KR100376086B1 - Film-forming agent for drug deliverly and preparation for percutaneous administration containing the same - Google Patents

Abstract

The present invention relates to a film former for forming a film on the skin, and also to a transdermal dosage form containing the film former and the active ingredient.

Transdermal dosage forms containing the film formers and active ingredients of the present invention have excellent elasticity and flexibility, show good adhesion when formed on the skin, and form non-sticky films.

Description

Film-forming agent for drug deliverly and preparation for percutaneous administration containing the same}

The present invention relates to a film former for forming a film on the skin, and also to a transdermal dosage form containing the film former and the active ingredient.

Recently, various transdermal absorption formulations have been developed for the purpose of delivering active ingredients such as drugs through the skin, or for supplying active ingredients to the skin itself.

Such formulations can be broadly classified into 'glue formulations' and 'coating formulations'. For example, the formulations include a patch such as plata and cataplasma, and the semi-solid formulations such as creams, ointments and gels are applied. have.

Of these, the patch has the advantage of continuously delivering the active ingredient to the initially attached position for as long as desired by the operator, while not only appearance appearance when attached to the exposed area, but also gives a sense of foreign body, especially flexion of the body It is difficult to apply to the site and may cause skin irritation if used repeatedly in the same place for a long time. In addition, since a separate support (side, film, release paper, etc.) is required, the cost burden is increased.

On the other hand, the coating semi-solid agent can be applied regardless of the shape and area of the application site, it can be freely applied to the exposed site. Moreover, even if repeated use in the same place, the degree of irritation is lower than that of the patch. However, ointments and cream formulations are sticky and stain well or dirty clothes or socks, because they are easily buried there is a disadvantage that must be applied repeatedly several times a day.

Therefore, there is a need for a film former that can overcome the disadvantages of these two formulations.

Generally, polyvinyl alcohol, cellulose, carboxyvinyl polymer, polyvinylpyrrolidone, etc. may be mainly used as polymers that may be applied to the skin to form a film.

As an example of a drug carrier using such a film-forming polymer, US Patent No. 4393076 describes an anti-inflammatory analgesic gel formulation composition using cellulose and carboxyvinyl polymer as a film-forming agent, and Korean Patent Publication No. 96-8225 describes polyvinyl chloride. Transdermal administration compositions such as anti-inflammatory analgesics and nicotine using fast-drying coating preparations using alcohol, polyvinylpyrrolidone, cellulose, pectin, and the like have been reported, and in Korean Patent Publication No. 98-076273 A film-forming gel composition for transdermal absorption using a oxyethylene maleic anhydride copolymer, a cellulose derivative, a vinyl acetate vinylpyrrolidone copolymer, and a polyvinyl alcohol has been reported, and in Korean Patent Publication No. 98-072361, polyvinylpyrrole Soft hydro consisting of donalphaacrylic acid and polyvinyl alcohol A gel external preparation is described, and Korean Patent Publication No. 97-5282 describes a gel formulation using poloxamer containing a propionic acid-based nonsteroidal anti-inflammatory analgesic drug.

However, the polymers forming the film on the skin used in the above documents do not have elasticity to interfere with the movement of the body, and because of the high glass transition temperature, the film formed after drying becomes hard and easily peels off from the skin. Has the disadvantages.

Therefore, in the present invention, a film forming agent incorporating polyurethane, which is a polymer having low glass transition temperature and flexible, and having high elasticity, can cope with movement of the body, can be developed.

On the other hand, existing researches on such polyurethanes include inventions related to biograft materials such as catheters and heart valves based on the high biocompatibility of polyurethanes. For example, U.S. Patent No. 5041100 has conducted a study to reduce the friction phenomenon caused by catheter insertion by modifying the surface of the catheter with polyurethane, and U.S. Patent No. 5017664 developed a biocompatible polyurethane for medical devices A study was conducted to improve the blood compatibility of the rats.

On the other hand, research has been conducted to develop polyurethane as a base of the external preparation. For example, WO 9914283 proposes the delivery of active ingredients as pressure-sensitive adhesives containing polyurethane, acrylic ester and vinyl acetate type polymers, fatty acids or polyols, and WO 9000066 contains external antimicrobials. A polyurethane drug delivery agent that requires a second substrate, such as a method of dissolving a polyurethane in a solvent and applying it to the skin and then covering the polyurethane film again, has been proposed.

In addition, the invention is applied in a solvent state without a second substrate (substrate) to form a drug delivery film on the skin, US Patent No. 4560555 in the external protection for drug delivery polyurethane film base that reacts directly with damaged skin Zero development, but in this case there is a problem in the safety (safety) due to the chemical reaction with the skin, there is a disadvantage that the film attached to the skin by chemical bonding does not peel freely at the desired time.

On the other hand, the polyurethane film former that is applied in a solvent state without reacting with the skin has the disadvantage of being easily peeled off from the skin due to the insufficient skin adhesion of the polyurethane.

Therefore, in order to secure such properties, studies have been conducted to introduce a second polymer having a functional group capable of secondary chemical bonding with the skin to the polyurethane. For example, US Pat. No. 4542012 discloses a film former composition containing an antimicrobial agent. Polyvinylpyrrolidone was introduced during polyurethane synthesis. However, in order to introduce polyvinylpyrrolidone during the synthesis of polyurethane, a new synthetic procedure for introducing isocyanate functional groups to polyvinylpyrrolidone must be added. However, such a synthesis method is difficult and difficult to control the molecular structure. In addition, the polyurethane synthesized by such a process does not form a fine phase separation structure, it is difficult to obtain the desired elasticity and flexibility, as well as to obtain a polyurethane of the desired molecular weight due to the steric hindrance by the side functional groups. There is difficulty. In addition, there is no advantage in terms of skin adhesion, it has a disadvantage that is difficult to apply to the body parts with repeated movement.

On the other hand, another method to secure the insufficient adhesion of the polyurethane is a method of physically mixing (blending, blending) a second polymer having a functional group capable of secondary chemical bonding with the skin. In this case, however, it is important that there is no phase separation because of compatibility between the polyurethane and the second polymer. In Korean Patent Application No. 2000-18566, a polyether was synthesized as a second polymer having a functional group capable of secondary chemical bonds with the skin, and synthesized to have the same main chain as the polyurethane to prevent phase separation.

However, in this case, if the main chain of the polyurethane is changed, there is a hassle to change the main chain of the polyether accordingly.

In contrast, US Pat. Nos. 5,156,601 and 5,258,421 discuss the preparation of a sticky dressing gel consisting of polyurethane and poly (N-vinyl lactam) dispersed in an aqueous solution to form a stable film on the skin. However, this formulation also showed no advantages in terms of flexibility and elasticity.

Accordingly, the present inventors have improved the problem of the existing invention to develop a film forming agent having elasticity, flexibility and excellent skin adhesion and transdermal dosage form containing the same.

As a result, the film-forming agent which can satisfy all of the above physicochemical properties, the present invention is (A) Thermoplastic polyurethane and (B) Carboxylic acid derivative functional group in the main chain (branch) or branch chain (side chain) 'Blend' water of the addition polymerization type polymer having a was developed.

1 is a graph showing the skin penetration rate of ketoprofen through guinea pig skin.

2 is a graph showing the skin penetration rate of diclofenac diethylammonium through guinea pig skin.

3 is an NMR spectrum of a polyurethane according to the present invention.

The present invention provides a film former for achieving the above object, and also provides a transdermal dosage form containing the film former and the active ingredient. More specifically, (A) 50 to 99% by weight of polyurethane, and (B) a derivative of carboxylic acid in the main chain or branched chain, that is, carboxylic acid alkyl ester of carboxylic acid and / or alkylamide of carboxylic acid It provides a film former comprising 1 to 50% by weight of an addition polymer type polymer containing a carboxylic acid alkyl amide and / or a carboxylic acid alkylaminoalkylester functional group.

In order for the film formed on the skin to have both flexibility, elasticity, and skin adhesion, the film former must have the following structural characteristics. That is, for flexibility, the glass transition temperature (Tg) is lower than room temperature to have a soft characteristic at room temperature, which can be expressed as a modulus value made of film, the smaller the modulus value, the more flexible This is big.

In addition, for stretchability, it must have a crosslinked moiety in the structure. Crosslinking includes chemical crosslinking and physical crosslinking, but physical crosslinking is preferable for the film to be dissolved in a solvent.

In addition, in order to maintain the adhesion of the film formed on the skin, a secondary chemical bond with the skin is required, and for this, a functional group capable of participating in a secondary chemical bond (hydrogen bond or van der Waals force) is required.

The thermoplastic polyurethane used in the present invention has a hard segment and a soft segment at the same time in the structure, and since the hard segment formed in the flexible soft segment forms a microphase separation structure serving as a physical crosslinking point, It is elastic due to its structural features.

