WO2007136176A1

WO2007136176A1 - Polyurethane foam dressing comprising drug-containing layer and method for manufacturing the same

Info

Publication number: WO2007136176A1
Application number: PCT/KR2007/002078
Authority: WO
Inventors: Won Il Kim; Jeong Yeol Kang
Original assignee: Wonbiogen Co., Ltd.
Priority date: 2006-05-19
Filing date: 2007-04-27
Publication date: 2007-11-29
Also published as: KR20070111758A; KR100780846B1

Abstract

Disclosed herein are a polyurethane foam dressing comprising a drug-containing layer and a method for manufacturing the same, which are suitable for healing an infected wound or a wound where there is a danger of infection. By formation of a drug-containing layer separated from a foam layer, the polyurethane foam dressing enables drugs to be favorably delivered to the wound, regardless of secretion/nonsecretion of exudates and the amount of exudates secreted. The method comprises forming a nonporous waterproof polyurethane film layer, forming a tacky gel-like polyurethane foam layer, laminating the polyurethane foam layer on the polyurethane film layer, and forming a drug-containing layer. The polyurethane foam dressing is capable of preventing drug waste which results from addition of excessive drugs, based on favorable release of drugs via the drug-containing layer separated from a foam layer. In addition, the polyurethane foam dressing enables favorable drug release, regardless of secretion/nonsecretion of exudates and the amount of exudates, thus rendering the drug to be sufficiently delivered even to wounds hardly secreting exudates as well as wounds in a middle or late stage.

Description

POLYURETHANE FOAM DRESSING COMPRISING DRUG- CONTAINING LAYER AND METHOD FOR MANUFACTURING THE SAME

Technical Field

[1] The present invention relates to a polyurethane form dressing and a method for manufacturing the same. More specifically, the present invention relates to a polyurethane foam dressing comprising a drug-containing layer and a method for manufacturing the same.

[2]

Background Art

[3] Wound care treatment has a long history as the basis of medicine. It is recorded in

Papyrus that animal oil, honey and raw cotton has been used to heal wounds since 5,000 B.C. Many changes in wound healing therapy had been made with the passage of time. According to a research paper published by zoologist Winter in 1962, in view of wound healing effects, it is preferable to keep a wound wet, rather than to allow the wound to be dried, rendering a scab to form over the wound. Since the research paper of Winter, the utility of wet treatments of wounds has been continuously demonstrated and emphasized. The wet dressing for preventing dehydration or dryness of body fluids secreted from the wound is proven to contribute to easy healing of the wound.

[4] Ideal dressings require maintenance of wet environment between a wound and a dressing for the wound, and suitable absorbability and permeability. In addition, such dressings necessarily prevent dryness on the surface of the wound and do not cause festering of a normal dermatome around the wound. Furthermore, dressings must prevent gas exchange, have antimicrobial property, and not adhere to the surface of the wound upon replacement, thus causing no damage to granulation tissue. Other requirements of dressings are easy observation of the process of wound healing, non- stimulation, easy handling, and low costs. Until now, no dressing has been established that can satisfy all of these requirements. Accordingly, continuous research is being conducted to develop such dressing.

[5] Various materials for dressing have been recently developed and used. For example,

"OpSite™" was introduced as a semipermeable transparent thin film in the early 1970s which keeps the wounded area wet, and facilitates lysis of necrotic tissues and formation of granulation tissues, thereby accelerating wound healing. However, OpSite involvescongestion of excessive exudates in the wounded area, and causes festering of the skin around the wound, thus allowing the exudates to flow out. For this reason, OpSite has a disadvantage, e.g., inconvenience associated with intentional release of exudates from the wound.

[6] DuoDERM was introduced as a hydrocolloidal dressing in 1982. When

DuoDERM™ is attached to a wounded area, it reacts with exudates secreted from the wound, thus imparting a wet environment as a gel state and promoting epithelialisation of the wound. However, DuoDERM™ is impermeable to a gas such as oxygen or carbon dioxide, or water vapor, thus disadvantageously involving congestion of excessive exudates and rendering the gel to remain on the wound after replacement.

[7] Dressings using a polymer have been generally prepared by gelation. In recent years, there is used foam preparation which forms open cells by foaming a synthetic polymer, e.g., polyurethane. U.S. Patent Nos. 5,674,917 and 5,744,509 disclose introduction of a super absorbent polymer to impart superior absorbability to polyurethane foams. The super absorbent polymer adsorbs exudates secreted from a wound, and swells, thus causing volume expansion of a foam dressing and pressing down the wound. When a pressure is applied to the dressing, the super absorbent polymer flows out or remains on the surface of the wound, thus adversely affecting wound healing. Accordingly, the super absorbent polymer is unsuitable for use as a material for a dressing.

[8] In addition, a drug-containing polyurethane foam dressing was suggested to use for healing an infected wound or a wound where there is a danger of infection as well as to form wet environment, enabling favorable healing of the wound. Korean Patent No. 0404140 discloses a method for preparing a polyurethane foam dressing which comprises mixing/stirring a polyurethane prepolymer having an isocyanate-terminal, a crossliking agent, a foaming agent, an antibacterial agent and other additives, and injecting the mixture in a mold, followed by foaming.

[9] The mentioned method, i.e., inclusion of drugs in foams has some problems associated with structural properties of porous polyurethane foams. First, drugs must be escaped from cells of polyurethane foams and reach on the surface of the wound so that they exhibit medicinal effects. In an early stage at which a great amount of exudates are secreted from the wound, the foam dressing is swollen, thus enabling favorable release of the drugs. On the other hand, in middle and late stages at which a small amount of exudates are secreted from the wound, release of the drugs is unfavorable. Accordingly, the amount of exudates secreted from the wound greatly affects a release amount of the drugs and release/unrelease of the drugs. For this reason, release behaviors become instable and significantly different according to the type and seriousness of the wound. Second, such an unfavorable release necessarily involves the addition of excessive drugs, but there is a risk that the drugs are not favorably delivered to the wound. Third, in a case where a wound secrets no exudate, although drugs are contained in foams, they cannot be delivered to the wound, thus showing no medicinal effect. [10]

Disclosure of Invention

Technical Problem

[11] In an attempt to solve the problems of the prior arts, it is one object of the present invention to provide a polyurethane foam dressing capable of favorably delivering a drug to a wound, regardless of secretion/nonsecretion of exudates and the amount of exudates secreted from the wound.

