Comparative Example 1	Comparative Example 2	Comparative Example 3	Comparative Example 4	Example 1	Example 2
Carrageenan Gum	Gel-forming polysaccharide polymer					0.5
Locust Bean Gum	Gel-forming polysaccharide polymer					0.5	0.5
xanthan gum	Gel-forming polysaccharide polymer						0.5
guar gum	Gel-forming polysaccharide polymer
glycerin	hydrophilic moisturizer	10.0	10.0	10.0	10.0	10.0	20.0
1,2-hexanediol	antiseptic	2.0	2.0	2.0	2.0	2.0	2.0
sodium polyacrylate	Water-soluble gel formation and adhesive	3.0	3.0	3.0	3.0
aluminum chloride	metal complex ion binder	0.5	0.5	0.5	0.5
tartaric acid	pH regulator	0.5	0.5	0.5	0.5
Poly(AMPS)	Tackifying Amphiphilic Polymer					5.0	5.0
Niacinamide	Skin whitening functional ingredient (water soluble)	2.0		2.0		2.0
methyl salicylate	Anti-inflammatory analgesic ingredient (usefulness)		0.5		0.5		0.5
Caprylic/caprylicglycerides	Oils (lipophilic humectants)		10		10		20.0
polyacrylic acid	tackifier	5.0	5.0	5.0	5.0	5.0	5.0
Purified water	solvent	To 100	To 100	To 100	To 100	To 100	To 100
Sum		100	100	100	100	100	100
Hydrogel coated fabric 1	skin-adhesive layer	release film				release film
Hydrogel coated fabric 2	Matrix protective layer	non-woven fabric, fabric				PU film non-woven fabric laminated fabric

In addition, Comparative Examples 5 to 8 in Table 4 correspond to transdermal patches including a fabric layer made of nonwoven fabric or fabric on the water-soluble adhesive matrix layer containing the active ingredient in FIG. 3 . Comparative Examples 5 to 8 were prepared to compare general cosmetic and medical pap hydrogel compositions with the adhesive matrix hydrogel composition containing the amphiphilic polymer of the present invention. In particular, Comparative Examples 6 and 8 contained some oil-soluble active ingredients and oils. The stability of the oil-soluble drug in the hydrogel was compared with that of Example 2. Example 2 compared the stability of the amphiphilic adhesive polymer in the hydrogel containing methyl salicylate, which is the same oil-soluble active ingredient as in Comparative Examples 6 and 8, and an excess of oil.

The following items were compared in the transdermal patches prepared including Comparative Examples 1 to 8 and the adhesive matrix hydrogel composition containing the amphiphilic polymer of the present invention.

One. Fabric bonding strength between the fabric and the gel matrix layer

The fabric bonding force between the fabric made of nonwoven fabric or fabric and the hydrogel matrix was evaluated by cutting a 2cm * 5cm specimen on a bakelite plate and attaching the surface attached to the skin and then separating it from the bakelite. It was evaluated as X when the fabric and the hydrogel were separated, and as O when the fabric and the hydrogel were not separated.

2. Completion rate (%)

In order to evaluate the water separation rate of the hydrogel, the hydrogel was cut into 2 cm * 5 cm, weighed initially, placed in an aluminum pouch, maintained in a thermostat at 25 ° C for a week, and then taken out. After wiping the surface of the hydrogel taken out with a hygroscopic tissue, the weight of the moisture absorbed in the absorbent tissue is measured (later weight), and the rate of water transfer in the hydrogel is measured by comparing the final weight to the initial weight through the following equation did

- Completion rate (%) = (final weight / initial weight) * 100

3. Stability of lipophilic active ingredient in matrix

In order to indirectly evaluate the emulsion stability of the active ingredient in which the lipophilic (oil-soluble) component is separated from water, the amount measured above is assumed to be the amount of water and oil, and the water is evaporated in a thermostat at 80 ° C for 3 hours. The remaining weight of the oil having a high evaporation temperature was evaluated. If the amount of oil remaining in the absorbed water is large, the oil layer moves to the surface of the hydrogel matrix and the oil is included when the hydrogel surface is wiped with an absorbent tissue, so the weight remaining after the water is completely evaporated was evaluated. If there is little remaining weight, it is evaluated that the oil is not separated, and the stability thereof is evaluated as O, and when it is not, it is evaluated as X.

