KR100340981B1 - Hydrophilic Polyurethane Foam Dressing and Method of Making the Same - Google Patents

Abstract

The present invention relates to a hydrophilic polyurethane foam dressing material for use as a closed wound coating material and a method for producing the same. It is a hydrophilic poly with high moisture permeability and window non-adhesive property with simple processing process to solve the problems of lack of continuous exudation ability, window attachment, and complicated processing process due to low moisture permeability, which is a disadvantage of the conventional hydrophilic polyurethane foam dressing material. It aims at manufacturing a urethane foam dressing material. According to the present invention, 40 to 79% by weight of a polyurethane prepolymer synthesized by reacting a diisocyanate with a polyether polyol; 15 to 45% by weight of blowing agent; Provided are a hydrophilic polyurethane foam dressing material which is prepared by mixing 5 to 35% by weight of a crosslinking agent with 1 to 15% by weight of an additive such as a surfactant, a moisturizing agent, and an antibacterial agent, and then foaming and molding a mold. . The hydrophilic polyurethane foam dressing material produced according to the present invention comprises a skin layer of a thin film having a pore having a diameter of 3 to 60 µm and an inner layer having an open cell having a diameter of 50 to 500 µm. It has excellent water vapor permeability and exudant absorption, prevents adhesion of window surface, and has excellent wound healing effect and can be applied to a wide range of wounds at low cost.

Description

Hydrophilic Polyurethane Foam Dressing and Method of Making the Same

The present invention relates to a hydrophilic polyurethane foam dressing material for use as a closed wound coating material and a method for producing the same, and more specifically, to mixing and stirring a polyurethane prepolymer having an isocyanate end group, a blowing agent, a crosslinking agent, and an additive at a predetermined ratio. The present invention relates to a method for producing a hydrophilic polyurethane foam dressing material which is injected into a mold of a predetermined shape and foamed and molded. Such a foam dressing material has a skin layer having a pore of 3 to 60 µm in diameter and a diameter of 50 to 500 µm. It relates to a method for producing a closed foam dressing material consisting of an inner layer having an open cell, and containing a surfactant, a humectant, a wound healing accelerator, an antibacterial agent and the like.

Skin is one of the organs that protects the human body from external stimuli, prevents water loss, and performs vital life protection functions such as controlling body temperature and preventing bacterial invasion. This can lead to functional impairment, which can cause various side effects due to water loss and bacterial infections from the outside, making it difficult to treat the affected area, or causing additional side effects such as secondary dysfunction or damage. It will also affect. Therefore, in order to quickly heal wounds and minimize secondary side effects, it is necessary to treat wounds with appropriate dressings.

Brief descriptions of the major factors involved in wound healing include a wet environment, infection, foreign body and necrotic tissue, temperature, oxygen concentration, and pH. The requirements of the ideal dressing material are the ability to maintain adequate moisture at the contact surface with the wound, the ability to absorb exudates, the ease of attachment and removal to the wound, the ability to transfer gas and water to the outside, the insulation from the outside, and the invasion of bacteria. Defense, non-toxic to human body, excellent mechanical properties, economics and the like.

Conventional gauze dressings are easy to absorb the wound secretion, but they do not have a protective function against bacterial infection, keep the wound dry and delay the treatment, and the dressing material adheres to the wound surface and is not easy to remove when exchanged. In the early stages of healing, there is a lot of exudate, so there are disadvantages such as changing dressings several times a day. Currently, various closed dressing materials have been developed and used to improve the problems of the gauze dressing materials, but due to their high price and hygroscopicity and the lack of control of moisture permeability, they are not applied to a wide range of wounds and are only applied to specific applications. Examples of the dressing material include a film type, a hydrocolloid type, a hydrogel type, a nonwoven fabric using sodium alginate, and a polyurethane foam type. In particular, the polyurethane foam type is expected to be a material that can easily control hygroscopicity and is easy to manufacture due to its versatility and wide application of wounds.

