JPH08141088A - Cannula with valve - Google Patents

Abstract

PURPOSE: To provide a cannula with a valve capable of preventing the infiltration of pathogenic microorganisms, etc., during in-vivo indwelling and sterilizing the microorganisms sticking onto the surface of the valve. CONSTITUTION: This cannula consists of a hollow tube having an introducing part 2 equipped with a flexible valve formed with an introducing hole for insertion of a body to be introduced and a valve part 8 of a Y-shaped tube is composed of an org. high polymer elastomer having flexibility and contg. a hardly water-soluble antimicrobial agent. High-polymer compds. having rubber-like elasticity at about ordinary temp.; for example, natural rubber and polymers of diene based monomers, such as butadiene, are used as the org. high-polymer elastomers. The hardly water-soluble antimicrobial agent is not particularly limited, insofar as the rate of dissolution in 100g distilled water of 20 deg.C is about 0.001 to 3.0g. Hydrochloride of chlorhexidine which exhibits an antimicrobial property to many kinds of bacteria and has a high sterilizing and bacteriostatic effect has good stability to thermal stresses at the time of molding and is most preferable.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a catheter, a conduit such as another cannula, a guide wire, etc., for introducing a body to be introduced into a body, with a valve left in the body of a patient temporarily or for a long time. More specifically, the present invention relates to a cannula with a valve capable of preventing invasion of pathogenic microorganisms during indwelling in the body.

[0002]

2. Description of the Related Art A conventional cannula is first used as a blood access for treatment such as hemodialysis or plasma exchange, or when a catheter such as an angiographic catheter or a percutaneous vasodilator is inserted. It is used as a guide wire for inserting the catheter and guiding the catheter through its lumen, or an insertion assisting tool for inserting and guiding the catheter.

When used as a blood access used for hemodialysis and the like, when the second cannula is inserted into the first cannula, the lumen of the second cannula and
The gap between the second cannula and the first cannula is used as an independent conduit, for example, as a route for blood removal and blood return. First placed in the living body, especially in the blood vessel
If another second cannula is inserted through the lumen of the first cannula, a large amount of body fluid will be lost from the first cannula during such operation. Such loss of body fluid is not only a burden on the patient, but the body fluid leaked into the vicinity may become a new source of infection, which is unclean.

[0004] Therefore, conventionally, there has been a proposal to install a backflow preventing valve in a part of the lumen passage of the cannula to maintain a watertight state between the inside of the cannula and the atmosphere and prevent such an unexpected loss of body fluid. Many have been done. For example, JP-A-2-111
No. 68, JP-A-3-29671, JP-A-4-
170966, JP-A-4-193182,
JP-A-4-221575, JP-A-6-63156
Although the publication with a valve etc. discloses a cannula with a valve,
The backflow prevention valve in these cannulas is made of a flexible material, and when another cannula or the like is inserted through the introduction hole provided near the center, the outer wall of the inserted cannula and the valve are in close contact with each other. In addition, when another cannula is removed, the introduction hole is in close contact with and hermetically sealed so as to block ventilation and liquid passage inside and outside the valve.

[0005]

However, when a tubular body such as a cannula is left in the living body, the inside and outside of the living body are opened by the cannula, so that invasion of microorganisms is facilitated. In particular, in the case of a cannula placed in a blood vessel, a thrombus is generated and attached around the tip of the cannula, which is a foreign substance to the living body. Microorganisms that have invaded the body through the cannula along the cannula proliferate with the thrombus adhering to the cannula as a suitable seed bed, resulting in fever and severe sepsis such as multiple organ failure in patients. It may progress. In particular, in the case of a cannula with a valve, a small amount of blood adheres to the valve portion when an operation of inserting and withdrawing another cannula or the like from the cannula is added. Therefore, in this part, the microorganisms first grow and eventually enter the cannula.
The risk of staged infection is very high.

[0006] Therefore, an object of the present invention is to provide a cannula with a valve capable of preventing the invasion of microorganisms such as pathogenic microorganisms during indwelling in the body and sterilizing the microorganisms adhering to the surface of the valve. is there.

[0007]

Means for Solving the Problems As a result of intensive studies for solving the above problems, the present inventors have found that an organic polymer elastomer constituting a valve for preventing backflow contains a poorly water-soluble antibacterial agent. It was found that the infection of pathogenic microorganisms during indwelling of the body can be prevented by doing so, and the present invention has been accomplished.
That is, the present invention is a cannula composed of a hollow tube having an introduction portion provided with a flexible valve (hereinafter, simply referred to as a valve) in which an introduction hole for inserting an introduction object is formed,
A gist of a cannula with a valve, wherein the valve is made of an organic polymer elastomer containing a poorly water-soluble antibacterial agent.

