KR100644932B1 - Antimicrobial polymer resin - Google Patents

Abstract

Provided is an antibacterial polymer which is harmless to the human body, shows an excellent antibacterial effect to various bacteria and can maintain the antibacterial effect semi-permanently. The antibacterial polymer is a polystyrene-based polymer whose terminal is substituted with an antibacterial molecule represented by the formula 1, 2, 3, 4, 5 or 6. Preferably the polystyrene-based polymer is aminomethyl polystyrene; and the antibacterial polymer has a size of 100-200 mesh. The antibacterial molecule represented by the formula 1, 2, 3, 4, 5 or 6 is bonded to the terminal of a polystyrene-based polymer in a dimethylacetamide solvent by covalent bond.

Description

Antimicrobial Polymer

The present invention relates to an antimicrobial polymer. More specifically, the present invention relates to an antimicrobial polymer that is harmless to the human body and can maintain antibacterial power semipermanently.

In general, most of the antimicrobial materials were mixed with physically added antimicrobial material to the polymer material or those that exhibited antimicrobial effect by hydrolysis in the liquid phase. Therefore, it is difficult to use for a long time, there was a problem that the antibacterial effect is lowered over time. Therefore, there is a demand for the development of a polymer-type antimicrobial material that is basically added to the organic polymer chain so that the antimicrobial effect is long and easy to use.

An object of the present invention for solving the above problems is to provide an antimicrobial polymer that can maintain the antimicrobial power semi-permanently.

Antimicrobial polymer according to an embodiment of the present invention for achieving the above object is represented by the following structural formula (1), (2), (3), (4), (5) or (6) at the end of the polystyrene-based polymer It has a structure in which the antimicrobial molecule is substituted.

---------[구조식 1]

--------- [Structure 1]

----------[구조식 2]

---------- [Structure 2]

-----------[구조식 3]

----------- [Structure 3]

-----------[구조식 4]

----------- [Structure 4]

----------[구조식 5]

---------- [Structure 5]

----------[구조식 6]

---------- [Structure 6]

 The antimicrobial molecule of Structural Formula (6) has a structure in which the nicotinamide group of R is substituted with a sulfonic acid derivative. Examples of the nicotinamide group include ethionamide, nicotinamide, 4-aminobenzoic hydrazide, nicotinic acid hydrazide, 3,5-di Nitromid (3,5-dinitromide), isonicotinic acid hydrazide (isonicotinic acid hydrazide), pyrazinamide (pyrazinamide), isonicotinamide (isonicotinamide) and the like.

As an example, the polystyrene-based polymer included in the polystyrene-based antimicrobial polymer is preferably aminomethyl polystyrene, and the size of the polystyrene-based antimicrobial polymer satisfies 100 to 200 mesh.

Since the antimicrobial polymer according to the present invention has a structure in which the antimicrobial molecule is substituted by a covalent bond to the polystyrene-based polymer, it is not only harmless to the human body but its antimicrobial performance can be semi-permanently maintained. In addition, since it has a very good antimicrobial activity against a variety of bacteria it can be widely applied in various industrial fields where antimicrobial activity is required.

Hereinafter, the antimicrobial polymer of the present invention will be described in more detail.

The antimicrobial polymer according to one feature of the present invention has a structure in which the antimicrobial molecule is substituted at the end of the polymer chain. As an example of the polymer applied to the antimicrobial polymer, a polystyrene polymer may be used. In particular, the following aminomethyl polystyrene resin is used as the polystyrene-based polymer.

Examples of the antimicrobial molecules applied to the antimicrobial polymers include molecules represented by the following structural formulas (1), (2), (3), (4), (5) and (6).

---------[구조식 1]

--------- [Structure 1]

----------[구조식 2]

---------- [Structure 2]

-----------[구조식 3]

----------- [Structure 3]

-----------[구조식 4]

----------- [Structure 4]

-----------[구조식 5]

----------- [Structure 5]

----------[구조식 6]

---------- [Structure 6]

Specifically, the antimicrobial molecule represented by Structural Formula (1) is 6-aminonicotinic acid, and the antimicrobial molecule represented by Structural Formula (2) is pyrazinoic acid. The antimicrobial molecule represented by Structural Formula (3) is nicotinic acid, and the antimicrobial molecule represented by Structural Formula (4) is isonicotinic acid, represented by Structural Formula (5) The antimicrobial molecule is 3,5-dinitro benzoic acid. In addition, the antimicrobial molecule of Structural Formula (6) has a structure in which a nicotinamide group (R) having a second antimicrobial property is substituted with a sulfonic acid derivative having a first antimicrobial property as shown in Structural Formula (6). Wherein R in the antimicrobial molecule of formula (6) corresponds to a nicotinamide group.

