JPH07223908A - Slow releasing antibacterial component - Google Patents

Abstract

PURPOSE:To obtain a slow releasing antibacterial component imparted with-a slow releasing effect on an antibacterial agent by adding mannitol, having a wide antibacterial spectrum and friendly with nature and environment. CONSTITUTION:This slow releasing antibacterial composition is obtained by mixing a softened lactic acid polymer or lactic acid-glycolic acid copolymer having a number average molecular weight of 1200-5000 with cinnamaldehyde, thymol and mannitol.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sustained release antibacterial composition, and more particularly to a sustained release antibacterial composition prepared by softening and mixing a lactic acid polymer having a specific molecular weight, an antibacterial agent derived from a natural product and mannite. According to the present invention, it is possible to provide a sustained-release antibacterial composition which is free from environmental pollution and has a long-term antibacterial effect with a broad antibacterial effect.

[0002]

2. Description of the Related Art As a method for controlling the release of a drug using a lactic acid-based polymer, 2,4-dichlorophenoxyacetic acid and a lactic acid polymer having a weight average molecular weight of 130,000 are melt-mixed and pelletized, A method for sustained release of 4-dichlorophenoxyacetic acid is known (Environ.Sci.Technol., 7 (10), 95.
5 (1973)). Further, herbicides, soil insecticides, pesticides such as soil fungicides and a solution of a lactic acid polymer having a molecular weight of 3,000 to 40,000 dissolved in an organic solvent are mixed, and an agricultural composition obtained by drying this is known. (JP-A-59-199603). The present inventors have also developed a sustained-release antibacterial composition containing a (co) polymer of lactic acid and / or glycolic acid having a number average molecular weight of 300 to 8,000 and hinokitiol (JP-A-5-97619). did.

However, in the former method, a polymer having an extremely high molecular weight is used, so that the melt mixing is not performed.
It needs to be heated to 80 ℃ or higher and cannot be applied to drugs that are unstable or decomposed by heat. Not only that, it is necessary to produce a high molecular weight polymer, which is extremely expensive. In addition, an agricultural composition that uses an organic solvent requires recovery of the organic solvent and the like, which complicates the manufacturing process and is expensive. Further, the antibacterial composition developed by the present inventors has a drawback that hinokitiol is expensive.

[0004]

Under such technical background, as a result of repeated research on an inexpensive antibacterial composition having high environmental safety and sustained release, the present invention described in detail below has been completed. .

[0005]

That is, the present invention provides a lactic acid polymer or lactic acid polymer having a number average molecular weight of 1,200 to 5,000.
The present invention relates to a sustained release antibacterial composition obtained by softening and mixing a glycolic acid copolymer, cinnamaldehyde, thymol and mannite.

[0006]

The lactic acid polymer or lactic acid glycolic acid copolymer, which is the sustained-release base of the present invention, has a number average molecular weight of 1,200 to 5,000.
Use the one in the range. When the number average molecular weight is less than 1,200, biodegradation of the polymer rapidly progresses due to environmental conditions, and even when biodegradation does not proceed, the molecular weight is small and elution is rapid, and a sustained release effect cannot be obtained.

Further, although depending on the polymer composition, it is 1,20
Products in the range of 0 to 3,000 have a low softening temperature and excellent moldability, but their sustained release properties are slightly smaller than those of products of 3,000 or more. When it is 3,000 or more, the softening temperature becomes high, but the sustained release sustainability becomes large. If the number average molecular weight exceeds 5,000, the softening temperature becomes high and the drug effect remarkably declines.

Regarding the method for producing the lactic acid-based polymer of the present invention, it may be produced by any known method as long as the number average molecular weight is within the range of the present invention. For example, it can be produced by direct dehydration polycondensation of lactic acid or lactic acid and glycolic acid under reduced pressure (Yuhara et al., Koka, 68 (5), 983 (1965)). In addition, lactic acid or lactic acid and glycolic acid are distilled under reduced pressure in the presence of a catalyst such as zinc oxide,
After obtaining lactide and glycolide, tin chloride, these can also be produced by polymerizing in the presence of a catalyst such as diethylzinc (Kulkarni, J. Biomrd. Mater. Res.,
5,169 (1971)).

The lactic acid used in the present invention may be any of D-form, L-form and DL-form. The composition ratio of the lactic acid-glycolic acid copolymer is preferably in the range of 35 to 100 in terms of lactic acid / glycolic acid (molar ratio). If it deviates from this range, a uniform composition cannot be obtained.

The lactic acid polymer or lactic acid-glycolic acid copolymer of the present invention is a biodegradable substance, which is used as a carrier or the like in the medical field and has no environmental pollution.

In the present invention, a lactic acid polymer or a lactic acid-glycolic acid copolymer, which does not cause environmental pollution, is used as a sustained-release base material and cinnamaldehyde and thymol, which are well-known as antibacterial substances derived from natural products, are used. It is a thing.

Cinnamaldehyde has a remarkable antibacterial effect against filamentous fungi and is inexpensive because it is used as a food flavoring agent for confectionery.

On the other hand, thymol is effective against bacteria and is used in cosmetics such as soap and cream.

As described above, the present invention is to produce a sustained-release antibacterial composition by using a raw material which is extremely gentle to nature and environment and has a wide antibacterial spectrum. Cinnamaldehyde and thymol are used in the present invention. It has been found that even if it is simply added to and mixed with the softened lactic acid-based polymer, a sustained-release antibacterial composition exhibiting antibacterial properties from the beginning and having a sustained effect cannot be obtained. Therefore, as a result of further studying a composition using these raw materials, which exhibits higher antibacterial properties than the initial stage of use and exhibits sustained release properties, it was discovered that mannitol is extremely effective in exhibiting these effects.