As a method for preparing a hydrophilic polyurethane foam dressing material, US Pat. No. 4,773,409 was prepared by mixing polyethylene glycol, isocyanate, catalyst, water, water-soluble or water swellable polymer by one-shot process, and US Pat. Nos. 4,860,737 and 5,571,529. It was prepared by mixing Grace & Co.'s HYPOL (polyether prepolymer having an isocyanate end group), a surfactant, and water. However, by using a catalyst for promoting the urethane reaction has a disadvantage that it is harmful to the human body, weak mechanical properties and foam collapse when absorbing exudates. In addition, by having a large pore by the open cell structure on the surface, bacteria invasion from the outside and regenerated cells on the wound surface adhere to the open cell of the polyurethane foam to exchange the dressing material. There is a drawback to causing pain in the patient. To compensate for this drawback, US Patent Nos. 5,296,528 and 5,571,529 manufacture a dressing material by laminating films on both sides of a hydrophilic polyurethane foam. However, it is difficult to apply to wounds in which a large amount of exudate is generated due to a complicated manufacturing process due to relatively high cost and lack of absorption ability, and it is difficult to continuously absorb exudates due to the moisture-permeable drying of the absorbent exudate. In addition, there is a problem that it is difficult to control the properties of the polyurethane foam itself, that is, tensile strength, elongation, modulus, absorbance, cell size (cell size).

The present invention is to improve the low water absorption, low moisture permeability, wound adhesion, low physical properties and the like problems of the conventional polyurethane foam dressing as described above, by reacting at least one polyether polyol with diisocyanate to make a polyurethane prepolymer After synthesis, the blowing agent, the crosslinking agent, and the additives are mixed and injected into a mold having a predetermined shape, and then foamed and molded to form an epidermal layer having pores having a diameter of 3 to 60 µm and an open cell having a diameter of 50 to 500 µm. It is an object of the present invention to provide a hydrophilic polyurethane foam dressing material consisting of an inner layer having an inner layer) and a method for producing the same. Another object of the present invention is to form pores having a diameter of 3 to 60 µm in a thin film of the epidermal layer, and Hydrophilic polyurethane foam that prevents bacteria from penetrating the wound and adheres to the dressing material by forming an open cell with a diameter of 50 to 500 µm in the layer The present invention also provides a dressing material and a method of manufacturing the same. The present invention also provides a hydrophilic polyurethane foam capable of promoting cleanliness of wounds and growth of regenerated cells by containing additives such as surfactants, humectants, wound healing accelerators, and antibacterial agents. It is another object of the present invention to synthesize the polyurethane prepolymer, and to adjust the NCO% of the polyurethane prepolymer and the amount of various raw materials to synthesize the polyurethane prepolymer. The present invention is to provide a polyurethane foam dressing material and a method of manufacturing the same, which can be used in a wide range of wounds with a small amount of exudates and many wounds while controlling tensile strength, elongation, modulus, absorbency, cell size, and the like.

1 is a schematic cross-sectional view of a hydrophilic polyurethane foam dressing material prepared according to the present invention.

Figure 2 is a scanning electron micrograph of the surface (a) and cross-section (b) of the hydrophilic polyurethane foam dressing material prepared according to the present invention. * Description of the symbols for the main parts of the drawings * 1: Epidermal layer 2: Inner layer

Hereinafter, the present invention will be described in detail. The hydrophilic polyurethane foam dressing material used as the closed wound coating material of the present invention has an open skin having a skin layer 1 having a diameter of 3 to 60 µm pores and a diameter of 50 to 500 µm, as shown in FIGS. 1 and 2. consisting of an inner layer 2 having an open cell, 40 to 79% by weight of a polyurethane prepolymer obtained by reacting at least one polyetherpolyol with a diisocyanate; 15 to 45% by weight of blowing agent; 5 to 35% by weight of the crosslinking agent and 1 to 15% by weight of the additive are added, mixed and stirred, and then injected into the mold to foam and mold.

