KR950013033B1 - Dithiocarbamate wool-metal-antimicrebial complex and preparation method thereof and its use - Google Patents

Abstract

The bactericidal fiber complex of formula(I) is produced by coupling a dithiocarbamate wool-metal with a bactericidal agent i. e. tetracycline, streptomycine, neomycine or pyritinone in the presence of a buffer agent i. e. phosphate salt. In(I), R1 and R2 are each peptide residual gp. comprising wool fiber; M is metal ion(Fe, Cu, Zn, Cd, Pb or Al); D is bactericidal agent; n is 1-4. Spec. dithiocarbamate wool-metal- tetracycline complex is produced by dipping 1g dithiocarbamate wool-metal chelate to 100mg tetracycline soln. of 50ml, 0.5M sodium phosphorate buffer soln.(pH4.5). The complex has a good prolonged antibacterial and deodoring effect, and is useful for bactericidal fibers and slowly releasable drug transfer systems.

Description

Dithiocarbamate wool-metal-antibacterial complex, preparation method and use thereof

The present invention relates to novel antimicrobial fibers, in particular the methods and uses of the dithiocarbamate wool-metal-antibacterial complexes.

Antimicrobial fiber is a fiber that is processed for the purpose of preventing infectious diseases, odor prevention, fiber contamination, discoloration, etc. by providing antimicrobial properties to the fiber itself, inhibiting microbial habitat and diet. This antimicrobial fiber has been put into practical use since the 1980s, when Japan was stimulated by the antibacterial deodorization process in 1981, when Japan developed antimicrobial deodorant fiber Biosil and Nonstac. to be. The first antimicrobial fiber was developed for a specific purpose, for example, for the military industry or for laboratory use, but as the desire for a pleasant living environment increases as human life changes gradually and the standard of living increases. The field is also expanding from basic household goods such as socks, shoes and underwear to general textile fields such as carpets, towels and clothes.

The most essential requirements for the antibacterial deodorization process for the production of antimicrobial fibers are three requirements: a certain antibacterial effect, durability against washing and stability to the human body. There are many antibacterial and deodorizing agents currently in use for this purpose, but typical ones include phenyl ether antibacterial agents (eg, 2,4,4'-trichloro-2'-hydroxy-diphenyl ether or 5-). Chemically combining chloro-2- (2,4-dichlorophenoxy) phenol and the like, and a reactive resin for fibers, and an organosilicon-based quaternary ammonium salt are mainly used. However, in view of the three requirements mentioned above, in particular, in terms of antibacterial effect and safety to the human body, it is preferable to combine existing antibiotics, that is, substances which have been clearly identified as antibacterial activity and stability, to the fiber so that the antimicrobial activity is maintained for a long time. . For this purpose, for example, bonding hexachlorophene to cotton fabric or attaching zirconium acetate and hydrogen peroxide to impart sustained antimicrobial activity, or zirconium to cotton fiber and chelates formed with antibiotics such as tetracycline antibiotics or pyrithione Attempts have been made to bind the materials to impart sustained release antimicrobial activity [CM Morris, TL Vigo, and CM Welec: Binding of organic antimicrobial agents to cotton fabrics as zirconium complexes, Tex. Res. J., 51 (2), 90 (1981) and L. Lifland and L. A. Stanley: "Bacteriostatic Finish for Cellulose Fabrics", US Pat. No. 3,594,113, 1971.

However, the antimicrobial deodorizing agents known to date provide relatively good effects on cotton fibers but do not provide antimicrobial effects consistently as desired for wool fibers. Therefore, the present inventors intensively studied the means that can provide a continuous antibacterial deodorizing effect on the wool fiber, which is an excellent natural fiber, as a result of introducing a dithiocarbamate group to the wool fiber to modify the structure, and then The present invention has been completed by confirming that wool fibers exhibiting excellent antibacterial and deodorizing effects can be obtained by binding chelates and binding antimicrobial compounds thereto.

Accordingly, the present invention relates to a novel dithiocarbamate wool-metal-antimicrobial complex that provides excellent sustained antibacterial deodorizing effect. The invention also relates to a process for the preparation of such novel dithiocarbamate wool-metal-antibacterial complexes and to their use, in particular as antimicrobial fibers and sustained release drug delivery systems.

Dithicarbamate Wool (DW) was developed for the purpose of removing heavy metals from wastewater. According to Korean Patent Publication No. 85-1079 (July 27, 1985), alkaline wool solution The dithiocarbamate wool (DW) formed by the reaction with carbon disulfide in the middle of the dithiocarbamate group has a very high affinity for heavy metals and thus easily forms chelates. Thus, the DW fiber acts as an effective removal agent for heavy metals in wastewater. It is revealed.