In particular, the thermoplastic polyurethane of the present invention comprises (a-1) polyethylene glycol; (a-2) polydiol having a hydroxyl group at both terminals, which is more hydrophobic than polyethylene glycol; And (a-3) is obtained from the reaction of the diisocyanate having an isocyanate group at both ends, the stretchability and flexibility (glass transition temperature) of the film-forming agent of the present invention can be controlled by the type and ratio of polydiol and diisocyanate.

However, the polyurethane thus prepared has excellent elasticity and flexibility, but is not satisfactory in terms of adhesion. Therefore, in order to give adhesion, a plurality of functional groups capable of secondary chemical bonding should be introduced into the main chain of the polyurethane, and the method of introducing functional groups into the polyurethane by chemical synthesis is difficult as described above, and molecular structure control is difficult. it's difficult. On the other hand, a method of physically mixing, ie, blending a polymer having a functional group capable of secondary chemical bonding with a polyurethane may be considered, but in this case, if the chemical properties between the two polymers are significantly different, a phase separation phenomenon may occur and similar chemical properties may be considered. Even so, in many cases, it breaks the microphase separation structure of the original polyurethane and loses its inherent flexibility and flexibility.

Therefore, in the present invention, a polymer having a functional group capable of secondary chemical bonding, which is essentially a derivative of carboxylic acid in the main chain or branched chain, that is, alkyl ester of carboxylic acid and / or alkylamide of carboxylic acid and / or alkylaminoalkyl ester of carboxylic acid. It was blended with polyurethane using the addition polymer containing polymer.

The film former of the present invention thus obtained has excellent elasticity, flexibility and skin adhesion properties without phase separation.

Hereinafter, the present invention will be described in more detail.

The terms used in the present invention have the following meanings:

Film formers are polymers that form a film that is not sticky to the skin and has excellent skin adhesion and elasticity, i.e., derivatives of carboxylic acids, i.e., alkyl esters of carboxylic acids, and / or in (A) polyurethanes and (B) main or branched chains. It means a polymer made of an addition polymerization type polymer which essentially contains an alkylamide of carboxylic acid and / or an alkylaminoalkyl ester functional group of carboxylic acid.

The film former composition is a composition prepared to apply to the skin including the above film former, and also includes a liquid and other additives in which the film former is dissolved.

A transdermal dosage form means a formulation containing the above film former, a solvent capable of dissolving it, an active ingredient and other additives.

Polyurethane (A) defined in the present invention is prepared by a polymerization reaction of the following components (a-1), (a-2) and (a-3), and the weight average molecular weight represented by the following general formula (A) This is a polyurethane of 10,000 to 500,000.

(a-1) polyethylene glycol;

(a-2) polydiol having a hydroxy group at both terminals, more hydrophobic than the (a-1) polyethylene glycol;

(a-3) diisocyanate having isocyanate groups at both terminals

(A)

(In the above meal,

m is an integer such that the weight average molecular weight of-(OCH ₂ CH ₂ ) m is 200 to 50,000;

p and p ', which are the same as or different from each other, are integers such that the weight average molecular weight of the polyurethane is 10,000 to 500,000;

q, q 'and q "are the same as or different from each other and are integers such that the weight average molecular weights of (R) q, (R) q' and (R) q" are 200 to 50,000;

R is a substituent using one selected from the following or a mixture of two or more selected from the following:

O (CH ₂ ) _n ; OCO (CH ₂ ) _n ; O-CO- (CH ₂ ) _n -CO-O- (CH ₂ ) _{n '} ; O (CH (CH ₃ ) (CH ₂ ) _n ) _{n '} ; O (C (CH ₃ ) ₂ (CH ₂ ) _n ) _{n '} (where n and n' are the same as or different from each other and are integers of 1 to 10); OCOCH (CH ₃ ) CH ₂ ; OSi (CH ₃ ) ₂ ; Or (OCH ₂ CH ₂ ) _x- (OCH (CH ₃ ) CH ₂ ) _y- (OCH ₂ CH ₂ ) _{x '} (where x, x' and y are the same as or different from each other, an integer from 1 to 100 to be.);

R 'is a substituent using one selected from the following or a mixture of two or more selected from the following.

(CH ₂ ) l (where l is an integer from 1 to 10);

As described above, the polyurethane of the present invention may be composed of various kinds of polyurethanes synthesized by allowing different R or R's to be contained in one molecule, that is, R and R 'each having two or more different structures. Can be.

According to one aspect of the invention, the polyurethane (A) is a water swelling body (hydrogel) synthesized using a polymer (polyol) having a hydroxyl group at both ends, having two different hydrophilicity, polyurethane (A) ) Use (a-1) and (a-2) as polyols.

The first polyol (a-1) is polyethylene glycol, which imparts hydrophilicity to the film former to determine the water function of the film former formed from the film former composition of the present invention. Polyethylene glycol (a-1) is preferably included in an amount of 10 to 90% by weight based on the total weight of (a-1) + (a-2) + (a-3), the molecular weight is 200 to 50,000 Good, Preferably it is 1,000-5000.

The second polyol (a-2) is a more hydrophobic polymer than polyethylene glycol, for example, polypropylene glycol, polybutylene glycol, polytetramethylene glycol, polyhexamethylene glycol, polypropylene glycol, polyethylene glycol and poly polyalkylene glycols, such as propylene glycol triblock copolymer (trade name: Pluronic ^ⓡ); And diols of polyesters obtained by ring-opening polymerization, that is, polycaprolactone diols, polylactone diols, polyglycolic acid diols, and the like. The second polyol (a-2) is preferably included in an amount of 10 to 90% by weight relative to the total weight of (a-1) + (a-2) + (a-3), the molecular weight is 200 to 50,000 It is good that it is preferable that it is 1,000-5,000.

As a molecule (a-3) which has an isocyanate group used for the synthesis | combination of a polyurethane (A),

Toluene diisocyanate, 4-chloro-m-phenylenedi isocyanate, 4-phenoxy-m-phenylenedi isocyanate, 4-methoxy-m-phenylenedi isocyanate, 4-butyl-m-phenylenedi isocyanate, m-phenylenedi Isocyanate, p-phenylene diisocyanate, m-xylene diisocyanate, p-xylene diisocyanate, cumene diisocyanate, durene diisocyanate, 1,4-naphthylene diisocyanate, 1,5-naphthylene diisocyanate, 1,8- Naphthylene diisocyanate, 2,6-naphthylene diisocyanate, 1,5-tetrahydronaphthylene diisocyanate, p, p'-diphenyl diisocyanate, diphenylmethane-4,4'- diisocyanate, 2,4 Aromatic diisocyanates such as -diphenyl hexane-1,6-diisocyanate, 3,3'-dimethoxy-4,4'-biphenylene diisocyanate, methylene diisocyanate, ethylene diisocyanate, trimethyl -Ω, Ω'-diisocyanate, tetramethylene-Ω, Ω'-diisocyanate, pentamethylene-Ω, Ω'-diisocyanate, hexamethylene-Ω, Ω'-diisocyanate, octamethylene-Ω , Ω'-diisocyanate, nonamemethylene-Ω, Ω'-diisocyanate, decamethylene-Ω, Ω'-diisocyanate, 2-chloro-trimethylene diisocyanate, 2,3-dimethyltetramethylene diisocyanate, Aliphatic diisocyanates, such as methylene bis (p-cyclohexyl isocyanate), can be used individually or in mixture. In particular, toluene diisocyanate, diphenylmethane-4,4'- diisocyanate, pentamethylene-Ω, Ω'-diisocyanate, hexamethylene-Ω, Ω'-diisocyanate, octamethylene-Ω, Ω ' -It is preferable to use diisocyanate and methylene bis (p-cyclohexyl isocyanate) individually or in mixture.

The diisocyanate (a-3) is used in the same number of moles as the sum of the number of moles of the polyethylene glycol (a-1) used in the polyurethane synthesis and the number of moles of the polydiol (a-2) which is more hydrophobic than the polyethylene glycol.

The weight average molecular weight of the polyurethane (A) produced by the above-described method is 10,000 to 500,000, and 30,000 to 300,000 is preferable in order to have desirable stretch, flexibility and strength.

Obtaining the polyurethane (A) having the desired physical properties from the respective monomers described above can be carried out using polymerization methods well known to those skilled in the art. For example, it can be manufactured by the method described in Polyurethanes in biomedical applications (New York, CRC Press, 1998) by Lamba et al. In the present invention, in order to synthesize the polyurethane (A), a polydiol (a-1) and a polydiol (a-2) having a hydroxy group at both ends with stronger hydrophobicity than polyethylene glycol are prepared in a desired ratio, and two polyols The same molar number ((a-1) + (a-2)) of diisocyanate (a-3) was prepared to carry out condensation polymerization. The reaction is carried out under heating conditions of at least the minimum room temperature, preferably at a temperature of room temperature to 80 ℃, the appropriate reaction temperature is determined according to the type and amount of the reactants and catalyst. Catalysts such as dibutytin dilaurate and the like can be used for the activation of the reaction. As the reaction solvent, an organic solvent such as tetrahydrofuran can be used.