As an example of the nicotine group, the nicotin group is ethionamide represented by the following structural formula (7), nicotinamide represented by the following structural formula (8), and 4-aminobenzoic acid represented by the following structural formula (9). Draginide (4-aminobenzoic hydrazide), nicotinic acid hydrazide represented by the following structural formula (10), 3,5-dinitromid represented by the following structural formula (11) ), Isisonicotinic acid hydrazide represented by the following structural formula (12), pyrazinamide represented by the following structural formula (13), isisonicotinamide represented by the following structural formula (14) ), And the like. Here, each of the molecules represented by the following structural formulas 7 to 14 has antimicrobial properties.

---------[구조식 7]

--------- [Structure 7]

---------[구조식 8]

--------- [Structure 8]

---------[구조식 9]

--------- [Structure 9]

---------[구조식 10]

--------- [Structure 10]

---------[구조식 11]

--------- [Structure 11]

---------[구조식 12]

--------- [Structure 12]

---------[구조식 13]

--------- [Structure 13]

---------[구조식 14]

--------- [Structure 14]

The antimicrobial polymer according to an embodiment of the present invention is a dimethylacetamide is an antimicrobial molecule represented by the formula (1), formula (2), formula (3), formula (4), formula (5) or formula (6) It forms as a covalent defect at the end of the polystyrene polymer under solvent. Polystyrene beads may be used as the polymer of the polystyrene, and it is particularly preferable to use aminomethyl polystyrene beads.

When 6-aminonicotinic acid, which is an antimicrobial molecule represented by Structural Formula (1), is bonded to the end of the polystyrene bead, a polystyrene-based antimicrobial polymer represented by Structural Formula (15) is formed.

----------[구조식 15]

---------- [Structure 15]

Specifically, the antimicrobial polymer represented by Structural Formula (15) is formed by a synthetic reaction as in Scheme 1 below. In the formula (15), the left sphere represents the polystyrene backbone portion.

Scheme 1

In addition, when a pyrazinoic acid, which is an antimicrobial molecule represented by the structural formula (2), is bonded to the end of the polystyrene bead, a polystyrene-based antimicrobial polymer represented by the following structural formula (16) is formed. In the formula (16), the left sphere represents the polystyrene backbone portion. Here, the synthesis reaction of the antimicrobial polymer represented by Structural Formula (16) is omitted since it is the same as the scheme (1), except that the type of antimicrobial molecule to be applied is different.

-----------[구조식 16]

----------- [Structure 16]

In addition, when a nicotinic acid, which is an antimicrobial molecule represented by the structural formula (3), is bonded to the end of the polystyrene bead, a polystyrene-based antimicrobial polymer represented by the following structural formula (17) is formed. In the formula (17), the left sphere represents the polystyrene backbone portion. Here, the synthesis reaction of the antimicrobial polymer represented by Structural Formula (17) is omitted since it is the same as the scheme (1), but the type of antimicrobial molecule is different.

------------[구조식 17]

------------ [Structure 17]

In addition, when an isonicotinic acid, which is an antimicrobial molecule represented by the structural formula (4), is bonded to the end of the polystyrene bead, a polystyrene-based antimicrobial polymer represented by the following structural formula (18) is formed. In the formula (18), the left sphere represents the polystyrene backbone portion. Here, the synthesis reaction of the antimicrobial polymer represented by Structural Formula (18) is omitted since it is the same as the above Scheme (1), except that the type of antimicrobial molecule to be applied is different.

-----------[구조식 18]

----------- [Structure 18]

In addition, when the 3,5-dinitro benzoic acid (3,5-dinitro benzoic acid) of the antimicrobial molecule represented by the structural formula (5) is bonded to the terminal of the polystyrene bead is represented by the following structural formula (19) Polystyrene-based antimicrobial polymer is formed. In the formula (19), the left sphere represents the polystyrene backbone portion. Here, the synthesis reaction of the antimicrobial polymer represented by Structural Formula (19) is omitted since it is the same as that of Scheme (1), except that the type of antimicrobial molecule to be applied is different.

----------[구조식 19]

---------- [Structure 19]

 The antimicrobial polymer according to another embodiment of the present invention has a structure in which the antimicrobial molecule represented by Structural Formula (6) is bonded to the terminal of the polystyrene polymer in a dimethylacetamide solvent. Polystyrene beads may be used as the polymer of the polystyrene, and it is particularly preferable to use aminomethyl polystyrene beads.