Since the chelates of DW fibers and heavy metals exhibit strong ionic binding power, the present inventors determined that it would be possible to provide continuous antimicrobial deodorizing effect to wool fibers if they could effectively bind antimicrobial agents to these chelates. will be.

The dithiocarbamate wool-metal-antibacterial complex according to the present invention may have a basic structure represented by the following general formula (I).

Wherein R ₁ and R ₂ are each independently peptide moieties constituting wool fibers, M represents a metal ion, D represents an antimicrobial agent capable of complexing to a metal, and n is an integer from 1 to 4.

The metal ion that can be used in the composition of the DW-metal-antimicrobial complex complex according to the present invention is not particularly limited as long as it is a metal capable of chelate formation by combining with a dithiocarbamate group, preferably alkaline earth Or ions of heavy metals are used, in particular metal ions such as Fe ^{+ 3} , Cu ^{+ 2} , Zn ^{+ 2} , Cd- ² , Pb ⁺³ , Al ⁺³ and the like.

Any antimicrobial agent that can be complexed with a metal ion can be used for the antimicrobial agent that can be used in the DW-metal-antibacterial complex complex of the present invention. However, in view of the continuous antimicrobial activity of the complex complex and the stability to the human body, it is preferable to use an antimicrobial agent that is clearly identified as acute toxicity, antimicrobial activity, for example tetracycline, streptomycin, neomycin and pyrithione. Antibacterial agents, such as these, are used. As used herein, the term "antibacterial" should be understood to mean both bactericidal and bacteriostatic action against fungi such as bacteria and fungi that inhabit and proliferate in the human body and the surrounding environment.

The invention also relates to a process for the preparation of the DW-metal-antimicrobial complex. According to the present invention, a DW prepared by dithiocarbamateizing wool fibers is first reacted with an acidic aqueous solution of a metal to form a DW-metal chelate, and the resulting DW-metal chelate is combined with a medicament in the presence of a buffer. DW-metal-antimicrobial complex complexes can be prepared. When explaining the production method of the present invention in more detail as follows.

In the first step, dithiocarbamate wool (DW) is prepared to dithiocarbamate the wool fibers so that they can easily chelate with the metal in the next step. The DW can be prepared by a known method or the like, as described in Korean Patent Publication No. 85-1079. For example, a certain amount of wool fibers are immersed in ether for a sufficient time to degrease, then dried, and then added to an aqueous alkali solution of a certain concentration, for example, 0.1N to 0.2N aqueous NaOH solution, followed by addition of a small amount of carbon disulfide and stirred. Dithiocarbamate wool (DW) is prepared. This reaction can be represented by the following equation.

In this reaction, the amine group in the keratin of the wool fiber is dithiocarbamateized, and at the same time, the amine group generated by partial hydrolysis of the amide bond of the peptide structure is also dithiocarbamateized. At this time, the concentration of the aqueous alkali solution such as NaOH is preferably maintained at 0.1 to 0.2N and the reaction time is preferably about 2 to 5 days, which is intrinsic properties of the wool fiber, if the concentration of the alkaline aqueous solution is too high or the reaction time is too long For example, the length of the staples, crimps may be damaged.

The dithiocarbamate wool (DW) thus prepared is combined with the metal ion in the second step to form a chelate of DW-metal. To this end, the DW is added to an aqueous metal nitrate solution and stirred at room temperature to slightly below temperature to chelate the DW. This reaction can be represented by the following equation.

In this reaction, any metal can be used as long as it can chelate with a dithiocarbamate group, preferably an alkaline earth metal or a heavy metal, particularly preferably Fe ⁺³ , Cu ⁺² , Zn ⁺² , Cd ^{+ 2} , Pb ^{+ 3} , Al ^{+ 3} and the like are used. Such metals are used in the form of water-soluble metal salts in the reaction, and are preferably used as aqueous nitrate solutions. At this time, the metal ion concentration in the aqueous solution is preferably 1-5 × 10 ^-3 M. The reaction is carried out at room temperature to warm, preferably at about 25 ° C., for 30 minutes to 5 hours, preferably for 30 minutes to 2 hours.

In the DW-metal chelate formed in this reaction, the bond of metal and dithiocarbamate wool appears to be a covalent bond between the dithiocarbamate group and the metal ion, which is very strong because the metal is not bonded to the surface of DW. It exhibits binding force and is not affected by stripping agents such as disodium EDTA.

