KR101741909B1 - System for evaluating antibiosis efficacy of photo-functional endotracheal tube for respiratory system in condition similar to in vivo environment - Google Patents

System for evaluating antibiosis efficacy of photo-functional endotracheal tube for respiratory system in condition similar to in vivo environment Download PDF

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KR101741909B1
KR101741909B1 KR1020150138937A KR20150138937A KR101741909B1 KR 101741909 B1 KR101741909 B1 KR 101741909B1 KR 1020150138937 A KR1020150138937 A KR 1020150138937A KR 20150138937 A KR20150138937 A KR 20150138937A KR 101741909 B1 KR101741909 B1 KR 101741909B1
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porphyrin
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김용록
정석훈
왕강균
정승진
황정욱
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연세대학교 산학협력단
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Abstract

The present invention relates to a system for evaluating the antimicrobial efficacy of a photofunctional intracoronary tube for a respiratory organ under similar environmental conditions in vivo, comprising a thermostat; A first container disposed in a thermostat; A second container disposed in a thermostat; A first catheter, one end of which is inserted into a first container, the first catheter containing a polymer resin and a photosensitizer, the light being blocked; A second catheter having one end inserted into the second container, the second catheter containing a polymer resin and a photosensitizer; And a light source for irradiating light to the second catheter.

Description

TECHNICAL FIELD [0001] The present invention relates to a photo-functional endotracheal tube for respiratory system in a vivo environment,

The present invention relates to a system for assessing the antimicrobial efficacy of a photofunctional endotracheal tube for a respiratory organ under similar environmental conditions in vivo.

A respiratory tract infection associated with the insertion of an endotracheal tube (ET tube) is an infection caused by a pathogenic organism colonized in the organ insertion tube inserted in the patient's respiratory tract. On the second chest radiogram, two or more of the three lung abscesses were found: a body temperature of 38 ° C or more, purulent organs and bronchial secretions, leukocytosis or increase (<4,000 or> 11,000 / ㎣) And may be diagnosed when the patient has evidence of the disease.

Patients with general anesthesia, apnea, cardiac arrest, respiratory insufficiency, upper respiratory tract injury, head and neck injuries, and severe facial burns are equipped with a respiratory insertion tube. The probability of having respiratory infection is about 9.7%. In intensive care unit patients, 90% of hospital-acquired pneumonia (HAP) occurs during the insertion of the tube, and the mortality rate of HAP is about 30-70%. The incidence of pneumonia in patients with tracheal inserting tubes increases with the duration of the placement. Most organ insertion tubes are short-term, so all associated pneumonia occurs within the first four days. The tube insertion procedure itself contributes to the risk of infection.

Bacteria that are resistant to broad-spectrum antimicrobial agents are common in infectious agents caused by the insertion of an insertion tube. Acinetobacter and Pseudomonas aeruginosa are the most common causative bacteria among non-fermented Gram-negative bacilli.

As for the types of the intraluminal endotracheal tube (catheter) for prevention of respiratory infections, the current status of development of the antimicrobial respiratory endotracheal tube is as follows. First, as a surface polishing catheter, it is a catheter that polishes the surface to inhibit bacterial deposition. Second, as a hydrophilic catheter, a catheter is coated with a hydrogel to delay the deposition of a bacterial microorganism. Third, as a drug release type catheter, a catheter is coated with an antimicrobial agent. Fourth, a mitochondrial activity inhibiting enzyme introduction catheter is an antimicrobial catheter that introduces mitochondria into a catheter. Fifth, as a photo-functional catheter, a catheter having a photosensitizer incorporated therein and having antimicrobial activity by the active oxygen generated through light energy induction.

A study on the necessity of evaluating the antimicrobial properties of respiratory tract insertion tubes to prevent respiratory infections suggests that respiratory diseases are the major cause of pneumonia in hospitals that account for 60% of deaths from hospital infections. According to the report, "Multicenter Intervention Research and Effect Analysis for Prevention of Pneumonia Associated with Respiratory Pneumonia," which was prepared by Hallym University Medical School with the request of the Disease Control Center, it was reported to KONIS from July 2009 to June last year Among the 3965 infections in the hospital, 699 cases (17.6%) were pneumonia. Of these, 410 (58.7%) were ventilator-associated pneumonia (VAP), a device that supplies oxygen to respiratory or anesthetic surgical patients.

