JPH06142181A - Wound coating material - Google Patents

Abstract

PURPOSE:To provide the wound coating material which exhibits an antimicrobial property even without releasing drugs and has a detoxication power to a bacterial toxin by immobilizing polypeptide antibiotics by cavalent bonding to the surfaces of fibers constituting cloth. CONSTITUTION:A polypeptide-based antibiotic is immobilized by covalent bonding to the surfaces of the fibers constituting cloth of a wound coating material. The ratio of the extension rate in the biaxial directions orthogonal to each other of the cloth surface is specified to >=50%. The cloth is formed of a knitted fabric cross knitted of blended fiber consisting of plural blank materials, combined filament yarns and/or plural fibers. As a result, the treatment of the wound is possible without allowing the intrusion of antibiotic into the body through the wound part, and therefore, side effects are prevented. Since an infection prevented, the treatment environment of the wound is improved and further the microbial cell toxin is adsorbed, and therefore an inflammation reaction is suppressed and healing is accelerated.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a wound dressing having both excellent bactericidal performance and detoxification against endotoxin.

[0002]

2. Description of the Related Art In our environment, various bacteria, viruses,
Molds are floating. Nosocomial infections are possible even in hospitals where modern expertise is used and managed, and infections from wounds are still high. Patients with reduced biological defense function, such as those after major surgery, multiple trauma, and severe burns, are prone to opportunistic infections, which may lead to serious pathologies such as sepsis and multiple organ failure. .

In the case of burns or trauma, a part of the skin is missing, so that the risk of infection is very high. In this case, local treatment of the wound, which is the entrance of pathogenic bacteria, is very important, and various wound dressing materials have been developed for the purpose of preventing infection and promoting wound healing by applying to the wound. In terms of active protection against infection, gauze has already been used by applying an antibiotic such as polymyxin B or fradiomycin in a paste form. In addition, recently, a coating material of a type in which an antibacterial substance such as a silver compound is fixed to a material and gradually released, and a coating material to which chitosan having a certain degree of antibacterial property is applied have been used.

However, for example, when a coating material coated with an antibiotic is applied to a wound, there is a problem that the coating material flows out together with the exudate from the wound, so that it is necessary to replace the coating material frequently. was there. Further, in the case of certain kinds of antibiotics, there is a problem that the drug flows into the blood through the wound, causing side effects and causing excessive biological reaction, which rather delays the healing of wounds. In addition, it is not easy to control the sustained release amount of the type that releases the drug slowly, and for example, in the case of releasing the antibiotics slowly, the efficacy is obtained if the concentration does not reach the minimum inhibitory concentration of bacteria. However, there is a problem in that it may result in promoting the development of resistant bacteria. In addition, when a material derived from a biological material is used, there is a problem that it may fall off from the wound when there is a large amount of exudate or that it melts easily once infected.

Further, when the microbial cells are destroyed by the bactericidal action, the intracellular components flow out and cause a strong biological reaction by themselves. However, in the conventional wound dressing, the treatment of the microbial components after the sterilization is performed. I didn't know anything about it.

[0006]

An object of the present invention is to solve the above-mentioned problems, that is, to exert antibacterial properties without releasing the drug so that the drug does not flow into the blood, Another object of the present invention is to provide a wound dressing material having an ability to detoxify bacterial toxins.

[0007]

An object of the present invention is to provide a wound dressing made of cloth, wherein a polypeptide antibiotic is covalently immobilized on the surface of fibers constituting the cloth. Is achieved by a wound dressing.

The structure and characteristics of the present invention will be described in detail below.

As the polymer material constituting the fiber molding used in the present invention, in order to immobilize an antibiotic by a covalent bond, it already has a suitable functional group available for immobilization in the molecular structure of the fiber. However, it is necessary to use one that can easily introduce a functional group. Fiber-forming polymers such as nylon, polyvinyl alcohol, polyvinyl chloride, polyvinylidene chloride, polystyrene can be used, but polystyrene is easy to introduce functional groups by polymer reaction and is hydrophobic. Moreover, it is particularly preferable as a material used in the present invention because it does not peel off even if it is applied to the wound surface because it is firmly bonded to the tissue.

These fiber-forming polymers can be used alone, but when they are used as core-sheath type composite fibers or sea-island type composite fibers, the strength of the fibers when a functional group is introduced by a chemical reaction described later is maintained. It is preferable above. In particular, the sea-island type composite fiber is particularly preferable because some island components are continuously present along the fiber axis and the strength of the sea component can be effectively reinforced.

The polymer used for the island component is particularly preferably polyethylene, polypropylene or the like, which has excellent chemical resistance, but is not limited to this.

