JP2583173B2 - Wound dressing - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a wound dressing, and more particularly, to a material having flexibility, adhesiveness, sustained release, and biocompatibility for the purpose of healing skin damaged by burns and wounds. It provides an excellent coating material.

[0002]

2. Description of the Related Art Conventionally, as a method for treating burns and wounds, a method of covering an affected part of a living body with gauze or the like, and a method of applying an antibacterial cream base and covering the applied part with gauze or the like are generally performed. Have been done.

However, in the conventional method, the former has a low ability to prevent bacterial infection, the body fluid is absorbed by gauze, and the affected part is too dry. The latter is too moist due to body fluids, and the antibacterial cream base soaks into the bandage, so that sufficient medicinal effects cannot be expected. Although there is a method of using a piece of tissue such as pig skin to solve the problem of body fluid, it is strongly rejected due to immunological properties and can only be used for a short time. Since any of these methods is not effective and places a heavy burden on the patient, it has been desired to develop a material which has good affinity with the living body and can treat the wound with only initial treatment.

[0004] In order to solve these problems, many coating materials composed of a support, an absorbent material, an antibacterial agent and a base material having excellent biocompatibility have been developed. The material was too viscous to be suitable as a wound dressing material.

In recent years, polylactic acid, polyglycolic acid, etc. have been used as materials which have biodegradability which gradually hydrolyzes in vivo and which can control the release of the drug when mixed with a drug. Molecular materials are in the limelight and have been applied to surgical sutures, various prosthetic materials, and the like. Further, a technique of applying such a polymer material to a wound dressing has also been disclosed.
That is, JP-A-2-19866 discloses a technique in which a fibrous material comprising a copolymer of ε-caprolactone and lactide is used as a wound dressing material as an example of its use. However, such a fibrous material is suitable for use only for covering the affected part, but since the shape is fibrous, and since it is a high molecular weight material to make it fibrous, it contains a drug. However, it is not suitable for use as a material that releases the drug within a predetermined period of time and does not affect epithelialization of the affected area in a wound.

[0006]

SUMMARY OF THE INVENTION In view of the above-mentioned circumstances, the present inventors have made it possible to contain a drug such as an antibacterial agent as a wound dressing material, and to add the drug within a desired predetermined period. Releases gradually to the affected area, has no effect on the epithelium formed with the healing of the affected area, and has good biocompatibility with no danger of safety due to the residue at the time of exfoliation seen in conventional coating materials We worked diligently to develop materials.

As a result, a mixture of a lactic acid polymer or a lactic acid-glycolic acid copolymer having a specific molecular weight range and a copolymer of lactic acid or glycolic acid and δ-valerolactone or ε-caprolactone is obtained by the above-mentioned method. It has been found that the wound dressing material has an excellent effect, and the present invention has been completed based on such findings.

[0008]

That is, the present invention relates to a lactic acid polymer or a lactic acid-glycolic acid copolymer (A) having a number average molecular weight of 500 to 5,000, a lactic acid or glycolic acid having a number average molecular weight of 500 to 5,000, and δ. A wound dressing comprising a mixture with a copolymer (B) with valerolactone or ε-caprolactone.

[0009]

The wound dressing of the present invention is characterized in that two kinds of polymers are mixed and used.

First, a lactic acid polymer or a lactic acid-glycolic acid copolymer (A) is used as one of these polymers. This polymer or copolymer may be one produced by a general method. Any of them may be used.

For example, it can be obtained by direct dehydration polycondensation of lactic acid or lactic acid and glycolic acid under reduced pressure (Yuasa et al., Koka, 68 (5), 983 (1965)). In addition, lactic acid, glycolic acid is subjected to vacuum distillation in the presence of a catalyst such as zinc oxide,
After obtaining lactide and glycolide, they can also be produced by carrying out polymerization in the presence of a catalyst such as tin chloride or diethyl zinc (Kulkarni, J. Biomed. Mater.Res., 5, 169 (197
1)). Further, the lactic acid monomer used in these cases may be any of D-form, L-form and DL-form.

In the present invention, a lactic acid polymer or a lactic acid-glycolic acid copolymer having a number average molecular weight in the range of 500 to 5,000 is used. In this case, the molecular weight range of these polymers or copolymers is particularly important in the present invention. When the molecular weight is less than 500, the acid strength of the polymer is high, and it is mixed with an agent such as an antibacterial agent described later. In this case, depending on the type of the drug used, there is a problem since the drug is decomposed, or inflammation or the like occurs when the drug comes into contact with a living body. Conversely, if the molecular weight exceeds 5,000, not only is the release of the drug reduced, but also the coating material becomes too hard and the adhesion to the epithelium decreases, which is not preferable.

Next, the copolymer (B) of lactic acid or glycolic acid and δ-valerolactone or ε-caprolactone, which is another polymer constituting the wound dressing of the present invention, will be described in detail.