In preparing a polyurethane prepolymer, 0.15 to 0.5 moles of one or more polyether polyols are added to 1 to 3 moles of diisocyanate, and isophorone diisocyanate, 2,4-toluene diisocyanate and its isomers and diphenyl are used as diisocyanates. Methane diisocyanate, hexamethylene diisocyanate, lysine diisocyanate, trimethylhexamethylene diisocyanate, 2,2-bis-4'-propane isocyanate, 6-isopropyl-1,3-phenyldiisocyanate, bis (2-isocyanate ethyl ) -Fumarate, 3,3'-dimethyl-4,4'-diphenylmethane diisocyanate, 1,6-hexanediisocyanate, 4,4'-biphenylene diisocyanate, 3,3'-dimethylphenylene diisocyanate , p-phenylenedi isocyanate, m-phenylenedi isocyanate, 1,5-naphthalenedi isocyanate, 1,4-xylene diisocyanate, 1,3-xylene diisocyanate Socyanate etc. can be used, Preferably 2, 4- toluene diisocyanate and its isomer, p-phenylene diisocyanate, isophorone diisocyanate, and hexamethylene diisocyanate are preferable. As polyether polyols, a single or mixed polypropylene glycol having two or more hydroxyl groups in a molecule having a molecular weight of 1,000 to 4,000 and an ethylene oxide / propylene oxide random copolymer having a molecular weight of 3,000 to 6,000 having three or more hydroxyl groups in a molecule Use it. Preferably, an ethylene oxide / propylene oxide random copolymer having three hydroxyl groups in a molecule and having a molecular weight of 3,000 to 6,000 is preferably used alone.

The blowing agent may be chlorofluorocarbon (CFC-141b), methylene chloride (Methylene chloride) as a physical blowing agent, distilled water may be used as a chemical blowing agent, preferably distilled water.

The crosslinking agent acts as an auxiliary agent, and has 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, neopentylglycol, propylene glycol, and ethylene having two or more hydroxyl groups in a molecule. Glycol, polyethylene glycol having a molecular weight of 200 to 2000, glycol, trimethylol ethane, trimethylolpropane, pentaerythritol, sorbose, sorbitol, and the like can be used alone or in combination. Preferably, glycerol, sorbitol, polyethylene glycol having a molecular weight of 200 to 2000, and trimethylol propane may be used.

As an additive, the surfactant plays a role in controlling the cell size of the polyurethane foam dressing material. As an ethylene oxide-propylene oxide block copolymer, L-62, F-68, F-127, and F- of BASF, Germany 108 or a silicone-based surfactant can be used O-5 L-5305, L-5302, L-3150, and as a moisturizer and wound healing accelerator, hyaluronic acid, alginate, pectin, xanthan gum, guar gum, karaya gum, sodium carboxymethylcellulose, Chondroitin sulfate, 3-aminopropyldihydrogen phosphate, chitomarin and the like can be used.

Hereinafter, the present invention will be described by synthesis examples, examples, and comparative examples, but these are merely provided to explain the present invention in detail, and the technical scope of the present invention is not limited thereto.

Synthesis Example 1

Polyurethane prepolymers having isocyanate end groups were prepared by adding 335 g of diphenylmethane diisocyanate using a 3-liter round bottom flask equipped with a stirrer and heating to 60 ° C., followed by three hydroxyl groups. It was prepared by reacting for 7 hours until reaching the theoretical NCO% while adding a small amount of 1665g of copolymer and 75% of ethylene oxide (TR-705 of Polyol Korea). Samples were taken in the middle of the reaction to determine NCO% and NCO% was determined by titrimetry using n-butylamine standard solution.

Synthesis Example 2

454 g of diphenylmethane diisocyanate was added to a 3 liter round bottom flask equipped with a stirrer, and heated to 60 ° C., followed by three hydroxyl groups. 1546 g of TR-705 (Korea Polyol Co., Ltd.) was added in small portions, and reacted for 7 hours until the theoretical NCO% was reached. Samples were taken in the middle of the reaction to determine NCO% and NCO% was determined by titrimetry using n-butylamine standard solution.

Synthesis Example 3

347 g of diphenylmethane diisocyanate was added to a 3 liter round bottom flask equipped with a stirrer, and the temperature was raised to 60 ° C., followed by three hydroxyl groups, 338 g of polypropylene glycol (GP-3000, Polyol Korea Co., Ltd.) and ethylene oxide / propylene oxide random air. It was prepared by reacting for 7 hours until the theoretical NCO% was reached while adding 1315 g of the compound, which had a ethylene oxide content of 75% (TR-705 of Polyol Korea) in small amounts. Samples were taken in the middle of the reaction to determine NCO% and NCO% was determined by titrimetry using n-butylamine standard solution.