In the film former of the present invention, the polymer (B) having a carboxylic acid derivative functional group in the main chain or branched chain is a derivative of the carboxylic acid and has an alkyl ester of carboxylic acid and / or an alkylamide of carboxylic acid and / or an alkylaminoalkyl ester functional group of carboxylic acid. It is a polymer obtained from an addition polymerization reaction of a monomer.

The monomer has the following formula, the polymer (B) has a monomer having the following formula by weight ratio of at least 10% or more, the weight average molecular weight is preferably 10,000 ~ 800,000.

The chemical formula of the monomer is as follows.

[In the above meal,

A and B are H or CH ₃ ,

R and R 'are the same as or different from each other, CH ₃ ; (CH ₂ ) _n CH ₃ ; CH (CH ₃ ) ₂ ; CH (CH ₃ ) (CH ₂ ) _n CH ₃ ; C (CH ₃ ) ₃ ; C (CH ₃ ) ₂ (CH ₂ ) _n CH ₃ ; CH ₂ CH (CH ₂ CH ₃ ) (CH ₂ ) _n CH ₃ ; (CH ₂ ) _n OH; CH ₂ CH (OH) CH ₃ ; CH ₂ CH (OH) (CH ₂ ) _n CH ₃ ; Or R ₁ N (R ₂ ) _{2 ,}

Where R ₁ is (CH ₂ ) _n ,

R ₂ is H; CH ₃ ; (CH ₂ ) _n CH ₃ ; CH (CH ₃ ) ₂ ; Or C (CH ₃ ) _{3 ,}

n is an integer from 1 to 15.]]

The monomer having the above formula is a derivative of carboxylic acid, that is, a monomer having an alkyl ester of carboxylic acid and / or an alkylamide of carboxylic acid and / or an alkylaminoalkyl ester of carboxylic acid, and an acrylic acid ester / amide. ), Methacrylic acid ester / amide, crotonic acid ester / amide, maleic acid ester / amide, maleic anhydride, and the like. have.

Specific examples of the acrylic acid ester monomers include methyl acrylate, ethyl acrylate, butyryl acrylate, isobutyl acrylate, isobornyl acrylate, hydroxyethyl acrylate, 2-hydroxypropyl acrylate, and the like.

Specific examples of the acrylic acid amide monomers include acrylamide, N-t-butyl acrylamide, octyl acrylamide and the like.

Specific examples of the methacrylic acid ester monomers include methyl methacrylate, ethyl methacrylate, buty methacrylate, isobuty methacrylate, 2-ethylhexyl methacrylate, lauryl methacrylate, and hydroxyethyl methacrylate. Acrylate, 2-hydroxypropyl methacrylate, dimethylaminoethyl methacrylate, t-butylaminoethyl methacrylate, and the like.

Specific examples of the methacrylic acid amide monomers include methacrylamidopropyl / trimethylammonium chloride.

Specific examples of the maleic acid ester monomers include methyl maleate, ethyl maleate, isopropyl maleate, buty maleate, and the like.

Specific examples of the crotonic acid ester monomers include methylcrotonate, ethyl crotonate, isopropyl crotonate, butyrol crotonate, and the like.

In the film-forming agent of the present invention, the polymer (B) contains at least 10% by weight of the above-mentioned monomers. This is because at least 10% or more should be included to give the proper adhesion to the skin.

As examples of the polymer obtained from the monomer having a functional group that promotes adhesion to the aforementioned skin, the following may be mentioned.

There typical example, can use the tray's (Gantrez ^ⓡ) family of between US ISP Corporation, poly (methyl vinyl ether -co- maleic acid anhydride) (Gantrez AN ^ⓡ), poly (methyl vinyl ether maleic acid -co- echil ester) refer to the like ^(ⓡ Gantrez ES 225), poly (methyl vinyl ether maleic acid -co- isopropyl ester) (Gantrez ES 335 ^ⓡ), poly (methyl vinyl ether maleic acid -co- Fanning ester) (Gantrez ES 425 ^ⓡ) can do.

Further, Italy may use the Ruhm GmbH's Eudragit (Eudragit ^ⓡ) family, a poly (di-methyl amino seven methacrylate -co- methacrylic acid ester) (Eudragit ^ⓡ E), poly (methacrylic acid -co - may be mentioned methacrylic acid esters) (Eudragit L or Eudragit ^{ⓡ ⓡ} S), poly (methacrylic acid ester -co- tree methyl amino seven methacrylate) (Eudragit RL or Eudragit ^{ⓡ ⓡ} RS) or the like.

In addition, Ultrahold, BASF, Germany, which is poly (acrylic acid-co-ethylacrylate-co-Nt-acrylic acrylamide), and Japan Mitsubishi Yuka, which is poly (acrylic acid ester-co-methacrylic acid ester) Mitsubishi Yuka) diamond's hold (Diahold ^ⓡ EX-55), octyl acrylamide, t- Fanning hit methacrylate and acrylic acid, methacrylic acid or a copolymer US National starch (National starch and those of the alkyl ester to amino) 's cancer formers (Amphomer) family of field-octyl acrylamide and acrylic acid, methacrylic acid or the Bessa butyl (Versatyl ^ⓡ) family's copolymer from National starch (National starch) of these alkyl esters, poly (vinyl acetate -co- crotonic acid) of BASF (BASF) Ruby's three CA 66 ^(ⓡ Luviset CA 66), poly (vinyl acetate -co- crotonic acid -co- vinyl propionic arose Et) of BASF (BASF) Ruby's set CAP (Luviset CAP ^ⓡ To mention) There.

The film former according to the present invention contains 50 to 99% by weight of the polyurethane (A) and 1 to 50% by weight of the addition polymerized polymer (B) having a carboxylic acid derivative functional group. Preferably it contains 70 to 99 weight% of polyurethanes (A) and 1 to 30 weight% of an addition polymerization type polymer (B).

The film former of the present invention can be used after being dissolved in a solvent applicable to the human body, for example, a mixed solution of water and ethanol. When using a mixed solution of water and ethanol as a solvent, 1 to 90% of ethanol is used, preferably 10 to 70%. The content of the film former (A + B) in the solvent is preferably 0.1 to 50%, preferably 1 to 30%. This is because when the content is 0.1% or less, it is difficult to form a film of an appropriate thickness, and when it contains more than 50% of the film-forming agent, it is difficult to spread because of high viscosity.

Tensile strength, Young's modulus and elongation of a film formed from the film former of the present invention obtained through the blending of an addition polymer type polymer (B) having a polyurethane (A) and a carboxylic acid derivative as a functional group Was measured according to 'Standard Test Method for Measuring Tensile Force of Plastic Material' among ASTM Test Methods, and the adhesion was measured based on the Peel Adhesion Test Method of the PSTC Test Method.

The physical property of the film formed by the film forming agent of the present invention preferably has a tensile strength of 0.5 MPa or more at a temperature of 20 ° C. or more, and preferably 1 MPa or more. This is because when the tensile strength is less than 0.5 MPa, the film may be broken in the middle of the film removal due to insufficient strength, making it difficult to remove the film easily and neatly.

It is preferable that Young's modulus is 0.1-80 Mpa, Preferably it is 1-50 Mpa. If it is less than 0.1 MPa, the strength is too weak to cause stickiness, and if it exceeds 80 MPa, it may cause discomfort and rejection by disturbing the movement of the portion where the film is formed.

On the other hand, the elongation rate (elongation%) according to the following Equation 1 may be at least 100% or more corresponding to the movement of the body.

In addition, the adhesive force is 20 g / in. For stainless steel. The above is preferable because it can impart proper adhesion to the skin.

Transdermal dosage formulations provided according to another aspect of the present invention include an addition polymer type polymer (B) having the polyurethane (A) and a carboxylic acid derivative functional group; A solvent applicable to the skin while dissolving the polyurethane (A) and the polymer (B); And an active ingredient.

The active ingredients contained in the transdermal dosage form according to the present invention are not particularly limited in kind, and include, for example, drugs or substances having dermatologically physiological activity.

