KR20010100284A - Film-forming composition for transdermal delivery of active ingredients and percutaneous administration formulation containing the same - Google Patents

Abstract

The present invention relates to a film-forming agent for drug delivery that forms a film that is non-sticky to the skin and has excellent skin adhesion and elasticity, and a transdermal dosage form containing the film-forming agent and an active ingredient. In particular, the drug delivery film-forming agent of the present invention is better than polyurethane and polyethylene glycol and polyethylene glycol obtained from a reaction product of a polydiol having a hydroxy group at both ends and a diisocyanate having an isocyanate at both ends. It is characterized by containing a polyether obtained from the reaction product of a hydrophobic strong polydiol having a hydroxy group at both ends and an aliphatic diglycidyl ether having an epoxide group at both ends

Description

Film-forming composition for transdermal delivery of active ingredients and percutaneous administration formulation containing the same}

<Technical field to which the invention belongs>

The present invention relates to a film-forming agent for drug delivery to the skin, and to a transdermal dosage form containing the same, and more particularly, to a film containing polyurethane and polyether, which is essential, to form a film having excellent adhesion and elasticity. A transdermal dosage form for delivering an active substance through a film former and skin containing the same.

Conventional technology and its problems

Recently, studies on transdermal absorption formulations, which are absorption systems of drugs through the skin, are being actively conducted. Transdermal absorption formulations are agents that deliver active substances through the skin to the topical or systemic area.They are characterized by local action and the ability to maintain a relatively constant effective blood level in the liver that may be of concern during oral administration. The first pass effect of the can be avoided, and the discomfort and rejection at the time of injection administration can be reduced. In particular, drugs that cause adverse side effects in the digestive system such as NSAIDs and antibiotics can reduce these side effects. Such formulations include patching agents such as plata and cataplasmas, and semisolid agents such as ointments and gels.

Of these, the patch has the advantage of continuously delivering the active ingredient in the correct dosage, while not only appearance appearance when attached to the exposed site, but also has a problem of being easily detached when attached to the bent part of the human body. . In addition, since a separate support (cotton, film, release paper, etc.) is required, the cost burden is increased.

Other transdermal absorption formulations include coated semi-solids such as ointments or gels. Such a coating formulation can be applied regardless of the shape and area of the application site, and can be applied freely to the exposed site. In addition, when used frequently, the degree of irritation to the skin is lower than that of the patch that causes irritation by repeated attachment and detachment. As an example of such a drug carrier for application, US Patent No. 4393076 describes an anti-inflammatory analgesic gel formulation composition wherein the cellulose and carboxyvinyl polymers are used as the film forming agent. Korean Patent Publication No. 96-8225 discloses transdermal administration compositions such as anti-inflammatory analgesics, nicotine, and the like, using fast-drying film preparations using polyvinyl alcohol, polyvinylpyrrolidone, cellulose, and pectin. Patent Publication No. 97-5282 describes a gel preparation using poloxamer containing pyrionic acid-based nonsteroidal anti-inflammatory analgesic drugs.

However, in the case of application formulations, such as ointments or creams are sticky and adhere well and have the disadvantage of soiling clothes or socks, and in the case of formulations which form a non-stick coating, polyvinyl alcohol, polyvinylpyrrolidone, carboxymethyl It is formulated with polymers such as cellulose, sodium alginate, gelatin or pectin, but these polymers have low elongation, which hinders the movement of the body, and because of their high glass transition temperature, the film produced after drying hardens easily and crumbles and peels easily from the skin. Has the disadvantages of being.

On the other hand, polyurethane is a polymer having excellent biocompatibility and excellent stretch and strength, and has been widely used as a base for implantation of living bodies such as catheters and heart valves. In US Patent No. 5041100, a study was conducted to reduce the friction phenomenon caused by catheter insertion by modifying the surface of the catheter with polyurethane. US Patent No. 5017664 developed a biocompatible polyurethane to improve blood compatibility of medical devices. The research was conducted to increase. Research into the development of such a polyurethane as a base for external preparations has also been conducted. In the US Patent No. 4542012, a polyurethane base containing polyvinylpyrrolidone was developed to study an external antibacterial agent for delivering iodine, and a US Patent No. 4560555 The issue aims to develop a polyurethane film base that reacts directly with damaged skin as an external protective agent for drug delivery. WO 9914283 also proposes compositions which deliver active ingredients containing polymers, fatty acids or polyols of the polyurethane, acrylic ester and vinyl acetate type.

However, when only polyurethane is used as the film-forming base, there is a problem that the adhesive force of the base is insufficient and can be easily detached by repeated body movements.

Accordingly, the present invention is a problem with conventional film-forming transdermal dosage forms without the disadvantages of conventional ointments or gel formulations, namely, impedes movement of the body, crumbles after drying, peels off the skin, or weak adhesion. It is an object to provide a film-forming agent for drug delivery of a new composition which does not have the problem of easily falling off the skin.

The present invention also provides a new type of transdermal dosage form containing such film formers and active substances.

The film former of the present invention and the transdermal dosage form containing the same have the following characteristics that are distinguished from conventional external preparations.

The film former of the present invention is easily applied to the skin in a state dissolved in a solvent, and forms a film within a few minutes after the application, the film is thin and transparent, it is difficult to visually distinguish it is possible to apply continuously to the exposed area. And, the quickly formed film does not stain clothes or socks, and does not bury in other body parts. And when the transdermal dosage form containing this film former is apply | coated to skin, since the formed film | membrane is excellent in adhesiveness, it lasts for a long time at an application site, and releases an active ingredient, it exhibits the outstanding effect even with few application times.

Since the film forming agent of the present invention is composed of polyurethane having excellent elasticity and polyether having excellent adhesiveness, it is adhered well to the movement of the body even if formed on the skin flexion site, and does not inconvenience the movement and is continuously attached. In addition, it has a low glass transition temperature below room temperature, and thus has the flexibility to match body movement at room temperature.