This copolymer can be obtained by the method described in JP-A-1-96139, which is a patent previously invented by the present inventors.

For example, lactic acid and / or glycolic acid (A) and δ-valerolactone and / or ε-caprolactone (B) have a molar ratio (A) / (B) of 3/1 to 1/3. While introducing nitrogen gas into the mixture at a rate of
A method for obtaining a paste-like copolymer by performing a direct dehydration polycondensation reaction in a non-catalyst system by heating for a predetermined time is exemplified.

The molecular weight of the copolymer is 500
5,000, which range is of particular importance in the present invention, as well as another polymer, as described above. Further, the reason for the upper and lower limits of this range is the same as in the above-mentioned polymer.

According to the present invention, these number average molecular weights are from 500 to 5,000.
Lactic acid polymer or lactic acid-glycolic acid copolymer (A) (solid) and a copolymer of lactic acid or glycolic acid having a number average molecular weight of 500 to 5,000 and δ-valerolactone or ε-caprolactone (B) ( (Paste)), and these are mixed and used.The mixing ratio of these polymers is (A) / weight ratio.
(B) is used in the range of 4/1 to 1/4.

That is, when the mixing ratio of these polymers deviates from this range and (A) increases, the viscosity of the mixture decreases, and the mixture becomes hard and lacks flexibility. Adaptation to the affected area becomes difficult, and vice versa
If the amount of (B) is too large, the mixture becomes too soft to show fluidity, and it is difficult to fix the mixture to the affected part for a long time, which is not preferable.

In the present invention, an antibacterial agent such as ofloxacin, ciprofloxacin hydrochloride, dibekacin sulfate, oxytetracycline hydrochloride, gentamicin sulfate or the like is usually mixed with such a mixture to be used as a wound dressing material. You don't need to do anything.

Examples of use of the wound dressing of the present invention are as follows. For example, the coating material of the present invention is mixed with an agent such as an antibacterial agent and applied to a generally used cloth material such as gauze. Apply this to the affected area damaged by burns etc.
Further, a method may be employed in which the patch is covered with an appropriate material, for example, a polyethylene film or the like.

As another example of use, there is a method in which the coating material of the present invention is mixed with an antibacterial agent, kneaded into a support such as a nylon mesh, and then applied to an affected area.
The present invention is not particularly limited to these use examples.

[0022]

The present invention will be further described below with reference to examples of the present invention, but the present invention is not limited to these examples. In Examples of the present invention, all percentages are by weight unless otherwise specified.

(Examples 1 to 3) 60 g of a 90% aqueous solution of DL-lactic acid was added to 2
Put into a reaction vessel of 00 ml, then react at 200 ° C. for 10 hours while introducing nitrogen gas at a flow rate of 200 ml / min, the number average molecular weight (Mn) by terminal group determination method 2300 solid polymer
(A) was obtained. 60 g of a mixture of 90% L-lactic acid aqueous solution and δ-valerolactone in an equimolar ratio is placed in a 200 ml reaction vessel, and then 20
The reaction was carried out at 200 ° C. for 18 hours while introducing nitrogen gas at a flow rate of 0 ml / min to obtain a paste-like copolymer (B) having Mn of 2600. (A) / (B) were 2/1 (Example 1), 1/1
20 g of the mixture (Example 2) or 1/2 (Example 3) was placed in a beaker and kneaded at 50 ° C. to obtain a colorless and transparent polymer mixture. Ofloxacin is added to this polymer mixture as an antibacterial agent.
By adding 5 g and kneading at 30 ° C., an almost transparent drug-containing complex was obtained. This composite was kneaded into a nylon mesh (support) as shown in FIG. 1, and one surface was covered with a polyethylene film to prepare a wound dressing material having a thickness of about 2 mm.

[0024] These wound dressings had moderate adhesiveness to the human epithelium, could withstand use for about two weeks, had sufficient flexibility in handling, and were able to adhere to the affected area. . In addition, these wound dressings could be peeled off after leaving the wound epithelium without leaving any complex in the affected area.

Comparative Examples 1 and 2 The weight ratio (A) / (B) of the solid polymer (A) and the paste copolymer (B) used in Example 1 was determined.
A wound dressing material having a thickness of about 2 mm was prepared in the same manner as in Example 1 except that 5/1 (Comparative Example 1) and 1/5 (Comparative Example 2) were used, respectively.
As a result of examining the compatibility with the human epithelium, in Comparative Example 1, the complex was too hard and lacked flexibility, the adhesiveness was low, and the coating material tended to peel off easily from the affected area. Conversely, in Comparative Example 2, the composite was too soft and flowable, so that it was impossible to keep the coating on the affected area.

