KR200323051Y1 - Antimicrobial hydrogel adhesives and biomedical electrode containing them - Google Patents

Abstract

The present invention relates to hydrogel adhesives having excellent antimicrobial properties and to biomedical electrodes including the same, specifically, obtained from a hydrogel composition containing a polymer monomer, a water-soluble chitosan, and a salt. The present invention relates to a hydrogel adhesive having excellent antimicrobial properties and a biomedical electrode including the hydrogel adhesive, all of which are excellent in antimicrobial properties and can be safely protected from contamination such as microbial infection.

Description

Antimicrobial hydrogel adhesive and biomedical electrode including the same {Antimicrobial hydrogel adhesives and biomedical electrode containing them}

The present invention relates to a hydrogel adhesive excellent in antimicrobial properties and a biomedical electrode comprising the same.

More specifically, the present invention relates to a hydrogel adhesive having excellent antimicrobial properties obtained from a hydrogel composition containing a polymer monomer, a water-soluble chitosan and a salt, and a biomedical electrode including the hydrogel adhesive.

Devices employing biomedical electrodes used in the treatment process include transcutaneous electric nerve stimulation (abbreviated as "TENS") devices for pain relief, neuromuscular muscles for treating conditions such as scoliosis, etc. A neuromuscular stimulation (NMS) device, a defibrillation electrode device that delivers electrical energy to the chest cavity of a mammalian patient to remove the fibrillation of the patient's heartbeat, or the electrical energy administered intrathecally during an electrosurgical procedure And a dispersive electrode device for accommodating the same. In addition, a device employing a biomedical electrode used in the diagnostic process includes an electric output monitor device generated from physical actions such as electrocardiogram (ECG) and electroencephalogram.

Among the therapeutic bioelectrodes, the low frequency TENS device is used to restore the motor function of the paralyzed nervous system or muscles due to damage of the central nervous system. Damage to the central nervous system due to diseases such as traffic accidents, industrial accidents, and strokes causes impairment of motor and sensory function, muscular dystrophy, ischemic necrosis, and among these symptoms, sensory function recovers to some extent as time passes. Motor function does not recover relatively, resulting in permanent sequelae. In this case, the low-frequency TENS device is used to regenerate and treat nerve and muscle functions by inducing movement effects by stimulating low-frequency nerve or muscle damage areas, and the biomedical electrodes used at this time relieve pain. It serves to deliver the mechanical electricity of the device to the human body as an electrical stimulus.

The biomedical electrode needs to be in direct contact with a part of the human body in order to induce and deliver mechanical electricity to the human body as an electrical stimulus, but the biomedical electrode and the skin are electrically connected only to the skin of the human body. The electrical stimulation cannot be accurately transmitted because complex potentials or impedances are generated due to unstable contact between the biomedical electrode and the skin without bonding. Therefore, the biomedical electrode is usually attached to the living body through a conductive hydrogel adhesive capable of inducing and delivering a stable electrical stimulus by bringing the biomedical electrode into close contact with the skin and at the same time.

That is, the low frequency TENS device uses a conductive medium called a hydrogel adhesive in the bioelectrode to deliver mechanical electricity to the human body as an electrical stimulus. The quality of the electrode depends on the degree of microcurrent reception due to the impedance difference of the conductive hydrogel adhesive. If the adhesion is not excellent, the economic value is lowered due to the impossibility of repeated use of the electrode.

Medical hydrogels are generally prepared by adding synthetic polymers such as polypyrrolidone, polyhydroxyacrylate, polyvinyl alcohol, polyamide, acrylic acid, and thickeners such as glycerol and polyethylene oxide to natural polymers such as gelatin and agar.

As a method of preparing the hydrogel, a chemical crosslinking method and a radiation crosslinking method are used. In the case of the chemical method, the polymer is crosslinked using an initiator and a crosslinking agent to prepare a hydrogel, whereas the radioactive crosslinking method crosslinks the hydrogel composition using radiation, for example, ultraviolet rays, in the above process. Let's do it.

In the case of the chemical method, for example, polyvinyl alcohol can be crosslinked by using formaldehyde as a crosslinking agent and repeatedly freezing and thawing, but it is not easy to remove residual aldehyde after crosslinking, so toxicity by aldehyde is a problem. Hydrogels produced by repeated freezing and thawing have problems in using them as adhesives due to poor mechanical properties.