- The amount of oil remaining from the water absorbed = the amount of water initially transferred - the amount remaining after evaporation

4. Indirect evaluation of the transferability of active ingredients to the skin according to the evaluation of the water absorption capacity of the gel layer (moisture absorption rate)

In order to evaluate the water absorption capacity of the hydrogel, the hydrogel was cut into 2 cm * 5 cm, weighed initially, put in purified water at room temperature, and the weight was measured after 12 hours, and calculated using the following formula.

- Water absorption rate (%) = ((final weight - initial weight) / initial weight) * 100

5. Adhesion evaluation

In order to evaluate the skin adhesion of the hydrogel, a 180o peel test was conducted according to the method presented in Korean Industrial Standards KS A1107 “Test Methods for Adhesive Tapes and Adhesive Sheets”. To prepare the specimen, the hydrogel layer was cut into 5cm*15cm and attached to the backlight plate, and then attached by bonding twice at a speed of 300mm/min with a pressure roller weighing about 2kg. Using the 180o peel test was measured.

6. Evaluation of liquid resistance of matrix layer

Five specimens cut into appropriate sizes to completely cover the glass container were tested as follows. After putting 10 mL of water in a cylindrical 250 mL glass container (diameter 70 mm × height 95 mm), fix the sample on top of it using a rubber band or other tool so that water does not leak, and then turn the glass container upside down to a certain height from the bottom. fix with space of When the glass plate was placed under the glass container and left for 30 minutes to 4 hours, the time for water to pass through the sample and fall on the lower glass was evaluated. The longer the time the water passes through the sample and falls on the glass, the better the liquid resistance of the sample can be evaluated.

The above experimental results are summarized in Table 5 and shown.

Test evaluation items	Comparative Example 1	Comparative Example 2	Comparative Example 3	Comparative Example 4	Comparative Example 5	Comparative Example 6	Comparative Example 7	Comparative Example 8	Example 1	Example 2
1. Evaluation of bonding strength between fabric and matrix	X	X	X	X	O	O	O	O	O	O
2. Completion rate (%)	22%	27%	24%	29%	2%	3%	One%	One%	2%	One%
3. Stability of lipophilic active ingredient in matrix	-	X	-	X	-	X	-	X	-	O
4. Indirect evaluation of the transferability of active ingredients to the skin according to the evaluation of the water absorption capacity (%) of the gel layer	250	240	220	245	280	275	270	275	120	120
5. Adhesion evaluation (180o peel test/KS A1107)	not measurable	not measurable	not measurable	not measurable	10gf	12gf	10gf	9gf	2ogf	18gf
6. Liquid resistance evaluation	0	0	0	0	1hr	1hr	1hr	1hr	4hr	4hr

As shown in Table 5, it was confirmed that the patches of Examples 1 and 2 effectively maintained the fabric bond between the fabric and the adhesive matrix layer, maintaining the fabric bond strength not only with the hydrophilic nonwoven fabric but also with the lipophilic polyurethane layer. did

In addition, Examples 1 and 2 had almost no water separation phenomenon compared to the water separation rate of 22 to 29% of Comparative Examples 1 to 3 having only the water-soluble adhesive matrix, and a level similar to that of Comparative Examples 5 to 8 having nonwoven or woven fabrics. showed low syneresis. In addition, compared to the low stability of methyl salicylate, which is an oil-soluble active ingredient in Comparative Examples 2, 4, 6, and 8, in Example 2 of the present invention, due to the characteristics of the amphiphilic polymer, when used by dissolving the lipophilic active ingredient in oil It was confirmed that the phase separation stability of the adhesive matrix layer was high.

In addition, unlike Comparative Examples 1 to 8, the ability of the gel layer to absorb moisture was high, which could inhibit the delivery of water-soluble active ingredients to the skin, Examples 1 and 2 of the present invention showed a relatively low water absorption capacity of the gel layer, It was confirmed that the active ingredient could be better transferred to the skin.

In terms of adhesive strength, compared to Comparative Examples 5 to 8 using a general water-soluble adhesive matrix, which showed 9 to 12 gf, Examples 1 and 2 showed 20 gf and 18 gf, respectively. It was confirmed that it was improved.

In terms of the liquid resistance of the fabric, unlike conventional nonwoven fabrics, it was confirmed that the properties of waterproof polyurethane, which can prevent wetting when external moisture enters, are maintained, and the liquid resistance is excellent.