It can be formed by performing the following reaction formula (2) of the synthesis reaction of the antimicrobial polymer comprising the structural formula (6).

Scheme 2

+

+

In order to form the anti-microbial polymer of the above reaction (2) para acetamiprid FIG benzenesulfonyl chloride (p -acetamidobenzenesulfonyl chloride) to the amino terminus was covalently attached to the methyl polystyrene polymer beads effective on gram-negative bacteria by hydrolyzing the resultant To form a primary antimicrobial polymer. Subsequently, in order to further increase the antimicrobial activity of the formed primary antimicrobial polymer, it is formed by introducing a nicotinamide group (nicotine amide group; R), which is an antimicrobial molecule having properties effective for Gram-positive bacteria, through a mannich reaction. .

Examples of the nicotinamide group (R) applied in Scheme 2 include ethionamide represented by the structural formula (7), nicotinamide represented by the structural formula (8), and the structural formula (9). 4-aminobenzoic hydrazide represented by (4-aminobenzoic hydrazide), nicotinic acid hydrazide represented by the above formula (10), 3,5-dinitro represented by the above formula (11) Amide (3,5-dinitromide), isonicotinic acid hydrazide represented by the formula (12), pyrazinamide represented by the formula (13), and the formula (14) The isisonicotinamide etc. which are mentioned are mentioned.

As an example, when the nicotinamide group applied in the reaction formula (2) for forming the antimicrobial polymer is ethionamide represented by the structural formula (7), the antimicrobial polymer finally formed is represented by the following structural formula (20) It has a structure. In the formula (20), the left sphere represents the polystyrene backbone portion.

----------[구조식 20]

---------- [Structure 20]

In addition, when the nicotinamide group applied in the reaction formula (2) is nicotinamide represented by the structural formula (8), the finally formed antimicrobial polymer has a structure represented by the following structural formula (21). In the formula (21), the left sphere represents the polystyrene backbone portion.

-----------[구조식 21]

----------- [Structure 21]

In addition, when the nicotinamide group applied in the reaction formula (2) is 4-aminobenzoic hydrazide represented by the structural formula (9), the finally formed antimicrobial polymer is represented by the following structural formula (22) It has a structure. In the formula (22), the left sphere represents the polystyrene backbone portion.

----------[구조식 22]

---------- [Structure 22]

In addition, when the nicotinamide group applied in Scheme (2) is nicotinic acid hydrazide represented by Structural Formula (10), the finally formed antimicrobial polymer is represented by Structural Formula (23) Has In the formula (23), the left sphere represents the polystyrene backbone portion.

--------[구조식 23]

-------- [Structure 23]

In addition, when the nicotinamide group applied in Scheme (2) is 3,5-dinitromid represented by Structural Formula (11), the antimicrobial polymer finally formed is represented by Structural Formula (24) Has the structure indicated. In the formula (24), the left sphere represents the polystyrene backbone portion.

--------[구조식 24]

-------- [Structure 24]

In addition, when the nicotinamide group applied in Scheme (2) is isonicotinic acid hydrazide represented by Structural Formula (12), the finally formed antimicrobial polymer is represented by Structural Formula (25) Has a structure. In the formula (25), the left sphere represents the polystyrene backbone portion.

--------[구조식 25]

-------- [Structure 25]

In addition, when the nicotinamide group applied in Scheme (2) is pyrazinamide represented by Structural Formula (13), the finally formed antimicrobial polymer has a structure represented by Structural Formula (26). In the formula (26), the left sphere represents the polystyrene backbone portion.

---------[구조식 26]

--------- [Structure 26]

In addition, when the nicotinamide group applied in the reaction formula (2) is isonicotinamide represented by the structural formula (14), the finally formed antimicrobial polymer has a structure represented by the following structural formula (27). In the formula (27), the left sphere represents the polystyrene backbone portion.

-----------[구조식 27]

----------- [Structure 27]

Therefore, the antimicrobial polymer represented by the above-described structural formulas 15 to 27 not only have excellent antibacterial effect, but also the antimicrobial effect can be maintained semipermanently.

Hereinafter, the present invention will be described in more detail with reference to manufacturing examples. However, the technical spirit of the present invention is not limited by the following preparation examples.