In order to solve the above problems, a method of preparing a hydrogel adhesive using a radiation crosslinking method has been developed. In the process of producing hydrogels using radiation, for example ultraviolet rays, initiators such as 1-hydroxycyclonuxylphenylketone, 2,2-dimethoxy-1,2-diphenylethan-1-one or 2 Initiators or crosslinking agents such as hydroxy-2-methyl-1-phenylpropan-1-one, for example polyethylene glycol dimethacrylate, polyethylene glycol methacrylate or polypropylene glycol methacrylate, By adjusting the dosage, it is possible to control the physical properties of the hydrogel without changing the composition.

Hydrogel prepared by the above method is composed of a three-dimensional network structure and contains a large amount of water by the hydrophilic functional group and capillary or osmotic pressure. The reason why the hydrogel does not dissolve in water is due to the covalent bonds of the polymer bonding properties, although there are some electrostatic and lipophilic interactions. That is the basic element of hydrogels.

Medical hydrogels have affinity with blood, body fluids and biological tissues, and thus are used in general biomedical materials such as hydrogel adhesives, contact lenses, image dressing agents and artificial cartilage. In particular, the conductive hydrogel adhesive should have electrical properties and properties that can adhere to the surface of the living body while maintaining the above properties.

U.S. Patent 5,258,421 describes a process for preparing hydrogel dressings using polyvinyllactam and polyurethane, including polyvinylpyrrolidone.

International Patent Publication No. WO 00/06214 discloses the use of acrylic acid substituted by 2-acrylamido-2-methylpropanesulfonate or sulfopropyl ester salt, polyethylene glycol diacrylate, Pluronics (BASF) and the like. Conductive hydrogel with excellent suitability was prepared and applied to biomedical electrodes, burn dressings and the like.

In US Pat. No. 5,868,136, a salt, acrylic acid, vinylpyrrolidone, a crosslinking agent, a thickening agent, etc. were combined to prepare a biomedical electrode, and a conductive hydrogel adhesive was prepared by using an ultraviolet crosslinking method. Hydrogel pressure-sensitive adhesive in the patent is configured to have a multi-layer structure, the electrode contact surface and the skin contact surface is characterized by having a different adhesive force.

However, the conductive hydrogel adhesive has no function of preventing contamination from microorganisms, and thus, it is very likely to be contaminated by microorganisms during the production process or use to infect a patient or to transfer contamination to other patients. In addition, during the period from the production of biomedical electrodes to the movement, storage and use, contaminated microorganisms may proliferate and spread the damage.

In particular, low-frequency TENS device is used by patients with paralysis of the central nervous system, and these patients have a high possibility of contamination from microorganisms and metastases to other patients due to weakened immune function and skin disease due to long bed life. In addition, the biomedical electrode of low frequency TENS device is a first-class non-sterile item under the Korean Medical Equipment Authorization Act, and the possibility of expanding contamination to relatively weak immunity to infants, children, and the elderly is also on the rise of the expansion of household low frequency treatment devices. Soybeans.

U.S. Patent No. 5,420,197 describes a method for preparing a tacky hydrogel by mixing polyvinyllactam and chitosan and radiocrosslinking crosslinking. The patent describes a correlation between chitosan and vinylpyrrolidone for application of the prepared hydrogel to a dressing agent for burn treatment, a matrix for drug delivery, and a cosmetic product.

However, the patent did not recognize any antibacterial properties due to chitosan, and none of them have been verified.

All references cited herein are hereby incorporated by reference in their entirety.

The present inventors have endeavored to impart antimicrobial activity to the existing conductive hydrogel pressure-sensitive adhesive, and completed the present invention by confirming that the antimicrobial activity of the hydrogel was remarkably improved when the hydrogel was prepared by adding a water-soluble chitosan to the hydrogel composition.

An object of the present invention is to provide a method for producing a hydrogel adhesive with excellent antimicrobial properties and a biomedical electrode comprising an antimicrobial hydrogel adhesive prepared by the method.

1 is a perspective view of a conductive hydrogel adhesive wound in a roll shape,

2 is a perspective view of a biomedical electrode of a low-frequency TENS device,

3 is a cross-sectional view of FIG. 2,

4 is an exploded perspective view of FIG. 2;

5a is a graph showing the number of unattached strains according to the contact time with the strain solution of the hydrogel,

Figure 5b is an electron micrograph showing the appearance of E. coli attached to the upper hydrogel surface of the hydrogel pressure-sensitive adhesive specimen used in the test example of Figure 5a,

Figure 5c is an electron micrograph showing the appearance of E. coli attached to the lower hydrogel surface of the hydrogel pressure-sensitive adhesive specimen used in the test example of Figure 5a,

Figure 6a is a graph showing the antimicrobial activity according to the contact time with the strain solution of the hydrogel,

FIG. 6B is an electron microscope photograph of the E. coli separated from the aqueous solution in the test example of FIG.