Patients receiving mechanical ventilation through a ventilator in the intensive care unit are at high risk for pneumonia in hospitals, among which VAP is known to contribute to higher mortality. Patients using artificial respirators are most likely to have severe facial weakness and may become contaminated with germs during ventilator operation or contaminate the joints if the ventilator is prolonged. Despite this seriousness, the standardized research system for the antimicrobial properties of catheters is a pity. Assessment of contaminant and antimicrobial efficacy for the currently used respiratory tract internal canal was primarily based on the catheter used. It is difficult to quantify the exact antimicrobial efficacy due to the fact that individual characteristics of the patient and environmental factors are not taken into consideration.

It is an object of the present invention to provide a system for evaluating the antimicrobial efficacy of a photofunctional intracoronary tube for a respiratory organ under similar environmental conditions in vivo.

In order to achieve the above-mentioned object, A first container disposed in a thermostat; A second container disposed in a thermostat; A first catheter, one end of which is inserted into a first container, the first catheter containing a polymer resin and a photosensitizer, the light being blocked; A second catheter having one end inserted into the second container, the second catheter containing a polymer resin and a photosensitizer; And a light source for irradiating light to the second catheter.

The device according to the present invention may further comprise an optical fiber connecting the second catheter and the light source.

In the present invention, the temperature of the thermostat may be 30 to 50 캜.

In the present invention, the photosensitizer may include at least one selected from the group consisting of a porphyrin compound and its substituent, a phthalocyanine compound, a substituent thereof, and a dye.

In the present invention, the photosensitizer is 5,10,15-triphenyl-20- (4-carboxyphenyl) -porphyrin platinum (PtCP), 5,10,15- 5,15-Bisphenyl-10,20-bis (4-methoxycarbonylphenyl) -porphyrin platinum, It has been found that the use of tetraphenyl porphyrin (H 2 TPP), hemato porphyrin (HP), proto porphyrin (PP), indocyanine green (ICG), meso-tetrakis Meso-tetrakis (p-sulfonatophenyl) porphyrin, TSPP).

In the present invention, the photosensitizer is composed of a photosensitizer A having a light absorption peak at the center wavelength region of the blue region, a photosensitizer B having a light absorption peak at the central wavelength region of the green region, and a light absorption peak at the central wavelength region of the red region And a photo-sensitizer C having a photo-sensitizer.

In the present invention, the photosensitizer A may be at least one selected from Hypocrellin B, Acridine orange and Coumarin; The photosensitizer B may be at least one selected from Rose Bengal, Rhodamine B and Merocyanine 540; The photosensitizer C may be at least one selected from methylene blue, Pheophorbide A, and cryptocyanine.

In the present invention, the concentration of the photosensitizer may be 1 × 10 -8 to 30 × 10 -7 mol per 1 g of the polymer resin.

In the present invention, the polymer resin may be at least one selected from silicone, latex, polyurethane, and polyethylene terephthalate.

In the present invention, the first catheter and the second catheter are manufactured by dispersing the photosensitizer by stirring the mixture containing the polymer resin and the photosensitizer, molding the stirred mixture into a catheter shape, and then curing the formed catheter .

In the present invention, the polymer resin is melted, and then the molten resin and the photosensitizer are mixed and stirred. Alternatively, a mixture of the polymer solution and the solution containing the photo-sensitizer and the solvent is stirred, or the solvent and the photo- After the sensitizer solution is prepared, the photosensitizer solution may be mixed with the non-solidified polymer and stirred.

In the present invention, stirring can be carried out at a speed of 10 to 1,000 rpm for 1 to 10 minutes, and curing may be thermosetting.

In the present invention, the first catheter and the second catheter are prepared by mixing a solvent and a photosensitizer to prepare a photosensitizer solution, and then carrying the photosensitizer to the catheter through a swelling method of absorbing the photosensitizer solution into the catheter .