[12]

Technical Solution

[13] In accordance with an aspect of the present invention, there is provided a method for manufacturing a polyurethane foam dressing comprising:

[14] (a) adding 20 to 70 parts by weight of methyl ethyl ketone, 5 to 30 parts by weight of dimethylformamide and 1 to 10 parts by weight of a pigment to 100 parts by weight of a polyurethane resin, stirring the mixture, defoaming the reaction mixture, and applying the mixture to a release sheet, followed by drying, to form a nonporous waterproof polyurethane film layer;

[15] (b) rapidly mixing 60 to 120 parts by weight of deionized water (DIW) and 1 to 10 parts by weight of a surfactant with 100 parts by weight of a polyurethane prepolymer to prepare a foaming mixture, and applying the foaming mixture to a thickness of 0.05 to 10 D on a release sheet, to produce an uncured tacky gel- like polyurethane foam layer;

[16] (c) laminating the gel-like polyurethane foam layer formed in the step (b) on the polyurethane film layer formed in the step (a), drying the laminate in a hot air drier, allowing cool to room temperature, and sequentially peeling off the release sheets from the polyurethane film layer and the polyurethane foam layer, to form a polyurethane foam dressing; and

[17] (d) applying a drug-containing solution with a viscosity of 2,000 to 4,000 cps/25°C to the foam layer of the laminated polyurethane dressing formed in the step (c), to form a drug-containing layer.

[18] The above and other objects, features and other advantages of the present invention will be described and more clearly understood from the following detailed description.

[19]

Brief Description of the Drawings

[20] The above and other objects, features and other advantages of the present invention will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which:

[21] FIGs. 1 to 6 are a schematic view illustrating a polyurethane foam dressing according to the present invention;

[22] FIGs. 7 to 9 are a scanning electron micrograph (SEM) of a polyurethane foam dressing according to the present invention; and

[23] FIG. 10 is a graph showing a drug release behavior of each sample in accordance with variation in an antibacterial agent concentration and a production method.

[24]

Best Mode for Carrying Out the Invention

[25] In one aspect, the present invention is directed to a method for manufacturing a polyurethane foam dressing, the method comprising: forming a nonporous waterproof polyurethane film layer, forming a tacky gel-like polyurethane foam layer; laminating the polyurethane foam layer on the polyurethane film layer; and forming a drug- containing layer. A detailed description for each step will be given as follows.

[26]

[27] Formation of Nonporous Waterproof Polvurethane Film Layer

[28] 20 to 70 parts by weight of methyl ethyl ketone, 5 to 30 parts by weight of dimethylformamide and 1 to 10 parts by weight of a pigment are added to 100 parts by weight of a polyurethane resin. The mixture is stirred and defoamed. The resulting mixture is applied to a release sheet, followed by drying, to form a nonporous waterproof polyurethane film layer. In one embodiment of the present invention, the defoamation is carried out using vacuum- agitation defoaming equipment. The defoamed polyurethane solution is applied to a predetermined thickness on a matt release sheet using a coating gauge and dried to obtain a nonporous waterproof polyurethane film layer. Preferably, the polyurethane resin used herein is a hydrophilic polyurethane resin into which at lease one hydrophilic group is introduced. By performance of this step using the hydrophilic polyurethane resin, a polyurethane film layer with waterproofing as well as moisture permeability is produced. The polyurethane film layer constitutes the outside of a dressing produced according to the present invention. The term a "moisture permeable/waterproof film" or "moisture permeable waterproof film" used herein refers to a polyurethane film with both moisture permeability and waterproofing which is produced with polyurethane having at least one hydrophilic group.

[29] As the pigment, there may be preferably used an organic or inorganic pigment well- known in the art which consists of a polyurethane resin as a vehicle, and methyl ethyl ketone and dimethylformamide as a solvent. Preferred is the use of an organic pigment.

[30] [31] Formation of Polvurethane Foam Layer

[32] (1) Preparation of Polyurethane Prepolymer

[33] First, isocyanate is added to a mixture of polyol and diol, followed by reacting each other, to prepare a polyurethane prepolymer.

[34] A detailed explanation for preparation of the polyurethane prepolymer will be given as follows. First, a mixture of polyol and diol is stirred at a rate of about 150 RPM until the temperature of the mixture reached 5O⁰C. After further stirring for 30 minutes, the reaction mixture is reacted with isocyanate under a nitrogen atmosphere until a NCO content (%) of the isocyanate reaches a theoretical value.

[35] The polyol may be selected from polypropylene oxide glycol, polyethylene oxide glycol, polytetramethylene ether glycol, ethylene oxide/propylene oxide copolymer, polytetrahydrofuran/ethylene oxide copolymer, polytetrahydrofuran/propylene oxide copolymer, polybutylene carbonate glycol, polyhexamethylene carbonate glycol, poly- caprolactone glycol, polyethylene adipate, polybutylene adipate, polyneopentyl adipate and polyhexamethylene adipate. These polyols may be used alone or in combination thereof. Preferred is the use of a mixture of polyethylene oxide glycol and polypropylene oxide glycol, each having at least two hydroxyl groups and a molecular weight of 500 to 6,000 in a molar ratio of 4 : 6 to 8 : 2, or an ethylene oxide/propylene oxide copolymer in which the content of ethylene oxide is 20 to 90%.

[36] The isocyanate may be selected from aromatic isocyanates, aliphatic isocyanates, substituted isocyanates and mixtures thereof. Specific examples of the isocyanate include 2,4-toluene diisocyanate, 2,6-toluene diisocyanate, methylene diphenyl di- isocyanate, 1,5-naphtalene diisocyanate, tolidine diisocyanate, hexamethylene- 1,6-diisocyanate, isoporone diisocyanate, xylene diisocyanate, cyclohexylene- 1,4-diisocyanate, lysine diisocyanate and tetramethylene-xylene diisocyanate. These polyols may be used alone or in combination thereof. Preferred is the use of isoporone diisocyanate, 2,4-toluene diisocyanate, 2,6-toluene diisocyanate and methylene diphenyl isocyanate.

[37] The diol may be selected from ethylene glycol, propylene glycol, 1,3-butanediol,

1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, Methylene glycol, diethylene glycol, tetraethylene glycol, dipropylene glycol, dibutylene glycol, neopentyl glycol, 1,4-cyclohexane dimethanol and 2-methyl-l,3-pentanediol. These diols may be used alone or in combination thereof. Preferred is the use of ethylene glycol, propylene glycol, 1,4-butanediol or a combination thereof.

[38] Preferably, an antioxidant well-known in the art may be added to a polyurethane prepolymer using a conventional method. Examples of suitable antioxidants include phenyl-beta-naphtalamine, cysteine hydrochloride, dibutylhydroxytoluene, nordihy- droguaiaretic acid, butylhydroxyanisole, phosphoric acid, citric acid, ascorbic acid, erythorbic acid, propyl gallate, and products available from Ciba Specialty Chemicals Corp., such as IRGANOX 1010™, IRGANOX 1035™, IRGANOX 1076™, IRGANOX 1330™, IRGANOX 1425WL™, IRGANOX 3114™, IRGANOX B215™, IRGANOX B220™, IRGANOX B225™, IRGANOX B561™, IRGANOX B313™, IRGANOX B501W™, IRGANOX B900™, IRGANOX B 1411™, IRGANOX B 1412 ™, IRGANOX PS800™, IRGANOX PS802™ and IRGAFOS P-EPQ™. Preferred is the use of phosphoric acid, citric acid, dibutylhydroxytoluene, butylhydroxyanisole, IRGANOX 1010™, IRGANOX 1035™, IRGANOX 1076™, IRGANOX 1330™ or a combination thereof. The antioxidant may be preferably added in an amount of 0.05% to 5% by weight, based on the total weight of the polyurethane prepolymer.