Preparation Examples 1 to 5

As shown in Table 1, antimicrobial polymers were prepared by applying five antimicrobial samples having nicotine amide groups. Since the antimicrobial molecules are less reactive, the samples were first cloned using oxalic chloride for 24 hours at 60 ° C. to synthesize antimicrobial molecules. As the polymer for the substitution reaction, aminomethyl polystyrene beads [100 mesh; Aminomethyl group 1 mmol / g substitution, 1% difinylbenzene crosslinking] was used. The polystyrene beads and the antimicrobial molecules were subjected to substitution reaction for about 24 hours under a dimethylacetamide solvent and a temperature of about 60 ° C. As a result, five kinds of antimicrobial polymers were formed. The amount of each component used to form the five kinds of antimicrobial polymers is shown in Table 1 below.

TABLE 1

Antimicrobial sample Aminomethyl polystyrene beads (mg) Dimethylacetamide (ml) Oxalic chloride (mg) Antimicrobial Molecule (mg) Preparation Example 1 6-aminonicotinic acid 2000 20 253.86 246.22 Preparation Example 2 Pyrazinoic acid 2000 20 253.86 246.22 Preparation Example 3 Nicotinic Acid 2000 20 253.86 276.26 Preparation Example 4  Isonicotic Acid 2000 20 253.86 248.2 Preparation Example 5 3,5-dinitrobenzoic acid 2000 20 253.86 424.24

Production Example  6 to 13

Antimicrobial polymers were prepared by applying various 8 kinds of antimicrobial molecules having sulfonamide and nicotine amide groups simultaneously. First, the amino sulfonic acid group was chlorination with oxalic chloride for 24 hours at a temperature of 60 ° C. to prepare aminomethyl polystyrene beads [100 mesh; Aminomethyl group 1 mmol / g substitution, 1% diffinylbenzene crosslinking]. The eight kinds of nicotine amide groups (antibacterial samples) were then attached to the polystyrene beads having the sulfonamide groups by using a Mannich reaction through formaldehyde. As a result, eight kinds of antimicrobial polymers having sulfonamide and nicotine amide groups were prepared. The amount of each component used is shown in Table 2 below.

TABLE 2

Antimicrobial sample Sulfanic acid (mg) Formaldehyde (mg) Aminomethyl polystyrene beads (mg) DMAc (ml) Oxalic chloride (mg) Antimicrobial Molecule (mg) Preparation Example 6 Ethionamide 346.38 60 2000 20 253.86 332.4 Preparation Example 7 Nicotinamide 346.38 60 2000 20 253.86 244.26 Preparation Example 8 4-aminobenzoichydrazide 346.38 60 2000 20 253.86 302.34 Preparation Example 9 Nicotinic acid hydrazide 346.38 60 2000 20 253.86 274.28 Preparation Example 10 3,5-dinithromid 346.38 60 2000 20 253.86 422.26 Preparation Example 11 Isonicotic acid hydrazide 346.38 60 2000 20 253.86 274.28 Preparation Example 12 Pyrazineamide 346.38 60 2000 20 253.86 246.24 Preparation Example 13 Isonicotinamide 346.38 60 2000 20 253.86 244.26

Experimental Example 1

In order to evaluate the antimicrobial activity of the antimicrobial polymers obtained in Preparation Examples 1 to 5, 200 mg of each antimicrobial polymer was analyzed under the nutrient medium conditions for 24 hours in contact with E. coli , which is a Gram-negative bacterial indicator microorganism, to analyze the total number of bacteria ( spread plate method) was investigated. The results of the analysis are shown in Table 3 below. (In the case of 'Control', the total number of bacteria after 24 hours under nutrient medium conditions in the absence of antimicrobial polymer.)

TABLE 3

E. coli Control 4.1 × 10 ⁸ Preparation Example 1 2 × 10 ⁵ Preparation Example 2 6.4 × 10 ⁴ Preparation Example 3 20 Preparation Example 4 7 × 10 ³ Preparation Example 5 1.3 × 10 ⁵

As shown in Table 3 it can be seen that the antimicrobial polymers prepared in Preparation Examples 1 to 5 show an excellent antimicrobial activity as a whole against E. coli , which is a Gram-negative bacterial indicator microorganism.

Experimental Example 2

In order to evaluate the antimicrobial activity of the antimicrobial polymers obtained in Preparation Examples 6 to 13, 200 mg of each antimicrobial polymer was applied to E. coli , which is a gram-negative bacterium, and to S. Aureus, K, and pneumonia , which are gram-negative bacteria. The result of the spread plate method of the whole bacteria after contact was investigated. The analytical results are shown in Table 4 below (number remaining at the initial value of 1,000,000).