6C is an electron micrograph of E. coli ruptured by rupturing the cell membrane by the antimicrobial activity of the conductive hydrogel adhesive in the test example of FIG.

* Explanation of symbols for main parts of the drawings

1: base; 1a: base adhesive;

2: connecting line; 2a: carbon fiber;

2b: insulation covering; 2c: connecting terminal;

3: film electrode; 4: antimicrobial hydrogel adhesive;

5: release film; 100: biomedical electrode

11: reinforcing material; 12b: bottom antimicrobial hydrogel;

12a: top antimicrobial hydrogel; 13a: upper release film;

13b: lower release film 200: antimicrobial hydrogel adhesive

In order to achieve the above object, the present invention provides a hydrogel excellent in antimicrobial properties obtained by cross-polymerizing the polymer monomer and water-soluble chitosan by radiation from a hydrogel composition comprising a polymer monomer, a water-soluble chitosan and a salt.

In another aspect, the present invention provides a biomedical electrode comprising an antimicrobial hydrogel according to the present invention.

Hereinafter, the present invention will be described in detail.

First, the present invention provides an antimicrobial hydrogel composition.

The hydrogel composition according to the present invention includes a polymer monomer, a water-soluble chitosan and a salt, and may optionally include a thickener and an ultraviolet initiator.

As the polymer monomer, all of the polymer monomers that can be used in the preparation of the hydrogel may be used, but it is preferable to include acrylic acid and vinylpyrrolidone, and more preferably polyethylene glycol dimethacrylate. Include.

The polymer monomer is preferably included in an amount of 40 to 50% by weight based on the total weight of the hydrogel composition, specifically, 30 to 40% by weight of vinylpyrrolidone, 5 to 15% by weight of acrylic acid and 0 to 0.2% by weight of polyolefin. Ethylene glycol dimethacrylate.

As the water-soluble chitosan, commercially available chitosan derivatives can be used.

Chitosan, which exists in nature, is insoluble, but it becomes water-soluble when protons are obtained from acids and become derivatives.

Specifically, it is preferable to include 3 to 10% by weight of water-soluble chitosan with respect to the total weight of the hydrogel composition.

In order to secure biological stability of biomedical materials, it is very important to prevent contamination from microorganisms. Depending on the condition of the patient when the biomedical material contaminated with microorganisms comes into contact with the human body, particularly in patients undergoing surgery, fatal consequences may occur. The microorganisms prefer to be attached to the surface of the biomedical material rather than to be suspended in a liquid, and in the case of the hydrogel adhesive, there is a high risk of exposure to such microorganisms. Factors involved in microbial adhesion include microbial characteristics, microbial properties such as surface charge and chemical composition of materials, and material surface properties such as surface charge, hydrophobicity, roughness and surface energy.

Chitin is contained in mollusks such as crustaceans such as crabs and shrimps, grasshoppers and crickets, squids and octopus, and deacetylated the chitin to produce chitosan. Chitosan is therefore a generic term for the deacetylated compounds of chitin and is the second most abundant natural polymer after cellulose on earth.

Chitosan is useful as a biomedical material because of its excellent biocompatibility, antimicrobial activity, and biohealing, and it is possible to prepare a polymer gel having excellent adhesiveness by crosslinking chitosan aqueous solution using a radiation crosslinking method. In addition, chitosan may be mixed with synthetic polymers such as polyvinyl lactam, polyvinylpyrrolidone, acrylic acid, acrylamide, and then crosslinked to prepare a hydrogel, and in the case of the above method, the adhesiveness, mechanical properties, and water functionality are excellent. Therefore, it is usefully used in general biomedical materials including artificial organ materials.

Uchida has claimed that chitosan has antimicrobial properties because it contains amine groups (Antimicrobial characteristics of chitin and chitosan, Food Chemistry , Vol. 2, pp 22-29; 1988), and Hughes The antimicrobial activity varies according to the number of amine groups, and it is generally described that the antimicrobial activity increases as the number of amine groups increases (The role of cellulosics in chitosan flocculation of Zymomonas mobilis, Biotechnology Techniques , Vol. 8, pp 541-546; 1994 .)

Regarding the principle of the antibacterial action of chitosan, first, the water-soluble chitosan is positively charged by the formation of ammonium ions (NH2 ⁺ ), and when the water-soluble chitosan is polymerized to form a gel, the surface of the hydrogel is positively charged.

