KR20080031184A - Medical instrument using photocatalyst - Google Patents

Abstract

A medical instrument using a photocatalyst is provided to prevent infection effectively and to be used by being embedded inside the body of mammalia or coming into contact with the body of the mammalia. A part of or an entire portion of a medical instrument using photocatalyst is embedded inside the body of a mammalia and is used by coming into contact with the body of the mammalia. A part of or an entire portion of the medical instrument is made of titan. Titanium oxide photocatalyst membrane is formed on a part of the titanic surface without an interface. The medical instrument is a metal material that is used by being inserted into a human body. The medical instrument is a dressing material. A coating material made of titan is used to coat a part of or an entire portion of a medical instrument used by coming into contact with the body of the mammalia with a photocatalyst membrane.

Description

Medical equipment using photocatalyst {MEDICAL INSTRUMENT USING PHOTOCATALYST}

The present invention relates to a medical device used in or in contact with the body, and a coating material applied to such a medical device. More specifically, the present invention relates to medical equipment and coating materials for medical equipment effective for the prevention and treatment of infectious diseases.

In the medical field, particularly in the area of orthopedic surgery, there are many aspects of using artificial objects in surgical treatment, so once an infection occurs, the treatment is very difficult. In particular, infection of the sterile area of bones and joints is a very big problem. In orthopedic surgery, metal medical equipment is often applied to the body for treatment, but since bacteria form a biofilm on the metal surface due to infection, antibiotic effects are difficult to obtain, and medical equipment needs to be removed. In some cases, treatment must be stopped. In particular, wire infections such as wire pinning or external fixation by inserting a metal pin from the body cannot avoid cloning of the skin flora against the metal exposed to the body surface, so the infection rate is high. It is an important complication.

For this reason, the prevention of infection becomes very important, but it is difficult to completely prevent the infection even by thorough pin cleaning. In addition, antibiotics are often administered in combination with external fixation therapy. However, as can be clearly seen from the emergence of multi-drug intestinal bacteria represented by MRSA, there is always a risk of the appearance of resistant bacteria in treatment with drugs. Carry around

In addition, attempts have been made to prevent infections using antibacterial metal materials. However, since they have an effect by adding antibiotics, disinfectants and silver, problems remain in terms of safety and cost.

On the other hand, there is an attempt to prevent in-hospital infection using a photocatalyst. Currently, however, hospital facilities such as floors and window frames, or inner surfaces of cannula sections used for infusion are targeted, and application to medical devices used in direct contact with the body or body has not been reported. In order to be applied to medical devices used directly in the body, such as external fixing pins, it is necessary to solve various problems such as safety and durability.

(Patent Document 1) Japanese Unexamined Patent Publication No. H07-102678

(Patent Document 2) Japanese Unexamined Patent Publication No. 2003-260134

(Problem that invention tries to solve)

The present invention has been made in consideration of the above problems, and is a medical device capable of effectively preventing an infection, and has excellent safety for being buried in a mammal's body or used in contact with a mammal's body. It is a problem to provide a coating material.

(Means to solve the task)

The present invention is a medical device that is used to bury a part or all of the body in or in contact with the body of a mammal, wherein part or all of the surface is formed of titanium, and at least a part of the titanium surface photocatalytic coating It relates to a medical device formed without an interface.

When the photocatalyst film is formed on the titanium substrate by applying a titanium oxide photocatalyst on the titanium substrate, the interface between the coating film and the substrate is clear and easily peeled off, and use of a binder or a dispersant is indispensable. In the present invention, the titanium oxide photocatalyst film is deposited on the titanium without a boundary surface by surface treatment, so that there is no fear of peeling, and no binder or dispersant is used at all. Therefore, while being excellent in durability, there is also a small possibility that the photocatalyst coating will peel off and remain in the body. In addition, since no binder or dispersant is used, it is not necessary to consider a metal allergy other than titanium allergy even when used in a living body. Titanium and titanium oxide are excellent in biocompatibility and high in chemical stability, and are therefore suitable for use in a living body.

Irradiation of the titanium oxide photocatalyst film on the surface of the medical equipment generates reactive oxygen species and decomposes bacteria attached to the film, thereby obtaining a bactericidal effect. In addition, antifouling effects such as adhesion of crusts can be expected by the photocatalytic hydrophilization reaction, which further increases the prevention of infection. The antibacterial activity by the photocatalyst is considered to be based on the organic matter decomposition activity of titanium oxide. Catalytic action is difficult to see the difference by bacterial species, and is considered to be a bactericidal effect rather than a bacteriostatic effect of losing proliferative capacity.