In the present invention, the swelling method may be a method of impregnating a catheter into a photosensitizer solution, or a method of injecting a photosensitizer solution into a catheter using a syringe.

Further, the present invention provides a method for evaluating antimicrobial activity using the above-described antimicrobial activity-evaluating apparatus.

The method according to the present invention comprises the steps of placing a bacteria-containing solution in a first container and a second container, irradiating light to the second catheter while evaporating the bacteria-containing solution for a period of time through the first catheter and the second catheter; Collecting the first catheter and the second catheter, adding the solution to the culture solution for agitation, and then culturing the agitation solution; And evaluating the antimicrobial activity after culturing.

The method according to the present invention comprises the steps of washing the first catheter and the second catheter after withdrawing the first catheter and the second catheter; And cutting the washed first catheter and the second catheter.

In the present invention, the bacterium may be at least one selected from the group consisting of Asnithobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

In the present invention, the evaporation period may be 3 to 10 days.

In the present invention, antimicrobial activity can be evaluated by a colony counting method.

In accordance with the present invention, the antimicrobial efficacy of a photofunctional intubation catheter (catheter) for a respirator can be assessed under similar environmental conditions in vivo.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 schematically shows the structure of an antimicrobial efficacy evaluation apparatus according to the present invention. FIG.
2 is a photograph of an antimicrobial efficacy evaluation device according to the present invention.
FIG. 3 is a graph showing the evaluation of antibacterial activity against Ashtonobacterbaumannii.
Fig. 4 is a photograph showing evaluation of antimicrobial activity against Ashinobacter baumannii.
FIG. 5 is a graph showing an evaluation of antibacterial activity against Klebsiella spp.
FIG. 6 is a photograph showing an evaluation of antibacterial activity against Klebsiella cannon.
7 is a graph showing an evaluation of antimicrobial activity against Pseudomonas aeruginosa.
8 is a photograph showing the evaluation of antibacterial activity against Pseudomonas aeruginosa.
FIG. 9 is a graph showing the results of evaluating six kinds of respiratory infectious bacteria.

Hereinafter, the present invention will be described in detail.

2 is a photograph of an antibacterial activity potentiometer according to the present invention. The antibacterial potency potentiometer according to the present invention comprises a constant temperature bath 10, The first catheter 40, the second catheter 50, the light source 60, the optical fiber 70, and the like.

The thermostatic chamber 10 serves to maintain a temperature similar to the in-vivo temperature in order to simulate similar in-vivo environmental conditions. The thermostatic chamber 10 can accommodate the water 12 and regulate the temperature of the first vessel 20 and the second vessel 30 through the water 12. The constant temperature bath 10 may include a heater and a temperature controller. The temperature of the thermostatic chamber 10 may be 30 to 50 占 폚, preferably 35 to 45 占 폚.

The first container 20 and the second container 30 serve to receive the bacteria solution 24 and 34 and to support the first catheter 40 and the second catheter 50. The first container 20 and the second container 30 are disposed in the thermostatic chamber 10 and may be arranged so as to be at least partially immersed in the water 12. [ The first container 20 and the second container 30 may have lids 22, 32 to be hermetically sealed. The lids 22 and 32 are openable and closable by screwing or the like. The first container 20 and the second container 30 may be made of plastic, glass, or the like, for example, a conventional laboratory tube may be used. The size and volume of the first container 20 and the second container 30 are not particularly limited and can be appropriately set. In addition to the first container 20 and the second container 30, additional containers can be arranged.

The bacteria are not particularly limited, and for example, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and the like can be used. The turbidity of the bacteria in the bacterial solution is not particularly limited, and may be, for example, 0.1 to 0.9. The turbidity 0.5 may be 1.5 x 10 8 cfu / mL.