Polyurethane and polyether constituting the film-forming agent of the present invention can be mixed without phase separation because they have the same backbone, have excellent compatibility and stability, and also because they are a multi-block copolymer having both a hydrophilic part and a hydrophobic part, It is excellent in blending with hydrophobic drugs and can be mixed with various skin absorption enhancers.

The film-forming agent of the present invention is a water swelling body (hydrogel) that can contain moisture, which itself contains moisture to maintain flexibility, and can continuously supply moisture to the skin to enhance skin permeability of the active ingredient. have.

The film formed of the transdermal absorbent of the present invention can be easily peeled off or removed by swelling in water after drug delivery is completed.

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

A film former means a polymer that forms a film on the skin itself, that is, a polyurethane (A) and a polyether (B), which forms a film that is not sticky to the skin and has excellent skin adhesion and elasticity.

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

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

A polyurethane / polyether film means the film formed by apply | coating the said film former on the surface, such as skin.

In the present invention, by blending the polyurethane and the polyether excellent in the adhesive force constituting the main chain of the same component it was intended to simultaneously give the stretching and adhesion to the film formed when the skin is applied. In addition, since the polyether and polyurethane of the present invention contain the same main chain, they can be sufficiently mixed without imparting phase separation to impart stability of the base. At the same time, the release of the active ingredient can be effectively achieved with sufficient swelling of each polymer ingredient.

In order to overcome the disadvantages of poor adhesion caused by using polyurethane alone, polyacrylates or polyvinyl birrolidones, which have been used for film formers, may be used. There is a problem in compatibility because it is different from polyurethane. Although apparently homogeneous, the physical and chemical properties of the polyurethane and the added third polymer do not sufficiently swell the main chain, thereby limiting the release through the base of the active ingredient. Therefore, in this invention, this problem was solved by using the polyether which has a general formula (B) mentioned later with polyurethane.

The film-forming agent having skin adhesion according to the present invention consists essentially of the following (A) 10-90 weight of polyurethane and (B) 10-90 weight of polyether.

(A) Polyurethanes produced by the polymerization of the following components (a-1), (a-2) and (a-3) and having a weight average molecular weight of 10,000-500,000 represented by the following general formula:

(a-1) polyethylene glycol;

(a-2) polydiol having a hydroxy group at both terminals having a higher hydrophobicity than the above (a-1) polyethylene glycol;

(a-3) diisocyanate having an isocyanate group at the sock end

(A)

In the above formula,

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 'are the same or different integers such that the weight average molecular weight of the polyurethane is from 10,000 to 500,000;

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

R uses one of the following or a combination of two or more of 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 or different integers from 1 to 10; OCOCH (CH ₃ ) CH ₂ ; OSi (CH ₃ ) ₂ ; (OCH ₂ CH ₂ ) x- (OCH (CH ₃ ) CH ₂ ) y- (OCH ₂ CH ₂ ) x ', wherein x, x' and y are the same or different integers from 1 to 100, inclusive;

R 'uses one selected from the following or a mixture of two or more selected from the following

(CH ₂ ) _l (where l is an integer of 1 or more and 10 or less);

(B) a polyether produced by the polymerization of the following components (b-1), (b-2) and (b-3) and having a weight average molecular weight of 6,000-500,000 represented by the following general formula:

(b-1) polyethylene glycol;

(b-2) polydiol having a hydroxy group at both terminals having a higher hydrophobicity than the (b-1) polyethylene glycol;

(b-3) Aliphatic diglycidyl ether having an epoxide group at the sock end

(B)

In the above formula,

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 'are the same or different integers such that the weight average molecular weight of the polyether is from 6,000 to 500,000;

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

R uses one selected from the following or a mixture of two or more selected from

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 or different integers from 1 to 10; OCOCH (CH ₃ ) CH ₂ ; OSi (CH ₃ ) ₂ ; (OCH ₂ CH ₂ ) x- (OCH (CH ₃ ) CH ₂ ) y- (OCH ₂ CH ₂ ) x ', wherein x, x' and y are the same or different integers from 1 to 100, inclusive;

R 'uses one selected from the following or a mixture of two or more selected from the following

CH ₂ -O- (CH ₂ ) ₁ -O-CH ₂ ; CH ₂ —O—CH ₂ CH (CH ₃ ) —O—CH ₂ ; CH ₂ O— (CH ₂ CH ₂ O) ₁ —CH ₂ ; CH ₂ O— (CH ₂ CH (CH ₃ ) O) ₁ —CH ₂ ; (CH ₂ ) _l (wherein l is an integer of 1 or more and 10 or less).

Polyurethanes or polyethers of the present invention are a variety of polyurethanes or polyethers synthesized by entering different R or R 'in one molecule, that is, R and R' are two or more different structures You can use what you have.

According to one aspect of the invention, polyurethane (A) and polyether (B) are synthesized using a polymer (polyol) having hydroxyl groups at both ends of two different hydrophilic. That is, in the case of polyurethane (A), (a-1) and (a-2) are used, and in the case of polyether (B), (b-1) and (b-2) are used. The first polyols (a-1) and (b-1) impart hydrophilicity to the film former as polyethylene glycol to determine the water functionality of the film former formed from the film former composition of the present invention. Polyethylene glycol (a-1) (b-1) is the total weight of (a-1) + (a-2) + (a-3) or (b-1) + (b-2) + (b-3) It is preferable that it is contained in the quantity of 10-90 weight with respect to, and its molecular weight is 200-50000, Preferably it is 1000-5000.

The second polyol (a-2) (b-2) is a hydrophobic polymer stronger than polyethylene glycol, for example, polypropylene glycol, polybutylene glycol, polytetramethylene glycol, polyhexamethylene glycol, polypropylene glycol , Or triple block copolymers of polyethylene glycol and polypropylene glycol (trade name Pluronic Polyalkylene glycols such as; 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) (b-2) is of (a-1) + (a-2) + (a-3) or (b-1) + (b-2) + (b-3) It is preferable that it is contained in the quantity of 10-90 weight with respect to a gross weight, It is preferable that molecular weight is 200-50000, Preferably it is 1000-5000.