[39] (2) Preparation of Polyurethane Foaming Mixture

[40] 60 to 120 parts by weight of deionized water (DIW) and 1 to 10 parts by weight of a surfactant are mixed with 100 parts by weight of the polyurethane prepolymer prepared in the previous step at a rate of 3,000 RPM, to prepare a polyurethane foaming mixture.

[41] As the surfactant, any surfactant well-known in the art may be used in accordance with a conventional use and method. Examples of suitable surfactants include: ethylene oxide/propylene oxide block copolymers available from BASF Corp., such as F-68 , F-87™, F-88™, F- 108™ and F- 127™; silicon-based surfactants available from BASF Corp., such as L-580™, L-603™, L-688™, L-5420™, SZ- 1703™, L-6900™, L-3150™, Y-7931™, L- 1580™, L-5340™, L-5333™, L-6701™, L-5740M™, L-3002™ and L- 626 ; and surfactants available from Dow chemicals Corp., such as DOWFAX 63N10 ™, DOWFAX 63N30™, DOWFAX 81N13TB™, DOWFAX DF- 111™, DOWFAX DF- 117™, DOWFAX DF- 103™, DOWFAX DF- 104™ and DOWFAX DF- 102™. The surfactant serves to control the size and the openratio of pores in a wound-contact layer 11 and an inner absorption layer 12 of a polyurethane foam dressing.

[42] The foaming mixture may comprise a moisturizer, e.g., glycerin. Any moisturizer may be used without particular limitation so long as it is applicable to human body and exists as a liquid phase. For example, a liquefied moisturizer prepared by dissolving an aqueous natural polymer in distilled water may be used. Preferred is the use of glycerin only in view of a preparation process.

[43] The foaming mixture may further comprise a well-known super absorbent polymer as an auxiliary absorber to improve the absorbability of polyurethane foams.

[44] (3) Formation of Polyurethane Foam Layer

[45] The foaming mixture is applied to a release sheet to a thickness of 0.05 to 10 D to produce an uncured polyurethane foam layer as a tacky gel.

[46] The foaming mixture stirred at a high speed in the previous step is applied to a uniform thickness on a release sheet using a coating gauge. After 1 to 2 minutes, a polyurethane foam layer in a tacky gel-state is obtained. In this step, a polyurethane foam layer is produced in a gel-like tacky state in which the applied foaming mixture is uncured, immediately followed by a subsequent process.

[47] As the release sheet, there is no particular limitation. Preferred is the use of a silicon-treated release sheet.

[48]

[49] Lamination

[50] The polyurethane film layer and the polyurethane foam layer thus produced in the previous step are laminated, followed by drying using a hot air drier. The resulting laminate is allowed cool to room temperature. The release sheets in contact with the polyurethane film layer and the polyurethane foam layer are sequentially peeled off to obtain a polyurethane foam dressing.

[51] The uncured gel- like tacky polyurethane foam layer and the polyurethane film layer are laminated, followed by drying using a hot air drier at about 100⁰C for one minute. The lamination can be carried out in a simple manner without using any adhesive agent. There must be attention paid to the fact that the polyurethane foam layer and the waterproof polyurethane film layer cannot be laminated for a tack- free time at which polyurethane foams lose gel properties and tack. In one embodiment of the present invention, a polyurethane prepolymer is mixed with a foaming mixture with stirring at a high speed of about 3,000 RPM. The mixture is applied to a uniform thickness on a silicon-treated release sheet. After about one minute, the polyurethane foam layer and the waterproof polyurethane film layer are laminated such that release sheet- free sides of the two layers face each other. Then, the laminate is dried in a hot air drier at about 100⁰C for one minute. After completion of the drying, the release sheet in contact with the polyurethane film layer is peeled off. The resulting layer is aged in a hot air drier at about 7O⁰C for a predetermined time. The release sheet in contact with the foam layer is peeled off to produce a laminated polyurethane foam dressing. The reason for removal of the release sheet of the waterproof polyurethane film layer after the drying in a hot air drier is that in a case where a polyurethane film layer is aged in a hot air drier at about 7O⁰C without hot-air drying, a polyurethane foam dressing is shrunken and curled, thus making it difficult to wind the dressing in a roll shape and inhibiting evaporation of the remaining moisture from the foam layer. Insufficient moisture evaporation causes a deterioration in the absorbability and absorption speed for wound exudates of the wound contact layer 11 of the polyurethane foam dressing. After the aging for a predetermined time, the polyurethane foam dressing is shrunken to some extent. At this time, the waterproof film layer is also shrunken to create natural wrinkles. Alternatively, a wrinkle-pattern release sheet (e.g., AS- 175 available from Asahi roll Co., Ltd.) may be used to obtain similar effects. [52]

[53] Formation of Drug-containing Layer

[54] A drug-containing solution with a viscosity of 2,000 to 4,000 cps/25°C is applied to the foam layer of the laminated polyurethane dressing, to form a drug-containing layer.

[55] The drug-containing solution is prepared by dissolving or dispersing a drug in a solvent e.g., deionized water (DIW) and adding a pharmaceutically acceptableexcipient or viscosity control agent thereto to adjust the viscosity of the solution to 2,000 to 4,000 cps/25°C.

[56] The term "drug" of thedrug-containing solution used in the present invention refers to all substances for directly or indirectly contributing to wound healing (e.g., moisturizers or wound-healing adjuvants) as well as substances (e.g., antimicrobial agents) conventionally known in the art as medicines.

[57] The drug may include an antimicrobial agent well-known in the art to prevent infection and growth of various germs. Examples of suitable antimicrobial agents include silver sulfadiazine, povidone iodine, iodine, iodide ionic salts, fradiomycin sulfate, acrinol, chlorohexidine, benzalkonium chloride, benzethonium chloride and sodium fusidate. Another well-known drug may be incorporated in the dressing of the present invention for treatment and prevention of the wound.

[58] A moisturizer or wound-healing adjuvant may be incorporated singly, or together with another drug e.g., antimicrobial agent. The moisturizer and wound-healing adjuvant impart a wet environment to a wound, prevent formation of a scab over the wound, enables favorable healing of the wound, and prevent precipitation of a drug (e.g., an antimicrobial agent) in the solution via uniform dispersion of the drug which results from enhancement in the viscosity of the solution. In addition, the moisturizer and wound-healing adjuvant enhance the viscosity of the solution, thus preventing the drug-containing solution from permeating into the polyurethane foam layer. Specific examples of the moisturizer and wound-healing adjuvant include propylene glycol alginate, methyl cellulose, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl starch, vaseline, sodiumalginate, ammonium alginate, potassium alginate, calcium alginate, sodium caseinate, guar gum, locust bean gum, xanthan gum, cyclodextrin, gum arabic, gellan gum, carrageenan, karaya gum, casein, tara gum, tamarind gum, tragacanth gum, pectin, glucomannan, gum ghatti, ara- binogalactan, furcelleran, pullulan, glucosamine, carboxymethyl cellulose, chitin, chitosan, hyaluronic acid, amino acid, L-asparaginic acid, L-sodium aspartate, DL- alanine, L-isoleucine, lysine hydrochloride, glycine, glycerin, L-glutamine, L-glutamic acid, L-sodium glutamate, pyridinate, L-threonine, sericin, serine, L-tyrosine, heparin, sodium chondroitin sulfate, gelatin, granulation promotion agents such as fibroblast growth factors (FGFs), hepatocyte growth factors (HGFs) and epidermal growth factors (EGFs).