The first catheter 40 and the second catheter 50 serve as a photo-functional catheter to inhibit biofilm formation through photodynamic inactivation (PDI). One end of the first catheter 40 and the second catheter 50 may be inserted into the first and second containers 20 and 30 respectively and preferably the lids 22, 32). Thus, the material evaporated from the bacterial solution 24, 34 can only be discharged through the catheter 40, 50, i.e., the catheter 40, 50 can be the only outlet of the evaporating material. The coupling structure of the vessels 20, 30 and the catheters 40, 50 is similar to that of the respiratory system and can mimic similar in vivo environmental conditions.

The first catheter 40 may be shielded from light to be used as a control and may be attached or coated with a black tape or film or the like to the first catheter 40 and the first catheter 40 itself It can also be made in black. The second catheter 50 may be irradiated with light. The catheters 40 and 50 may be made of a polymer resin or the like, and may also contain a photosensitizer. The size of the catheter 40, 50 or the like is not particularly limited, and may be, for example, 1 to 100 cm in length. In addition to the first catheter 40 and the second catheter 50, additional catheters may be deployed.

The light source 60 irradiates light to the second catheter 50 to guide the PDI. As the light source 60, for example, a light emitting diode (LED), a laser, a xenon lamp, or the like can be used, and preferably a green LED can be used. The output of the light source 60 may be, for example, 1 to 10 mW / cm 2, and the output of the optical fiber 70 at the end toward the second catheter 50 may be, for example, 0.1 to 5 mW / cm 2.

The optical fiber 70 connects the second catheter 50 and the light source 60 and transmits the light output from the light source 60 to the second catheter 50. However, it is also possible to direct the light from the light source 60 to the second catheter 50 without the optical fiber 70. [ The optical fiber 70 may be made of plastic, glass, or the like. The length of the optical fiber 70 is not particularly limited, and may be, for example, 1 to 100 cm in length.

The polymer resin constitutes the body of the catheter (40, 50), and the polymer resin is not particularly limited, and all kinds of resins can be used. For example, one type of silicone, latex, silicone-latex mixture, gore-tex, polyurethane, polyethylene terephthalate (PET) may be selected or used in combination. Silicone resins have the advantage of being easy to obtain and being easily deformable by heat. In addition, silicon has the advantage of being biocompatible polymer material and having no biological toxicity of the material itself.

The photosensitizer is contained in the polymer catheter body to impart antimicrobial properties. Specifically, the photosensitizer absorbs light energy in an absorption wavelength region of 400 nm to 800 nm and generates active oxygen by the induced light energy And exhibits antibacterial activity.

The photo-sensitizer is not particularly limited and any kind of photo-sensitizer may be used. For example, a porphyrin compound and its substituent, a phthalocyanine compound, a substituent thereof, and a dye can be used alone or in combination of two or more. Specifically, 5,10,15-triphenyl-20- Bis (4-methoxycarbonylphenyl) - &lt; / RTI &gt; Tetraphenyl porphyrin (H 2 TPP), hemato porphyrin (HP), and tetraphenyl porphyrin (HPP), which are used in the present invention, (PP), indocyanine green (ICG), meso-tetrakis (p-sulfonatophenyl) porphyrin (TSPP), and perofibrid A (pheophorbide A) or the like can be used.

Particularly, PtCP has an advantage of high production efficiency of singlet oxygen. In addition, the porphyrin-based photosensitizer including PtCP has an advantage that there is almost no change in the photophysical properties (absorption of the photosensitizer or fluorescence wavelength range) even after being introduced into a polymer such as silicon.

Further, by combining a plurality of light-sensitive agents having light absorption peaks in different wavelength bands, it is possible to absorb more light and exhibit excellent antibacterial properties.

Specifically, a light-sensitive agent A having a light absorption peak at a central wavelength band of the blue region; A photosensitizer B having a light absorption peak at the central wavelength band of the green region; And a photosensitizer C having a light absorption peak at a central wavelength band of the red region may be used. Thus, a catheter having a uniform light absorption efficiency in a wavelength range of 400 to 750 nm can be obtained.

Blue region The central wavelength band means a region in which light having a blue color is mainly distributed in the visible light region, and may include, for example, a range of 430 to 495 nm.