That is, the transdermal patch prepared including the adhesive matrix hydrogel composition containing the amphiphilic polymer of the present invention, the fabric layer, and the air permeable polyurethane film layer has the properties of the adhesive matrix hydrogel containing the amphiphilic polymer and the fabric and the matrix. It has excellent interlayer fabric bonding strength, has a low water separation rate, can stably maintain not only water-soluble active ingredients but also oil-soluble active ingredients, and can better deliver active ingredients to the skin due to its low water absorption ability. In addition, since it includes a breathable polyurethane film layer with micropores, it enables skin to breathe, blocks germs and fine dust, and achieves a waterproof effect, providing convenience in use when in contact with water. there is.

In the above, specific parts of the present invention have been described in detail, and for those skilled in the art, it is clear that these specific descriptions are only preferred embodiments, and the scope of the present invention is not limited thereby. something to do. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (20)

1. It is a sequentially layered transdermal patch,

   An adhesive matrix hydrogel layer containing an active ingredient, an amphiphilic polymer and an adhesive material, and a first support layer; and a second supporting layer.
2. The method of claim 1, wherein the amphiphilic polymer is low saponification polyvinyl alcohol, polyacrylamidomethylpropanesulfonic acid (Poly (AMPS)), polyvinylpyrrolidone, polyvinylpyrrolidone / vinyl acetate copolymer and polyvinyl A transdermal patch, characterized in that it is at least one selected from the group consisting of pyrrolidone/alkyl acrylate copolymers.
3. The transdermal patch according to claim 1, wherein the amphiphilic polymer is contained in an amount of 1 to 40% by weight.
4. The patch according to claim 1, wherein the adhesive material is polyacrylic acid.
5. The transdermal patch according to claim 4, wherein the polyacrylic acid is contained in an amount of 2 to 20% by weight.
6. The transdermal patch according to claim 1, wherein the primary support layer is at least one selected from the group consisting of cotton, nonwoven fabric, rayon, and cellulose.
7. The transdermal patch according to claim 1, wherein the secondary support layer is polyurethane, polyethylene phthalate or polyethylene.
8. The method of claim 1, wherein the primary support layer and the secondary support layer are laminated; or a transdermal adhesive patch in which a secondary support layer is coated on the primary support layer.
9. The transdermal patch according to claim 1, wherein the secondary support layer is formed to a thickness of 10 to 40 μm.
10. The transdermal patch according to claim 1, wherein the secondary support layer is a porous support layer including pores having a diameter of 0.01 to 0.5 μm or less.
11. The transdermal patch according to claim 1, wherein the secondary support layer has a moisture permeability of 90 to 150 g/m ² *h.
12. 1) preparing an adhesive matrix hydrogel containing an active ingredient, an amphiphilic polymer and an adhesive material;

    2) laminating a first support layer on one side of the hydrogel prepared in step 1); and

    3) coating or laminating a second support layer on the first support layer prepared in step 2); Method for manufacturing a transdermal patch comprising a.
13. [Claim 13] The method of claim 12, wherein the secondary support layer is manufactured to have porosity by forming air bubbles.
14. An adhesive matrix hydrogel composition for preparing a transdermal patch comprising an amphiphilic polymer and an adhesive material.
15. The adhesive matrix hydrogel composition for preparing a transdermal patch according to claim 14, wherein the amphiphilic polymer and the adhesive material are included in a weight ratio of 1:1 to 1:2.
16. The adhesive matrix hydrogel composition for preparing a transdermal patch according to claim 14, wherein the composition includes an amphiphilic polymer, an adhesive material, and a gel-forming polysaccharide polymer.
17. The adhesive matrix hydrogel composition for preparing a transdermal patch according to claim 16, wherein the composition comprises 1 to 40% by weight of an amphiphilic polymer, 2 to 20% by weight of an adhesive material, and 0.05 to 10% by weight of a gel-forming polysaccharide polymer.
18. 17. The method of claim 16, wherein the gel-forming polysaccharide polymer is carrageenan gum, locust bean gum, xanthan gum, agar, algin, guar gum, mannan, agar, chitosan, gellan gum, starch, pectin, karaya gum, tamarind gum and tara gum. At least one selected from the group consisting of, an adhesive matrix hydrogel composition for preparing a transdermal patch.
19. The adhesive matrix hydrogel composition for preparing a transdermal patch according to claim 16, further comprising a moisturizer, a preservative and an active ingredient.
20. The hydro-adhesive matrix for preparing a transdermal patch according to claim 19, comprising 1 to 40% by weight of the amphiphilic polymer, 2 to 20% by weight of an adhesive material, 0.05 to 10% by weight of a gel-forming polysaccharide polymer, and 1 to 60% by weight of a humectant. gel composition.

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