Mannitol is a sugar alcohol widely distributed in the plant kingdom and is contained in a large amount in kelp, manna and the like, and is particularly useful as a diluent or an excipient in pharmaceutical preparations.

The method most recommended by the present inventors as a mode of use of mannitol in the present invention is a method in which mannitol and cinnamaldehyde are mixed well, and then this is added to a lactic acid-based polymer and softened and mixed. In this case, however, uniform mixing is best achieved and sustained release can be maintained. Another embodiment is a method in which mannitol, cinnamaldehyde, and thymol are thoroughly mixed, then this is added to a lactic acid polymer, and the mixture is softened and mixed. In yet another embodiment, mannitol, cinnamaldehyde and thymol may be separately added to the lactic acid polymer and softened and mixed. Although the action of mannitol in the present invention is not clear, it is expected that the affinity for cinnamaldehyde, thymol, and lactic acid-based polymers with each other is increased by the action of a lubricant, and that the antibacterial effect and the durability are higher than those at the start of use. Presumed.

With respect to the proportion of each raw material used in the present invention, cinnamaldehyde 7 to 4 relative to the lactic acid polymer is used.
0% by weight, thymol 5 to 15% by weight. If the amount is less than the lower limit, antibacterial properties cannot be expected, and if added in excess of the upper limit, an economic effect commensurate with the amount added cannot be obtained in relation to the antibacterial effect.

Further, the use ratio of mannitol is preferably 1 to 8 times the total amount of cinnamaldehyde and thymol.
When the amount is 1 time or less, it becomes difficult to achieve the object of the present invention such as the initial antibacterial effect, and when the amount is 8 times or more, the sustained-release sustained effect decreases.

Next, regarding the method for producing the sustained-release antibacterial agent composition of the present invention, the lactic acid-based polymer produced by a known method is heated to 40 to 80 ° C. to soften it. The heating temperature is increased as the number average molecular weight increases. The other ingredients premixed with the softened polymer are added: antimicrobial agent and mannitol. Of course, they may be added individually, but the best method is as described above. As another method, all the raw materials may be added to the mixing container and then heated to 40 to 80 ° C. for mixing. The mixing time is generally 0.1 to 1 hour, depending on the heating temperature and the usage ratio of each raw material. The composition thus heated, softened, and mixed can be molded into an arbitrary shape such as a plate shape, a rod shape, or a granular shape by a conventional method.

The composition of the present invention can be used as a single molded body as described above, or various fibers, non-woven fabrics,
You may add and use it at the time of manufacture of paper, plastics, etc. Further, it may be mixed with an adhesive or the like and attached to the surface of various materials for use.

[0021]

EXAMPLES Examples of the present invention will be further described below.
Unless otherwise specified,% means% by weight.

65 g of 88% L-lactic acid was placed in a 200 ml reaction vessel and a polymerization reaction was carried out at about 200 ° C. for 12 hours while introducing nitrogen gas at a flow rate of 230 ml / min. As a result of measuring the molecular weight of the obtained polymer by a terminal group quantitative method, the number average molecular weight was 2,300. 20 g of this lactic acid polymer was transferred to a stainless steel container and heated to 50 ° C. to soften it, and cinnamaldehyde 3.8 g, thymol 2.2 g and mannite 11 g
Was added and mixed thoroughly for about 20 minutes and allowed to cool to room temperature to produce the sustained release antibacterial agent of the present invention (Invention Example 1). Further, the sustained release antibacterial agent composition of the present invention was prepared in the same manner as in Example 1 of the present invention except that 31 g of 90% DL-lactic acid and 29.3 g of 97% glycolic acid were used in place of L-lactic acid. It was produced (invention example 2).
The number average molecular weight of the lactic acid-glycolic acid copolymer in this case was 2,800.

On the other hand, an antibacterial agent composition was produced by the same method as in Example 1 of the present invention except that mannitol was not added (Comparative Example).

The test method was as follows: 2 mg of the composition was placed on the medium containing the test bacterium, cultured at 30 ° C., and the diameter of the growth-inhibiting circle was measured after a lapse of a predetermined time. The results are shown in Table 1.

[0025]

[Table 1] (1) Test Bacteria --- Pseudomonas
as solanacearum) MAFF 13-01857 (2) Medium --- Potato decoction from 200 g of potato, 5 g of peptone, 3 g of disodium phosphate 12-hydrate, 3 potassium monophosphate 0.5
A solution obtained by dissolving g, salt 3 g, and agar 15 g was made up to 1000 ml with distilled water, and 10 ml of an agar medium was placed in a sterile petri dish of φ90 mm and solidified. (3) Bacterial concentration --- 6.3 × 10 ⁸ CFU / medium 10 ml

[0026]

INDUSTRIAL APPLICABILITY The present invention uses a lactic acid polymer or a lactic acid-glycolic acid copolymer having a number average molecular weight of 1,200 to 5,000 as a sustained-release base, uses cinnamaldehyde and thymol as an antibacterial agent, and further adds mannitol. The sustained release effect of the antibacterial agent has been sustained, has a broad antibacterial spectrum, and is composed entirely of raw materials derived from natural products, making it environmentally friendly and suitable for agricultural materials, construction materials, etc. Of course, use
It can be applied to a wide range of materials such as kitchen utensils, clothes and other household materials.

Claims (1)

[Claims] 1. A sustained-release antibacterial composition obtained by softening and mixing a lactic acid polymer or a lactic acid-glycolic acid copolymer, cinnamaldehyde, thymol and mannitol having a number average molecular weight in the range of 1,200 to 5,000.