Green region The central wavelength band means a region in which light having a green color is mainly distributed among visible light regions, and includes, for example, a range of 505 to 570 nm.

Red region The central wavelength region means a region in which light having a red-based color is mainly distributed among the visible light region, and may include, for example, a range of 610 to 720 nm.

The range of the central wavelength band for each of the above-mentioned areas indicates a range in a normal state, and may deviate from the above range depending on conditions such as the surrounding environment.

As the photosensitizer A, hypochlorelin B, acridine orange (λ max 492 nm), coumarin and the like can be used. As the photosensitizer B, Rose Bengal (λ max 549 nm), Rhodamine B (λ max 554 nm ), Merocyanine 540 (λ max 555 nm), and the like can be used. As the photosensitizer C, methylene blue (λ max 665 nm), perofluoride A, cryptocyanine (λ max 648 nm, 703 nm) Can be used.

According to the experimental results, the sterilization efficiency of about 50% was obtained when only one photo-sensitizer was introduced, but the sterilization efficiency was 75% or more when two photo-sensitizers were combined.

Also, at least one or more of photosensitizer A, photosensitizer B, and photosensitizer C; PtCP, t-PtCP, H 2 TPP, HP, PP, ICG and TSPP may be mixed and used.

The photosensitizer may preferably be mixed at a concentration of 1 x 10 -8 to 30 x 10-7 mol per gram of the polymer resin. Excellent dispersibility can be obtained at such a concentration range. This concentration range is a range in which the introduced photosensitizer does not cause entanglement and also expresses active oxygen depending on the concentration of the introduced photosensitizer.

A catheter according to one embodiment of the present invention may be manufactured using an agitation method. Specifically, the mixture may be prepared by dispersing the photosensitizer by stirring the mixture containing the polymer resin and the photosensitizer, molding the stirred mixture into a catheter shape, and then curing the molded catheter.

A method for manufacturing a catheter using an agitation method according to an embodiment of the present invention is roughly comprised of a stirring step, a molding step, and a curing step.

First, the stirring step is a step of dispersing the photosensitizer by stirring the mixture containing the polymer resin and the photo-sensitizer. The first step is a case of using a molten resin, the second step is a step of dispersing the photo- .

The first stirring method is a method in which the polymer resin is melted and then the molten resin and the photo-sensitizer are mixed and stirred. In this method, only the polymer resin and the photo-sensitizer are used, and no solvent is required. However, a solvent may be used if necessary, or an additive such as a dispersing agent may be used.

The stirring method is not particularly limited, and can be preferably carried out at a rate of 10 to 1,000 rpm for 1 to 10 minutes. Excellent dispersibility can be obtained in this range of stirring speed and stirring time.

The second stirring method is a method of stirring a mixture in the form of a solution containing a polymer resin, a photosensitizer and a solvent. Specifically, a solution of the photosensitizer may be prepared by mixing a solvent and a photosensitizer, and then the solution of the photosensitizer may be mixed with the non-solidified polymer (including the liquid crystal surface coating polymer) and stirred.

The use of a solvent is advantageous in terms of dispersibility in comparison with the case of using a molten resin. That is, although the photo-sensitizer can be directly dispersed in the molten resin, when the photo-sensitizer is dissolved in the solvent, there is an advantage that it is more uniformly stirred with the molten resin.

The solvent is not particularly limited and any kind of solvent can be used. Further, one solvent or two or more mixed solvents can be used. For example, dichloromethane, ethanol, toluene, tetrahydrofuran and the like can be used. Ethanol in this solvent has the advantages of good volatility and low organic toxicity. It is preferable to use a solvent which is capable of dissolving the photosensitizer efficiently, without using any solvent for dissolving the polymer resin.

Next, the molding step is a step of molding a stirred mixture to obtain a molded product in the form of a catheter. The molding method is not particularly limited and may be formed into a catheter through a coating method such as spin coating.

Next, the curing step is a step of curing the molded catheter to obtain the finished product. The curing method is not particularly limited, and for example, a thermosetting method can be used. As the thermal curing method, for example, a method using a water bath, a method using an oven, or the like can be used.