Specifically, for example, ketoprofen, indomethacin, ibuprofen, diclofenac, flubiprofen, ketorolac, pyroxhamm, mefenic acid, salicylic acid, etc., which are nonsteroidal anti-inflammatory drugs which exhibit antipyretic, analgesic and anti-inflammatory effects And pharmaceutically acceptable derivatives thereof; Steroids dexamethasone, hydrocortisone, prednisolone, betamethasone, triamcinolone acetonide, fluorosinol acetonide and the like and pharmaceutically acceptable derivatives thereof; Beta blockers propranolol, atenolol, pindolol, timolol, bufranolol, metoprolol, alprenolol, oxprenolol and the like and pharmaceutically acceptable derivatives thereof; Anticholinergic agents atropine, oxybutynin, clidinium, scopolamine and the like and pharmaceutically acceptable derivatives; Nifedipine, verapamil, diltiazem and the like and pharmaceutically acceptable derivatives of calcium blockers; Other cardiovascular drugs, clonidine, prazosin, nitroglycerin, isosorbate dinitrogen, and the like, and pharmaceutically acceptable derivatives thereof; Female hormones estradiol, ethynylestradiol, progesterone and the like and pharmacologically acceptable derivatives thereof; Testosterone and the like of the male hormone and pharmaceutically acceptable derivatives thereof; Local anesthetics lidocaine hydrochloride, procaine, tetracaine, prilocaine, bupivacaine, dibucaine and the like and pharmaceutically acceptable derivatives thereof; Antihistamines, diphenhydramine, maleic acid diphenhydramine, chlorpheniramine, ketotifen, and the like and pharmaceutically acceptable derivatives thereof; Synthetic drugs buprenopine, fentanyl, sufentanil and the like and pharmaceutically acceptable derivatives thereof; Bronchodilators salbutamol and terbumalin and the like and pharmaceutically acceptable derivatives thereof; The antibiotics gentamycin, erythromycin, neomycin, fusidic acid and the like and pharmaceutically acceptable derivatives thereof; Antifungal agents econazole, itraconazole, ketoconazole, terbinafine and the like and pharmaceutically acceptable derivatives thereof; Antiviral agents acyclovir, ribavirin, alpha interferon and the like and pharmaceutically acceptable derivatives thereof; Skeletal muscle relaxants such as eferison hydrochloride, tolperisone hydrochloride, baclofen, biferdene hydrochloride, tizanidine hydrochloride and the like and pharmaceutically acceptable derivatives thereof; Exfoliants salicylic acid, lactic acid, glycolic acid and the like and pharmaceutically acceptable derivatives thereof; Benzoyl peroxide used as an acne treatment agent; Skin protective agents alatonin, dimenchicon, petrolatum, dexpanthenol, zinc oxide and the like and pharmaceutically acceptable derivatives thereof; Vitamins A, B, C, D, E and pharmaceutically acceptable derivatives thereof such as tretinoin, isotretinoin, retinol, retinoic acid, ascorbic acid, tocopherol; Nicotine and pharmaceutically acceptable derivatives thereof used as a smoking cessation aid; Albumin, kojic acid, hydroquinone, oxybenzone, and the like, used as skin lightening agents, and pharmaceutically acceptable derivatives thereof; Centella asiatica, an herbal extract; Minoxidil used for alopecia; It may be one or a mixture of two or more selected from other heparin sodium, capsaicin and the like. The active ingredient referred to in the present invention is not limited to the drugs listed above, but includes all other ingredients or ingredients beneficial to the human body that can be expected to have a good effect by supplying to the skin.

The amount of these drugs contained in the transdermal dosage form of the present invention may be used in an amount sufficient to obtain a desired effect, and the amount may be determined by those skilled in the art in consideration of the condition, weight, frequency of administration, type of drug, etc. However, for example, it is preferable to use within 0.01 to 50% of the total weight of the formulation.

In addition, the transdermal dosage form preparation of the present invention is a skin absorption enhancer for enhancing the skin permeation of the above-mentioned effective ingredient, higher fatty acids such as oleic acid; Higher alcohols such as lauryl alcohol; Polyols such as polyethylene glycol; Higher fatty acid esters such as isopropyl myristate; Fatty acid esters of glycerin, such as glycerol monolaurate; Fatty acid ethers of polyethylene glycol, such as polyethylene glycol lauryl ether; Fatty acid esters of polyethylene glycol, such as polyethylene glycol laurate; Fatty acid ethers of propylene glycol, such as propylene glycol lauryl ether; Propylene glycol fatty acid esters such as propylene glycol laurate; Sorbitan fatty acid esters such as sorbitan monolaurate (span20); Polyethylene glycol sorbitan fatty acid esters such as polyethylene glycol sorbitan monostearate (twin 60); Terpenes such as menthol, menthol derivatives and limonene; Sulfoxides such as dimethyl sulfoxide and dodecyl sulfoxide; Pyrrolidones such as N-methyl-2-pyrrolidone; Amides such as lauryl diethanolamide; Ethoxydiglycol, N-hydroxy methyllide, sorbitol, urea, squalene, squalane, olive oil, pajama oil and derivatives thereof may be included within the range of 0.5-30% of the total weight of the formulation.

The formulations of the present invention may also contain humectants or softeners. Examples of these moisturizers or softeners include glycerin, polyethylene glycol, propylene glycol, 1,3-butanediol, lactic acid, mineral oil, lanolin, waxes, glucose derivatives, and the like. It is suitable and preferably 1 to 30%. This is because the effect is not sufficient at less than 0.1%, and if it exceeds 50%, it causes excessive stickiness or slipperiness in the formulation.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited only to these Examples.

Example 1 Synthesis of Polyurethane (A)

20 g of polyethylene glycol having a hydroxyl group at both terminal groups and 20 g of polytetramethylene glycol having a molecular weight of 2,000 g were dried in vacuo to remove water, and then dissolved in 500 ml of tetrahydrofuran (THF) purified under Na. The resulting solution was slowly added to a mixed solution of 3.3 ml of hexamethylene diisocyanate (HDI) and 0.1 ml of dibutyltin dilaurate, and the reaction was continued for 24 hours while stirring at 60-70 ° C. with a Teflon stirrer. The composite was precipitated in excess distilled water and then dried in a 50 ° C. vacuum oven for 2 days.

[Examples 2 to 6] Synthesis of Polyurethane (A)

A series of polyurethane series was synthesized in the same manner as in Example 1 using the components shown in Table 1 below.

Composition of Polyurethane (A) Example Polyethylene glycol Polytetramethylene glycol Molar ratio 2 2,000 2,000 1: 2 3 3,400 2,000 1: 1 4 3,400 2,000 1: 2 5 4,600 2,000 1: 1 6 4,600 2,000 1: 2

Example 7 Synthesis of Polyurethane (A)

35 g of polyethylene glycol having a hydroxyl group at both terminal groups and 35 g of a molecular weight 1,500 polystyrene glycol and a polypropylene glycol ^triglycol copolymer (trade name Pluronic®, BASF) of 10 g were removed by vacuum drying to remove water, and then purified by tetra It was added to 500 ml of hydrofuran and dissolved. The solution was slowly added to a mixed solution of 5.2 mL of HDI and 0.1 mL of dibutyltin dilaurate, and the reaction was continued for 24 hours with continued stirring with a Teflon stirrer at 60-70 ° C. The composite was precipitated in excess distilled water and dried in a 50 ° C. vacuum oven for 2 days.

Example 8 Synthesis of Polyurethane (A)

40 g of polyethylene glycol having a molecular weight of 2,000 g having a hydroxyl group at both terminal groups and 10 g of polytetramethylene glycol having a molecular weight of 1,000 were dried under vacuum to remove water, and then added to 500 ml of purified tetrahydrofuran under Na to dissolve. The solution was slowly added to a mixed solution of 7.6 g of diphenylmethane-4,4'-diisocyanate (MDI) and 0.1 ml of dibutyltin dilaurate, and the reaction was continued for 24 hours with stirring at 60-70 ° C. with a Teflon stirrer. . The composite was precipitated in excess distilled water and dried in a 50 ° C. vacuum oven for 2 days.

Example 9 Synthesis of Polyurethane (A)

20 g of polyethylene glycol having a hydroxyl group at both terminal groups and 20 g of poly-ε-caprolactone diol having a molecular weight of 2,000 g were dried in vacuo to remove water, and then dissolved in 500 ml of THF purified under Na. The solution was slowly added to a mixed solution of 5.3 ml of methylene bis (p-cyclohexyl isocyanate) and 0.1 ml of dibutyltin dilaurate, and reacted for 24 hours with continuous stirring at 60-70 ° C with a Teflon stirrer. The composite was precipitated in excess distilled water and dried in a 50 ℃ vacuum oven for 2 days.

Test Example 1 Confirmation of Structure of Polyurethane (A)

NMR spectrum was used to confirm the structure of the polyurethane according to the present invention. Specifically, 1H-NMR spectrum measured by 300 MHz Varian Gemini 2000 FT-NMR and CDCl ₃ were used as the solvent.