On the other hand the microbial cells such as bacteria consist of cell membrane and the cell wall, and a carboxyl group (COO ^-) surface charge of the cell wall when in contact with the hydrogel adhesive surface which is charged to a positive charge it is charged to the same negative charge and generate electrostatic each charge It is joined by force. Iii) microbial cell wall permeation and migration of the hydrogel tackifier positive charge after the positive charge adsorption and adsorption step of the hydrogel tackifier on the microbial cell surface; Iii) binding to the microbial cell membrane of the positive charge of the hydrogel adhesive; Iii) disruption of the microbial cell membrane; Iii) releasing cell membrane constructs such as potassium ions, deoxyribonucleic acid (DNA), ribonucleic acid (RNA) from the disrupted cell membrane of the microorganism; And iii) microbial dissociation (bacterocide) process is carried out as a step of destruction of microbial cells.

Therefore, the hydrogel of the present invention containing water-soluble chitosan is charged to the surface of the present invention to be electrostatically coupled to the cell wall of the microorganism and then to have an antimicrobial activity through the microbial dissociation process.

The salts may be any salts that can be used in the manufacture of a conductive hydrogel, but preferably include salts capable of releasing chlorine ions, and more preferably potassium chloride.

The composition of the present invention may optionally include a thickener, and all of the thickeners commonly used in the preparation of hydrogels may be used. It is preferable to use polyethylene oxide as a thickener, and it is more preferable to use polyethylene oxide of about 30,000-40,000 in molecular weight.

In addition, the composition of the present invention may include an ultraviolet initiator, which is ionized to dissociate with ultraviolet radiation to form a radical, and is transferred to the vinyl group of the polymer composition to cause polymerization of the polymer composition. Let's do it. Usually, all the UV initiators that can be used in the hydrogel production method by ultraviolet irradiation can be used, but preferably includes 1-hydroxycyclonucleophenylphenyl ketone.

Specifically, in the present invention, 30 to 40% by weight of vinylpyrrolidone, 5 to 15% by weight of acrylic acid, 0 to 0.2% by weight of polyethylene glycol dimethacrylate, 0 to 5% by weight of polyethylene oxide, 3 to 10 A hydrogel composition is provided comprising wt% water soluble chitosan, 0-0.1 wt% 1-hydroxycyclonuxylphenylketone, 3-7 wt% potassium chloride and distilled water.

In the present invention, an antimicrobial hydrogel is prepared by cross-polymerizing the polymer monomer and the water-soluble chitosan by treating UV with a hydrogel composition including a polymer monomer, a water-soluble chitosan, a thickener, an ultraviolet initiator, and a salt.

Specifically, in the present invention 30 to 40% by weight of vinylpyrrolidone, 5 to 15% by weight of acrylic acid, 0 to 0.2% by weight of polyethylene glycol dimethacrylate, 0 to 5% by weight of polyethylene oxide, 3 to A hydrogel composition comprising 10% by weight of water-soluble chitosan, 0-0.1% by weight of 1-hydroxycyclonuxylphenylketone, 3-7% by weight of potassium chloride and distilled water was irradiated with ultraviolet light to vinylpyrrolidone, acrylic acid, polyethylene Hydrogels are prepared by cross-polymerizing glycoldimethacrylate and water-soluble chitosan.

In one embodiment of the present invention, to provide a multi-layer hydrogel pressure-sensitive adhesive in order to improve the adhesiveness and durability in using the hydrogel as a biomedical adhesive.

Specifically, the present invention 1) preparing a hydrogel composition stirred solution containing a water-soluble chitosan; 2) impregnating the reinforcing material and irradiating with ultraviolet rays to primary crosslinking; 3) It provides a multi-layer hydrogel pressure-sensitive adhesive prepared by the step of sprinkling a hydrogel composition stirring solution on the top of the cross-linked product prepared by the above process and irradiating with ultraviolet rays.

The reinforcing material is used to improve the physical strength of the hydrogel adhesive, and it is preferable to use a nonwoven fabric having a mesh structure. More preferably, non-woven fabrics prepared in a wet and spunbonded manner and containing a synthetic resin such as polyester, polyethylene, polypropylene, nylon, cellulose, and the like are used.

Specifically, the present invention uses a nonwoven fabric having a thickness of 0.1 to 0.25 mm and a weight of 10 to 35 g.