The above-mentioned functional group is preferably an amino group, a carboxyl group, an α-chloromethyl group, an α-chloroacetamidomethyl group, etc., but in the molecular structure of the polypeptide antibiotics described later, Since there is a primary amino group, a carboxyl group, α-chloromethyl group, α
The -chloroacetamidomethyl group is preferred. Furthermore, in the case of a carboxyl group, a condensing reagent such as carbodiimide is required to bond with an amino group in an antibiotic, but when an α-chloromethyl group or α-chloroacetamidomethyl group is used, an active halogen group can be obtained. Is particularly preferred because it easily causes a binding reaction in the presence of an alkali.

The amount of the functional group introduced may be such that the antibiotic can be immobilized on the surface of the fiber. For example, the conversion rate when the α-chloroacetamidomethyl group is introduced into polystyrene is preferably 20 to 100. %, 50-100
% Is more preferable.

As the cloth constituting the covering material, a non-woven fabric of fibers, a knitted fabric or the like can be applied. When applied as a wound dressing, it must first adhere well to the wound surface. Since stiff ones do not adhere well along the curved surface of the body, they must be flexible, and the diameter of the fibers used is preferably 5 to 100 μ, and particularly preferably 10 to 50 μ. When the fiber diameter at this time is non-circular, the average of the maximum inscribed circle diameter and the minimum circumscribed circle diameter of the fiber cross-sectional shape is used. In addition, the cross-sectional shape of the fiber in the case where the composite yarn or the like has the inner surface of the separation surface is represented by the outer envelope of the fiber.

It is important that the wound dressing made of the cloth according to the present invention extends along the skin and the wound surface. For this reason, it is preferable that the sum of the elongation rates of the cloth in the biaxial directions orthogonal to each other is 50% or more. . Furthermore, it is particularly preferable that the sum of the elongation ratios is 100% or more from the viewpoint of adaptability to the skin and the wound surface having high curvature and deformability.

On the other hand, in view of the handling property of the covering material at the time of operation and the stability of the covering material after the operation, a large deformation is not preferable, and the sum of elongation ratios is preferably 800% or less, It is particularly preferably 500% or less.

The stretch rate is 2% for the cloth which is the pre-operative covering material.
It is calculated from the standing dimension in each axial direction orthogonal to each other after standing at 0 ° C. and 65% RH for 24 hours without tension, and the extension dimension when the fibers constituting the fabric are sufficiently strained within the range where plastic deformation does not occur. The elongation rate is expressed by {(elongation dimension-stationary dimension) / stationary dimension} x 100%, and the sum of the elongation rates measured separately in the two axial directions is the sum of the elongation rates. Here, the extension dimension refers to the maximum extension dimension within the range where plastic deformation does not occur.

The elongation rate of the fabric surface in the direction perpendicular to the two axes is not particularly limited, but in the case of knitted fabric, for example,
The first direction is the weaving direction of the fabric (the warp direction) and the knitting direction of the knitted fabric.
The axis and the direction perpendicular to this is the second axis (horizontal). In addition, a non-directional material such as a non-woven cloth or a material with unclear directionality has two orthogonal axes.

Further, it is necessary that the wound dressing has a structure capable of easily discharging the exudate from the wound surface.
There is a merit that can be easily achieved by using a knitted fabric, particularly by using a knitted fabric. If the voids between the fiber yarns are too large, the immobilized antibiotic will not contact the wound surface to form a portion where the effect cannot be exerted. If it is too small, the exudate will be difficult to drain. For this reason, the basis weight of the covering material fabric is 100 g / m ² or more and 700 g / m ² or more.
It is preferably m ² or less.

Among the fabrics used in the present invention, a knitted fabric provides appropriate wound surface coverage, ease of surgery, stretchability, flexibility and breathability, and further, the coating material of the present invention is produced. It is also preferable in improving the productivity. As the structure of the knit, any structure such as flat knitting, rib knitting, and pearl knitting can be adopted. Further, in order to impart particularly appropriate extensibility, flexibility, softness, and liquid immersion property, it is preferable that the yarn constituting the knitted fabric has a twisted yarn or spiral structure. This can be achieved by, for example, constructing a single or double covered yarn.

In general, fibers to which an antibiotic is immobilized by covalent bonds have lower practical properties such as strength as fibers, so it is preferable to improve the practical properties by composite spinning with a polymer having excellent practical properties. Further, it is also preferable to improve the practical properties by mixing fibers or improve by knitting at the time of knitting.