In the case of the polyurethane obtained by polymerizing polytetramethylene glycol as (a-2), hexamethylene diisocyanate as (a-3), and polyethylene glycol as (a-1), which is a representative example of the polyurethane according to the present invention [ Polyurethanes of Examples 1 to 6], -OC H ₂ C H ₂ -of polyethylene glycol is 3.6 ppm (multiple), and -OCH ₂ C H ₂ O-CONH- of the terminal portion connected to the urethane group is 4.2 ppm (triplet) ), 3.4 ppm (multiple) of -OC H ₂ (CH ₂ ) ₂ C H ₂ -of polytetramethylene glycol, -OCH ₂ CH ₂ CH ₂ C H ₂ O-CONH- of the terminal connected to the urethane group is 4.1 ppm (triplet), -OCNH-C H ₂ (CH ₂ ) ₄ C H ₂ -NHCO- of hexamethylene diisocyanate 3.1 ppm (multiple), -OCNH-CH ₂ (C H ₂ ) ₄ CH ₂ -NHCO -And peaks of -OCH ₂ (C H ₂ ) ₂ CH ₂ -of polytetramethylene glycol were measured over 1.3 to 1.7 ppm (multiple). The NMR measurement results are shown in FIG. 3.

Test Example 2 Confirmation of Molecular Weight of Polyurethane

The molecular weight of the polyurethane synthesized in Examples 1 to 9 was measured. That is, after dissolving the polyurethane synthesized in Examples 1 to 9 at a concentration of 0.05% in THF, the molecular weight was measured using gel permeation liquid chromatography (GPC). The results are shown in Table 2.

<Gel Permeation Liquid Chromatography (GPC) Analysis Conditions>

Column: Three consecutive columns of Ultrastyragel ^TM HR1, HR2, HR4

Mobile phase: THF

Flow rate: 1ml / min

Detector: Refractometer (Water Differential Refractometer 410)

Example Molecular Weight Molecular weight distribution (polydispersity) One 200,000 2.9 2 198,000 2.2 3 180,000 2.8 4 210,000 2.4 5 170,000 2.3 6 165,000 2.6 7 148,000 2.3 8 170,000 2.1 9 166,000 2.4

Test Example 3 Measurement of tensile strength, elongation% and Young's modulus

The physical properties (tensile strength, elongation, Young's modulus) of the film-forming agent for drug delivery formed through the blending of the addition polymer type polymer (B) having the polyurethane (A) and the carboxylic acid derivative functional group of the present invention were measured.

The measurement was measured using a universal testing machine (UTM), a universal testing machine (HOUNSFIELD H25K-S), in accordance with ASTM-D-638M standard among ASTM standard test methods.

The film former of the present invention, ie, for the fabrication of specimens for the measurement of physical properties

Blending product of polyurethane (A) with addition polymer type (B) having carboxylic acid derivative functional group was added to acetone at a concentration of 7wt% to dissolve it, cast on a release paper, dried and dried to a thickness of 100-200 μm. To come. The types and compositions of (A) and (B) are shown in Table 3. For comparison, the physical properties of the film formed of polyurethane (A) alone were also measured.

In addition, for comparison, the physical properties of the film obtained through blending the polyurethane (A) with another polymer (C) other than the polymer (B) of the present invention were also measured in the same manner. In particular, polymers (C) other than the polymer (B) of the present invention are polymers (C) known to be able to impart adhesion to skin having other functional groups in the main chain or branched chain.

The types and compositions of these comparative examples are shown in Table 4.

The films of Examples and Comparative Examples obtained were cut in the same manner as the Type M-III specimens of ASTM-D-638M specification, and tensile strength, elongation and Young's modulus were measured while pulling at a speed of 20 mm / min with a universal testing machine. The measured results are shown in Table 5.

No phase separation phenomenon was observed in both the film former solution prepared in Examples 10 and 20 and the film former produced in the specimen.

Types and Compositions of Comparative Examples 1 to 5 Comparative example Film forming agent Compounding cost Phase separation Polyurethane (A) Polymer (C) (A) (B) One Example 1 Poly (acrylic acid) (Carbopol 934P, BFGoodrich) 80 20 Phase Separation (Partially Gelled) 2 Example 1 Poly (vinylpyrrolidone) (PVP K30, ISP) 80 20 Phase Separation (Milk) 3 Example 1 Poly (ethylene glycol-b-propylene glycol) (Pluronic F127, BASF) 80 20 No phase separation 4 Example 1 Poly (vinyl alcohol) (PVP 217, Wako) 80 20 Phase Separation (Milk) 5 Example 1 Hydroxypropyl Methyl Cellulose (Metocell K4M, Dow Chemical) 80 20 Phase Separation (Partially Gelled)

Young Small Modulus (MPa) Tensile Strength at Break (MPa) Elongation (%) Example 1 41 35 3,800 Example 2 45 43 3,800 Example 3 39 36 3,500 Example 4 52 46 4,000 Example 5 50 41 3,800 Example 6 58 52 4,200 Example 7 20 16 2,500 Example 8 61 55 4,600 Example 9 42 39 3,600 Example 10 41 35 3,200 Example 11 43 36 2,800 Example 12 53 49 1,900 Example 13 60 52 1,000 Example 14 52 43 2,600 Example 15 70 62 3,000 Example 16 42 39 3,000 Example 17 50 42 2,900 Example 18 62 52 3,100 Example 19 59 51 2,800 Example 20 72 62 2,500 Comparative Example 1 250 28 60 Comparative Example 2 350 35 120 Comparative Example 3 12 One 20 Comparative Example 4 480 39 90

From the above results, it was confirmed from modulus and elongation that the film formers of Examples 10 to 20 of the present invention showed no phase separation phenomenon and maintained the inherent elasticity and flexibility of polyurethane (Examples 1 to 9). Could.

On the other hand, the comparative example showed that phase separation and / or elasticity and flexibility were significantly reduced from the modulus and elongation measurements.

Test Example 4 Test of adhesion force (Peel adhesion test)

An experiment was conducted to confirm the adhesion of the film-forming agent for drug delivery of the present invention. It measured using the universal testing machine (INSTRON, Autograph DSC-500, Shimadzu) based on PSTC test method. To prepare the specimen, the polymers of the polyurethane and film forming agent examples were added and dissolved in a 70% ethanol aqueous solution at a concentration of 10 wt%, cast on a stainless steel base, and then dried to a thickness of 2 mm and width. 1 inch. The attached film was peeled off at a speed of 20 mm / min with a universal testing machine, and the adhesive force was measured. The results are shown in Table 6.

Adhesive force (g / in.) Polyurethane of Example 1 15 Polyurethane of Example 2 18 Polyurethane of Example 3 17 Polyurethane of Example 4 10 Polyurethane of Example 5 15 Polyurethane of Example 6 13 Polyurethane of Example 8 12 Polyurethane of Example 9 15 Film Forming Agent of Example 10 600 Film Forming Agent of Example 11 1,400 Film Forming Agent of Example 12 1,100 Film Forming Agent of Example 13 200 Film former of Example 14 1,500 Film former of Example 15 1,300 Film former of Example 16 920 Film former of Example 17 900 Film former of Example 18 1,000 Film former of Example 19 950 Film former of Example 20 1,000

From Table 6, it can be seen that the film former of the present invention has excellent adhesion. In particular, it can be seen that the adhesion force insufficient by polyurethane alone increased by 100 to 1,000 times or more due to the polymer (B) having a carboxylic acid derivative functional group. In addition, it can be seen that the mixing ratio of the polyurethane and the polymer (B) shows the best adhesion at 80/20.

[Test Example 5] Test for confirming the duration of skin adhesion of film former

An experiment was conducted to confirm the adherence persistence in the flexion site of the drug delivery film forming agent of the present invention. The adhesion duration was confirmed using the film forming agent of Example 11, the polyurethane and polyvinyl alcohol (PVA) of Example 1 was used as a comparative base. The polyurethane of Example 1, the film former of Example 11, and polyvinyl alcohol (PVA 217, Wako) were added to a 65% ethanol aqueous solution so as to have a 10 wt% solution, respectively, to prepare the skin. 0.3 g of the film-forming agent thus prepared was evenly applied over 16 cm 2 of the wrist joint area, and the solvent was completely dried to form a film. The bending and unfolding of the joints in the area where the film was formed was repeated 60 times / min to measure the change in time and properties until the film was detached. The results are shown in Table 7.

time Film Forming Agent of Example 11 Polyurethane of Example 1 Polyvinyl alcohol ~ 3 minutes Lifting is observed along skin and outer area ~ 15 minutes At least 50% of the area of the formed film is peeled off ~ 30 minutes Lifting of the outer part is observed Fully detached ~ 1 hour Lifting due to skin texture is seen, but no peeling At least 50% of the area of the formed film is peeled off

Test Example 6 Skin Stimulation Experiment

Samples for confirming skin irritation were prepared by adding and dissolving the film formers of Examples 10, 16, 18 and 19 in 65% ethanol aqueous solution to 10 wt%, respectively. In order to confirm the skin irritation of the film former of the present invention, the following experiment was conducted.