The hydrogel pressure-sensitive adhesive for reinforcing material to improve the physical strength of the hydrogel; An upper antimicrobial hydrogel attached to one side of the reinforcing material; And a lower antimicrobial hydrogel attached to the other side of the reinforcement. At this time, the upper antimicrobial hydrogel includes a soft upper layer by one crosslinking treatment and a hard lower layer by two crosslinking treatments.

In addition to the above, it is preferable to include a release film applied to the non-contact surface of the upper and lower hydrogel for hydrogel protection. In this case, as the release film, a film in which silicon or fluorine is treated on one surface of a polyethylene terephthalate material may be used.

Hydrogel adhesive 200 of the present invention as shown in Figure 1 is a reinforcing material (11); An upper antimicrobial hydrogel 12b attached to one surface of the reinforcing material; A lower antimicrobial hydrogel 12a attached to the other side of the reinforcing member; The upper release film 13a covering the upper surface of the upper hydrogel and the lower release film 13b covering the lower surface of the lower hydrogel are included.

The multi-layer hydrogel thickener according to the present invention contains water-soluble chitosan, which has excellent antibacterial properties, includes a reinforcing material, improves physical strength, and includes a multi-layered hydrogel having different structures and physical properties, thereby effectively mediating electrodes and skin. Can be. That is, the lower hydrogel bonded to the bottom of the reinforcing material is thin and has relatively hard physical properties through primary and secondary crosslinking, resulting in poor adhesion repeatability but excellent adhesion, and thickening due to spreading after primary crosslinking. The upper hydrogel loses the adhesive strength, but the additional spreading portion has a relatively flexible physical property due to UV treatment only once, and thus has excellent adhesive repeatability. Therefore, the upper and lower surfaces can be selected and used appropriately according to the use and the physical properties of the adhesive surface.

In addition, the multi-layer hydrogel pressure sensitive adhesive according to the present invention is produced continuously on a continuous moving means, it is preferable to be wound and stored in a roll shape (see Fig. 1).

The hydrogel adhesive is used by appropriately cutting according to the use form and conditions.

Hydrogel according to the present invention is not limited to the pressure-sensitive adhesive can be used in any use mode in which the biomedical hydrogel can be used, it can be particularly useful as a biomedical pressure-sensitive adhesive for mediating the living body and medical devices or devices.

The present invention provides a biomedical electrode excellent in antimicrobial including the antimicrobial hydrogel according to the present invention.

Specifically, the biomedical electrode of the present invention has a pressure-sensitive adhesive surface coated with an adhesive on one surface of the base to support the film electrode and the connection line; A film electrode attached to the adhesive surface of the base; A connection line positioned between the adhesive face of the base and the film electrode and connected to a power source; Antimicrobial hydrogel pressure-sensitive adhesive according to the present invention covering one surface of the film electrode; And a release film for protecting the other surface of the hydrogel pressure-sensitive adhesive.

The base is composed of a foam pad, a nonwoven fabric or a woven fabric containing a polymer material, and the polymer material may be a synthetic polymer such as polyethylene, polypropylene, nylon, or the like, and is formed into a film. At this time, it is preferable that the acrylic non-irritating adhesive is applied to the adhesive surface of the base.

The film electrode may be an electrode of any material and form used in a conventional biomedical electrode, but is preferably composed of a polyethylene film mixed with carbon powder.

The connection line is for connecting to a power source of a medical device to which the biomedical electrode is coupled, and specifically, in the present invention, is connected to a lead wire of a low frequency TENS device. In the present invention, the connecting line is a string-shaped member covering carbon fibers with an insulating material, and a connecting terminal covering the insulating material with nickel plated brass material is mounted at the tip thereof.

According to one embodiment of the present invention, as shown in Figures 2 to 4, the biomedical electrode 100 is a film-based base of the polyethylene non-woven material consisting of a pressure-sensitive adhesive surface (1a) coated with an acrylic pressure-sensitive adhesive on one surface (One); A film electrode (3) of polyethylene material attached to the adhesive face (1a) of the base (1) and mixed with carbon powder; Nickel is present between the film electrode 3 and the base adhesive surface (1a), insulated carbon fiber (2a) with a soft fibrous (2b) and connected to the lead wire (not shown) of the low-frequency TENS device at the tip A connecting line 2 equipped with a connecting terminal 2c having a soft fibish insulated covered with this plated brass material; An antimicrobial hydrogel adhesive (4) provided to cover the exposed portion of the polyethylene film electrode (3); And a release film 5 treated with silicon or fluorine on one surface of a polyethylene terephthalate material protecting the other surface of the hydrogel adhesive.

On the other hand, it is well known that the biomedical electrode 100 is not limited in shape and may be modified depending on the intended use.