As a molecule | numerator (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-phenylene diisocyanate, 4-methoxy- m-phenylene diisocyanate, 4-butyl-m-phenylene diisocyanate, m-phenylene diisocyanate, p-phenylene diisocyanate, m-xylene diisocyanate, p-xylene diisocyanate, cumene diisocyanate, duren 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-diphenylhexane-1,6-diisocyanate, 3,3'-dimethoxy-4,4'-biphenylene diisocyanate, etc. Aromatic diiso Acrylate and methylene diisocyanate, ethylene diisocyanate, trimethylene-Ω, Ω'-diisocyanate, tetramethylene-Ω, Ω'-diisocyanate, pentamethylene-Ω, Ω'-diisocyanate, hexamethylene -Ω, Ω'-diisocyanate, octamethylene-Ω, Ω'-diisocyanate, non-methylene-Ω, Ω'-diisocyanate, decamethylene-Ω, Ω'-diisocyanate, 2-chloro-trimethyl Aliphatic diisocyanates, such as a rendiisocyanate, 2, 3- dimethyl tetramethylene diisocyanate, and a methylene bis (p-cyclohexyl isocyanate), can be used individually or in mixture. The number of moles of diisocyanate (a-3) used is the same as the sum of the number of moles of polyethylene glycol (a-1) and the number of moles of polydiol (a-2) that is more hydrophobic than polyethylene glycol. . Among the diisocyanates listed above, toluene diisocyanate, diphenylmethane-4,4'-diisocyanate, pentamethylene-Ω, Ω'-diisocyanate, hexamethylene-Ω, Ω'-diisocyanate, octa Methylene- ?,? '-Diisocyanate, and methylene bis (p-cyclohexyl isocyanate) may be used alone or in combination.

As a molecule | numerator (b-3) which has a diepoxy group used for the synthesis | combination of a polyether (B), ethylene glycol diglycidyl ether, butanediol diglycidyl ether, neopentyl diglycidyl ether, poly ethylene glycol diglycidyl Alkylene glycol diglycidyl ether, such as an ether and polypropylene glycol diglycidyl ether, or 1,2,3,4- diepoxy butane, 1,2,7,8- diepoxy octane, 1,2,9 Diepoxy alkanes, such as a 10-diepoxy decane, can be used individually or in mixture.

The number of moles of the molecule (b-3) having a diepoxy group is the same as the sum of the number of moles of the polyethylene glycol (b-1) and the number of moles of the polydiol (b-2), which is more hydrophobic than the polyethylene glycol, used in the synthesis of the polyether. Is used. Of the molecules having a diepoxy group listed above, preferably, ethylene glycol diglycidyl ether, butanediol diglycidyl ether, polyethylene glycol diglycidyl ether, and polypropylene glycol diglycidyl ether may be used alone or in combination. have.

The weight average molecular weight of the polyurethane (A) described above is 10,000 to 500,000, 30,000 to 300,000 is good in order to have a desirable elongation, flexibility and strength, polyether (B) is preferably a weight average molecular weight of 6,000 to 500,000, Preferably it is 10,000-300,000.

Obtaining a polyurethane (A) or a polyether (B) having desired physical properties from each of the monomers described above can be carried out using polymerization methods well known to those skilled in the art. Polyurethane (A) can be synthesized through known synthesis methods known to those skilled in the art. For example, Lamba et al. Are described in detail in Polyurethanes in biomedical applications (New York, CRC Press, 1998). In the present invention, in order to synthesize the polyurethane (A), a polydiol (a-1) and a polydiol (a-2) having a hydroxyl group at both ends having a stronger hydrophobicity than polyethylene glycol are prepared at a desired ratio, and two poly The same molar number ((a-1) + (a-2)) of diisocyanate (a-3) is prepared to carry out condensation polymerization. The reaction is carried out under heating conditions of at least room temperature, preferably at a temperature from room temperature to 80 ° C., and the appropriate reaction temperature is determined depending on the type and amount of the reactants and the 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.

Polyethers (B) can be synthesized through well-known synthesis methods known to those skilled in the art, for example, described in detail in Journal of applied polymer science, 13, 1473 (1969) by Aivery et al. In the present invention, in order to synthesize the polyether (B), a polydiol (b-1) and a polydiol (b-2) having a hydroxy group at both ends having a hydrophobicity stronger than that of the polyethylene glycol are prepared in a desired ratio, and two poly The same mole number ((b-1) + (b-2)) of diepoxide (b-3) is prepared and condensation polymerization is carried out. The reaction is carried out under heating conditions of at least room temperature, preferably at a temperature from room temperature to 100 ° C., and the appropriate reaction temperature is determined depending on the type and amount of the reactants and the catalyst. Catalysts, for example borontrifluoride die ether ether, 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.

The film former according to the invention essentially contains 10-90 weight of polyurethane (A) and 10-90 weight of polyether (B). Preferably it contains essentially 50 to 90 weight of polyurethane (A) and 10 to 50 weight of polyether.

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 a mixed solution of water and ethanol is used as the solvent, 1 to 90 ethanol is used, preferably 10 to 70 is preferable. The content of the film former (A + B) in the solvent is preferably 0.1 to 50, preferably 1 to 30. If the content is less than 0.1, it is difficult to form a film of a suitable thickness, and if it contains more than 50 film-forming agent, it is difficult to spread the high viscosity.

The tensile strength, Young's modulus and elongation of the film formed from the film former of the present invention obtained through the blending of polyurethane (A) and polyether (B) are the 'plastic materials' of the ASTM test method. It was measured according to the 'standard test method for measuring the tensile force of, and the adhesion force was measured based on the peel adhesion test method of the PSTC test method. The physical properties of the film have the following characteristics at temperatures above -20 ℃. It is preferable that tensile strength is 0.5-100 Mpa, Preferably it is 1-50 Mpa. If the tensile strength is 0.5 MPa or less, the strength is insufficient, so that the film breaks in the middle of the film removal, making it difficult to remove the film easily and neatly. In addition, when having a tensile strength of 100 MPa or more, discomfort and rejection are impeded by disturbing the movement of the portion where the film is formed. Young's modulus is preferably 0.1 to 80 MPa, preferably 1 to 50 MPa.