100 mg of each film-forming agent was evenly applied to the forearm region of 10 healthy adult males who had previously been marked with a size of 9 cm 2. After 30 minutes had elapsed and the solvent was dried, the forming agent layer applied using the adhesive cloth was protected. After 24 hours, the applied forming agent was removed and the degree of primary irritation at the application site was judged according to the following criteria, and the reactivity was calculated from the following equation (2).

<Decision Criteria>

Judgment number Stimulation degree 01234 No irritationMinimal irritationSlightly irritating (erythema) Severe irritation (erythema, edema) Extremely irritated (erythema, edema)

As a result, the reactivity of the film formers of Examples 10, 16, 18, and 19 were 1.5, 1.9, 1.5, and 1.4%, respectively, and thus, showed little irritation to the skin.

As confirmed in the above experiments, the film forming agent of the present invention contains a film forming agent and an active ingredient of the present invention because the film forming agent of the present invention not only forms a flexible and soft film consistent with the movement of the body but also is continuously attached to the lesion. Transdermal dosage forms can effectively deliver the active ingredient.

The film former of the present invention may be applied as a transdermal dosage form topical skin disease treatment agent with an active ingredient, and may be prepared as follows.

Example 21

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 1 9 (B): poly (methylvinyl ether-co-maleic acid ethyl ester) (Gantrez ES 225) One Ketoprofen 3 Ethoxydiglycol One menthol 2 glycerin 2 Polyethylene Glycol 400 3 65% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. On the other hand, ketoprofen, ethoxydiglycol, menthol, glycerin and polyethylene glycol were added to 20 parts of ethanol aqueous solution, and it stirred and dissolved. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 22

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 1 8 (B): poly (methylvinyl ether-co-maleic acid ethyl ester) (Gantrez ES 225) 4 Dichlorophenac diemmonium One Polyoxyethylene sorbitan monooleate (twin 80) 3 Dimethyl sulfoxide 5 glycerin 2 Polyethylene Glycol 400 5 70% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. On the other hand, diclofenac diethyl ammonium, tween 80, dimethyl sulfoxide, glycerin, and polyethylene glycol 400 were added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. The solution is slowly added to the aqueous solution in which the film-forming agent is dissolved while stirring, and then the remaining amount of the ethanol aqueous solution is added and stirred until uniform.

Example 23

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 2 7 (B): poly (methylvinyl ether-co-maleic acid isopropyl ester) (Gantrez ES 335) 3 Piroxycam 0.5 Polyethylene glycol (2) lauryl ether 2 Dimethylsulphoxide 5 glycerin 2 Propylene glycol 3 Polyethylene Glycol 400 5 90% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. On the other hand, 20 parts of ethanol aqueous solution was added pyroxicamp, polyethylene glycol (2) lauryl ether, dimethyl sulfoxide, glycerin, propylene glycol, and polyethylene glycol 400, and stirred and dissolved. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 24

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 3 7 (B): poly (methylvinyl ether-co-maleic acid butyl ester) (Gantrez ES 425) 7 Plubiprofen 4 Capsaicin 0.025 Methyllaurate 2 d, l-campa 5 glycerin 2 menthol 3 Polyethylene Glycol 400 5 80% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. Meanwhile, flubipropene, capsaicin, methyllaurate, d, l-campa, glycerin, menthol, and polyethylene glycol 400 were added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 25

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 3 8 (B): poly (dimethylaminoethyl methacrylate-co-methacrylic acid ester) (Eudragit E) 5 Ketorolac tromethamine 5 Glycerol Monolaurate 2 Cerafil-31 5 glycerin 2 menthol 3 Polyethylene Glycol 400 5 50% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. Meanwhile, ketorolac tromethamine, glycerol monolaurate, cerafil-31, glycerin, menthol, and polyethylene glycol 400 were added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 26

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 9 8 (B): poly (methacrylic acid-co-methacrylic acid methyl ester) (Eudragit S) 2 Sodium fucidic acid 2 Polyethylene glycol laurate One olive oil One glycerin 2 Polyethylene Glycol 400 3 30% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. On the other hand, sodium fucidic acid, polyethylene glycol laurate, olive oil, glycerin, and polyethylene glycol were added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. The solution was slowly added to the aqueous solution in which the film former was dissolved while stirring, and then the remaining amount of ethanol aqueous solution was added and stirred until uniform.

Example 27

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 1 6 (B): poly (dimethylaminoethyl methacrylate-co-methacrylate ester) (Eudragit E) 4 Dipropionate Betamethasone 0.064 Clotrimazole One Gentamicin Sulfate 0.1 N-Methyl-2-pyrrolidone One glycerin 2 Polyethylene Glycol 400 3 50% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. On the other hand, dipropionate betamethasone, clotrimazole, gentamicin, N-methyl-2-pyrrolidone, glycerin and polyethylene glycol were added to 20 parts of ethanol aqueous solution, and it stirred and dissolved. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 28

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 4 8 (B): poly (acrylic acid-co-ethylacrylate-co-N-t-butyrylamide) (Ultrahold) 5 Prednisolone 0.5 Diphenhydramine hydrochloride 0.1 Neomycin sulfate 0.5 Isopropyl myristate 2 glycerin 3 Polyethylene Glycol 400 3 60% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. On the other hand, prednisolone, diphenhydramine hydrochloride, neomycin sulfate, isopropyl myristate, glycerin, and polyethylene glycol were added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 29

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 4 10 (B): poly (vinylacetate-co-crotonic acid) (Luviset CA 66) 3 Heparin sodium 0.4 Dexpanthenol 2.5 Dimethylsulphoxide 15 glycerin 3 Propylene glycol 2 85% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. On the other hand, heparin sodium, dexpanthenol, dimethyl sulfoxide, glycerin, and propylene glycol were added to 20 parts of ethanol aqueous solution, and it stirred and dissolved. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 30

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 5 6 (B): poly (acrylic acid ester-co-methacrylic acid ester) (Diahold EX-55) 5 Ketoconazole 2 Sorbitol monolaurate (span 20) One glycerin 3 Polyethylene Glycol 400 2 70% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. Meanwhile, ketoconazole, sorbitol monolaurate, glycerin, and propylene glycol were added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 31

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 6 5 (B): poly (methylvinyl ether-co-maleic acid ethyl ester) (Gantrez ES 225) 5 Acyclovir 5 Polyethylene Glycol 600 5 glycerin 3 Propylene glycol 2 40% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. Meanwhile, acyclovir, polyethylene glycol, glycerin, and propylene glycol were added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 32

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 7 20 (B): poly (methacrylate ester-co-trimethylaminoethyl methacrylate) (Eudragit RL) 10 Tritinoin 0.025 Glycerol Monooleate One glycerin 3 Propylene glycol 2 55% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. On the other hand, tretinoin, glycerol monooleate, glycerin, and propylene glycol were added to 20 parts of ethanol aqueous solution, and it stirred and dissolved. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 33

The film former composition for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 8 7 (B): poly (octyl acrylamide-co-acrylic acid-co-methacrylic acid ester) (Versatyl) 5 Benzoyl peroxide 10 Sorbitan monooleate (span 80) One Sorbitol 2 menthol One glycerin 3 Propylene glycol 2 40% ethanol aqueous solution to 100

(A) and (B) were added and stirred for 40 parts of ethanol aqueous solutions, and it melt | dissolved. Benzoyl peroxide, sorbitan monooleate, sorbitol, menthol, glycerin and propylene glycol were added to 20 parts of ethanol aqueous solution, and it stirred and dissolved. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 34

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 9 10 (B): poly (acrylic acid-co-ethylacrylate-co-N-t-butyrylamide) (Ultrahold) 5 Kojic acid One Ethoxydiglycol 3 Sorbitol 2 Glycerin 3 Vitamin E 2 Propylene glycol 2 90% ethanol aqueous solution to 100

(A) and (B) were added and stirred for 40 parts of ethanol aqueous solutions, and it melt | dissolved. Kojic acid, ethoxydiglycol, sorbitol, glycerin and propylene glycol were added to 20 parts of ethanol aqueous solution, and it stirred and dissolved. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 35

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 5 25 (B): poly (vinylacetate-co-crotonic acid) (Luviset CA 66) 5 Ephericone hydrochloride 10 Lauryl diethanolamine One Limonene 3 Glycerin 3 Propylene glycol 2 50% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. On the other hand, 20 parts of ethanol aqueous solution was added eferison, lauryl diethanolamide, limonene, glycerin, and propylene glycol, and it stirred and dissolved. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 36

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 9 8 (B): poly (acrylic acid ester-co-methacrylic acid ester) (Diahold EX-55) 6 Salicylic acid 16.7 Lactic acid 16.7 Element 3 Vitamin E 2 glycerin 2 1,3-butanediol 2 Polyethylene Glycol 400 5 40% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. On the other hand, salicylic acid, lactic acid, urea, vitamin E, glycerin, 1,3-butanediol, and polyethylene glycol were added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Example 37

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 1 10 (B): poly (acrylic acid ester-co-methacrylic acid ester) (Diahold EX-55) 6 Minoxidil 3 Dexpanthenol 1.5 Polyethylene glycol (10) monolaurate 3 glycerin 5 Polyethylene Glycol 400 8 40% ethanol aqueous solution to 100

(A) and (B) were added, stirred, and dissolved in 40 parts of ethanol aqueous solutions, and the film former aqueous solution was obtained. On the other hand, minoxidil, dexpanthenol, polyethylene glycol (10) monolaurate, glycerin, and polyethylene glycol were added and stirred in 20 parts of ethanol aqueous solution. The solution was slowly added to the aqueous solution in which the film former was dissolved while stirring, and then the remaining amount of the ethanol aqueous solution was added to the solution and stirred until uniform.