Since the medical equipment according to the present invention does not use antibiotics, there is no worry of the appearance of resistant bacteria, and it can be used safely in patients with low immune function, such as children and the elderly.

Since the titanium oxide photocatalyst generally responds to light having a wavelength of 380 nm or less, patients to whom the medical equipment according to the present invention is applied can prevent and treat infections by subjecting the affected part to sunlight. In the case of using black light, sterilization effect can be obtained by irradiating topically for about 30 minutes. In addition, since a small amount of ultraviolet rays are emitted from the fluorescent lamp, the effect can be expected even by exposure to the fluorescent lamp for a long time.

In addition, the treatment can be carried out more simply by using a titanium oxide capable of expressing a photocatalytic function even in visible light (wavelength range: about 400 nm to 800 nm). Visible light is generated not only from the sun, but also from various kinds of lights. Therefore, by using a visible light-responsive titanium oxide photocatalyst, room light does not expose the affected part to sunlight or black light. You can get it. In addition, since 90% or more of sunlight is visible light, the use of an active titanium oxide photocatalyst for visible light makes the treatment effect more effective in treating infection using sunlight. In addition, since visible light is more harmless than ultraviolet light, the safety of treatment can be further improved by using a visible light-responsive titanium oxide photocatalyst.

As a representative example of the medical device according to the present invention, a metal material such as a pin or a wire inserted into the body (used for trauma treatment, leg extension, etc.), or a dressing material for covering a wound surface (a wound covering material) ), And the like.

The present invention also relates to a titanium coating material for covering at least a part of medical equipment used in buried part or all of the body of a mammal or in contact with the body of a mammal with a photocatalytic coating, wherein at least a part of the surface of the coating material is titanium oxide It relates to a coating material in which a photocatalytic film is formed without an interface.

By using the coating | covering material which concerns on this invention, infection can be prevented and treated, using existing medical equipment. In addition, when mechanical strength is required and the desired strength cannot be obtained only with titanium, by using the coating material according to the present invention, infection can be prevented while securing the required strength. For example, the external fixing pins or wires used for the lower limbs need mechanical strength, but they are made of stainless steel and 6Al-4V titanium alloy pins or wires that are currently in circulation. It is also possible to coat the coating material according to the present invention, which is formed in a cylindrical shape, only in a portion to pass, to prevent infection.

(Effects of the Invention)

The medical equipment and coating material of the present invention are effective for the prevention and treatment of infectious diseases. Moreover, since it is excellent in safety and durability, and there is no worry of generation of resistant bacteria, it can be used safely for living bodies.

( Implement the invention  Best form for

The fact that the titanium oxide photocatalyst film is formed on the titanium surface without an interface is not obtained by applying the titanium oxide photocatalyst on titanium, but refers to the formation of the titanium oxide photocatalyst film on the titanium surface by surface treatment of titanium. For example, it can manufacture by the method of Unexamined-Japanese-Patent No. 3370290. As a preferable material of the medical equipment and coating | covering material of this invention, Titanystar (registered trademark) of Ilde Co., Ltd. is mentioned. The titanium constituting the surface of the medical device or the covering material of the present invention is not titanium alloy but 95% or more, preferably 99% or more pure titanium.

The medical equipment according to the present invention may be entirely composed of titanium, or may be made of a different material inside and only the surface layer part is made of titanium. In addition, the surface of the medical device according to the present invention is formed of titanium at least in contact with the biological tissue, and with respect to the medical device used by partially buried in the body, at least the skin surface of the portion protruding from the skin surface The part located in the vicinity is made of titanium. More preferred are medical devices in which all of the surfaces are formed of titanium.

In the medical device and the coating material according to the present invention, the titanium oxide photocatalyst coating on the surface of titanium may be formed only in a portion necessary to prevent infection, or may be formed on the entire surface of titanium. The parts necessary to prevent the infection are, for example, external pins or wires, which describe the parts that pass through the soft tissues or the parts that pass through the skin (among the parts inside and outside the skin, near the skin surface). Part). More preferred are medical equipment and coating materials in which a photocatalytic coating film is formed on the entire surface of titanium.