[59] Sugar for showing bacteriostasis and granulation growth activities may be added as a wound-healing adjuvant. Specific examples of the sugar include sucrose, sorbitol, mannitol, fructose, dextrose,xylitol, lactose, maltose, maltitol and trehalose.

[60] Further, there may be added a natural material capable of exhibiting antiinflammatory, antibacterial and antifungal actions, and skin regeneration effect. Specific examples of the natural material include teatree oil, Sophora angustifolia extract, iris extract, Glycyrrhiza glabra extract, bioflavonoids derived from grapefruit seeds, naringin, polypeptides, tocopherols, asiatic acid derived from Centella asiatica, madecasic acid, β-glucan extracted from mushrooms, Neem extract, witch hazel extract, allantoin, Portulace oleracea extract, Ponciri fructus extract, phytosphingosine, aloe extract and a combination thereof.

[61] The solvent used herein may be a pharmaceutically acceptable solvent. Any solvent may be used without particular limitation so long as it is pharmaceutically acceptable, and dissolves or disperse a target drug. Examples of suitable solvents include, but are not particularly limited to deionized water (DIW), ethanol and methanol. Preferred is the use of deionized water.

[62] Any excipient well-known in the pharmaceutical industry may be used herein without limitation. For example, glycerin may be used.

[63] Any viscosity control agent may be used without particular limitation so long as it is pharmaceutically acceptable. For example, there may be mentioned carboxymethyl cellulose, sodiumalginate and carrageenan.

[64] The drug may be used singly or in combination thereof in a predetermined dosage.

Generally, the drug may be added in an amount of 2 to 50 parts by weight, based on 100 parts by weight of a solvent, e.g., deionized water (DIW). The drug (e.g., a moisturizer and wound-healing adjuvant) included in the drug-containing layer acts as both a thickening agent for enhancing the viscosity of the solution and a stabilizer for preventing precipitation of another drug (e.g., an antimicrobial agent) in the solution via uniform dispersion of the drug, in addition to as an aid forwound healing. Accordingly, by appropriate addition of the moisturizer or wound-healing adjuvant to the drug-containing solution, the viscosity of the drug-containing solution can be adjusted to 2,000 to 4,000 cps/25°C without using any excipient or viscosity control agent. When the viscosity of the drug-containing solution is 2,000 cps/°C or less, the drug- containing solution may be dis advantageously permeated into the polyurethane foam dressing. On the other hand, when the viscosity is 4,000 cps/25°C or higher, there may be a difficulty in applying the drug-containing layer to the surface of the polyurethane foam dressing.

[65] The application may be carried out using a method such as knife-over-roll coating or release sheet mold processing. There is no particular limitation as an application method. In one embodiment of the present invention, knife-over-roll coating is used. The drug-containing solution is applied to a roll whose surface has a negative of a uniform pattern (e.g., circle or line), followed by drawing with a knife, allowing the solution to be in contact with the surface of the polyurethane foam dressing. As a result, the polyurethane foam dressing is coated with the solution in the desired pattern. The dressing is dried in a hot air drier at 100⁰C for 30 sec to produce a drug-containing layer. The viscosity of the solution suitable for application ranges from 2,000 to 4,000 cps/25°C. When the solution has a low viscosity of 2,000 cps/25°C or less, there is a risk that the solution is insufficiently adhered to the negative of the roll. On the other hand, when the viscosity is 4,000 cps/25°C or higher, there may be a difficulty in transcribing the drug-containing layer to the surface of the polyurethane foam dressing.

[66] Alternatively, the formation of the drug-containing layer may be carried out by applying the solution to a uniform pattern-embossed release sheet or a perforated release sheet to a desired thickness using a coating gauge, laminating a polyurethane foam dressing on the sheet and drying the laminate in a hot air drier. Taking process conditions or the state of products into the consideration, those skilled in the art process will be able to select a suitable method.

[67] The drug-containing layer 30 may have various shapes via the mentioned methods.

FIGs. 4 to 6 show various shapes of a drug-containing layer 30. FIG. 4 shows the surface of a polyurethane foam dressing to which the drug-containing layer 30 is applied in circle patterns. FIG. 5 shows the surface of a polyurethane foam dressing to which the drug-containing layer 30 is applied in a region except for the circle patterns. FIG. 6 shows the surface of a polyurethane foam dressing to which the drug-containing layer 30 is applied in a continuous lattice pattern. The shapes of the drug-containing layer 30 according to the present invention shown in FIGs. 4 to 6 are given for illustrative purposes. Accordingly, the drug-containing layer 30 may have a variety of shapes such as a simple linear shape, e.g., straight, perpendicular, inclined, or curved line.

[68] In the polyurethane foam dressing, on which a drug-containing layer is formed, the area of the drug-containing layer is preferably 30 to 90% with respect to the total area of the foam layer. When the area of the drug-containing layer is 30% or less, the drug cannot be evenly delivered to the wound. On the other hand, when the area of the drug- containing layer is 90% or higher, exudate absorption is slow due to an excessive area of the drug-containing layer.

[69] The polyurethane foam dressing having the drug-containing layer produced according to the present invention includes: an outer film layer composed of a nonporous waterproof polyurethane film; a foam layer arranged on the outer film layer, the foam layer composed of polyurethane foams; and a drug-containing layer arranged on the foam layer wherein the drug of the drug-containing layer is immiscible with polyurethane constituting the foam layer. The structure of the polyurethane foam dressing according to the present invention will be explained in more detail with reference to the accompanying drawings.

[70] FIG. 1 is a cross-sectional view illustrating schematically a polyurethane foam dressing according to the present invention. As shown in FIG. 1, the polyurethane foam includes an outer film layer 20 composed of a nonporous waterproof polyurethane film; a foam layer 10 composed of expandedpolyurethane foams; and a drug-containing layer 30 in this order.

[71] The outer film layer 20 is composed of a moisture permeable/waterproof polyurethane film and constitutes an outermost side of the dressing, i.e. an outermost layer on the opposite side of the surface in contact with skin. The outer film layer 20 has a high moisture permeability of 400 to 3,000 g/D/day (relative humidity: 10 to 90%, 37⁰C, Desiccant Method), prevents infection of bacteria and microbe from the outside, prevents escape of exudates, and imparts a moisture environment to the wound.