Meanwhile, the following expression:

{(Length of specimen at break point-length of original specimen) /

Length of original specimen} X 100)

The elongation indicated by is preferably at least 30 and not more than 5000. Adhesion of 20 to 3000 g / in. For stainless steel gives proper adhesion to skin but does not give stickiness.

Transdermal dosage formulations provided according to another aspect of the invention include the above polyurethanes (A) and polyethers (B); A solvent which can dissolve the polyurethane (A) and the polyether (B) and is applicable to the skin; 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 thereof; Nifedipine, verapamil, diltiazem and the like of calcium blockers and pharmaceutically acceptable derivatives thereof; Other cardiovascular drugs such as 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 of the male hormone and the like 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; Antibiotics gentamicin, erythromycin, neomycin, fusidic acid and the like and pharmaceutically acceptable derivatives thereof; Antifungal agents econazol, 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; Ephericone hydrochloride, toferrisone 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 their pharmaceutically acceptable derivatives, such as tretinoin, isotretinoin, retinol, retinoic acid, ascorbic acid, tocopherol; Nicotine and its pharmaceutical tongue derivatives used as smoking cessation aids; 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 the range of 0.01 to 50 of the total weight of the formulation.

In addition, the transdermal dosage form of the present invention is a skin absorption enhancer for enhancing skin permeation of the above-mentioned effective ingredient, and includes 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 to 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. Preferably, it is 1-30. Below 0.1, the effect is not sufficient, and a content above 50 will cause excessive stickiness or slippery in the formulation.

Furthermore, the preparation of the present invention may contain polycarboxylic acid, cellulose, alginic acid, pectin, hyaluronic acid and derivatives thereof, which are water-soluble polymers for enhancing adhesion to the skin, if necessary, in which case the content is based on the total weight of the preparation. Can be selected within the range of 0.1 to 10.

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

Example 1 Synthesis of Polyurethane (A)

10 g of polystyrene glycol having a molecular weight of 1000 having a hydroxy group and 20 g of polytetramethylene glycol having a molecular weight of 2000 were vacuum dried to remove water, and then added to 500 ml of tetrahydrofuran (THF) purified under Na. Dissolved. 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 with a Teflon stirrer at 60-70 ° C. for 24 hours. The composite was precipitated in excess distilled water and dried in a 50 ℃ vacuum oven for 2 days.

Examples 2 to 7 Synthesis of Polyurethane (A)

A series of polyurethane series was synthesized using the same experimental method as in Example 1. The molecular weights of each of the polyethylene glycol and polytetramethylene glycol used are shown in Table 1.

Composition of Polyurethane (A) Example Polyethylene glycol Polytetramethylene glycol Use molar ratio One 1000 2000 1: 1 2 1000 1000 1: 1 3 1500 1000 1: 1 4 1500 2000 1: 0.5 5 2000 2000 1: 1 6 3400 2000 1: 1 7 4600 2000 1: 1

Example 8 Synthesis of Polyurethane (A)

Triblock copolymer of 35 g of polyethylene glycol having a hydroxyl group at both terminal groups and a molecular weight of 1500 g and a polypropylene glycol having a molecular weight of 1100 and polypropylene glycol (trade name Pluronic 10 g of BASF) was dried in vacuo to remove moisture, and then dissolved in 500 ml of tetrahydrofuran purified as Na. 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 to 70 ° C. The composite was precipitated in excess distilled water and dried in a 50 ℃ vacuum oven for 2 days.

Example 9 Synthesis of Polyurethane (A)

40 g of polyethylene glycol having a molecular weight of 2000 having a hydroxy group and 10 g of polytetramethylene glycol having a molecular weight of 1000 were dried under vacuum to remove water, and then added to 500 ml of tetrahydrofuran purified 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 continuous stirring with a Teflon stirrer at 60 to 70 ° C. . The composite was precipitated in excess distilled water and dried in a 50 ℃ vacuum oven for 2 days.

Example 10 Synthesis of Polyurethane (A)

20 g of polystyrene glycol having a molecular weight of 2000 having a hydroxy group and 20 g of poly-ε-caprolactonediol having a molecular weight of 2000 were dried in vacuo to remove water, and then dissolved in 500 ml of THF purified as 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 the reaction was continued with a Teflon stirrer at 60 to 70 ° C for 24 hours. The composite was precipitated in excess distilled water and dried in a 50 ℃ vacuum oven for 2 days.

Example 11 Synthesis of Polyether (B)

50 g of polystyrene glycol having a molecular weight of 2000 having a hydroxy group and 50 g of polytetramethylene glycol having a molecular weight of 2000 were dried under vacuum to remove water, and then added to 1 L of purified THF under Na to dissolve. 0.15 g of boron trifluoride diether etherate and 10.66 ml of butanediol diglycidyl ether were added to the solution, and the mixture was stirred at 45 ° C. with a Teflon stirrer for 72 hours. The composite was precipitated in hexane. The precipitated compound was washed several times with hexane and distilled water and then dried in a vacuum oven for 2 days.

Examples 12 to 13 Synthesis of Polyether (B)

Another polyether was synthesized using the same experimental method as in Example 11. The molecular weights of polyethylene glycol and polytetramethylene glycol used are shown in Table 2.