Example 1

The hydrophilic polyurethane foam dressing material is 60% by weight of the polyurethane prepolymer prepared in Synthesis Example 1, 24% by weight of distilled water, 13% by weight of glycerin, 2.5% by weight of F-127 (BASF) as an additive, STARTEX 201 Yellow (Songwon Color) ) 0.5 wt% was added and stirred at 3,000 to 5,000 rpm for 5 seconds, and then injected into a mold of a predetermined shape to prepare a foam. At this time, the temperature of the mold was set to 30 to 50 ° C, and the mold was opened and closed for demolding 10 to 15 minutes after the injection.

The obtained hydrophilic polyurethane foam dressing material was measured by the following method, the results are shown in Table 1 below.

① Mechanical Properties (tensile strength, elongation, modulus)

It measured by the tensile tester (Universal Test Machine, USA, Instron) based on JIS-K-6401.

② Absorbance%

Take the hydrophilic polyurethane foam dressing material in the size of 3Cm × 3Cm and dry it in the 70 ℃ oven for 24 hours, measure the initial weight (A), impregnate it in distilled water at 25 ℃ for 48 hours, take it out and drain the surface with dust-free tissue. After wiping off the weight (B) was measured. Finally, the following equation was used.

Absorbance% = (B-A) / A × 100

③ moisture permeability

It was measured according to the test method of KS M 6886 using a constant temperature and humidity device. At this time, the temperature was 40 ° C, the relative humidity was 90%, and the moisture permeability was calculated according to the following equation.

P = A / S

A = ((a ₁ -a ₀ ) + (a ₂ -a ₁ ) + (a ₃ -a ₂ )) / 3

Here, P: moisture vapor permeability (g / m ² / 24hr)

A: average amount of increase per hour (g)

S: moisture permeation area of the test piece (m ² )

④ Cell size

The cell size of the surface and the cross section of the hydrophilic polyurethane foam dressing material was measured using a scanning electron microscope.

⑤ Toxicity test on cells

IS0 10993-5 was used to evaluate the toxicity of the hydrophilic polyurethane foam dressings to the cells. Cells were used 3T3 cells, mouse fibroblasts provided by the National Institute of Sanitation. 3T3 cells were seeded at 2 × 10 ⁴ / cm 2 using RPMI-1640 (Roswell Park Memorial Institute-1640) containing 10% FCS (Fetal Calf Serum) in a 12 well plastic culture dish. Secondary incubation for 4 days under CO ₂ . The hydrophilic polyurethane foam dressing material was directly contacted and incubated for 1 day and 3 days, respectively, harvested using trypsin / EDTA (Ethylene Diamine Tetraacetic Acid) solution, and stained with 0.4% trypan blue solution. The number was measured with a hemasitometer.

⑥ Measurement of wound healing effect

In order to observe the wound healing effect of the hydrophilic polyurethane foam dressing material, an average age of 5 weeks and a weight of 25-30 g were used. Rats were anesthetized with ether, and two skin defects of 6-30 mm in diameter were made on the back and one was dressed and the other was not dressed as a control. At 3, 6, and 9 days after dressing, changes in the size of skin defects and detachment of tissue cells were observed.

Example 2

Hydrophilic polyurethane foam dressing material is a polyurethane prepolymer prepared in Synthesis Example 1 53% by weight of distilled water 24% by weight, glycerin 19% by weight, F-127 2.5% by weight, hyaluronic acid 1.0% by weight, STARTEX 201 Yellow 0.5% by weight After the addition was stirred for 5 seconds at 3000 ~ 5,000rpm and injected into a mold of a predetermined shape to prepare a foam. At this time, the temperature of the mold was set to 30 to 50 ° C, and the mold was opened and closed for demolding 10 to 15 minutes after the injection. Physical properties were measured by the method illustrated in Example 1, and the results are shown in Table 1 below.

Example 3

Hydrophilic polyurethane foam dressing material is 26% by weight of distilled water, 13.5% by weight of glycerin, 2.9% by weight of F-127, 0.1% by weight of silver sulfur diazine (Silver Sulfadiazine), 57% by weight of polyurethane prepolymer prepared in Synthesis Example 1 0.5 wt% of STARTEX 201 Yellow was added thereto, stirred at 3,000 to 5,000 rpm for 5 seconds, and then foamed into a mold of a predetermined shape. At this time, the temperature of the mold was set to 30 to 50 ° C, and the mold was opened and closed for demolding 10 to 15 minutes after the injection. Physical properties were measured by the method illustrated in Example 1, and the results are shown in Table 1 below.