[72] The polyurethane foam layer 10 is composed of expanded polyurethane foams which are formed by subjecting expansion molding to polyurethane on a sheet. The polyurethane foam layer 10 has a bilayer structure including: a wound contact layer 11, in which a plurality of open cells with a diameter of 1 to 50 D are formed; and an inner absorption layer 12, in which a plurality of open cells with a diameter of 1 to 600 D are formed. The bilayer structure is naturally formed during the production process. More specifically, upon application of the high-speed stirred mixture of the polyurethane prepolymer and the foaming mixture to a uniform thickness on a release sheet, a film- type layer having finer open cells, as compared to open cells of the non-contact surface, is formed on the surface in contact with the release sheet. FIG. 2 is a schematic view illustrating the surface of the wound contact layer 11. FIG. 3 is a schematic view illustrating the surface of the inner absorption layer 12. The wound contact layer 11 has open cells with a diameter of 1 to 50 D, absorbs exudates and does not adhere to the wound. The inner absorption layer 12 has a plurality of open cells with a diameter of 1 to 600 D, exhibits exudate absorbability of 100 to 1,000 wt%, based on the weight thereof and has a density range of 0.1 to 0.5 g/D.

[73] The drug-containing layer 30 is formed on the foam layer and contains a drug immiscible with polyurethane constituting the foam layer. The drug-containing layer 30 takes up 30 to 90% of the total area of the foam layer and has a thickness range of 10 D to 1 D. As shown in FIGs. 4 to 6, the drug-containing layer 30 may have a variety of shapes.

[74] FIGs. 7 to 9 are a scanning electron micrograph (SEM) of the polyurethane foam dressing according to the present invention. FIG. 7 is a scanning electron micrograph (SEM) of the wound contact layer 11. FIG. 8 is a scanning electron micrograph (SEM) of the inner absorption layer 12. FIG. 9 is a scanning electron micrograph (SEM) of the outer film layer 20. It can be confirmed from FIGs. 7 and 8 that the inner absorption layer 12 has a great deal of large-size open cells, as compared to the wound contact layer 11. As can be seen from FIG. 9, the outer film layer 20 is non-porous, allowing waterproofing.

[75]

Mode for the Invention

[76] The present invention will be better understood from the preferred following examples. However, these examples are given for the purpose of illustration and are not to be construed as limiting the scope of the invention. Those skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.

[77] [78] Synthesis Example 1 [79] Synthesis of Polvurethane Prepolvmer [80] A polyurethane prepolymer was synthesized in accordance with conditions and methods shown in Table 1 below:

[81] Table 1

[82] [83] Synthesis Example 2 [84] Synthesis of Moisture-Permeable Waterproof Polyurethane [85] A moisture-permeable waterproof polyurethane resin was synthesized in accordance with conditions and methods shown in Table 2 below:

[86] Table 2

[87] [88] Production Example of Moisture Permeable Waterproof Polyurethane Film [89] To 100 parts by weight of the moisture permeable waterproof polyurethane resin prepared in Synthesis Example 2 were added 50 parts by weight of methyl ethyl ketone, 15 parts by weight of dimethylformamide and 5 parts by weight of a pigment (SF-Pink 1013™ available from Ilsam. Co., Ltd.) with stirring, to prepare a polyurethane mixture solution.

[90] The polyurethane mixture solution was applied to a predetermined thickness on a matt release sheet (available from Youlchon Chemical Co., Ltd.) using a thickness gauge. The sheet was dried in a hot air drier at 100⁰C for 30 minutes to form a moisture permeable waterproof polyurethane film on one surface of the release sheet. The thickness of the moisture-permeable waterproof polyurethane film thus formed was 30 D.

[91]

[92] Production Example 1

[93] (1) To 100 parts by weight of the polyurethane prepolymer prepared in Synthesis

Example 1 were added 80 parts by weight of deionized water (DIW), 20 parts by weight of glycerin as a moisturizer and 2 parts by weight of a surfactant (F-68 available from BASF Corp.). After stirring at a rate of 3,000 RPM for 10 sec, the mixture was applied to a silicon release sheet (available from Youlchon Chemical Co., Ltd.), rendering the sheet to be coated with the mixture using a 2.2 mm thickness gauge.

[94] (2) After one minute, the film with a thickness of 30 D produced in Production

Example of a moisture permeable waterproof polyurethane filmwas laminated on the coating such that a gap between the film and the coating was adjusted to 2.2 mm, immediately followed by drying in ahot air drier at 100⁰C for one minute.

[95] (3) The matt release sheet arranged on the moisture permeable waterproof polyurethane film was peeled off. The resulting laminate was aged in a hot air drier at 7O⁰C for 24 hours. Then, the release sheet in contact with the foam layer was peeled off, to produce a 2 mm thickness of a polyurethane foam dressing which includes a 30 D thickness of an outer film layer with moisture-permeable waterproofing.

[96] (4) 100 parts by weight of deionized water (DIW), 2 parts by weight of sodium alginate and 3 parts by weight of sodium fusidate and 3 parts by weight of Centella asiatica extract were stirred to prepare a mixture solution. Then, a polyurethane foam dressing was produced using knife-over-roll coating such that it includes a drug- containing layer taking up 30% of the total area of the foam layer and having a thickness of 0.2 mm, as shown in FIG. 1.

[97] Physical properties of the polyurethane foam dressing thus produced were measured in accordance with the following exemplary methods. The results were shown in Table 3 below.

[98]

[99] Test Methods [100] ® Mechanical Properties (tensile strength, modulus of elongation)

[101] The mechanical properties were measured using a universal test machine (Instron) under conditions of 50 N load cell, 20 mm gauge width, 30 D gauge length, and 100 D/min cross head speed.

[102]

[103] © Absorption (%)

[104] A sample with a size of 5 cm x 5 cm was prepared from the dressing. After the sample was stood at room temperature for 24 hours, an initial weight A of the sample was measured. After dipping in distilled water at 37⁰C for 24 hours, the sample was drawn off and subjected to removal of moisture present on the surface thereof. Then, a final weight B of the sample was measured. The water absorption was calculated from the following equation:

[105] Absorption (%) = (B-A)ZAxIOO

[106]

[107] ® Moisture Absorption

[108] The moisture absorption of the dressing was measured using a thermohydrostat in accordance with ASTM E96-94 (desiccant method). The temperature of the thermohydrostat was 37⁰C and the relative humidity was 80%.

[109]

[110] © Morphology

[111] The size of pores of the dressing according to the present invention, and the thickness of the film layer were measured using a scanning electron microscope (SEM).

[112]

[113] © Wound Healing Effect

[114] A 6 to 8 week-old rat (weight: 250 to 300 g) was targeted for the test. The rat was intraperitoneally anesthetized with nenbutal. The rat was allowed spontaneous respiration without additional endotracheal intubation or oxygen supply. The dorsal part of the rat was sheared and completely subjected to hair removal with a razor. The target site was sterilized with povidone and alcohol, and surgically operated under sterile environment. A skin defect of 80 πD was made on the dorsal part. The wound site was washed with a physiological saline solution and subjected to moisture removal using a dry gauze. A dressing was attached to the wound site such that the size of the dressing was about 1 D larger than that of the wound site. The dressing was covered with two gauzes, and was slightly fitted on the rat body using an elastic bandage to prevent the dressing from being detached. After initial dressing, dressing exchange was performed at an interval of 3 days which ranges from 3 days to 15 days. Epithelium growth of the skin defect site, detachment of granulation tissue upon dressing exchange and wound healing effects were measured via biopsy using an optical microscope with the passage of time.