Composition of Polyether (B) Example Polyethylene glycol Polytetramethylene glycol Use molar ratio 11 2000 2000 1: 1 12 1000 1000 1: 1 13 3400 2000 1: 1

Example 14 Synthesis of Polyether (B)

50 g of polystyrene glycol having a molecular weight of 2000 having a hydroxy group and 50 g of polyhexamethylene glycol having a molecular weight of 2000 were dried under vacuum to remove moisture, and then dissolved in 1 L of purified THF under Na. 0.15 g of boron trifluoride die ether ether and 4.4 g of 1,2,3,4-diepoxybutane were added to the solution, and the mixture was stirred at 45 ° C. with a Teflon stirrer for 72 hours. The composite was precipitated in hexane. The precipitated compound was washed several times with hexane and distilled water and then dried in a vacuum oven for 2 days.

Example 15 Synthesis of Polyether (B)

50 g of polystyrene glycol having a molecular weight of 2000 having a hydroxy group and 50 g of a polylactonediol having a molecular weight of 2000 were dried in vacuo to remove water, and then added to 1 L of THF purified as Na to dissolve. 0.2 g of boron trifluoride die ether ether and 12 g of polyethylene glycol (200) diglycidyl ether were added to the solution, followed by 72 hours of stirring at 45 ° C. with a Teflon stirrer. The composite was precipitated in hexane. The precipitated compound was washed several times with hexane and distilled water and then dried in a vacuum oven for 2 days.

Example 16

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) Polyurethane (A) of Example 1 Polyether ketopropene ethoxydiglycol menthol glycerin polyethylene glycol 40050% ethanol aqueous solution of Example 11 Appropriate amount to be 9131223 100%

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, ketoprofen, ethoxydiglycol, menthol, glycerin, and polyethylene glycol are added to 20 parts of ethanol aqueous solution, and it melt | dissolves. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid and stirred until uniform.

Example 17

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) Polyurethane film former of Example 1 Polyether film former of Example 11 Diclofenac diethyl ammonium polyoxy ethylene sorbitan monooleate (Twin 80) Dimethyl sulfoxide glycerin polyethylene glycol 40040% ethanol aqueous solution Appropriate to be 8313525 100%

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, diclofenac diethyl ammonium, tween 80, dimethyl sulfoxide, glycerin, and polyethylene glycol 400 are added to 20 parts of ethanol aqueous solution, and it is dissolved by stirring. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid and stirred until uniform.

Example 18

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) Polyurethane (A) of Example 2 Polyether (B) pyrocampham polyethylene glycol of Example 11 (2) lauryl ether dimethyl sulfoxide glycerin propylene glycol polyethylene glycol 40090 ethanol aqueous solution Appropriate to be 730.525235100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, pyoxycamp, polyethylene glycol (2) lauryl ether, dimethyl sulfoxide, glycerin, propylene glycol, and polyethylene glycol 400 are added and stirred in 20 parts of ethanol aqueous solution. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid and stirred until uniform.

Example 19

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) Polyurethane (A) of Example 1 Polyether (B) Flubipropene capsaicin methyllaurate d of Example 12, I-campaglycerin d, I-methol polyethylene glycol 40080 ethanol aqueous solution Appropriate to be 5540.02525235100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, flubipropene, capsaicin, methyllaurate, d, l-campa, glycerin, d.l-menthol, and polyethylene glycol 400 are added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid and stirred until uniform.

Example 20

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) Polyurethane (A) of Example 2 Polyether (B) Ketorolac tromethamine glycerol monolaurate cerafil-31 glycerin d of Example 11, I-menthol polyethylene glycol 40050 ethanol aqueous solution Appropriate to be 85525235100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. Meanwhile, ketorolac tromethamine, glycerol monolaurate, cerafil-31, glycerin, d, l-menthol, and polyethylene glycol 400 are added to 20 parts of ethanol aqueous solution, and dissolved by stirring. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid and stirred until uniform.

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) Polyurethane (A) of Example 2 Polyether (B) Fushidic acid sodium polyethylene glycol laurate olive oil glycerin polyethylene glycol 40030 ethanol aqueous solution of Example 13 The right amount to be 8221123100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, sodium fucidic acid, polyethylene glycol laurate, olive oil, glycerin, and polyethylene glycol are added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid 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) Polyurethane (A) of Example 3 Polyether (B) dipropionate betamethasone clotrimazole gentamicin N-methyl-2-pyrrolidoneglycerine polyethylene glycol 40050 ethanol aqueous solution of Example 11 The right amount to be 640.06410.1123100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, dipropionate betamethasone, clotrimazole, gentamicin, N-methyl-2-pyrrolidone, glycerin, and polyethylene glycol are added to 20 parts of ethanol aqueous solution, and it melt | dissolves. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid 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) Polyurethane (A) of Example 3 Polyether (B) Prednisolone hydrochloride diphenhydramine sulfate neomycin isopropyl myristate glycerin polyethylene glycol 40060 ethanol aqueous solution of Example 12 Appropriate to be 850.50.10.5233100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, prednisolone, diphenhydramine hydrochloride, neomycin sulfate, isopropyl myristate, glycerin and polyethylene glycol are added to 20 parts of ethanol aqueous solution, and it melt | dissolves. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid 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) Polyurethane (A) of Example 4 Polyether (B) Heparin sodium dexpanthenyl methyl sulfoxide glycerin propylene glycol 40 ethanol aqueous solution of Example 11 The right amount to be 1030.42.51532100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, heparin sodium, dexpanthenol, dimethyl sulfoxide, glycerin, and propylene glycol are added to 20 parts of ethanol aqueous solution, and it melt | dissolves. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid 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) Polyurethane (A) of Example 4 Polyether (B) ketoconazole sorbitol monolaurate of Example 12 (span 20) glycerin propylene glycol 40 ethanol aqueous solution Appropriate to be 652132 100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. Meanwhile, ketoconazole, sorbitol monolaurate, glycerin, and propylene glycol are added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid 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) Polyurethane (A) of Example 5 Polyether (B) Acyclover polyethylene glycol 600 glycerin propylene glycol 40 ethanol aqueous solution of Example 11 The right amount to be 555532100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. Meanwhile, acyclovir, polyethylene glycol, glycerin, and propylene glycol are added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid 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) Polyurethane (A) of Example 5 Polyether (b) Tretinoin glycerol monooleate glycerine propylene glycol 70 ethanol aqueous solution of Example 12 The right amount to be 20100.025132100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, tretinoin, glycerol monooleate, glycerin, and propylene glycol are added to 20 parts of ethanol aqueous solution, and it dissolves by stirring. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid and stirred until uniform.