A catheter according to another embodiment of the present invention may be manufactured using a swelling method. Specifically, a solvent and a photosensitizer may be mixed to prepare a photosensitizer solution, and then the photosensitizer solution may be absorbed into a catheter, thereby swelling the catheter. Followed by heating to a temperature of 25 to 135 캜, followed by solvent removal and deswelling, and washing the catheter with an ultrasonic cleaner or the like.

In the method using the swelling method, the swelling method may be a method of impregnating a catheter into a photosensitizer solution, or a method of injecting a photosensitizer solution into a catheter using a syringe.

When the stirring method and the swelling method described above are compared, the stirring method is advantageous in various aspects. When the swelling method is used, the dispersibility of the photosensitizer is decreased, and the concentration of the photosensitizer may be nonuniform depending on the position of the catheter. Also, when the photosensitizer is introduced at a specific concentration or more, . On the other hand, when the photofunctional catheter is manufactured using the stirring method, the dispersibility of the photosensitizer can be improved, and thus the active oxygen production efficiency can be improved.

Further, the present invention provides a method for evaluating antimicrobial activity using the above-described antimicrobial activity-evaluating apparatus.

Specifically, the method according to the present invention comprises the steps of placing a bacteria-containing solution in a first container and a second container, evaporating the bacteria-containing solution for a period of time through the first catheter and the second catheter, step; Collecting the first catheter and the second catheter, adding the solution to the culture solution for agitation, and then culturing the agitation solution; And evaluating the antimicrobial activity after culturing, and also after washing the first catheter and the second catheter, washing the first catheter and the second catheter; And cutting the washed first catheter and the second catheter.

The evaporation period may be 3 to 10 days, preferably 5 days or more. The evaporation is preferably carried out only through the catheter. That is, by inserting the catheter into the hermetically sealed container so that it is sealed, evaporation can be made only through the catheter, which is the only outlet. The catheter can be cleaned using, for example, saline or the like, and washed with, for example, 0.1 to 10 mL of saline 1 to 10 times. After washing, the catheter may be cut into a plurality of pieces, for example, 2 to 20 operations. The size of each piece can be, for example, 0.1 to 5 cm. As the culture solution, for example, saline may be used, and the volume of the culture solution may be, for example, 5 to 100 mL. The stirring speed may be, for example, 100 to 500 rpm, and the stirring time may be, for example, 1 to 10 minutes. The volume of the stirring solution to be inoculated may be, for example, 10 to 500 μl. The culture can be carried out, for example, on a Mac plate. The incubation time may be, for example, 10 to 50 hours, the incubation temperature may be, for example, 25 to 45 ° C, and the incubation can be carried out under dark conditions. Antimicrobial activity can be assessed, for example, by means of a colony counting method.

Control conditions can be set through in vivo simulated environment simulations. For example, the evaporation period can be calculated using the following equation.

[Equation 1]

Figure 112015095513126-pat00001

Wherein, MC is the moisture content (water 1 kg / air 1 kg ), P sat is the saturation vapor pressure (mmHg), B is the absolute pressure (bar), 18 / 28.9 is H 2 O and air at a given temperature in the air in the The molecular weight ratio of N 2 + O 2 , and RH is the relative humidity (%).

Specifically, for example, when the condition of room temperature 22 ° C, P sat 19.827 mmHg, B 1.01325 bar (= 759.9 mmHg at 22 ° C and RH 40% is set, MC calculated from the above equation is 4.9 × 10 -3 and kg H2O / kg air, in consideration of the density of water (0.99777 g / mL) and the density of air (1.19488 × 10 -6 kg / mL ) at 22 ℃, MC is 5.87 × 10 -3 mL H2O / 1L air The tidal volume of the ventilator is 3.2 L air / min for an adult male, multiplied by MC to 13.5 mL H2O / 12 h, that is, According to the literature, the largest number of biofilms are formed in ET tubes on day 2. During the two days when biofilms are most commonly formed, 54 mL of water passes through the ET tubes The evaporation amount of saline contained in a 50 mL Falcon tube at a constant temperature of 40 ° C is 11.5 mL / 1day (experimental value), and It takes about 5 days (57.5 mL / 5day) to evaporate 54 mL of water from the above conditions.