In the case of interlaced knitting, it is preferable that the surface of the cloth is made different by double-sided knitting or plating, and the above-mentioned fixed fibers are concentrated on the wound surface side. Also,
The elemental techniques of composite yarn production, mixed fiber (including cross twisting), and cross knitting (including plating) can be used alone or in combination to make a knitted fabric. As the fiber-forming polymer having excellent practical properties, polypropylene, polyethylene terephthalate, polyethylene and the like are preferably applied.

Polypeptide antibiotics can be used as the antibiotics. Among the polypeptide antibiotics, polymyxin B and polymyxin E not only have strong antibacterial activity against Gram-negative bacteria which are a problem in burns and trauma, but also lipopolysaccharide which is an outer membrane component of Gram-negative bacteria. Since it has a function of binding with (endotoxin), the wound dressing material that has immobilized these not only has the function of preventing infection by bactericidal action, but also has the function of adsorbing and removing the bacterial components produced by sterilization, especially endotoxin. Therefore, it is particularly preferable. The immobilized amount of polymyxin B and polymyxin E is preferably 1 to 20 mg, and particularly preferably 3 to 10 mg, per 1 g of fiber. If the amount of immobilization is small, the sufficient effect of antibiotics cannot be obtained.

[0024]

The present invention will be described in more detail by the following examples.

Example 1 Polypropylene ("Noblene" J, manufactured by Mitsui Toatsu Co., Ltd.)
3H-G) 50 parts as an island component, polystyrene (Asahi Kasei Kogyo Co., Ltd., "Stylon" 679) 46 parts and polypropylene (Mitsui Toatsu Co., Ltd., "Nobren" J3H-
G) Using a raw material containing 4 parts of the mixture as a sea component, 280
After melt-spinning at ℃, it was drawn 3.1 times to obtain a multicore sea-island type composite fiber (16 islands). 700 g of a knitted fabric of this composite fiber (flat knit) was wound on an open bobbin and packed in a column having a diameter of 200 mm and a height of 300 mm.

Nitrobenzene 1 in a stainless steel container
5 kg, 98% concentrated sulfuric acid 15 kg, N-methylol-α-
A reaction solution was prepared by mixing 2.25 kg of chloroacetamide and 32.3 g of paraformaldehyde. This reaction liquid was supplied to the hollow bobbin core hollow portion by a pump, and the reaction liquid was flown through the knitted fabric. The reaction liquid that passed through the knitted fabric and flowed out of the column was circulated again.

After reacting at 10 to 20 ° C. for 2 hours, the reaction solution was extracted from the column and the stainless steel container. At room temperature, 20 kg of nitrobenzene and 20 kg of purified water were used in this order, and the knitted fabric in the column was washed by the same operation as the reaction. The residual sulfuric acid was neutralized with a 24% aqueous sodium hydroxide solution. The remaining nitrobenzene was extracted and removed with methanol, and washed with hot water at 70 ° C. to obtain 980 g of purified α-chloroacetamidomethylated polystyrene fiber.

14.2 g of polymyxin B sulfate was dissolved in 20 liters of purified water to prepare an immobilization reaction solution, which was supplied to the knitted fabric and circulated in the same route as in the amide methylation reaction. A 0.1 N sodium hydroxide aqueous solution was continuously added dropwise to the reaction solution to control the pH to 9.5. After reacting for 1 hour, it was washed with 0.1N hydrochloric acid and purified water to obtain a knitted fabric of polymyxin B-immobilized fiber. The diameter of the monofilament of the fiber is 30 to 40 μ, the elongation of the knitted fabric is 60.0% in the vertical direction, 78.2% in the horizontal direction, and the basis weight is 251.
It was g / cm ² .

The amount of polymyxin B immobilized by amino acid analysis was about 8 mg per 1 g of fiber.

Example 2 1 g of a polymyxin B-immobilized fiber knitted fabric was taken, 15 ml of physiological saline was added, and the mixture was infiltrated for 60 minutes and washed. The washing liquid was examined for the presence or absence of polymyxin B activity. That is, Bordetella bronchiseptica ATCC 4617 was used as a test bacterium, and the standard curve method of the Japanese antibiotic drug standard and the titer test method was used. No growth inhibition of the test bacteria was observed, and E. coli grew uniformly. No stopping circle was seen.

According to the diffusion method, a 2 cm × 2 cm knitted fabric was cultivated at 37 ° C. for 24 hours on an E. coli flat coating medium. No inhibition circle was observed on the surface of the petri dish after culturing, and it was confirmed from the above results that polymyxin B was not eluted.