[115]

[116] Production Example 2

[117] (1) To 100 parts by weight of the polyurethane prepolymer prepared in Synthesis

Example 1 were added 80 parts by weight of deionized water (DIW), 20 parts by weight of glycerin as a moisturizer and 2 parts by weight of a surfactant (F-68 available from BASF Corp.). After stirring at a rate of 3,000 RPM for 10 sec, the mixture was applied to a silicon release sheet (available from Youlchon Chemical Co., Ltd.), rendering the sheet to be coated with the mixture using a 2.2 D thickness gauge.

[118] (2) After one minute, the film with a thickness of 30 D produced in Production

Example of a moisture-permeable waterproof polyurethane film was laminated on the coating such that a gap between the film and the coating was adjusted to 2.2 D, immediately followed by drying in ahot air drier at 100⁰C for one minute.

[119] (3) The matt release sheet arranged on the moisture permeable waterproof polyurethane film was peeled off. The resulting laminate was aged in a hot air drier at 7O⁰C for 24 hours. Then, the release sheet in contact with the foam layer was peeled off to produce a 2 D thickness of a polyurethane foam dressing which includes a 30 D thickness of an outer film layer with moisture-permeable waterproofing.

[120] (4) 100 parts by weight of deionized water (DIW), 2 parts by weight of sodium alginate and 3 parts by weight of sodium fusidate and 3 parts by weight of Centella asiatica extract were stirred to prepare a mixture solution. Then, a polyurethane foam dressing was produced using knife-over-roll coating such that it includes a drug- containing layer taking up 50% of the total area of the foam layer having a thickness of 0.2 D, as shown in FIG. 1.

[121] Physical properties of the polyurethane foam dressing thus produced were measured in the same manner as in Production Example l.The results were shown in Table 3 below.

[122]

[123] Production Example 3

[124] (1) To 100 parts by weight of the polyurethane prepolymer prepared in Synthesis

[125] (2) After one minute, the film with a thickness of 30 D produced in Production

[126] (3) The matt release sheet arranged on the moisture-permeable waterproof polyurethane film was peeled off. The resulting laminate was aged in a hot air drier at 7O⁰C for 24 hours. Then, the release sheet in contact with the foam layer was peeled off to produce a 2 D thickness of a polyurethane foam dressing which includes a 30 D thickness of an outer film layer with moisture-permeable waterproofing.

[127] (4) 100 parts by weight of deionized water (DIW), 2 parts by weight of sodium alginate and 3 parts by weight of sodium fusidate and 3 parts by weight of Centella asiatica extract were stirred to prepare a mixture solution. Then, a polyurethane foam dressing was produced using knife-over-roll coating such that it includes a drug- containing layer taking up 80% of the total area of the foam layer having a thickness of 0.2 D, as shown in FIG. 1.

[128] Physical properties of the polyurethane foam dressing thus produced were measured in the same manner as in Production Example l.The results were shown in Table 3 below.

[129]

[130] Production Example 4

[131] (1) To 100 parts by weight of the polyurethane prepolymer prepared in Synthesis

Example 1 were added 80 parts by weight of deionized water (DIW), 20 parts by weight of glycerin as a moisturizer and 2 parts by weight of a surfactant (F-68™ available from BASF Corp.). After stirring at a rate of 3,000 RPM for 10 sec, the mixture was applied to a silicon release sheet (available from Youlchon Chemical Co., Ltd.), rendering the sheet to be coated with the mixture using a 2.2 mm thickness gauge.

[132] (2) After one minute, the film with a thickness of 30 D produced in Production

[133] (3) The matt release sheet arranged on the moisture-permeable waterproof polyurethane film was peeled off. The resulting laminate was aged in a hot air drier at 7O⁰C for 24 hours. Then, the release sheet in contact with the foam layer was peeled off to produce a 2 D thickness of a polyurethane foam dressing which includes a 30 D thickness of an outer film layer with moisture-permeable waterproofing.

[134] (4) 100 parts by weight of deionized water (DIW), 2 parts by weight of sodium alginate and 3 parts by weight of sodium fusidate and 3 parts by weight of Centella asiatica extract were stirred to prepare a mixture solution. Then, a polyurethane foam dressing was produced using knife-over-roll coating such that it includes a drug- containing layer taking up 90% of the total area of the foam layer and having a thickness of 0.2 D, as shown in FIG. 1.

[135] Physical properties of the polyurethane foam dressing thus produced were measured in the same manner as in Production Example l.The results were shown in Table 3 below.

[136]

[137] Comparative Production Example 1

[138] (1) To 100 parts by weight of the polyurethane prepolymer prepared in Synthesis

Example 1 were added 80 parts by weight of deionized water (DIW), 20 parts by weight of glycerin as a moisturizer, 2 parts by weight of a surfactant (F-68 available from BASF Corp.), 3 parts by weight of sodium fusidate and 3 parts by weight of Centella asiatica extract. After stirring at a rate of 3,000 RPM for 10 sec, the mixture was applied to a silicon release sheet (available from Youlchon Chemical Co., Ltd.), rendering the sheet to be coated with the mixture using a 2.2 mm thickness gauge.

[139] (2) After one minute, the film with a thickness of 30 D produced in Production

[140] (3) The matt release sheet arranged on the moisture-permeable waterproof polyurethane film was peeled off. The resulting laminate was aged in a hot air drier at 7O⁰C for 24 hours. Then, the release sheet in contact with the foam layer was peeled off to produce a 2 D thickness of a polyurethane foam dressing which includes a 30 D thickness of an outer film layer with moisture-permeable waterproofing.

[141] Physical properties of the polyurethane foam dressing thus produced were measured in the same manner as in Production Example l.The results were shown in Table 3 below.

[142]

[143] Comparative Production Example 2

[144] (1) To 100 parts by weight of the polyurethane prepolymer prepared in Synthesis

[145] (2) After one minute, the film with a thickness of 30 D produced in Production

Example of a moisture-permeable waterproof polyurethane film was laminated on the coating such that a gap between the film and the coating was adjusted to 2.2 D, immediately followed by drying in ahot air drier at 100⁰C for one minute. [146] (3) The matt release sheet arranged on the moisture-permeable waterproof polyurethane film was peeled off. The resulting laminate was aged in a hot air drier at 7O⁰C for 24 hours. Then, the release sheet in contact with the foam layer was peeled off to produce a 2 D thickness of a polyurethane foam dressing which includes a 30 D thickness of an outer film layer with moisture-permeable waterproofing.