As a specific example of the medical device according to the present invention, pins, wires, half pins used for external fixation in orthopedics, titanium beads for use in bedsores, nonwoven fabric for covering wound surfaces, mesh-shaped dressing materials, artificial joints, etc. Implants and the like. These are described in more detail below.

pin, wire , Half pin

Trauma treatment such as fracture, leg extension surgery, etc. are often treated using external fixation, and fracture treatment is also generally performed by transdermal peening. The most frequent of these complications is infection of the pin insertion. Exposed pins embedded in bones or soft tissues are exposed to the surface of the skin, so bacteria and other bacteria are easily settled, and infections are caused by stimulation of surrounding soft tissues or the presence of necrotic tissues. The presence of foreign bodies on the surface of the skin is not abnormal even when the infection occurs at any time. Including the minor, the infection can occur at a frequency of 70 to 80%. At present, we are dealing with purifying around the pin and administration of antibiotics, but if it does not respond to these treatments, it must be removed. If removed, the fixing device's strength decreases, causing loosening, and the result of treatment is poor. Infection can be prevented by applying this invention to such a pin and a wire. The pins and wires that may be relatively small in strength, such as the pins and wires used for upper limbs, can be used instead of the pins and wires currently used, and the pins and wires according to the present invention formed entirely of titanium. On the other hand, since titanium is a metal having a relatively small hardness, it is necessary to use pins and wires made of stainless steel or titanium alloy, and only necessary portions are used in the present invention for a certain strength, such as pins and wires used in the base. It can be used by covering with the coating material according to the above.

Dressing material , Titanium Bead

By forming a titanium oxide photocatalyst film on the surface of titanium processed into a nonwoven fabric or mesh and using it as a coating material for dressings and wounds (dressing material), infection of the wound can be prevented and treated.

In particular, extensive bedsores and chronic osteomyelitis are still very intractable diseases, and even surgery requires several surgical treatments and long-term care. In case of infection with such tissue defects, a titanium mesh and a titanium nonwoven fabric having a titanium oxide photocatalytic coating formed on the surface are brought into close contact with the wound surface with bare hands, and irradiated with ultraviolet light for a certain period of time (visible light response type titanium oxide photocatalyst). In this case, the infection can be treated by irradiating with visible light.

In addition, when the wound is deep and you want to have a role as a spacer, infection treatment is performed without worrying of resistant bacteria by using titanium beads with holes having a titanium oxide photocatalytic coating instead of cement beads currently used. can do.

In addition, in order to affix and fix each of the titanium materials to the wound surface, to maintain an appropriate wet environment, to prevent invasion of new bacteria and moisture from the outside, etc. When the film material is installed on the surface that is not in direct contact, when using a film material that transmits light (wavelength light capable of activating the photocatalyst) corresponding to the photocatalyst to be used, the photocatalyst may be removed without removing the film material. It is preferable because it can be activated. For example, a transparent film having a high transmittance of ultraviolet light (visible light in the case of visible light response type) is used.

The treatment may also be carried out by attaching hydroxyapatite to the titanium oxide photocatalyst film, adsorbing bacteria or toxins when no light shines, and decomposing them upon irradiation.

Implant

Adding photocatalytic functions to implants such as artificial hips and knees may reduce the likelihood of contamination of the implant during surgery and consequently reduce the infection rate. Even when the surface of the joint surface or the surface of fracture fixation materials such as plates, screws, nails, spinal vertebral spacers, instrumentation materials, etc. is formed of titanium with a titanium oxide photocatalytic coating, an infection may occur. Ultraviolet light (visible light when using a visible light-responsive titanium oxide photocatalyst) is introduced as a thin fiber to the metal surface, or the wound is released to irradiate ultraviolet light (or visible light) so that infection can be treated without removing the internal fixation material. do.

1 is a graph showing the antimicrobial activity of titanium oxide photocatalyst (10 ⁵ MRSA).

2 is a graph showing the antimicrobial activity of titanium oxide photocatalyst (10 ⁴ MRSA).

3 is a graph showing the antimicrobial activity of titanium oxide photocatalyst (10 ⁵ Pseudomonas aeruginosa).

4 is a graph showing the relationship between the irradiation distance and the ultraviolet ray intensity.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail based on an Example.

Example  One

Review of infection prevention effects 1

In order to verify the infection prevention effect of the medical equipment and the coating material according to the present invention, the antimicrobial effect was examined by using the bacterial counting film adhesion method. As an experimental model of the present invention, a plate-shaped Titanystar (registered trademark) MI-C (manufactured by Ild Co., Ltd.) was used. Titanium star is manufactured by surface treatment of pure titanium, and a titanium oxide photocatalyst film is formed on the surface of pure titanium without an interface. In comparison, an untreated pure titanium plate was used.