(Examples 4 and 5) Polymerization was carried out under the same conditions as in Example 1 except that 60 g of a mixture of 90% L-lactic acid and glycolic acid in an equimolar ratio was used, and the polymerization time was changed to 10 hours. Was obtained as a solid copolymer (C). Next, equimolar ratios of glycolic acid and δ-valerolactone (D), and glycolic acid and ε-
Polymerization was performed under the same conditions as in Example 1 except that 60 g of the mixture of caprolactone (E) was used, and the polymerization time was changed to 12 hours.
Paste copolymers of 2900 (D) and 3100 (E) were obtained.

(C) and (D) thus obtained (Example 3)
And (C) and (E) (Example 4) by weight ratio (C) / (D), (C) / (E)
Was placed in a beaker, and kneaded at 40 ° C. to obtain a colorless and transparent mixture. 7 g of ofloxacin was added to the mixture and kneaded at 30 ° C., and a wound dressing material having a thickness of about 2 mm was prepared in the same manner as in Example 1. The adaptability (adhesiveness, flexibility, peelability) of these wound coverings to human epithelium was all good.

(Comparative Examples 3 and 4) Polymerization was carried out under the same conditions as in Example 1 except that the polymerization time was 1.5 hours using 60 g of a 90% aqueous solution of DL-lactic acid. ). Polymerization was carried out under the same conditions as in Example 1 except for using 60 g of a mixture of glycolic acid and ε-caprolactone in an equimolar ratio, and the polymerization time was changed to 40 hours.
(G) was obtained. The wound dressing material was prepared in the same manner as in Example 1 except that the weight ratio (F) / (B) of the paste polymer (F) and the paste polymer (B) used in Example 1 was changed to 1/1. Comparative Example 3) was prepared. When this coating material was applied to human epithelium, it had high fluidity and could not be adhered to the epithelium, and the site where it was applied was slightly inflamed. Next, the polymer (A) and the gum copolymer (G) used in Example 1 were mixed at a polymerization ratio (G) / (A) of 1
A wound dressing (Comparative Example 4) was prepared in the same manner as in Example 1 except that the ratio was changed to / 2. When this coating material was applied to human epithelium, it could not be applied because it was too hard and lacked in flexibility and had low tackiness.

Example 6 Wound dressing obtained by the present invention
(Examples 1 and 4) were evaluated using Wistar rats aged 6 to 8 weeks. A skin full-thickness injury (3 cm x 3 cm, thickness 250 μm) was surgically created on one side of the back of the rat, and a wound dressing was applied thereto, and after one week, the wound dressing was peeled off from the affected area. A normal neodermis was formed in the affected area, and the efficacy of the wound dressing was proved with a cure rate of 100%.

Example 7 Using the wound dressing obtained in Example 1, an in vitro release test of ofloxacin was performed (see FIG. 2), and the results are shown in FIG. This confirmed a sustained release of ofloxacin at a concentration sufficient to inhibit bacterial growth for about 30 days.

[0031]

The wound dressing of the present invention is excellent in flexibility and adhesiveness, and can exert its sustained release effect by using an antibacterial agent mixed therewith. In addition, since this material has excellent affinity with the living body, it does not cause rejection, and epithelial cells of the affected area are formed only by initial treatment, so that secondary infection of the affected area can be prevented, and Eliminate patient distress. Further, the ability to regenerate the affected tissue only by the initial treatment is very useful because the conventional operation of replacing the therapeutic agent can be reduced. Therefore, the wound dressing material of the present invention can be applied not only to such a use but also to a therapeutic material for hypertrophic scars, decubitus and the like.

[0032]

[Brief description of the drawings]

FIG. 1 is a sectional view of a wound dressing.

FIG. 2 is a schematic view of the device in an in vitro release test of a wound dressing. The single arrow indicates the direction in which the physiological saline flows.

FIG. 3 is a graph showing the cumulative release amount of ofloxacin in a wound dressing with respect to time.

[Explanation of symbols]

 1-Polyethylene film 2-Drug-containing lactic acid polymer complex 3-Support such as nylon mesh 4-Drug-containing lactic acid polymer complex 5-Pig dermis 6-Pump 7-37C physiological saline

Continuation of the front page Examiner Tetsuo Taki (56) References JP-A-60-14861 (JP, A) JP-A-61-149160 (JP, A)

Claims (2)

(57) [Claims] A lactic acid polymer or a lactic acid-glycolic acid copolymer (A) having a number average molecular weight of 500 to 5,000, and a number average molecular weight of 5
A wound dressing comprising a mixture of 00 to 5,000 lactic acid or glycolic acid and a copolymer (B) of δ-valerolactone or ε-caprolactone. 2. The mixing ratio of a lactic acid polymer or a lactic acid-glycolic acid copolymer (A) and a copolymer of lactic acid or glycolic acid and δ-valerolactone or ε-caprolactone (B) is a weight ratio. 2. The wound dressing according to claim 1, wherein (A) / (B) ranges from 4/1 to 1/4.