[147] (4) 100 parts by weight of deionized water (DIW), 2 parts by weight of sodium alginate and 3 parts by weight of sodium fusidate and 3 parts by weight of Centella asiatica extract were stirred to prepare a mixture solution. Then, a polyurethane foam dressing was produced using knife-over-roll coating such that it includes a drug- containing layer taking up 10% of the total area of the foam layer of the dressing produced in the step (3) and having a thickness of 0.2 D, as shown in FIG. 2.

[148] Physical properties of the polyurethane foam dressing thus produced were measured in the same manner as in Production Example l.The results were shown in Table 3 below.

[149]

[150] Comparative Production Example 3

[151] (1) To 100 parts by weight of the polyurethane prepolymer prepared in Synthesis

[152] (2) After one minute, the film with a thickness of 30 D produced in Production

[153] (3) The matt release sheet arranged on the moisture-permeable waterproof polyurethane film was peeled off. The resulting laminate was aged in a hot air drier at 7O⁰C for 24 hours. Then, the release sheet in contact with the foam layer was peeled off to produce a 2 D thickness of a polyurethane foam dressing, including a 30 D thickness of an outer film layer with moisture-permeable waterproofing.

[154] (4) 100 parts by weight of deionized water (DIW), 2 parts by weight of sodium alginate and 3 parts by weight of sodium fusidate and 3 parts by weight of Centella asiatica extract were stirred to prepare a mixture solution. Then, the mixture solution was applied to a release sheet and coated using a coating gauge. A polyurethane dressing was laminated on the coating, followed by drying in a hot air drier to produce a polyurethane foam dressing which includes a drug-containing layer taking up 100% of the total area of the foam layer and has a thickness of 0.2 D. [155] Physical properties of the polyurethane foam dressing thus produced were measured in the same manner as in Production Example l.The results were shown in Table 3 below.

[156] [157] Comparative Example 1 [158] For comparison in physical properties, Mediform T¹M"¹ (Ildong Pharmaceutical Co., Ltd.) was tested. The physical properties of the Mediform were measured in the same manner as in Production Example 1. The results were shown in Table 6.

[159] [160] Comparative Example 2

TM [161] For comparison in physical properties, Polymem¹"¹ (available from Sinsin Pharmaceutical Co., LTD.) was tested. The physical properties of the Polymem were measured in the same manner as in Production Example 1. The results were shown in Table 6.

[162] [163] Comparative Example 3

TM [164] For comparison in physical properties, Careform¹"¹ (available from Hanmi Pharmaceutical Co., LTD.) was tested. The physical properties of the Careform were measured in the same manner as in Production Example 1. The results were shown in Table 6.

[165] Table 3

[166] *: Conditions = 37⁰C, 80% RH [167] **: Conventional Products [168] E: Excellent G: Good F: Fair P: Poor [169] [170] It could be confirmed from Table 3 that when the area of a drug-containing layer was 30 to 90%, wound healing effect of the dressing was excellent. In Comparative Production Example 3, since a drug-containing layer covers the overall dressing, it inhibits exudate absorption of the dressing upon dressing exchange, and causes an increase in the amount of an antibacterial agent in contact with the wound, thus involving a relatively low speed of wound healing. Meanwhile, in Comparative Production Examples 1 and 2, exudate absorption speed was excellent, but wound healing speed was relatively low. In particular, in Production Examples 2 and 3, reep- ithelialization and wound contraction were significantly excellent, and wound healing speed was excellent, as compared to other Production Examples, Comparative Production Examples and Comparative Examples.

[171] [172] Comparative Production Examples 4 to 6 [173] (1) To 100 parts by weight of the polyurethane prepolymer prepared in Synthesis Example 1 were added 80 parts by weight of deionized water (DIW), 20 parts by weight of glycerin as a moisturizer, 2 parts by weight of a surfactant (F-68™ available from BASF Corp.) and silver sulfadiazine in accordance with the following content:

[174] Comparative Production Example 4 (Sample 1): 10 D/D [175] Comparative Production Example 5 (Sample 2): 30 D/D [176] Comparative Production Example 6 (Sample 3): 60 D/D [177] After stirring at a rate of 3,000 RPM for 10 sec, the mixture was applied to a silicon release sheet (available from Youlchon Chemical Co., Ltd.), rendering the sheet to be coated with the mixture using a 2.2 D thickness gauge.

[178] (2) After one minute, the film with a thickness of 30 D produced in Production

[179] (3) The matt release sheet arranged on the moisture-permeable waterproof polyurethane film was peeled off. The resulting laminate was aged in a hot air drier at 7O⁰C for 24 hours. Then, the release sheet in contact with the foam layer was peeled off, to produce a 2 D thickness of a polyurethane foam dressing which includes a 30 D thickness of an outer film layer with moisture-permeable waterproofing.

[180] A drug release test for the polyurethane foam dressing thus produced was conducted to obtain the release speedand release amount of the drug contained therein. The test was carried out in accordance with the following conditions and methods. The drug release behavior was observed for 48 hours. The results were shown in Table 4 and FIG. 10.

[181]

[182] Test methods

[183] ( 1 ) Obtainment of Maximum Absorption Wavelength

[184] An absorption spectrum was obtained in a 0.2 mg/D solution of silver sulfadiazine in a pH 7.4 phosphate buffer solution at 200 to 1,000 D using a UV Spectrometer (Jasco, V-550™). A maximum absorption peak (254 D) was determined from the absorption spectrum.

[185]

[186] (2) Standard Calibration

[187] 0.01, 0.05, 0.1, 0.25, 0.5 and 1.0 D/D of silver sulfadiazine was each dissolved in distilled water to prepare standard samples. A standard curve was plotted in each standard sample at 254 nm. A slope (B) and an intercept (Y) were determined from the standard curve. The concentration of each sample was calculated from the following equation:

[188] Cone = B x ABS + Y

[189]

[190] (3) Test

[191] A segment of 2 cm x 2 cm was prepared from a silver sulfadiazine-containing polyurethane foam dressing. Drug release test for the segment was conducted in a shaking incubator (DA-SI-LL, Donga Science) under conditions of a temperature range of 37+5⁰C and a rate of 100 RPM. A released drug of 3 mL was collected using a microsyringe at regular intervals. To maintain the desired sink conditions of the released drug, a drug was supplemented in an amount and temperature equivalent to the collected one. The concentration of the sample collected was detected at 254 nm using a UV Spectrometer and plotted as a graph representing a ratio (D/D) of a released drug amount to a total drug amount contained in the polyurethane foam dressing. The results were shown in Table 4 and FIG. 10.

[192]

[193] Production Examples 5 to 7

[194] (1) To 100 parts by weight of the polyurethane prepolymer prepared in Synthesis

[195] (2) After one minute, the film with a thickness of 30 D produced in Production

[196] (3) The matt release sheet arranged on the moisture-permeable waterproof polyurethane film was peeled off. The resulting laminate was aged in a hot air drier at 7O⁰C for 24 hours. Then, the release sheet in contact with the foam layer was peeled off to produce a 2 D thickness of a polyurethane foam dressing which includes a 30 D thickness of an outer film layer with moisture-permeable waterproofing.

[197] (4) 100 parts by weight of deionized water (DIW), 2 parts by weight of sodium alginate and silver sulfadiazine in accordance with the following content were stirred to prepare a mixture solution.