"Bacterial counting film adhesion method"

Sample: titanium oxide photocatalyst plate (Titanista MI-C)

      Pure Titanium Plate (No Treatment)

Shape: 5 cm × 5 cm plate (1 mm thick)

Bacterial fluid: MRSA adjusted to 10 ⁵ CFU dose

order of experiment

After washing with alcohol and performing pre-irradiation for 1 hour, the sterilized pure titanium plate and the photocatalyst plate were placed one by one on a culture dish, respectively, and 0.2 ml of bacterial solution was added dropwise to the center. The upper and lower cells were plated with a low density polyethylene (LDPE) film to prevent drying of the cells. Irradiation was carried out from 3 cm above (ultraviolet intensity 1.1 mW / cm 2 on the surface of the plate) with 15 W of black light, and the culture dish was left standing under a temperature condition of 25 degrees. Ultraviolet irradiation was carried out for a predetermined time, and the bacterial solution on the surface of the sample was washed with sterile physiological saline to raise the surface and diluted. 0.1 ml of the diluted solution was collected, and the colony was inoculated in agar medium, and colony formation after 24 hours was counted. The microbial fluid was collected after 30, 60, 120 and 180 minutes, respectively. One having passed through the same procedure without irradiating light was prepared, and a case where the recovery rate was 0.8 to 1.1 was employed as reliable data, and data was obtained from six culture dishes for each time (N = 6). Neither titanium oxide photocatalyst plates nor pure titanium plates were placed, and bacteria were covered with LDPE films and light irradiation was used as a control.

The overall result of the experiment is shown in Table 1, and the average value is shown in Table 2 and FIG. In the table, the initial value is the CFU value of the bacterial solution when loaded onto the plate.

As shown in Table 2, in the titanium oxide photocatalyst plate, despite the amount of 100,000 or more bacteria on the surface, the titanium oxide photocatalyst plate was reduced from 30 minutes to 1/4 or less and from 60 minutes to 2000, and the untreated pure titanium plate and There was a big difference. From these results, it was found that the use of the medical equipment and the coating material according to the present invention can prevent bacterial colonization itself and is effective in preventing the onset of infection.

Example  2

Review of infection prevention effect 2

Experiments were carried out in the same manner as in Example 1 using MRSA adjusted to a 10 ⁴ CFU dose as a bacterial solution. Observation was performed after 30 minutes, 60 minutes, and 120 minutes. The number of data of each time was 6 (N = 6). Moreover, the experiment was performed in the same order without irradiating light, and the antimicrobial effect of the photocatalyst plate in the case of not irradiating light was examined. The overall result is shown in Table 3, and an average value is shown in Table 4 and FIG. In the tables and drawings, dark conditions and controls mean that neither photocatalyst plates nor pure titanium are covered, and bacteria are covered with LDPE films and are not irradiated with light.

As shown in Table 4, the photocatalyst plate almost killed the bacteria on the surface at 60 minutes when irradiated with ultraviolet rays, and the bacteria were not detectable at 120 minutes, but the number of bacteria at 60 minutes without irradiation with ultraviolet rays. Only half of the time, at 120 minutes the bacteria was growing again. From this result, it turned out that light irradiation is necessary for the medical equipment and coating material which concern on this invention to exhibit an antimicrobial effect effectively.

Example  3

Review of infection prevention effect 3

The irradiation position of black light was changed to 5 cm (surface ultraviolet intensity 0.65 mW / cm <2>) and 10 cm upward (surface ultraviolet intensity 0.40 mW / cm <2>), and experiment was performed in the same procedure as Example 1. Observations were performed after 30, 60, 120 and 180 minutes. The number of data of each time was 6 (N = 6). The overall results are shown in Tables 5 and 6, and the average values are shown in Tables 7 and 8.

In addition, the ultraviolet intensity and the survival rate of the bacteria on the surface of the plate are summarized in Table 9.

As shown in Table 9, as the distance from the black light was enlarged and the ultraviolet ray intensity on the surface of the photocatalyst plate was decreased, the survival rate of the bacteria at each time was increased, and the bactericidal effect was moderated. However, even if the distance was dropped (even if the UV intensity fell), the overall tendency did not change, and the number of bacteria on the photocatalyst plate was steadily decreased after 60 minutes, and became almost zero after 120 minutes. In contrast, the number of bacteria in pure titanium plates and controls was not constant over time, and the decrease tended to be extremely slow or increased. From this result, it turned out that sufficient sterilization effect can be acquired within several hours, even if the ultraviolet intensity of the photocatalyst plate surface is weakened to 0.40 mW / cm <2>.