Example 28

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) Polyurethane (A) of Example 6 Polyether (B) benzoyl peroxide sorbitan monooleate (Span 80) of sorbitol menthol glycerin propylene glycol 40 ethanol in Example 11 Appropriate to be 751012132100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, and it melt | dissolves, stirring. Benzoyl peroxide, sorbitan monooleate, sorbitol, menthol, glycerin and propylene glycol are added to 20 parts of ethanol aqueous solution, and it melt | dissolves. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid 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) Polyurethane (A) of Example 6 Polyether (B) Ethoxydiglycol sorbitol glycerin propylene glycol 30 ethanol aqueous solution of Example 14 Appropriate to be 10513232100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, and it melt | dissolves, stirring. Kojic acid, ethoxydiglycol, sorbitol, glycerin and propylene glycol are added to 20 parts of ethanol aqueous solution, and it melt | dissolves by stirring. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this solution and stirred until homogeneous.

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) Polyurethane (A) of Example 8 Polyether (B) hydrochloride acid Esperisonlauryl diethanolamide limonene glycerin propylene glycol 50 ethanol aqueous solution of Example 15 Appropriate to be 255101332100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, 20 parts of ethanol aqueous solution is added eferison, lauryl diethanolamide, limonene, glycerin, and propylene glycol, and it melt | dissolves. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid 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) Polyurethane (A) of Example 7 Polyether (B) Lidocaine Glycerin 30 Ethanol Aqueous Solution of Example 15 Appropriate to be 3123100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, lidocaine hydrochloride and glycerin are added to 20 parts of ethanol aqueous solution, and it melt | dissolves by stirring. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid 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) Polyurethane (A) of Example 10 Polyether (B) Urea salicylic acid urea vitamin E glycerin 1,3-butanediol Polyethylene glycol 40040 ethanol aqueous solution of Example 15 Appropriate to be 8616.716.732225100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, salicylic acid, lactic acid, urea, vitamin E, glycerin, 1,3-butanediol, and polyethylene glycol are added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid and stirred until uniform.

Example 33

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) Polyurethane of Example 1 (A) Polyether of Example 14 (B) Minoxidildex panthenol Polyethylene glycol (10) Monolaurate glycerin Polyethylene glycol 40040 Ethanol aqueous solution Proper to be 10631.5358100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. Meanwhile, minoxidil, dexpanthenol, polyethylene glycol (10) monolaurate, glycerin, and polyethylene glycol are added to 20 parts of ethanol aqueous solution, followed by stirring to dissolve. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid 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) Polyurethane (A) of Example 9 Polyether (B) of Example 11 Alatonin Dimethicone Camperglycerin Polyethylene Glycol 40040 Ethanol Aqueous Solution The right amount to be 155120.558100

Polyurethane (A) and polyether (B) are added to 40 parts of ethanol aqueous solution, stirred, and dissolved to obtain an aqueous film former solution. On the other hand, alatonin, dimethicone, camphor, glycerin and polyethylene glycol are added to 20 parts of ethanol aqueous solution, and it melt | dissolves. This solution is slowly added to the aqueous solution in which the film former is dissolved while stirring. The remaining amount of aqueous ethanol solution is added to this liquid and stirred until uniform.

Test Example 1 Confirmation of Structure of Film Forming Agent

NMR spectrum was used to confirm the structure of the polyurethane and polyether 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 a polyurethane obtained by polymerizing polytetramethylene glycol as (a-2) and hexamethylene diisocyanate and (a-1) polyethylene glycol as (a-3), which are representative examples of the polyurethane according to the present invention, 3.6 ppm (multiple) of -OC H ₂ C H ₂ -of glycol, 4.2 ppm (triplet) of -OCH ₂ C H ₂ O-CONH- of the terminal linked to the urethane group, -OC H of polytetramethylene glycol 3.4 ppm (multiple) of ₂ (CH ₂ ) ₂ C H _2- , 4.1 ppm (triplet) of -OCH ₂ CH ₂ CH ₂ C H ₂ O-CONH- of the terminal portion connected to the urethane group, and hexamethylene diisocyanate. -OCNH-C H ₂ (CH ₂ ) ₄ C H ₂ -NHCO- is 3.1 ppm (multiple), -OCNH-CH ₂ (C H ₂ ) ₄ CH ₂ -NHCO- and -OCH of polytetramethylene glycol The peak of ₂ (C H ₂ ) ₂ CH ₂ -was measured over 1.3-1.7 ppm (multiple).

Furthermore, in the case of the polyether obtained by polymerizing polytetramethylene glycol and (b-1) polyethylene glycol as (b-2) which is a representative polyether according to the present invention, -OC H ₂ C H ₂ -of polyethylene glycol is 3.6 ppm (multiple), -OC H ₂ (CH ₂ ) ₂ C H ₂ -of polytetramethylene glycol, 3.4 ppm (multiple), -OCH ₂ (C H ₂ ) ₂ CH ₂ -has a peak of 1.3 It was measured over ˜1.7 ppm (multiple).

These results are independent of the molecular weight of the synthesized polyurethane / polyether or the molecular weight of polyethylene glycol and polytetramethylene glycol.

Test Example 2 Confirmation of Molecular Weight of Polyurethane and Polyether

The molecular weight of the polyurethane or polyether synthesized in Example 1-15 was measured. The film former was dissolved in THF at a concentration of 0.05 and the molecular weight was measured using gel permeation liquid chromatography (GPC). The results are shown in Table 3.