Example 3 Escherichia coli (ATCC 25922) was suspended in physiological saline and adjusted to a concentration of 10 ⁶ CFU / ml. Bacteria suspension 5
0.25 g of polymyxin B-immobilized fiber was added to ml and shaken at room temperature. The bacterial solution was collected 1 hour and 4 hours after shaking, and quantitatively cultivated to examine the change in the number of bacteria. The number of bacteria after 1 hour was 136 × 10 ¹ , and the number of bacteria after 4 hours was 0.

Comparative Example 1 In the same manner as in Example 3, the antibacterial activity was examined using amidomethylated fibers on which polymyxin B was not immobilized as fibers. The number of bacteria after 1 hour was 4 × 10 ⁵ , and the number of bacteria after 4 hours was 7 × 10 ⁵ , and no antibacterial activity was observed.

Example 4 Two 4 cm × 4 cm polymyxin B-immobilized fiber knitted fabrics were placed on an agar medium in an overlapping manner. From above, 10 μl of a suspension of Pseudomonas aeruginosa 8.1 × 10 ⁴ CFU / ml was dropped. Three
After culturing at 7 ° C. for 48 hours, the knitted fabric was removed and the growth state of the bacteria immediately below the knitted fabric was observed, but no growth was observed.

Comparative Example 2 By the same method as in Example 4, four pieces of gauze of the Pharmacopoeia were stacked and placed on an agar medium, and the bacterial solution was added dropwise to observe the growth state of the bacteria immediately under the gauze after culturing. did. The formation of a large number of colonies was observed, and it was revealed that the gauze cannot prevent the invasion of bacteria.

Example 5 Escherichia coli-derived purified lipopolysaccharide (E.co.
li 0111: B4 W, Difco) dissolved, concentration 10 ng / ml
An endotoxin solution of was prepared.

1 g of the polymyxin B-immobilized fiber knitted fabric was added to 30 ml of the solution, and the mixture was shaken at 37 ° C. for 2 hours. Non-turbidity time analysis method using Limulus reagent for concentration change (Wako Pure Chemical,
It was measured with a toxinometer ET-20 1. The concentration after 2 hours had dropped to 1 ng / ml or less, and it was found that this knitted fabric also has endotoxin detoxifying ability.

Example 6 A multicore sea-island type composite fiber yarn consisting of 48 filaments of 120 denier obtained in the same manner as in Example 1 was single-covered at a span of 40 denier at 500 turns / m, and this single covering yarn was used. Number of stitches 240
This is made into a flat knit with a knitting machine having a shuttle diameter of 3 1/2 inches, and after spandex is eluted and removed, polymyxin B is prepared in the same manner as in Example 1.
A knitted fabric of immobilized fibers was obtained. This knitted fabric has a total elongation of 180% in two orthogonal directions, and a basis weight of 260 g / m ^2.
Met. This knitted fabric was excellent in stretchability, flexibility, covering the wound surface, and had good permeability to the exudate.

Example 7 The single covering yarn obtained in Example 6 has 168 needles,
After knitting with a 1: 1 rib knitting machine having a shuttle diameter of 4 inches, a knitted fabric of polymyxin B-immobilized fiber was obtained in the same manner as in Example 6. The sum of the elongation rates in the directions of the two axes perpendicular to this knitted fabric was 260%, and the basis weight was 295 g / m ² . This knitted fabric had a particularly high stretchability and was good as a covering material having excellent flexibility, covering properties, and liquid immersion properties.

[0040]

EFFECTS OF THE INVENTION The application of the present invention has an advantage that side effects can be prevented because an antibiotic can treat a wound without entering the body through the wound. Since the infection can be prevented, the wound healing environment can be improved, and the bacterial toxin can also be adsorbed, so that a wound dressing having advantages such as suppressing an inflammatory reaction and promoting healing can be obtained.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Mutsuo Murakami 1-1-1, Sonoyama, Otsu City, Shiga Toray Co., Ltd. Shiga Works (72) Inventor Tomoko Suyama 2-2-1 Nihombashi Muromachi, Chuo-ku, Tokyo No. Toray Co., Ltd. Tokyo Plant (72) Inventor Naoto Nagayasu 1-1-1, Horikoshi, Nishi-ku, Nagoya-shi, Aichi Toray Co., Ltd. Aichi factory

Claims (3)

[Claims] 1. A wound dressing comprising a cloth, wherein a polypeptide antibiotic is covalently immobilized on the surface of fibers constituting the cloth. 2. The wound dressing material according to claim 1, wherein the sum of the elongation rates in the biaxial directions orthogonal to the fabric surface is 50% or more. 3. The wound dressing material according to claim 1, wherein the fabric is a composite yarn made of a plurality of materials, a mixed fiber, and / or a knitted fabric made of a plurality of fibers.