TABLE 4

E. coli S. Aureus K. pneumonia Contorl 2.5 × 10 ⁸ 5.6 × 10 ⁸ 3.7 × 10 ⁸ Sulphonamide 8 × 10 ⁷ 8.2 × 10 ⁷ 1.5 × 10 ⁷ Preparation Example 6 5.5 × 10 ⁴ 0 0 Preparation Example 7 9 × 10 ³ 0 0 Preparation Example 8 0 0 0 Preparation Example 9 6.4 × 10 ⁵ 0 0 Preparation Example 10 0 0 0 Preparation Example 11 40 0 0 Preparation Example 12 0 0 0 Preparation Example 13 1.0 × 10 ⁶ 1.0 × 10 ² 1.1 × 10 ²

As shown in Table 4, it can be seen that when the sulfonamide group and the nicotinamide group are simultaneously substituted than the sulfonamide group alone, the antimicrobial activity is excellent overall. In addition, the antimicrobial polymers prepared in Preparation Examples 6 to 13 showed more excellent antimicrobial activity on Gram-positive bacteria S. Aureus, K and pneumonia than Gram-negative bacteria indicator microorganism E. coli .

Based on the data of Table 4, it can be seen that the sulfonamide group is effective in Gram-negative bacteria, while the nicotinamide group is effective in Gram-positive bacteria. This is because the antimicrobial activity of the nicotinamide group is greater than that of the sulfonamide group. In addition, since the nicotinamide group is substituted in the outer portion relative to the sulfonamide group, it is judged to have high antibacterial activity.

According to the present invention, since the antimicrobial polymer is harmless to the human body and the antimicrobial molecule is replaced by a covalent bond, the antimicrobial performance can be semi-permanently maintained. Furthermore, the antibacterial activity is also very good. In particular, the antimicrobial polymer formed when the antimicrobial polymer is formed by simultaneously substituting two antimicrobial groups at the end of the polymer has a high antimicrobial effect. In addition, since the antimicrobial polymer has a very good antimicrobial activity against various bacteria, it can be widely applied to various industrial fields requiring antimicrobial activity.

As described above, although described with reference to a preferred embodiment of the present invention, those skilled in the art various modifications of the present invention without departing from the spirit and scope of the present invention described in the claims below. And can be changed.

Claims (5)

A polystyrene antimicrobial polymer having a structure in which an antimicrobial molecule represented by the following structural formulas (1), (2), (3), (4), (5) or (6) is substituted at a polystyrene terminal.

--------- [Structure 1]

---------- [Structure 2]

----------- [Structure 3]

----------- [Structure 4]

----------- [Structure 5]

---------- [Structure 6] (Wherein R is a nicotinamide group) According to claim 1, wherein the nicotinamide group is represented by ethionamide (ethionamide) represented by the following structural formula (7), nicotinamide represented by the following structural formula (8), 4-amino represented by the following structural formula (9) Benzoic hydrazide (4-aminobenzoic hydrazide), nicotinic acid hydrazide represented by the following structural formula (10), 3,5-dinitromid (3,5) represented by the following structural formula (11) -dinitromide), isonicotinic acid hydrazide represented by the following structural formula (12), pyrazinamide represented by the following structural formula (13), isonicotinamide represented by the following structural formula (14) (isonicotinamide) polystyrene-based antimicrobial polymer, characterized in that any one selected from the group consisting of.

--------- [Structure 7]

--------- [Structure 8]

--------- [Structure 9]

--------- [Structure 10]

--------- [Structure 11]

--------- [Structure 12]

--------- [Structure 13]

--------- [Structure 14] The polystyrene-based antimicrobial polymer according to claim 1, wherein the polystyrene-based polymer is aminomethyl polystyrene. According to claim 3, wherein the antimicrobial polymer is the following structural formula (15), (16), (17), (18), (19), (20), (21), (22), (23), (24) ), (25), (26) or a polystyrene-based antimicrobial polymer characterized by having a structure represented by (27).

---------- [Structure 15]

----------- [Structure 16]

------------ [Structure 17]

----------- [Structure 18]

---------- [Structure 19]

---------- [Structure 20]

----------- [Structure 21]

---------- [Structure 22]

-------- [Structure 23]

-------- [Structure 24]

-------- [Structure 25]

--------- [Structure 26]

--------- [Structure 27]       (The sphere on the left side in the above formulas (15) to (27) represents the main chain portion of the polystyrene resin) The antimicrobial polymer of claim 1, wherein the antimicrobial polymer has a size of 100 to 200 mesh.