Finally, in the third step, the DW-metal chelate complex thus formed is coupled with a drug such as an antimicrobial drug in the presence of a buffer to prepare a desired DW-metal-antibacterial complex. Antimicrobial drugs that can be used in this third stage reaction are those that provide effective ligands for metal ions, for example, antimicrobial agents having hydroxy groups, amino groups, guanidino groups, aldehyde groups and the like as binding ligands to metals. Is used. As such an antimicrobial agent, tetracycline, streptomycin, neomycin, pyrithione and the like can be preferably used. The antimicrobial agent is dissolved in a buffer such as a buffer of sodium phosphate and phosphate to form an aqueous solution at a substantially neutral pH, and the solution is immersed in the DW-metal chelate by dipping the DW-metal chelate prepared above. To adsorb antimicrobial drugs. In this way, the complex complex of the desired DW-metal-antimicrobial drug can be obtained.

DW-metal-antimicrobial drug complex prepared as described above according to the present invention exhibits excellent sustained antimicrobial activity that is not damaged even by washing, satisfactory antimicrobial deodorization processing by providing a deodorizing effect as an anhydrous effect by this antimicrobial effect To meet the needs of the prior art for finished wool fibers.

The present invention therefore relates to the use of the novel DW-metal-antimicrobial complexes according to the invention as antimicrobial fibers. The present invention also provides the use of the DW-metal-antibacterial complex as a sustained release drug delivery system based on the persistent antimicrobial activity of the DW-metal-antibacterial complex.

The present invention is explained in more detail by the following examples, but the present invention is not limited in any way by these examples.

Example 1

Preparation of Dithiocarbamate Wool (DW)

50 g of wool obtained from the sheep of Australian merino species are immersed in ether 1 and left to stand at room temperature for 2 days to degrease. After drying the degreased wool fiber, 20 g of the degreased wool is weighed out, introduced into 1000 ml of 0.1 N NaOH aqueous solution, and about 10 ml of carbon disulfide (CS ₂ ) is added thereto, and the mixture is left to stir at 25 ° C. for 2 days. The product is filtered, washed five times with water and dried to give a pale yellow dithiocarbamate wool (DW).

The content of sulfur in wool before and after the dithiocarbamate reaction was determined by the AOAC method [Association of Official Analytical Chemists, USA, "Official Methods of Analysis", 12th Ed. 22,050 p400. 1975]. As a result, the sulfur content of untreated wool before dithiocarbamateization was 14.4 mg per g wool, and 40.5 mg per g wool after treatment (n = 5, standard deviation = 9.8 mg). This result confirmed that the wool was dithiocarbamate.

Example 2

Preparation of Dithiocarbamate Wool (DW) -Metal Chelates

1 g of DW obtained in Example 1 is introduced into 100 ml of an aqueous metal nitrate solution having an ion concentration of 5 × 10 ⁻³ M as shown in Table 1, and left to stir at 25 ° C. for 30 minutes. The product is then filtered, washed three times with 0.02 M sodium phosphate buffer and dried in air to afford the desired DW-metal chelate. For filtrates, the amount of metal remaining on the DW was measured by atomic absorption spectroscopy to calculate the amount of metal adsorbed on the DW. The results are shown in Table 1 below.

Table 1. Adsorption amount of metal on dithio carbamate wool

From the results of Table 1, it can be seen that DW has a very large adsorption capacity for metal ions.

Example 3

Preparation of Dithiocarbamate Wool-Metal-Tetracycline Complex

1 g of dithiocarbamate wool-metal chelate obtained in Example 2 was washed twice with 30 ml of 0.02 M sodium phosphate buffer (pH 5.1) and then immersed in a solution of 100 mg of tetracycline in 50 ml of 0.5 M sodium phosphate buffer (pH 4.5). Let's do it. The mixture is held at 4 ° C. for 2 hours to bind tetracycline to the DW-metal. The obtained DW-metal-tetrahycline complex was washed five times in succession in the order of 30 ml of 0.1 M sodium phosphate buffer (pH 5.1), 30 ml of 0.5 M sodium chloride in sodium phosphate buffer and middle water. The product is dried and then washed three times with ethanol and diethyl ether each to finally give the desired DW-metal-tetracycline complex.

Example 4

Preparation of Dithiocarbamate Wool-Metal-Pyrithione Complexes

The desired DW-metal-pyrithione complex is obtained following the same method as described in Example 3, except that pyrithione is used instead of tetracycline as the antibacterial agent.

Example 5

Characterization of Dithiocarbamate Wool-Metal-antimicrobial Complexes

In order to measure the antimicrobial activity of the dithiocarbamate wool (DW) -metal-antibacterial complex according to the present invention and the fastness by washing thereof, the following experiment was performed.