Hereinafter, the present invention will be described in more detail by way of examples. However, the following examples are intended to illustrate the present invention and the scope of the present invention is not limited by the following examples.

[Example]

The antimicrobial efficacy was evaluated using the apparatus and the method with the same specifications and conditions as Tables 1 to 3, respectively. Specifically, the device as shown in Figs. 1 and 2 was used to evaporate only through the optical functional catheter for 5 days. After 5 days, the catheter was washed 5 times with 1 mL of saline. The catheter was then placed in 25 mL saline, followed by stirring at 300 rpm for 5 minutes. 100 ㎕ of the stirred solution was then plated on a Mc plate and incubated for 24 hours at 35 캜 and dark.

Factor Description Sample H 2 TPP @ catheter (8 cm) Bacteria A. baumannii ATCC 19606 Solvent Saline (25 mL) Bacteria resuspension turbidity 0.5 (1.5 x 10 &lt; 8 &gt; cfu / mL) Environmental condition 36 ℃ Vaporization time 5 day Light source Green LED (with plastic optical fiber 7 cm) Light power 1.2 mW / cm 2 Assay Colony count method Number 3

Factor Description Sample H 2 TPP @ catheter (8 cm) Bacteria K. pneumoniae KPC-2 Solvent Saline (25 mL) Bacteria resuspension turbidity 0.5 (1.5 x 10 &lt; 8 &gt; cfu / mL) Environmental condition 36 ℃ Vaporization time 5 day Light source Green LED (with plastic optical fiber 7 cm) Light power 1.2 mW / cm 2 Assay Colony count method Number 3

Factor Description Sample H 2 TPP @ catheter (8 cm) Bacteria Pseudomonas aeruginosa IMP-6 Solvent Saline (25 mL) Bacteria resuspension turbidity 0.5 (1.5 x 10 &lt; 8 &gt; cfu / mL) Environmental condition 36 ℃ Vaporization time 5 day Light source Green LED (with plastic optical fiber 7 cm) Light power 1.2 mW / cm 2 Assay Colony count method Number 3

As shown in FIGS. 3 to 8, the biofilm was formed in the catheter (control group) that blocked the light, but no biofilm was formed in the PDI-advanced group.

As shown in FIG. 9, the results of evaluating six respiratory infectious microorganisms (including three resistant microorganisms), namely, A. baumannii and resistant strains, P. aeruginosa and resistant strains, K. pneumoniae and resistant strains, The efficiency of inhibiting the formation of biofilm (colonies) of the optical functional catheter was 99.999%. The photo-functional catheter according to the present invention inhibited the formation of biofilm for more than 5 days, far exceeding 2 days in which the maximum bacterial infectivity was shown in the catheter.

10: thermostat
12: water
20, 30: container
22, 32: Lid
24, 34: Bacterial solution
40, 50: catheter
60: Light source
70: Optical fiber

Claims (20)