Gel Permeation Liquid Chromatography (GPC) Assay Conditions

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

Mobile phase: THF

Flow rate: 1ml / min

Detector: Refractometer (Differential Refractometer 410 by Waters)

Molecular Weight of Polyurethane / Polyether Example Molecular Weight Molecular weight distribution (polydispersity) One 200,000 2.9 2 108,000 2.2 3 150,000 2.8 4 120,000 2.4 5 220,000 2.3 6 115,000 2.6 7 98,000 2.3 8 70,000 1.5 9 110,000 2.4 10 131,000 1.5 11 29,000 1.2 12 31,000 2.1 13 25,000 1.9 14 41,000 2.4 15 33,000 2.1

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

The physical properties (tensile strength, elongation, Young's modulus) of the drug delivery polyurethane / polyether film formed through the blending of the polyurethane and polyether of the present invention were measured. For comparison, the physical properties of the film formed from polyurethane alone, the film formed from polyether alone and the polyvinyl alcohol (PVA) film were also measured in the same manner. In accordance with ASTM-D-638M specification of the ASTM standard test method was measured using a universal testing machine (UTM), a universal testing machine (HOUNSFIELD H25K-S).

In order to fabricate the specimen, the polyurethane of Example 1 and the polyether of Example 11 were dissolved in acetone at a concentration of 7 wt in various mixing ratios, dissolved, cast on release paper, and dried to have a thickness of 100 to 200 μm. . To prepare a polyvinyl alcohol specimen, 11 g of PVA 217 (Wako) and 4 g of PVA 205 (Wako) were added to 75 g of purified water, and the solution was heated to 50 ° C. to completely dissolve it. The solution was cooled to room temperature, and again, 10 g of ethanol was added thereto, sufficiently stirred to dissolve, cast, and dried to have a thickness of 100 to 200 μm. The resulting film was cut in the same manner as the Type M-III specimens specified in ASTM-D-638M, and pulled at a speed of 20 mm / min with a universal testing machine, and the tensile strength and elongation ratio (elongation = {(test specimen at break point). Length of original specimen) / length of original specimen} X 100) and Young's Modulus were measured.

Young's modulus, tensile strength, elongation of polyurethane / polyether film Compounding ratio () Young's Modulus (MPa) Tensile Strength (MPa) kidney() Polyurethane Polyether 100 0 41 35 3800 70 30 26 22 3100 60 40 21 16 2800 50 50 19 9 1700 40 60 19 4 1000 30 70 18 2 200 0 100 10 0.4 20 Polyvinyl alcohol film 3502 126 4

Test Example 4 Adhesion Check Test (Peel adhesion test)

An experiment was conducted to confirm the adhesion of the polyurethane / polyether film for drug delivery formed through the blending of the polyurethane and polyether of the present invention. It measured using the universal testing machine (INSTRON, Autograph DSC-500, Shimadzu) based on PSTC test method. In order to fabricate the specimen, the polyurethane of Example 1 and the polyether of Example 11 were dissolved in an aqueous solution of 70 ethanol at a concentration of 15 wt in various mixing ratios, dissolved, cast on a stainless steel base, and 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.

Adhesion of Polyurethane / Polyether Film Compounding ratio () Adhesive force (g / in.) Polyurethane Polyether 100 0 15 70 30 200 60 40 800 50 50 700 40 60 1200 30 70 1300 0 100 1400

As the compounding ratio of the polyether added to give the adhesion increased, the adhesion of the film increased. That is, it can be seen that the adhesion to the base is increased by the polyether.

[Test Example 5] Skin adhesion duration confirmation experiment of the polyurethane / polyether film

Experiments were conducted to confirm the adherence persistence in the flexion site of the drug delivery polyurethane / polyether film former formed through the blending of the polyurethane and polyether of the present invention. As a comparison base of the adhesive force, the film former made of the polyurethane alone of Example 1 and polyvinyl alcohol (PVA) were used. The polyurethane film former of Example 1 (7 wt) and the polyether film former (3 wt) of Example 11 were added to and dissolved in an aqueous 60 ethanol solution to prepare a film former through blending of polyurethane and polyether. For comparison, the polyurethane film former (10 wt) of Example 1 was added to and dissolved in an aqueous 60 ethanol solution to prepare a polyurethane film former. PVA 217 (Wako, 7 wt) and PVA 205 (Wako, 3 wt) were added and dissolved in an aqueous 20 ethanol solution to prepare a film former.

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 of the film-forming areas were repeated 60 times / minute to measure the change in time and properties until the film was detached. The results are shown in Table 6.

Polyurethane Polyether Film Forming Agent Polyurethane Polyvinyl alcohol film former 3 minutes Lifted along skin texture and outside area -15 minutes Uplift from the outside Over 50 area peeling of the formed film -30 minutes Uplift from the outside ~ 1 hour Less than 10 peeling of the formed film 50 area peeling of formed film Over 90 area peeling of the formed film

Test Example 6 Skin Stimulation Experiment

The polyurethane of Example 1 and the polyether of Example 11 were added to and dissolved in 50 ethanol aqueous solution so as to be 10 wt, respectively, to prepare a sample for checking skin irritation. 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 former was evenly applied to the forearm region of 10 healthy adult men who had previously been marked with a size of 9 cm 2. After 30 minutes had evaporated, the coating layer was protected using an adhesive cloth after the solvent was dried. After 24 hours, the applied forming agent was removed, and the degree of primary irritation at the application site was determined according to the following criterion, and the reactivity was calculated from the following equation.

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

The observed degree of stimulation is calculated using the following equation.

Reactivity () = [{Sum of Number of Responders Х Judgment Number} Х100] / (Number of Testers Х4)

The reactivity of the polyurethane and polyether film formers was 1.5 and 1.9, respectively, thus showing 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.