The present invention will be described in detail below. First, the cannula of the present invention has a catheter, a conduit such as another cannula, an introducing portion for inserting a body to be introduced such as a guide wire into the body, and the introducing portion is provided with a valve. The body to be introduced is inserted into the introduction hole of the valve. The valve is flexible and is composed of an organic polymer elastomer containing a poorly water-soluble antibacterial agent.

The flexible organic polymer elastomer constituting the above-mentioned valve is a polymer compound having rubber-like elasticity at around room temperature, such as natural rubber or butadiene, isoprene, pentadiene, hexadiene, heptadiene, chloroprene. Polymers or copolymers of diene monomers, butylene-ethylene-styrene copolymers, ethylene-vinyl acetate copolymers, silicone rubbers such as organopolysiloxane, polyurethane, soft polyvinyl chloride,
Examples thereof include styrene-butadiene rubber. This valve is
Since it is necessary to pass the cannulas through the through hole without deformation, it depends on the application, but is softer than the material forming the generally used cannula,
It is preferable to use an elastomer having a JIS hardness of 100 A or less. Further, from the viewpoint of preventing abnormal elution of the antibacterial agent in the initial stage, it is preferable to use a substantially hydrophobic elastomer.
The water absorption capacity in an atmosphere of ℃ and relative humidity of 60% is about 1.
Refers to 0% by weight or less of elastomer.

Next, as a method for forming the valve, a mixture of the above elastomer and a poorly water-soluble antibacterial agent may be molded into a required shape by a known method used for molding an elastomer. The molding method includes, for example, an injection molding method. Alternatively, a dipping method or the like may be employed in which a molded product formed by injection molding or the like using only an elastomer into a required valve shape is immersed in a mixed liquid of an elastomer and a poorly water-soluble antibacterial agent.

As an example, an antibacterial structure containing the above antibacterial agent is prepared by melt-kneading and extruding a sparingly water-soluble antibacterial agent into an elastomer by a known extruder by a known extruder and then chipping. A material for molding is obtained. A disc-shaped valve molded product is obtained by injection molding using this material. The slit-shaped introduction hole formed in the valve may be formed at the time of injection molding, or may be formed after the disk is molded.

Next, the above organic polymer elastomer contains a poorly water-soluble antibacterial agent, and this antibacterial agent is applied to disinfect general skin or the like, or sterilized to be administered for sterilization, Any antibacterial agent such as an antibiotic or a synthetic antibacterial agent may be used as long as it is a drug having a bacteriostatic effect and is poorly water-soluble.

Here, “poorly water-soluble” means distilled water 10 at 20 ° C.
The amount dissolved in 0 g (hereinafter referred to as solubility) is 0.00
1 to 3.0 g. Preferably 0.005-
It is 2.0 g. If the solubility in water is less than 0.001 g, the effect as an antibacterial agent is insufficient, while 3.0
When it exceeds g, the elution of the antibacterial agent increases, which may be unfavorable in terms of safety and durability of antibacterial activity.

As the antibacterial agent used in the present invention, any antibacterial agent having any property can be used as long as it is substantially water-insoluble.
Chlorhexidine hydrochloride, which has antibacterial properties against many kinds of bacteria and has a high bactericidal and bactericidal effect, is extremely stable against the thermal stress applied during molding, and is therefore adopted as the most preferable example. .

The amount of the slightly water-soluble antibacterial agent contained in the above organic polymer elastomer is preferably 0.01 to 10.0% by weight, more preferably 0.1 to 3.0% by weight. When the content is less than 0.01%, sufficient antibacterial activity is not exerted on the surface of the valve, while when it exceeds 10.0% by weight, initial abnormal elution occurs when contacting with water, etc. It may not be preferable from the viewpoint of safety.

Further, the above organic polymer elastomer includes
It is also possible to mix two or more kinds of antibacterial agents, or to add additives such as a plasticizer, an antioxidant, a coloring pigment, a surfactant, a crosslinking agent, and a softening agent.

The valve provided in the cannula of the present invention is formed of a material containing an organic polymer elastomer containing a poorly water-soluble antibacterial agent as described above, but its shape is not particularly limited. Alternatively, any shape may be used as long as the watertight state of the inside of the cannula and the atmosphere can be maintained through the operation of inserting and removing the introduced body.

The cannula of the present invention is provided with a valve made of an elastomer containing a poorly water-soluble antibacterial agent at the introduction part, and another cannula, catheter,
It has an introduction hole that guides the introduction target such as a long guide wire, etc., but this introduction hole is usually in close contact and completely closed, but when the introduction target is inserted, the outer wall of the introduction target And the valve come into close contact with each other, and when the valve is removed, the valve contracts again to block ventilation and liquid passage inside and outside the valve. The pathogenic microorganisms are sterilized or sterilized by the antibacterial agent contained in the valve.