The biomedical electrode according to the present invention uses an antimicrobial hydrogel pressure sensitive adhesive according to the present invention, and thus has excellent antibacterial properties and is safe against microbial infection.

The present invention is described in more detail with reference to the following examples, but the scope of the present invention is not limited to these examples, and various modifications and variations are possible within the protection scope of the present invention described in the claims. It will be apparent to those of ordinary skill in the art.

Example 1. Preparation of Hydrogel Adhesive

40 g of potassium chloride, 80 g of acrylic acid, 340 g of vinylpyrrolidone, 40 g of water-soluble chitosan, 1.2 g of polyethylene glycol dimethacrylate, 20 g of polyethylene oxide and 0.4 g of 1-hydroxycyclonucleosilphenylketone were sequentially injected and then stirred at 100 rpm for 20 minutes.

On the continuous transfer system moving at 10 meters per minute, the hydrogel stirred solution was continuously impregnated with a non-woven mesh prepared in a wet manner, and firstly crosslinked by exposing ultraviolet rays to an intensity of 250 W / cm, and then the first crosslinked product. A hydrogel pressure-sensitive adhesive was prepared by spreading a hydrogel stirring solution on the top and secondly crosslinking by exposing ultraviolet light at an intensity of 150 W / cm.

In order to protect the upper and lower hydrogels of the hydrogel pressure-sensitive adhesive obtained in the above process, the release film was reinforced on both sides, and the above-mentioned manufacturing process was carried out continuously, and the final pressure-sensitive adhesive product was wound in a roll shape using a finish recovery roller or the like.

4 shows a hydrogel adhesive prepared by the above process.

Test Example 1. Adhesion Test of Hydrogel Adhesive

The hydrogel adhesive obtained according to the method of Example 1 was cut to a size of 1 x 1 cm and placed in a sterilized plastic dish plate (Petri dish) and sealed with a Para film, and then in a clean bench. UV sterilization was carried out to prepare a hydrogel adhesive specimen for adhesion measurement.

Gram-positive strains such as Staphylococcus aureus ( S. aureus ) and Gram-negative strains ( E. coli ) and P. aerginosa were used as strains to confirm the adhesion of the strain according to the contact time of the hydrogel adhesive. . In addition, the strain seeds were inoculated and sealed in a refrigerated test tube filled with agar medium.

Strain solution was taken from the strain seed stored in the refrigerator in a clean bench sterilized by ultraviolet light, and each strain was taken from platinum by flame sterilization, and the strain was put in 100 ml of a pre-prepared strain propagation medium. Incubated at 150 rpm for 20 hours in a pre-maintained stirred incubator at 20 ° C. to prepare a strain solution of about 10 ^9, which was refrigerated.

As a culture medium for strain propagation, put 1 l of distilled water, 3 g of Beef extract, 5 g of eptone, and 15 g of Agar in a sterilized sterilized 1 L Erlenmeyer flask, boil until bubbles are raised, and seal with aluminum foil and sterilize in a pressure sterilizer. What was prepared was used.

According to the hydro-contact time of the gel adhesive specimen and strain to determine the number of the strain attached to the pressure sensitive adhesive samples, 10 ⁵ per number ㎖ of strain into the strain solution and sterilized distilled water in a test tube of a high pressure sterilization 15 ㎖ capacity It was prepared to maintain the degree, and the hydrogel pressure-sensitive adhesive specimen was added to the solution and contacted at 100 rpm in a stirring incubator maintained at 37 ℃ while the degree of adhesion of the strain to the surface of the hydrogel adhesive was observed according to the contact time. The water was identified by distilled water dilution method.

Number of strains unattached to antimicrobial hydrogel adhesive Strain type Strain contact time (minutes) 0 15 30 45 60 Escherichia coli 2.6 × 10 ⁵ 2.6 × 10 ⁴ 7.1 × 10 ² 6.2 × 10 ² 3.3 × 10 ² Staphylococcus 1.7 × 10 ⁵ 8.2 × 10 ² 8.7 × 10 ¹ 3.4 × 10 ¹ 3.1 × 10 ¹ Rust 3.1 × 10 ⁵ 4.8 × 10 ⁴ 1.2 × 10 ⁴ 7.2 × 10 ² 6.7 × 10 ²

As shown in the log value graph of Table 1 and Figure 5a, the number of strains attached to the hydrogel pressure-sensitive adhesive generally increased with the contact time between the strain and the hydrogel pressure-sensitive adhesive, showing different differences depending on the type of strain It was.