Example  4

Review of infection prevention effect 4

As a representative of the Gram-negative bacillus, Pseudomonas aeruginosa adjusted to a dose of ¹⁰⁰ CFU was used as a bacterial solution, and the irradiation position of the black light was 3 cm (surface ultraviolet intensity 1.1 mW / cm 2), and the experiment was carried out in the same procedure as in Example 1. It was. Observation was performed after 30 minutes, 60 minutes, 120 and 180 minutes. The number of data of each time was 6 (N = 6). The overall result is shown in Table 10, and an average value is shown in Table 11 and FIG.

As shown in Table 11, even when experiments were carried out using a representative Gram-negative bacillus Pseudomonas aeruginosa, the titanium oxide photocatalyst plate exhibited a sufficient bactericidal effect, and nearly 200,000 Pseudomonas aeruginosas on the surface were reduced from 30 minutes to 1/3 or less. The number was reduced to 5000 at 60 minutes, showing a clear difference from the untreated pure titanium plate. From these results, it was found that the medical equipment and the coating material according to the present invention showed sufficient sterilizing effect regardless of the type of bacteria.

Example  5

In order to investigate the relationship between the distance to the object and the ultraviolet ray intensity, the relationship between the irradiation distance and the ultraviolet ray intensity was examined using an ultraviolet ray meter. The test used 40W black light and examined the relationship of the vertical distance to an ultraviolet-ray, and ultraviolet intensity. The results are shown in Table 12 and FIG. 4.

Since the ultraviolet intensity of sunlight is 2-3 mW / cm2 in summer, when 40W of black light is used, if the distance of 50 mm or more is used, the treatment can be performed without irradiating the ultraviolet rays of sunlight or more to the patient. Could know.

Example  6

in vivo Safety review

In order to verify the safety of the medical equipment and the coating material according to the present invention, an external fixation pin model was created and its safety was examined in animal experiments.

A 12-week-old SD rat was created with a model consisting of a pin made of titanista MI-C and a pin made of pure titanium (untreated) inserted under the left lower leg. Then, 40W of black light was irradiated perpendicularly to the buried part at a distance of 5 cm for 14 days from the day. The ultraviolet intensity corresponds to about 3 mW / cm 2 at the skin surface, which corresponds to the ultraviolet intensity in the summer outdoors.

Similarly, a model in which a pin made of titanista MI-C is inserted at the right lower leg of the rat and a pin made of pure titanium (untreated) at the lower left leg is inserted vertically through the bone (hereinafter referred to as 'model 2'). ) Were irradiated with ultraviolet rays under the same conditions.

In addition, models prepared in the same manner as Model 1 (hereinafter referred to as 'model 3') were bred for 1 month, 2 months, and 3 months, respectively, and these histological examinations were conducted after the end of the period.

Two weeks later, rats of Model 1 and Model 2 were euthanized and histological examination of the surrounding tissues was performed.

Histologically, mild infiltration of inflammatory cells around the fin was recognized, but this was not a clear difference between pure titanium and titanium oxide photocatalysts, and was thought to be a response to foreign bodies. In addition, necrosis is not seen in the cells and tissues around the titanium oxide photocatalyst, and at least histologically, it is considered that there is no influence by active oxygen species occurring on the surface of the titanium oxide photocatalyst.

In addition, in model 3, the effect on the surrounding tissue after long-term burial at 1 month, 2 months, and 3 months was examined, but in this case, only the infiltration of inflammatory cells into the surrounding area was observed, and the surrounding tissues such as apparent necrosis. No adverse effects were observed.

From the above result, the safety at the time of using the medical equipment and coating | covering material which concern on this invention in a living body was confirmed.

Claims (5)

A medical device used to bury a part or all of a mammal or to contact a mammal's body, A medical device in which part or all of the surface is formed of titanium, and a titanium oxide photocatalyst coating is formed on at least a part of the titanium surface without an interface. The method of claim 1, Medical equipment is a metal material that is used by inserting the medical equipment into the body. The method of claim 1, Medical equipment wherein the medical equipment is a dressing material. A titanium coating material for embedding a part or all of a mammal into a body or covering at least a part of a medical device used in contact with a mammal's body with a photocatalytic coating, A coating material in which a titanium oxide photocatalyst film is formed on at least a part of the surface of the coating material without an interface. The method of claim 4, wherein A covering material, wherein the medical material is a metal material used by being inserted into a body.

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