The valved cannula of the present invention will be described in detail below with reference to the drawings. FIG. 1 shows an example of a cannula with a valve of the present invention, in which an introducing portion 2 is attached to one end of a Y-shaped tube 3, and an extension tube 5 and a hub 6 are attached to the other end.
The first tube path 7 is formed by, and the indwelling tube 1 is connected to the tip of the Y-shaped tube 3 through the joint 4. The thickness and size of the indwelling tube 1 can be arbitrarily selected according to the purpose of use such as the position of indwelling.

FIG. 2 shows the Y of the cannula with valve shown in FIG.
FIG. 3 is an exploded perspective view of a main part of the character tube 3, in which a valve part 8 includes a first valve 10 having a slit 9 as an introduction hole near the center,
No. 10 of the valve 10 and a similar second valve 11 having a slit in a direction orthogonal to the slit 9 are combined. This valve 1
0 and 11 are fixed between the upper presser 13 and the Y-tube 3 main body by screwing the fitting part 12 of the upper presser 13 of the introduction part and the fitting part 12 of the Y-tube 3 main body. It In addition, 14
Indicates the lumen of the Y-tube. Although two valves are combined in the present invention, the number of valves may be only one, or three or more. Further, the shape of the slit is not limited.

FIG. 3 is a front view showing an example of use of the valved cannula shown in FIG. 1, which is an example used as a blood access for hemodialysis. The cannula of FIG. 3 has the same structure as the cannula of FIG. 1 except that a side hole 19 is provided at the tip. In FIG. 3, the second cannula 15
Is inserted through the inlet 2 of the valved cannula to form a second conduit 16. Second cannula 15
Consists of a tube 18 and a hub 17 communicating with it, and a side hole 19 is provided at the tip of the tube 18. A first flow path is formed between the outer wall of the cannula 15 and the inner wall of the indwelling tube 1 and communicates with the extension tube 5 and the hub 6.
The conduit 7 is used as a blood removal route from the body, and the second conduit 16 formed by the cannula 15 is used as a blood return route to the body.

Here, in the case of the valved cannula having the above-mentioned structure, when the second cannula is removed from the valved cannula during non-dialysis, the second conduit is quickly sealed by the valve portion 8, Physically preventing leakage of blood and invasion of foreign substances such as microorganisms, and inserting a second cannula during dialysis allows rapid blood flow. During such cannula removal / intubation operations, it is inevitable that a small amount of blood leaks from the gap between the slit and the cannula, forming a blood clot on the valve surface, and pathogenic microorganisms attach to this blood clot. As they may proliferate, clot formation gradually leads to the induction of cannula-derived infections. The polymeric elastomer, which is the base material forming the valve of the introduction portion provided in the valved cannula of the present invention, contains a poorly water-soluble antibacterial agent, and thus suppresses the growth of microorganisms on the surface, and further effects Since this antibacterial agent has a low solubility in water, unnecessary elution can be controlled to a very low level, it is highly safe for the living body, and the antibacterial property on the valve surface is long. It can be expected to last for a period of time.

The valved cannula of the present invention is used as a blood access for hemodialysis or the like as described above, or as a treatment catheter such as another coronary artery dilatation catheter, a guide wire, endoscopes including a blood vessel endoscope, drainage. It can be used in a wide range of applications as an auxiliary tool for securing an insertion site such as a catheter or an imaging catheter.

[0024]

Since the valve of the cannula of the present invention contains a poorly water-soluble antibacterial agent, the adhered microorganisms can be effectively sterilized on the surface of the valve or its growth can be suppressed. Therefore, the incidence of cannula-derived infections via the valve can be significantly reduced. Furthermore, since the contained antibacterial agent has low solubility in water, elution from the flexible material forming the valve, which is the base material, is extremely small, and biostimulation is suppressed, so it is safe and can be used for a long period of time. It is possible to maintain antibacterial properties on the substrate surface.

[0025]

EXAMPLES Next, the valved cannula of the present invention will be described in detail with reference to Examples. Example 1 Ethylene-vinyl acetate copolymer resin [Evaflex (E
VAFLEX) (manufactured by Mitsui DuPont Polychemical Co., Ltd.)] and chlorhexidine hydrochloride (manufactured by Mutual Chemical Co., Ltd .: solubility of 0.01 g) to give a final concentration of about 1.0% by weight after kneading chlorhexidine hydrochloride. By a twin-screw melt-kneading extruder PCM-30 (made by Ikegai Tekko Co., Ltd.)
The mixture was melt-kneaded at 0 ° C. to obtain a molding antibacterial material in which chlorhexidine hydrochloride was uniformly dispersed. Injection molding machine J-100 (manufactured by Nippon Steel Works, Ltd.) using the obtained antibacterial material for molding
The valves 10 and 11 shown in FIG. 2 were injection molded.