Thermostat;
A first container disposed in a thermostat;
A second container disposed in a thermostat;
A first catheter, one end of which is inserted into the first container, and the catheter itself contains a polymer resin and a photosensitizer;
A second catheter having one end inserted into the second container and containing a polymer resin and a photosensitizer in the catheter itself; And
An apparatus for evaluating antimicrobial efficacy in an in vitro similar environmental condition of a photofunctional intracoronary tube for a respirator comprising a light source for irradiating light to a second catheter.
The method according to claim 1,
A second catheter, and an optical fiber connecting the light source.
The method according to claim 1,
Wherein the temperature of the thermostatic chamber is 30 to 50 占 폚.
The method according to claim 1,
Wherein the photosensitizer comprises at least one member selected from the group consisting of a porphyrin compound and its substituent, a phthalocyanine compound, a substituent thereof, and a dye.
The method according to claim 1,
The photosensitizer is 5,10,15-triphenyl-20- (4-carboxyphenyl) -porphyrin platinum (PtCP), 5,10,15-triphenyl- Bisphenyl-10,20-bis (4-methoxycarbonylphenyl) -porphyrin platinum, t-PtCP), tetraphenylporphyrin (tetraphenyl porphyrin, H 2 TPP), hemato porphyrin (HP), proto porphyrin (PP), indocyanin green (ICG), meso-tetrakis Porphyrin, meso-tetrakis (p-sulfonatophenyl) porphyrin, TSPP).
The method according to claim 1,
The photosensitizer is composed of a photosensitizer A having a light absorption peak at the central wavelength region of the blue region, a photosensitizer B having a light absorption peak at the central wavelength region of the green region, and a light sensitive agent having a light absorption peak at the central wavelength region of the red region (C). &Lt; / RTI &gt;
The method according to claim 6,
The photosensitizer A is at least one selected from Hypocrellin B, Acridine orange and Coumarin; The photosensitizer B is at least one selected from Rose Bengal, Rhodamine B and Merocyanine 540; Wherein the photosensitizer C is at least one selected from the group consisting of methylene blue, pheophorbide A, and cryptocyanine.
The method according to claim 1,
Wherein the concentration of the photosensitizer is 1 × 10 -8 to 30 × 10 -7 mol per 1 g of the polymer resin.
The method according to claim 1,
Wherein the polymer resin is at least one selected from silicon, latex, polyurethane, and polyethylene terephthalate.
The method according to claim 1,
The first catheter and the second catheter are manufactured by dispersing the photosensitizer by stirring the mixture containing the polymer resin and the photosensitizer, molding the stirred mixture into a catheter shape, and then curing the molded catheter Wherein the antimicrobial activity-evaluating device comprises:
11. The method of claim 10,
After the polymer resin is melted, the molten resin and the photosensitizer are mixed and agitated, or the mixture of the polymer resin and the solution containing the photosensitizer and the solvent is stirred, or the solvent and the photosensitizer are mixed to form the photosensitizer solution Wherein the photosensitizer solution is mixed with the non-solidified polymer and stirred.
11. The method of claim 10,
Stirring is performed at a speed of 10 to 1,000 rpm for 1 to 10 minutes, and curing is thermosetting.
The method according to claim 1,
The first catheter and the second catheter are manufactured by preparing a solution of a photosensitizer by mixing a solvent and a photosensitizer, and then carrying the photosensitizer through a catheter through a swelling method of absorbing the solution of the photosensitizer into the catheter Wherein the antimicrobial activity-evaluating device comprises:
14. The method of claim 13,
The swelling method is a method of impregnating a catheter into a photosensitizer solution, or a method of injecting a photosensitizer solution into a catheter using a syringe.
A method for evaluating antimicrobial efficacy using the antimicrobial efficacy evaluation device according to claim 1.
16. The method of claim 15,
Placing a bacteria-containing solution in the first container and the second container, irradiating light to the second catheter while evaporating the bacteria-containing solution for a certain period of time through the first catheter and the second catheter;
Collecting the first catheter and the second catheter, adding the solution to the culture solution for agitation, and then culturing the agitation solution; And
And evaluating the antimicrobial activity after culturing.
17. The method of claim 16,
Cleaning the first catheter and the second catheter after withdrawing the first catheter and the second catheter; And
Further comprising cutting the washed first catheter and the second catheter.
17. The method of claim 16,
Wherein the bacterium is at least one selected from the group consisting of Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
17. The method of claim 16,
And the evaporation period is 3 to 10 days.
17. The method of claim 16,
Wherein the antimicrobial activity is evaluated by a colony counting method.
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JP2001517507A (en) 1997-09-23 2001-10-09 ファーマサイクリクス，インコーポレイテッド Light delivery catheter and PDT treatment method
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JP2001517507A (en) 1997-09-23 2001-10-09 ファーマサイクリクス，インコーポレイテッド Light delivery catheter and PDT treatment method
KR101509625B1 (en) 2013-04-04 2015-04-07 주식회사 지에스엠코리아 Catheter having enhanced steering performance

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