[198] Production Example 5 (Sample 4): silver sulfadiazine 10 D/D

[199] Production Example 6 (Sample 5): silver sulfadiazine 30 D/D

[200] Production Example 7 (Sample 6): silver sulfadiazine 60 D/D

[201] Then, a polyurethane foam dressing was produced using knife-over-roll coating such that it includes a drug-containing layer taking up 80% of the total area of the foam layer of the dressing produced in the step (3) and having a thickness of 0.2 D, as shown in FIG. 2.

[202] The release speed and release amount of the drug contained in the polyurethane foam dressing thus produced were measured in the same manner as in Comparative Production Examples 4 to 6. The results were shown in Table 4 and FIG. 10.

[203] Table 4

[204] [205] As can be seen from Table 4 and FIG. 10, when an equivalent amount of silver sulfadiazine was added, the surface-coating on the dressing exhibits a high release amount of the drug, as compared to the inclusion of the drug in a polyurethane dressing. When comparing the sample 3 with the sample 5, it can be confirmed that the sample 3 where a two-fold amount of silver sulfadiazine is included in the polyurethane dressing exhibited a drug release amount, comparable to the sample 5 where a one-fold amount of silver sulfadiazine is coated on the surface of the dressing. This is the reason that the drug in an isolated state exists in a urethane polymer due to foam structural characteristics. In comparison in a drug release amount between samples 1 and 4, the smaller the added amount, the larger the difference in the drug release amount. Accordingly, a novel method for coating a drug on the surface of the dressing according to the present invention enables production of a polyurethane foam dressing capable of decreasing a use amount of an expensive antibacterial agent and increasing a drug release amount, as compared to conventional methods wherein a wound healing adjuvant (e.g., antibacterial agent) is included in the polyurethane dressing. As a result, the method of the present invention contributes to a reduction in production costs and an efficient delivery of a drug to the wound. [206]

Industrial Applicability

[207] As apparent from the above description, the present invention provides a polyurethane foam dressing comprising a novel drug-containing layer to which an improved drug addition method is applied. According to the polyurethane foam dressing of the present invention, drug release can be favorably carried out by a drug- containing layer separated from a foam layer. Accordingly, there can be prevented drug waste which results from addition of excessive drugs. In addition, the polyurethane foam dressing enables drug release, regardless of secretion/nonsecretion of exudates and the amount of exudates secreted, thus enabling sufficient delivery of drugs even to wounds hardly secreting exudates as well as wounds in a middle or late stage. Further, the use of the manufacturing method of a polyurethane foam dressing according to the present invention enables appreciate adjustment of the area and thickness of the drug-containing layer according to the concentration, type and wound healing effects of drugs. Accordingly, a foam dressing in any shape suitable for wound conditions can be manufactured and be put to practical use.

Claims

[1] A method for manufacturing a polyurethane foam dressing comprising:

(a) adding 20 to 70 parts by weight of methyl ethyl ketone, 5 to 30 parts by weight of dimethylformamide and 1 to 10 parts by weight of a pigment to 100 parts by weight of a polyurethane resin, stirring the mixture, defoaming the reaction mixture, and applying the mixture to a release sheet, followed by drying, to form a nonporous waterproof polyurethane film layer;

(b) rapidly mixing 60 to 120 parts by weight of deionized water (DIW) and 1 to 10 parts by weight of a surfactant with 100 parts by weight of a polyurethane prepolymer to prepare a foaming mixture, and applying the foaming mixture to a thickness of 0.05 to 10 D on a release sheet, to produce an uncured tacky gel-like polyurethane foam layer;

(c) laminating the polyurethane film layer formed in the step (a) and the gel-like polyurethane foam layer formed in the step (b), drying the laminate in a hot air drier, allowing cool to room temperature, and sequentially peeling off the release sheets from the polyurethane film layer and the polyurethane foam layer, to form a polyurethane foam dressing; and

(d) applying a drug-containing solution with a viscosity of 2,000 to 4,000 cps/ 25⁰C to the foam layer of the laminated polyurethane dressing formed in the step (c), to form a drug-containing layer.

[2] The method according to claim 1, wherein the drug-containing layer is formed on the foam layer within a range of 30 to 90% of the area of the foam layer.

[3] The method according to claim 1, wherein the drug-containing layer has a thickness range of 10 D to 1 D.

[4] The method according to claim 3, wherein the formation of the drug-containing layer is carried out by coating the drug-containing solution on the foam layer by means of knife-over-roll coating.

[5] The method according to claim 3, wherein the drug-containing solution consists of:

(a) 2 to 50 parts by weight of a drug;

(b) 100 parts by weight of a solvent selected from deionized water (DIW), methanol and ethanol;

(c) 20 to 40 parts by weight of anexcipient; and

(d) 1 to 10 parts by weight of a viscosity control agent selected from car- boxymethyl cellulose, sodium alginate and carrageenan.

[6] The method according to any one of claims 1 to 5, wherein the drug is selected from the group consisting of teatree oil, Sophora angustifolia extract, iris extract, Glycyrrhiza glabra extract, grapefruit (seeds) extract, Centella asiatica, Neem extract, witch hazel extract, Portulace oleracea extract, Ponciri fructus extract, aloe extract, sodium fusidate, silver sulfadiazine, sucrose, sorbitol, mannitol, fructose, dextrose,xylitol, lactose, maltose, maltitol, thehalose, povidone and vaseline.

[7] A polyurethane foam dressing including: an outer film layer composed of a nonporous waterproof polyurethane film; a foam layer arranged on the outer film layer, the foam layer composed of polyurethane foams; and a drug-containing layer arranged on the foam layer, wherein the drug of the drug- containing layer is immiscible with polyurethane constituting the foam layer.

[8] The polyurethane foam dressing according to claim 7, wherein the drug- containing layer is formed on the foam layer within a range of 30 to 90% of the total area of the foam layer.

[9] The polyurethane foam dressing according to claim 8, wherein the drug- containing layer has a thickness range of 10 D to 1 D.

[10] The polyurethane foam dressing according to claim 7, wherein the polyurethane foam layer has a bilayer structure including: a wound contact layer having a plurality of fine open cells with a diameter of 1 to 50 D; and an inner absorption layer having a plurality of open cells with a diameter of 1 to 600 D.

[11] The method according to any one of claims 7 to 10, wherein the drug-containing solution consists of:

(a) 2 to 50 parts by weight of a drug;

(c) 20 to 40 parts by weight of anexcipient; and

[12] The method according to claim 11, wherein the drug is selected from the group consisting of teatree oil, Sophora angustifolia extract, iris extract, Glycyrrhiza glabra extract, grapefruit (seeds) extract, Centella asiatica, Neem extract, witch hazel extract, Portulace oleracea extract, Ponciri fructus extract, aloe extract, sodium fusidate, silver sulfadiazine, sucrose, sorbitol, mannitol, fructose, dextrose,xylitol, lactose, glucose, maltitol, thehalose, povidone and vaseline.