These results were due to the degree of movement of the strains, showing a relatively high degree of adhesion of Staphylococcus aureus compared to Escherichia coli or Rustic bacteria. 5A to 5C show electron micrographs of the hydrogel adhesive to which E. coli is attached from the results of FIG. 5A. FIG. 5B shows the upper hydrogel surface (12a, see FIG. 1) of the hydrogel pressure sensitive adhesive, and FIG. 5C shows the lower hydrogel surface (12b, see FIG. 1) of the hydrogel pressure sensitive adhesive. The results show that E. coli adherence to the gel surface is excellent.

From the results of FIGS. 5A to 5C, the adhesion degree of the strains to the surface of the hydrogel adhesive was confirmed, and the adhesion repeatability of the hydrogel was superior to the adhesion of the microorganisms to the surface of the upper hydrogel, which is advantageous to be applied to the human body. When using a medical electrode was confirmed that the possibility of skin infection.

Test Example 2 Antimicrobial Test of Hydrogel Adhesive

The antimicrobial activity of the hydrogel adhesive prepared according to Example 1 was evaluated by observing the growth inhibitory effect of bacteria (bacteria) using a shake flask technique. Specifically, the antimicrobial activity was measured by the growth inhibition rate of the bacteria by putting the specimen of the hydrogel adhesive of a certain size in a strain solution and shaking the culture in a stirrer for a certain time and then measuring the number of living bacteria.

Strain solution, antibacterial culture and hydrogel pressure-sensitive adhesive specimens for antimicrobial measurement were used in the same manner as in Test Example 1. In order to measure the antimicrobial activity of the hydrogel adhesive, 9 ml of the strain propagation culture medium, 1 ml of the strain solution, and the prepared hydrogel adhesive specimen were placed in a 15 ml test tube, and sealed using a polymer foam which was unable to pass the bacteria. The culture was carried out with stirring at 150 rpm in a stirred incubator maintained at 37 ℃.

And distilled water dilution method was used to measure the number of fleshy bacteria according to the contact time between the hydrogel specimen and the strain by the culture.

1 ml of the solution was taken from the specimen-strain culture at regular contact time intervals, and then diluted into 10 ^-1 times by homogeneous mixing using a ball stirrer (Vortex) and repeating the above procedure. By dilution to 10 ^-10 fold.

Take 100 μl from each dilution water and drop it in the center of flat agar medium in a plastic watch plate prepared in advance and homogeneously spread it on the whole surface of the agar medium using a sterilized spreader glass rod. The number of living bacteria was measured by confirming the number of colonies of the strains formed by culturing for 15 hours or more with the upper part of the watch plate as the upper surface of the dryer in the maintained dryer.

The flat agar medium used in the above was placed in a sterilized 2 L Erlenmeyer flask with 1 L of distilled water and 23 g of Nutrient agar, boiled until bubbles were raised, and then added with aqueous sodium hydroxide solution to pH 6.8. After preparing the agar medium solution by sealing and sterilizing in a pressure sterilizer, the agar medium solution maintained at 50 ° C. in a plastic petri dish of 100 ml in diameter in a clean bench sterilized by ultraviolet rays was applied to one third. Fill it to a constant height and keep it at room temperature for 30 minutes to make it solid, and then, in the dryer previously maintained at 37 ℃, direct the top of the agar medium to the bottom of the dryer and dry it for 2 hours to remove moisture. Agar medium was prepared.

Number of live strains unattached to antimicrobial hydrogel adhesive Strain type Strain contact time (hours) 0 12 24 36 48 60 Escherichia coli 1.2 × 10 ⁸ 6.7 × 10 ⁴ 6.2 × 10 ³ 4.7 × 10 ² 4.5 × 10 ² 8.8 × 10 ¹ Staphylococcus 1.4 × 10 ⁸ 8.6 × 10 ² 7.4 × 10 ² 2.8 × 10 ² 5.1 × 10 ¹ 4.8 × 10 ¹ Rust 1.3 × 10 ⁸ 8.9 × 10 ⁶ 2.3 × 10 ⁵ 6.8 × 10 ² 9.1 × 10 ¹ 8.8 × 10 ¹

As can be seen in the graph of Table 2 and Figure 6a, the number of live strains decreased with increasing contact time of the hydrogel pressure-sensitive adhesive specimen and the strain solution, the antimicrobial activity of the hydrogels Staphylococcus, E. coli, and It was found in the order of rust.