Comparative Example 6

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A): Polyurethane of Example 1 10 Ketoprofen 3 Ethoxydiglycol One menthol 2 glycerin 2 Polyethylene Glycol 400 3 65% ethanol aqueous solution to 100

(A) was added to 40 parts of ethanol aqueous solutions, and it stirred and dissolved, and obtained the comparative film forming agent aqueous solution. On the other hand, ketoprofen, ethoxydiglycol, menthol, glycerin and polyethylene glycol were added to 20 parts of ethanol aqueous solution, and it stirred and dissolved. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Comparative Example 7

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) Polyvinyl alcohol 10 Ketoprofen 3 Ethoxydiglycol One menthol 2 glycerin 2 Polyethylene Glycol 400 3 65% ethanol aqueous solution to 100

Polyvinyl alcohol was added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain a comparative film former aqueous solution. On the other hand, ketoprofen, ethoxydiglycol, menthol, glycerin and polyethylene glycol were added to 20 parts of ethanol aqueous solution, and it stirred and dissolved. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Comparative Example 8

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) (A) Polyurethane of Example 1 12 Dichlorophenacdiammonium One Polyoxyethylene sorbitan monooleate (twin 80) 3 Dimethylsulphoxide 5 glycerin 2 Polyethylene Glycol 400 5 70% ethanol aqueous solution to 100

(A) was added to 40 parts of ethanol aqueous solutions, and it stirred and dissolved, and obtained the comparative film forming agent aqueous solution. On the other hand, diclofenac diethyl ammonium, tween 80, dimethyl sulfoxide, glycerin, and polyethylene glycol 400 were added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Comparative Example 9

The film formation type | mold for skin application | coating comprised with the following component and compounding quantity was obtained by the method of describing below.

ingredient % (W / W) Polyvinyl alcohol 12 Dichlorophenacdiammonium One Polyoxyethylene sorbitan monooleate (twin 80) 3 Dimethylsulphoxide 5 glycerin 2 Polyethylene Glycol 400 5 70% ethanol aqueous solution to 100

Polyvinyl alcohol was added to 40 parts of ethanol aqueous solution, and it stirred and dissolved, and obtained the comparative film former aqueous solution. On the other hand, diclofenac diethyl ammonium, tween 80, dimethyl sulfoxide, glycerin, and polyethylene glycol 400 were added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. The solution was slowly added to the aqueous solution in which the film-forming agent was dissolved, and then slowly added. Then, the remaining amount of the ethanol aqueous solution was added and stirred until uniform.

Test Example 7 Evaluation of Percutaneous Dosage Formulation: Skin Absorption Experiment 1

200 μl of the transdermal dosage form of Example 21 and the transdermal dosage form of Comparative Examples 6 to 7 were applied to the resected skin of the abdominal region of the hair of healthy guinea pigs. The coated skin was installed with the coated part facing the Franz-type diffusion cell facing upward. Phosphate buffer solution (pH 7.4) was added to the bottom space and the diffusion apparatus temperature was maintained at 37 ° C. The buffer solution of the receptor was stirred at a constant speed of 300 rpm, and after a certain time, a certain amount of the solution of the receptor was taken, and the same amount of fresh buffer was taken up. The collected solution was analyzed by high pressure liquid chromatography to measure the concentration of the drug.

High pressure liquid chromatography (HPLC) analysis conditions are as follows.

Column: YMC-Pack ODS-AM (150 × 6.0㎜, I.D. 5㎛)

Mobile phase: 70:30 (V / V) = methanol: 0.1% acetic acid aqueous solution

Flow rate: 1ml / min

Detector: 254nm UV

The experimental results are shown in FIG.

Test Example 8 Evaluation of Percutaneous Dosage Formulation: Skin Absorption Experiment 2

200 μl of the transdermal dosage form formulation of Example 22 and the transdermal dosage form formulations of Comparative Examples 8 to 9 were applied to the excised skin of the abdominal region of healthy guinea pigs, and tested in the same manner as in Test Example 7. The concentration of the drug was determined by analysis by liquid chromatography.

High pressure liquid chromatography (HPLC) analysis conditions are as follows.

Column: YMC-Pack ODS-AM (150 × 6.0㎜, I.D. 5㎛)

Mobile phase: 53:47 (V / V) = acetonitrile: 0.02 M sodium acetate buffer (pH 5.8)

Flow rate: 1ml / min

Detector: 280nm UV

The experimental results are shown in FIG.

As can be seen in the above test examples, the transdermal dosage form prepared from the film former of the present invention not only provides convenience to the user due to the excellent elasticity and flexibility of sticking, but also shows keto, as shown in FIGS. 1 and 2. It can be seen that active ingredients such as propene and diclofenac diemmonium can also be effectively delivered.

According to the present invention, the film forming agent composed of a thermoplastic polyurethane and an addition polymer type polymer had no phase separation despite the different structure of the polyurethane and the addition polymer type polymer backbone, and had excellent elasticity and flexibility. Therefore, it can be seen that the addition polymerization type polymer of the present invention does not change the microphase separation structure of the polyurethane to maintain the elasticity and flexibility of the polyurethane as it is. Moreover, the obtained film former also has the skin adhesion which polyurethane alone did not have. Accordingly, in the present invention, the problem of having a conventional film-forming transdermal dosage form without the disadvantages such as smearing or sticking of an existing ointment or gel formulation, that is, to hinder the movement of the body due to lack of elasticity and flexibility, or drying It was possible to provide a film-forming agent for drug delivery of a new composition and a transdermal dosage form containing the same and containing the active ingredient, without having a problem of crumbing or desorption later. Furthermore, the film former and the transdermal dosage form containing the same according to the present invention have the following characteristics which are distinguished from the existing external preparations.

The film forming agent of the present invention is easily applied to the skin in a state dissolved in a solvent applicable to the human body, and forms a film within a few minutes after the application, and this film is thin and transparent so that the appearance is not easily distinguished so that it is continuously applied to exposed areas. Is possible. In addition, the quickly formed film does not stain clothes or socks, and does not bury in other body parts.

When the transdermal dosage form containing the film-forming agent of the present invention is applied to the skin, the formed film is excellent in adhesion and lasts for a long time at the site of application, and releases the active ingredient, thereby exhibiting an excellent effect even with a small number of applications.

The film forming agent according to the present invention is applied to any part of the body due to the excellent elasticity and flexibility of elasticity does not give a rejection at all. In addition, the film formed at the joint area with high movement is free from cracking despite repeated movement.

In addition, it has good skin adhesion and does not push or detach in its original in situ position.

In addition, polyurethane, which is a component of the film forming agent of the present invention, is a water swelling body (hydrogel) which may contain water, and thus contains water itself to maintain flexibility and to supply moisture to the skin continuously. It can enhance the skin transmittance of the components.

The film formed of the transdermal absorbent of the present invention can be easily removed by peeling by hand after drug delivery is completed, and can be more easily removed by swelling with water.