Example 4

Hydrophilic polyurethane foam dressing material is 24% by weight of distilled water, 13% by weight of glycerin, 2.0% by weight of F-127, 0.5% by weight of hyaluronic acid, 0.5% by weight of STARTEX 201 Yellow to 60% by weight of the polyurethane prepolymer prepared in Synthesis Example 2. After the addition was stirred for 5 seconds at 3,000 ~ 5,000rpm and injected into a mold of a predetermined shape to prepare a foam. At this time, the temperature of the mold was set to 30 to 50 ° C, and the mold was opened and closed for demolding 10 to 15 minutes after the injection. Physical properties were measured by the method illustrated in Example 1, and the results are shown in Table 1 below.

Example 5

Hydrophilic polyurethane foam dressing material is 60% by weight of the polyurethane prepolymer prepared in Synthesis Example 3, 23% by weight of distilled water, 13% by weight of glycerin, 3.0% by weight of F-127, 0.5% by weight of hyaluronic acid, 0.5% by weight of STARTEX 201 Yellow The mixture was stirred for 5 seconds at 3,000 to 5,000 rpm and then injected into a mold of a predetermined shape to prepare a foam. At this time, the temperature of the mold was set to 30 to 50 ° C, and the mold was opened and closed for demolding 10 to 15 minutes after the injection. Physical properties were measured by the method exemplified in Example 1, and the results are shown in Table 1 below.

Comparative Example 1

Polyurethane prepolymer was applied to commercially available S company (Allevyn), for reference, the manufacturing method is as follows. 347 g of 2,4-toluene diisocyanate was added to a 3-liter round bottom flask equipped with a stirrer and heated to 60 ° C., followed by three hydroxyl groups. 1315 g of ethylene oxide / propylene oxide random copolymer (WRGrace & Co., Ltd. WRG-7000) Was added in small portions, and the polymerization was carried out until the theoretical NCO% was reached. Samples were taken in the middle of the reaction to determine NCO% and NCO% was determined by titrimetry using n-butylamine standard solution.

Hydrophilic polyurethane foam dressing material was added to 50% by weight of the polyurethane prepolymer synthesized as described above, 48% by weight of distilled water and 2% by weight of F-68 were stirred at a high speed of 3000 to 5000rpm, and then the mixture was cast. Prepared by lamination.

Physical properties were measured by the method exemplified in Example 1, and the experimental results are shown in Table 1 below.

As can be seen in Examples 1, 2, and 3 of Table 1, when the NCO% of the polyurethane prepolymer and the amount of glycerin as a crosslinking agent are increased, the urethane bond (hard segment) increases, thereby increasing the mechanical properties and the relatively hydrophilic part (soft The number of segments) decreases and the absorbance decreases. In Example 4 it can be seen that the degree of swelling can be adjusted according to the content ratio of the hydrophobic polypropylene glycol and hydrophilic ethylene oxide / propylene oxide random copolymer used in preparing the polyurethane prepolymer. That is, as the content of the ethylene oxide / propylene oxide random copolymer increases, the absorbency increases. As can be seen in Figure 2, the surface of the polyurethane foam dressing material is made of a thin film having a pore (pore) of 3 ~ 60㎛ diameter and the cross section is composed of a foam of open cell (open cell) structure of 50 ~ 500㎛ diameter . From this structural feature, the moisture permeability is higher than that of the existing products, and it is possible to continuously absorb the exudates due to the moisture-permeable drying of the absorbent exudates, and it is also applicable to wounds in which a large amount of exudate is generated for a relatively long time.

The hydrophilic polyurethane foam dressing material (Example 1) of the present invention showed that the number of living cells decreased by 7% and 30% for the control cell number after 1 day and 3 days, respectively, and showed excellent survival rate compared to Comparative Example 1. In addition, as a result of animal experiments, the control and the existing products were wound healing progressed by shrinkage and crust was formed, but the hydrophilic polyurethane foam dressing material of the present invention was wound healing progressed by re-epithelialization Not formed.