These results were due to the degree of movement and morphological aspects of the strains. Staphylococcus aureus, which has more contact with hydrogel than Staphylococcus aureus and Escherichia coli, has many contact opportunities with hydrogel, and Staphylococcus aureus. Is a gram-negative bacterium that has only a simple cell membrane, and thus has a weaker structure compared to E. coli or rust bacillus, which has a double structure of cell membrane and cell wall.

6A to 6C show the appearance of dead Escherichia coli due to the antibacterial activity of the antimicrobial hydrogel adhesive in the strain solution from the results of FIG. 6A. Figure 6b shows the appearance of Escherichia coli, the cell membrane and cell wall of the Escherichia coli are broken and completely lost activity due to the infiltration of some of the external strain solution into the cell, Figure 6c is a cell membrane and cell wall of Escherichia coli completely collapsed through the process of Figure 6b It is a result that shows the lost form as an individual.

From the above results, it was confirmed that the antimicrobial activity of the hydrogel adhesive according to the present invention is excellent.

As described above, the hydrogel adhesive according to the present invention and the biomedical electrode using the same have excellent antibacterial properties and have an advantage of being able to be safely protected from infection of microorganisms.

Claims (15)

Reinforcing materials to improve the physical strength of the hydrogel; An upper antimicrobial hydrogel attached to one side of the reinforcing material; A hydrogel pressure-sensitive adhesive further comprising a lower release film covering a lower antimicrobial hydrogel attached to the other side of the reinforcing material and optionally covering an upper surface of the upper antimicrobial hydrogel and a lower release film covering the lower surface of the lower antimicrobial hydrogel. The hydrogel adhesive of claim 1, wherein the upper and lower antimicrobial hydrogels comprise water soluble chitosan. 3. The polymer monomer and water soluble chitosan according to claim 1 or 2, wherein the upper and lower antimicrobial hydrogels comprise a polymer monomer, a water soluble chitosan and a salt, and optionally from a hydrogel composition comprising a thickener and an ultraviolet initiator. Hydrogel adhesive obtained by crosslinking polymerization. The hydrogel pressure-sensitive adhesive according to claim 3, wherein the upper antimicrobial hydrogel comprises a soft upper layer by one crosslinking treatment and a hard lower layer by two crosslinking treatments. The hydrogel adhesive of claim 1, wherein the reinforcing material is a nonwoven fabric. The method of claim 5, wherein the reinforcing material is produced in a wet and spunbonded manner, containing polyester, polyethylene, polypropylene, nylon or cellulose having a thickness of 0.1 to 0.25 mm and a weight of 10 to 35 g Hydrogel adhesive composed of material. The hydrogel adhesive according to claim 1, wherein the release film is made of polyethylene terephthalate and treated with silicon or fluorine on one surface thereof. A base having a pressure-sensitive adhesive surface coated with a pressure-sensitive adhesive on one surface and attaching a film electrode and a connection line; A film electrode attached to the adhesive surface of the base; A connection line positioned between the adhesive face of the base and the film electrode and connected to a power source; A hydrogel adhesive covering one surface of the film electrode; And Biomedical electrode comprising a release film to protect the other surface of the hydrogel pressure-sensitive adhesive. The biomedical electrode of claim 8, wherein the base is made of a foam pad, a woven fabric, or a nonwoven fabric including a polymer material. The biomedical electrode according to claim 8 or 9, wherein an acryl-based bio-non-irritating adhesive is applied to the adhesive surface of the base. The biomedical electrode according to claim 8, wherein the film electrode is made of a polyethylene film mixed with carbon powder. The biomedical electrode according to claim 8, wherein the connecting line is a string-shaped member covering carbon fibers with an insulating material, and a tip thereof is provided with a connecting terminal covering the insulating material with a nickel plated brass material. The biomedical electrode according to claim 8, wherein the hydrogel adhesive comprises a polymer monomer, a water-soluble chitosan and a salt, and optionally cross-polymerizes the hydrogel composition by irradiating ultraviolet rays to a hydrogel composition including a thickener and an ultraviolet initiator. The hydrogel composition according to claim 8 or 13, wherein the hydrogel pressure-sensitive adhesive comprises a polymer monomer, a water-soluble chitosan and a salt, and optionally impregnates a reinforcing material into the hydrogel composition including a thickener and an ultraviolet initiator, and then irradiates with ultraviolet rays to form a primary crosslinking. A biomedical electrode which is polymerized, and further spreads the hydrogel composition, and is irradiated with ultraviolet rays to undergo secondary crosslinking polymerization. The biomedical electrode according to claim 8, wherein the release film is a material in which silicon or fluorine is treated on one surface of polyethylene terephthalate.