Claims (15)

A skin-adhesive film former consisting essentially of the following polyurethane (A) 10-90 weight and polyether (B) 10-90 weight. (A) Polyurethane having a weight average molecular weight of 10,000-500,000 made by polymerization of the following components (a-1), (a-2) and (a-3) and represented by the following general formula (A): (a-1) polyethylene glycol; (a-2) polydiol having a hydroxy group at both terminals having a higher hydrophobicity than the above (a-1) polyethylene glycol; (a-3) diisocyanate having an isocyanate group at the sock end (A) In the above formula, 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 'are the same or different integers such that the weight average molecular weight of the polyurethane is from 10,000 to 500,000; q, q 'and q' 'are the same or different integers such that the weight average molecular weights of (R) q, (R) q' and (R) q '' are from 200 to 50,000; R uses one of the following or a combination of two or more of 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 or different integers from 1 to 10; OCOCH (CH ₃ ) CH ₂ ; OSi (CH ₃ ) ₂ ; (OCH ₂ CH ₂ ) x- (OCH (CH ₃ ) CH ₂ ) y- (OCH ₂ CH ₂ ) x ', wherein x, x' and y are the same or different integers from 1 to 100, inclusive; R 'uses one selected from the following or a mixture of two or more selected from the following (CH ₂ ) _l (where l is an integer of 1 or more and 10 or less); (B) a polyether produced by the polymerization of the following components (b-1), (b-2) and (b-3) and having a weight average molecular weight of 6,000-500,000 represented by the following general formula: (b-1) polyethylene glycol; (b-2) polydiol having a hydroxy group at both terminals having a higher hydrophobicity than the (b-1) polyethylene glycol; (b-3) Aliphatic diglycidyl ether having an epoxide group at the sock end (B) In the above formula, 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 'are the same or different integers such that the weight average molecular weight of the polyether is from 6,000 to 500,000; q, q 'and q' 'are the same or different integers such that the weight average molecular weights of (R) q, (R) q' and (R) q '' are from 200 to 50,000; R uses one selected from the following or a mixture of two or more selected from 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 or different integers from 1 to 10; OCOCH (CH ₃ ) CH ₂ ; OSi (CH ₃ ) ₂ ; (OCH ₂ CH ₂ ) x- (OCH (CH ₃ ) CH ₂ ) y- (OCH ₂ CH ₂ ) x ', wherein x, x' and y are the same or different integers from 1 to 100, inclusive; R 'uses one selected from the following or a mixture of two or more selected from the following CH ₂ -O- (CH ₂ ) ₁ -O-CH ₂ ; CH ₂ —O—CH ₂ CH (CH ₃ ) —O—CH ₂ ; CH ₂ O— (CH ₂ CH ₂ O) ₁ —CH ₂ ; CH ₂ O— (CH ₂ CH (CH ₃ ) O) ₁ —CH ₂ ; (CH ₂ ) _l (wherein l is an integer of 1 or more and 10 or less). The film former according to claim 1, wherein the polyurethane (A) and the polyether (B) are dissolved in a solvent capable of dissolving them and being applicable to the skin. The film forming agent according to claim 1 or 2, wherein the polyurethane (A) and the polyether (B) are in a weight ratio of 90:10 to 50:50. 3. The film former of claim 2, wherein the solvent is an aqueous alcohol solution. The film forming agent according to claim 2 or 4, wherein the polyurethane (A) and the polyether (B) are mixed and dissolved in the solvent in an amount of 0.1 to 50 weight. The method according to claim 1 or 2, wherein (a-2) or (b-2) is polypropylene glycol, polybutylene glycol, polytetramethylene glycol, polyhexamethylene glycol, polypropenylene glycol and 1 type of polyalkylene glycols selected from the group consisting of a triple block copolymer of polyethylene glycol and polypropylene glycol; And one or more combinations of one or more polyester diols selected from the group consisting of polycaprolactone diol, polylactone diol, and polyglycolic acid diol. The film former according to claim 1 or 2, wherein the component (a-3) is one or two or more combinations selected from aromatic diisocyanates or aliphatic diisocyanates. The film forming agent according to claim 1, wherein the film-forming agent containing the polyurethane and the polyether is applied to the skin and when the film is formed, the film has a tensile strength of 0.5 to 100 MPa and an elongation of 30 to The film forming agent, characterized in that up to 5000, the adhesive strength measured according to the peel adhesion test method of PSTC test method is 20 ~ 3000 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. 10. The formulation according to claim 9, wherein the film former is present in an amount of 0.1 to 50 weight based on the solvent, and the active ingredient is contained in an amount of 0.01 to 50 weight based on the total weight of the formulation. The method according to claim 9 or 10, wherein the active ingredient capable of administering the skin is non-steroidal 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 their pharmaceutically acceptable derivatives; Skin whitening agents; Herbal extracts; Heparin sodium; Or one or a mixture of two or more selected from capsaicin. 12. The active ingredient according to claim 11, wherein the active ingredient is ketoprofen, diclofenac dimethylammonium, pyoxycamp, flubiprofen, ketorolac tromethamine, sodium fucidic acid, capsaicin, dipropionate betamethasone, clotrimazole, genta sulfate Mycin, prednisolone, diphenhydramine hydrochloride, erythromycin sulfate, neomycin sulfate, sodium heparin, dexpanthenol, ketoconazole, acyclovir, tretinoin, benzoyl peroxide, kojic acid, eferison hydrochloride, lidocaine hydrochloride, salicylic acid, lactic acid, urea, vitamin A Formulation characterized in that one or two or more selected from vitamin C, vitamin E, minoxidil or alatonin. The formulation according to claim 9 or 10, which contains one or two or more additives selected from skin absorption enhancers, softeners, humectants or water-soluble polymers for enhancing viscosity and skin adhesion. The method of claim 13, 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; A formulation characterized in that one or two or more of ethoxydiglycol, N-hydroxy methyllide, sorbitol, urea, squalene, squalane, olive oil, pajama oil and derivatives thereof. The preparation according to claim 13, wherein the moisturizer or softener is one or a mixture of glycerin, polyethylene glycol, propylene glycol, 1,3-butanediol, lactic acid, mineral oil, lanolin, waxes or glucose derivatives.