As can be seen from Table 1 above, by adjusting the amount of NCO% and various raw materials of the polyurethane prepolymer, the physical properties of the polyurethane foam itself, that is, tensile strength, elongation, modulus, water absorption, moisture permeability, and cell size, etc. It is possible to produce polyurethane foam dressings which can be adjusted and are widely used from wounds with few exudates to many wounds. The hydrophilic polyurethane foam of the closed dressing material of the present invention has a thin film-like skin layer 1 having a pore size of 3 to 60 µm in diameter and an open cell structure of 50 to 500 µm in diameter. It consists of an inner layer 2 of the form. From this structure, it is possible to prevent bacterial invasion from the outside and prevent regeneration cells on the wound surface from adhering to the dressing material surface, thereby preventing the pain of the patient due to the attachment during dressing material exchange. And instead of the conventional manufacturing method of manufacturing the dressing material by laminating the thin film on the polyurethane foam, it was simplified to the manufacturing process of the dressing material to simultaneously form the thin film on the foam itself by the mold foam molding method. In addition, the hydrophilic polyurethane foam dressing material of the present invention contains a surfactant, a humectant, a wound healing accelerator, an antimicrobial agent, and the like to clean the wound surface and promote the growth of regenerative cells to speed up the healing rate. In addition, it is excellent in both air permeability and moisture permeability, so that a large amount of exudates can be applied to wounds that are generated for a relatively long time, and continuous absorption of wound secretions is possible.

Claims (6)

In the hydrophilic polyurethane foam dressing material used as a closed wound covering material, The hydrophilic polyurethane foam dressing material has a thin film-like skin layer 1 having pores of 3 to 60 μm in diameter and an inner layer 2 having open cells of 50 to 500 μm in diameter. Hydrophilic polyurethane foam dressing material, characterized in that made. The method of claim 1, wherein the hydrophilic polyurethane foam dressing material and the absorbency of 760 ~ 980% by weight, physical properties, water vapor transmission rate is 7250 ~ 8500g / m hydrophilic polyurethane foam dressing material according to that characteristic ² / 24hr. In the manufacturing method of the hydrophilic polyurethane foam dressing material used as a closed wound covering material, 40 to 79% by weight of polyurethane prepolymer synthesized from at least one polyetherpolyol and diisocyanae; 15 to 45 weight percent blowing agent; 5 to 35% by weight of crosslinking agent and 1 to 15% by weight of additives including surfactant, humectant, wound healing accelerator and antibacterial agent are mixed and injected into a mold, and a thin film having a pore having a diameter of 3 to 60 μm. A method for producing a hydrophilic polyurethane foam dressing material, characterized in that the foaming and molding are carried out so that an inner layer (2) having a skin layer (1) in the form and an open cell having a diameter of 50 to 500 µm is formed. 4. The method of claim 3, wherein the polyurethane prepolymer is synthesized in a ratio of 0.15 to 0.5 molar ratio of polyether polyol to 1-3 moles of diisocyanate; The diisocyanate compound is diphenylmethane diisocyanate, 2,4-toluene diisocyanate and isomers thereof or isophorone diisocyanate or hexamethylene diisocyanate, wherein the polyether polyol has three or more hydroxyl groups in a molecule and has a molecular weight of 3,000 to A method for producing a hydrophilic polyurethane foam dressing material, characterized in that the ethylene oxide / propylene oxide random copolymer of 6,000 and 75% ethylene oxide content. 4. The method of claim 3, wherein the blowing agent is chlorofluorocarbon (CFC-141b), methylene chloride or distilled water, and the crosslinking agent is glycerol, sorbitol, polyethylene glycol or trimethylolpropane having a molecular weight of 200 to 2,000. A method for producing a hydrophilic polyurethane foam dressing material characterized by the above. The method of claim 3, wherein the additive surfactant is L-62, F-127, which is an ethylene oxide-propylene oxide block copolymer, L-5302, L-5305, or L-3150, which is a silicone-based surfactant, and the moisturizing agent and the wound. A healing promoter is hyaluronic acid, chondroitin sulfate, pectin, chitomarin or karaya gum, and the antimicrobial agent is a method for producing a hydrophilic polyurethane foam dressing material, characterized in that the silver sulferazine.