Claims (18)

50 to 99% by weight of the following polyurethane (A) and 1 to 50% by weight of the addition polymerization type polymer (B) having a carboxylic acid derivative functional group. (A) Polyurethane made by the polymerization reaction of the following components (a-1), (a-2) and (a-3) and having a weight average molecular weight of 10,000 to 500,000 represented by the following general formula (A): (a-1) polyethylene glycol; (a-2) polydiol having a hydroxy group at both terminals, more hydrophobic than the (a-1) polyethylene glycol; (a-3) diisocyanate having isocyanate groups at both terminals [Formula 1] (A) (In the above meal, m is an integer such that the weight average molecular weight of-(OCH ₂ CH ₂ ) m is 200 to 50,000; p and p ', which are the same as or different from each other, are integers such that the weight average molecular weight of the polyurethane is 10,000 to 500,000; q, q 'and q ", which are the same as or different from each other, are integers such that the weight average molecular weights of (R) q, (R) q' and (R) q" are 200 to 50,000; R is a substituent using one selected from the following or a mixture of two or more selected from the following: O (CH ₂ ) _n ; OCO (CH ₂ ) _n ; O-CO- (CH ₂ ) _n -CO-O- (CH ₂ ) _{n '} ; O (CH (CH ₃ ) (CH ₂ ) _n ) _{n '} ; O (C (CH ₃ ) ₂ (CH ₂ ) _n ) _{n '} (where n and n' are the same as or different from each other and are integers of 1 to 10); OCOCH (CH ₃ ) CH ₂ ; OSi (CH ₃ ) ₂ ; Or (OCH ₂ CH ₂ ) _x- (OCH (CH ₃ ) CH ₂ ) _y- (OCH ₂ CH ₂ ) _{x '} (where x, x' and y are the same as or different from each other, an integer from 1 to 100 to be.); R 'is a substituent using one selected from the following or a mixture of two or more selected from the following. (CH ₂ ) l (where l is an integer from 1 to 10); (B) The addition polymerization type polymer having a carboxylic acid derivative functional group includes a carboxylic acid alkyl ester of carboxylic acid and / or a carboxylic acid alkyl amide of carboxylic acid in the main chain or the side chain. / Or a polymer having a weight average molecular weight of 10,000 to 800,000 containing a carboxylic acid alkylaminoalkylester functional group. The film-forming agent according to claim 1, wherein the addition polymer type polymer (B) having the polyurethane (A) and the carboxylic acid derivative functional group can be dissolved therein and dissolved in a solvent applicable to the skin. The polymer according to claim 1, wherein the addition polymer type polymer (B) having a carboxylic acid derivative functional group has a polymer ester having a alkyl ester of carboxylic acid and / or an alkylamide of carboxylic acid and / or an alkylaminoalkyl ester function of carboxylic acid in the main chain or branched chain. As the monomer to impart the above functional group, acrylic acid ester / amide, methacrylic acid ester / amide, crotonic acid ester / amide, maleic acid A film former comprising at least 10% by weight of at least one monomer selected from the group consisting of maleic acid ester / amide, maleic anhydride and vinyl ester. The method of claim 3, wherein the acrylic ester monomer is methyl acrylate, ethyl acrylate, butyl acrylate, isobutyl acrylate, isobornyl acrylate, hydroxyethyl acrylate, 2-hydroxypropyl acrylate Selected; The acrylic acid amide monomer is selected from the group consisting of acrylamide, N-t-butyrylamide and octyl acrylamide; Methacrylic acid ester monomers are methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobuty methacrylate, 2-ethylhexyl methacrylate, lauryl methacrylate, hydroxyethyl methacrylate, 2 Hydroxypropyl methacrylate, dimethylaminoethyl methacrylate, t- Butylaminoethylmethacrylate; Methacrylic acid amide monomers are methacrylamidopropyl / trimethylammonium chloride; The maleic acid ester monomer is selected from the group consisting of methyl maleate, ethmaleate, isopropyl maleate, butyl maleate; The crotonic acid ester monomer is selected from the group consisting of methyl crotonate, ethyl crotonate, isopropyl crotonate, and butyl crotonate; The vinyl ester monomer is a film forming agent, characterized in that selected from the group consisting of vinyl acetate, vinyl propionate, vinyl neodecanoate. The polymer according to claim 1, wherein the polymer having a derivative functional group of carboxylic acid in the main chain or branched chain is poly (methylvinylether-co-maleic anhydride), poly (methylvinylether-co-maleic acid ethyl ester), poly (methyl Vinyl ether-co-maleic acid isopropyl ester), poly (methylvinylether-co-maleic acid butyl ester), poly (dimethylaminoethyl methacrylate-co-methacrylic acid ester), poly (methacrylic acid -co-methacrylic acid ester), poly (methacrylic acid ester-co-trimethylaminoethylmethacrylate), poly (acrylic acid-co-ethylacrylate-co-Nt-butyrylamide), poly (acrylic acid Ester-co-methacrylic acid ester), poly (octylacrylamide-co-butylaminoethylmethacrylate-co-acrylic acid (or ester)), poly (octylacrylamide-co-butylaminoethylmethacrylate -co-methacrylic acid (or S Le)), poly (octylacrylamide-co-acrylic acid (or ester)), poly (octylacrylamide-co-methacrylic acid (or ester)), poly (vinylacetate-co-crotonic acid), poly (vinylacetate -co-crotonic acid-co-vinylpropionate) film forming agent, characterized in that selected from the group consisting of. The film-forming agent according to claim 1, wherein the addition polymer type polymer (B) having a polyurethane (A) and a carboxylic acid derivative functional group is in a weight ratio of 50:50 to 99: 1. 3. The film former of claim 2, wherein the solvent is an aqueous alcohol solution. 8. The addition polymer type polymer (B) having the polyurethane (A) and the carboxylic acid derivative functional group is mixed and dissolved in the solvent in an amount of 0.1 to 50% by weight. Film formers. The method of claim 1, wherein (a-2) is polypropylene glycol, polybutylene glycol, polytetramethylene glycol, polyhexamethylene glycol, polypropenylene glycol and triple block air of polyethylene glycol and polypropylene glycol One polyalkylene glycol selected from the group consisting of copolymers; And a polycaprolactone diol, a polylactone diol, and a polyglycolic acid diol. The film former according to claim 1, wherein the component (a-3) is at least one selected from aromatic diisocyanates or aliphatic diisocyanates. The method according to claim 1, wherein when the film forming agent is applied to the skin to form a film, the film has a tensile strength of 0.5 MPa or more, an elongation% of 100% or more, and PSTC test A film forming agent, characterized in that the adhesion strength measured based on the peel adhesion test method of the method is more than 20 g / in. For stainless steel. The film former of claim 1; A solvent capable of dissolving the film former and applying it to the skin; And Active ingredients that can be delivered to the skin Percutaneous dosage form, characterized in that it contains. The method of claim 12, wherein the film former is present in an amount of 0.1 to 50% by weight based on the solvent, wherein the active ingredient is contained in an amount of 0.01 to 50% by weight based on the total weight of the formulation. Dosage Forms. The method according to claim 12 or 13, wherein the active ingredient capable of administering the skin comprises: nonsteroidal anti-inflammatory drugs; steroid; Local anesthetics; Antihistamines; Antibiotic; Antifungal agents; Antiviral agents; Skeletal muscle relaxants; Exfoliants; Acne treatments; Skin protectants; Vitamins A, B, C, D, E and pharmaceutically acceptable derivatives thereof; Skin whitening agents; Herbal extracts; Heparin sodium; Or one or two or more mixtures selected from capsaicin. 15. The method according to claim 14, wherein the active ingredient is ketoprofen, diclofenac diethyl ammonium, pyroxicam, flubiprofen, ketorolac tromethamine, sodium fucidic acid, capsaicin, dipropionate betamethasone, clotrimazole, genta sulfate Mycin, prednisolone, diphenhydramine hydrochloride, erythromycin, neomycin sulfate, heparin sodium, dexpanthenol, ketoconazole, terbinapine hydrochloride, acyclovir, tretinoin, benzoyl peroxide, A transdermal dosage form, characterized in that it is one or two or more selected from kojic acid, eferison hydrochloride, lidocaine hydrochloride, salicylic acid, lactic acid, urea, vitamin A, vitamin C, vitamin E, minoxidil or alatonin. The transdermal dosage form according to claim 12 or 13, further comprising at least one additive selected from skin absorption enhancers, softeners, moisturizers or water soluble polymers for enhancing viscosity and skin adhesion. The method of claim 16, wherein the skin absorption enhancer is higher fatty acid; Higher alcohols; Polyols; Higher fatty acid esters; Fatty acid esters of glycerin; Fatty acid ethers of polyethylene glycol; Fatty acid esters of polyethylene glycol; Fatty acid ethers of propylene glycol; Propylene glycol fatty acid esters; Sorbitan fatty acid esters; Polyethylene glycol sorbitan fatty acid esters; Terpenes; Sulfoxides; Pyrrolidones; Amides; Percutaneous dosage form, characterized in that one or more mixtures of ethoxydiglycol, N-hydroxy methyllide, sorbitol, urea, squalene, squalane, olive oil, pajama oil and derivatives thereof. 17. The transdermal dosage form according to claim 16, wherein the moisturizer or softener is a mixture of at least one selected from glycerin, polyethylene glycol, propylene glycol, 1,3-butanediol, lactic acid, mineral oil, lanolin, waxes or glucose derivatives.