As a test DW-metal-antibacterial complex for the measurement, 20 g of DW-Cu (II) -tetracycline, DW-Zn (II) -tetracycline and DW-Fe (III) -tetracycline complex prepared according to Example 3 Use each. For control, wool fibers obtained by simply immersing the same weight of wool as used in the preparation of the test complex in the same amount of tetracycline are used. As a method for measuring antimicrobial activity, 20 g of test and control antimicrobial fibers were added to 500 ml of distilled water and left to stir for 20 minutes. The resultant was filtered by suction, the antimicrobial fibers were spread on a filter paper, stored in a cow for 24 hours, and dried. Considered as. Each washed antibacterial fiber was subjected to a halo test using a ditch plate similar to the American Association of Textile Chemists and Colorists (AATCC) method (see AATCC Technical Manual, 1974) to determine the antibacterial activity. [Y. M. Kim. S. K. Han, K. J. Lee and Y. T. Kim: Deve1opment of cotton fabrics with prolonged antimicrobial action, Arch. Pharm. Res, 12, 2, 119, 1989, 10 mm in diameter in deodorized plates made using Staphylococcus aureus and Staphylococcus epidermidis as test strains. 30 mg of test and control antibacterial fibers were added to the decanter and incubated at 37 ° C. for 24 hours. After that, the diameter of the inhibition zone (inhibition zone) was measured and used as an indicator of antimicrobial activity. The results are shown in Table 2 below.

Table 2. Antimicrobial Activity of Dithiocarbamate Wool-Metal-Tetracycline Complexes

The antimicrobial effect of the DW-metal-pyrithione complex prepared using pyrithione as an antimicrobial agent in Example 4 was measured using the same method as described above. The results are shown in Table 3 below.

Table 3. Antimicrobial Activity of Dithiocarbamate Wool-Metal-Pyrithione Complexes

From the results of Tables 2 and 3, it can be clearly seen that the dithiocarbamate wool-metal-antimicrobial complex according to the present invention is stable to washing and shows an antibacterial effect continuously for a long time. On the other hand, the antimicrobial wool fibers obtained by simply dipping in the same concentration of antimicrobial agent were 31 mm after washing once with Staphylococcus aureus and 26 mm after washing twice when washing with Tethacycline. The diameter of the restraint was 20 mm after washing, 15 mm after washing four times, and 10 mm after washing five times, but did not show antimicrobial activity after washing six times or more. After washing once for Staphylococcus epidermis The diameter of the restraint was 28 mm, 23 mm after 2 washes, 17 mm after 3 washes, and 15 mm after 4 washes, but no antibacterial activity was observed after 5 washes or more. In addition, the wool fibers deposited on pyrithione also showed the diameter of the restraint of Staphylococcus aureus 33 mm after washing once, 22 mm after washing twice, 12 mm after washing three times, and 10 mm after washing four times. For epidermidis, 38mm after 1 wash, 26mm after 2 washes, 16mm after 3 washes, and 8mm after 4 washes, but both Staphylococcus aureus and Epidermidis after 5 washes There was no antimicrobial effect against. However, the antimicrobial DW-metal-antimicrobial composite fiber according to the present invention showed a strong and lasting antimicrobial effect even when washed 20 times or more.

Such antimicrobial wool fiber composed of a complex of dithiocarbamate wool-metal-antibacterial agent according to the present invention can provide sustained antimicrobial effect as described above, as well as an antimicrobial deodorized processed fiber as well as a sustained release delivery of various drugs. It can also be used as a system. In particular, by combining the pesticide field, for example insecticides, fungicides, herbicides, etc., with dithiocarbamate wool-metal chelates, which need to provide long-term sustained efficacy, the DW-metal-drug complex can be used in water. It can be used as a sustained release drug delivery system that can be exerted for a long time without loss.

Claims (9)

An antimicrobial fiber composite characterized by consisting of dithiocarbamate wool-metal-antibacterial agent. The antimicrobial fiber composite according to claim 1, which can be represented by the following general formula (I). Wherein R ₁ and R ₂ are each independently peptide moieties constituting wool fibers, M represents a metal ion, D represents an antimicrobial agent capable of complexing to a metal, and n is an integer from 1 to 4. The antimicrobial fiber composite according to claim 2, wherein the metal ion is an alkaline earth metal or a heavy metal ion. The antimicrobial fiber composite according to claim 3, wherein the metal ion is Fe (III), Cu (II), Zn (II), Cd (II), Pb (III) or Al (III). The antimicrobial fiber composite of claim 2 wherein the antimicrobial agent is an antimicrobial agent selected from tetracycline, streptomycin, neomycin and pyrithione. Use of the dithiocarbamate wool-metal-antibacterial complex as a sustained release drug delivery system. A method for preparing an antimicrobial fiber composite according to any one of claims 1 to 5, characterized in that the dithiocarbamate wool-metal is coupled with an antimicrobial agent to form a dithiocarbaate wool-metal-antimicrobial complex. . 8. The method of claim 7, wherein the coupling reaction is carried out in the presence of a buffer. 9. The method of claim 8 wherein the buffer is a phosphate buffer.