The antibacterial activity of the surface of the obtained valve was measured.
The measurement method is a disk-shaped valve with no slits formed as a sample, placed in a vial, and about 10
⁷ / ml Staphylococcus aureus
Brain Heart including coccus aureus; ATCC6538P)
Infusion medium (Brain Heart Infusion broth)
[Becton Dickinson & C
Ompany)] was inoculated. Further, another valve was placed on the valve inoculated with the bacterial solution, and the bacterial solution was sandwiched between the two valves, followed by culturing at 37 ° C. for 4 hours. The number of bacteria after 4 hours of culture was counted by the colony counting method.

For comparison, the valve was injection-molded with Evaflex containing no antibacterial agent and subjected to the same test as above.
As a control, the cells were cultured for 4 hours, and the number of bacteria after the culture was counted.

Table 1 shows the result of counting the number of bacteria by each sample. An increase in the number of bacteria was found in valves that did not contain antibacterial agents. On the other hand, in the valve containing chlorhexidine hydrochloride, the number of bacteria was remarkably reduced, and it was confirmed that the embedded chlorhexidine hydrochloride effectively acted also on the bacteria on the surface.

[0029]

[Table 1]

Next, in order to confirm the persistence of antibacterial activity,
Among the samples used in the above measurement, the valve containing chlorhexidine hydrochloride was sterilized with 70% aqueous ethanol solution, and the surfactant Tween80 (a nonionic surfactant obtained by adding ethylene oxide to sorbitan fatty acid ester manufactured by Becton Dickinson) was used. After thoroughly stirring and washing in a 0.1% physiological saline solution (agent), the culture was again subjected to the above-mentioned culture experiment, and the increase / decrease in the number of bacteria was measured. Here, the logarithmic value of the number of bacteria after 4 hours of culture was taken, the difference from the logarithmic value of the initial number of bacteria was obtained, and the difference between this value in the control and the sample was determined as the difference between the increase and decrease.
This increase / decrease difference can be treated as a parameter indicating that the larger the value, the higher the antibacterial activity of the test material.

The graph of FIG. 4 shows the transition of the difference between the increased and decreased values when the cleaning and re-measurement are repeated up to 6 times. From these results, it was shown that the molded article maintained sufficient antibacterial activity even during the sixth measurement in the washing test under severe conditions, and that the antibacterial activity could be maintained for a sufficient period of time under actual use conditions. .

Next, a Y-shaped tube 3 provided with the introduction part 2 shown in FIG. 2 was experimentally manufactured using the above antibacterial valve. The Y-shaped tube 3 main body and the upper presser 13 were injection-molded from a polycarbonate resin (trade name Novarex 7022A; manufactured by Mitsubishi Kasei Co., Ltd.) and then assembled so that the fitting portions 12 sandwich the valves 9 and 10. The indwelling tube 1 extruded by polyurethane resin [trade name TECOFLEX 65D Thermedics (made by Thermedics)] was bonded to the joint 4 at the tip of the obtained Y-shaped tube 3 to complete the cannula with a valve. .

[0033]

EFFECTS OF THE INVENTION As is clear from the above description, the valved cannula of the present invention is capable of sterilizing microorganisms adhering to the valve surface, and thus can prevent infectious diseases derived from the cannula regardless of the length of the indwelling period. You can

[Brief description of drawings]

FIG. 1 is a front view showing an example of a valved cannula of the present invention.

FIG. 2 is an exploded perspective view of a main part of the valved cannula shown in FIG.

FIG. 3 is a front view showing an example of use of the cannula with valve shown in FIG.

FIG. 4 is a graph showing the persistence of valve antibacterial activity in the cannula of the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Indwelling tube 2 Introductory part 3 Y-shaped tube 4 Joint part 5 Extension tube 6 Hub 7 1st pipeline 8 Valve part 9 Slit 10 1st valve 11 2nd valve 12 Fitting part 13 Upper part presser 14 of an introductory part 14 Lumen 15 Second cannula 16 Second conduit 17 Hub 18 Tube 19 Side hole

Claims (2)

[Claims] 1. A cannula comprising a hollow tube having an introduction portion provided with a flexible valve having an introduction hole for inserting an introduction object, wherein the valve contains a poorly water-soluble antibacterial agent. A cannula with a valve, which is made of an organic high molecular weight elastomer. 2. The valved cannula according to claim 1, wherein the antibacterial agent is a poorly water-soluble acid salt of a biguanide compound.