KR20110058258A - Antimicrobial composition comprising synthesized nonallergenic urushiol derivatives - Google Patents

Abstract

PURPOSE: An antimicrobial composition containing a synthesized non-allergenic urushiol derivative as an active ingredient is provided to secure the strong antimicrobial effect of the composition. CONSTITUTION: An antimicrobial composition for preventing the food spoilage contains a non-allergenic urushiol derivative with the antibacterial activity for food decomposition bacteria as an active ingredient. The non-allergenic urushiol derivative is 3-pentylcatechol or 3-eicosylcatechol. The food decomposition bacteria are selected from the group consisting the following: gram-positive bacteria including staphylococcus aureus and staphylococcus epidermidis; gram-negative bacteria including escherichia coli, pseudomonas aeruginosa, and bacillus subtilis; and yeast.

Description

Antimicrobial composition comprising allergy non-induced synthetic urushiol derivatives as an active ingredient {Antimicrobial composition comprising synthesized nonallergenic urushiol derivatives}

The present invention relates to a synthetic urushiol derivative, and more particularly, to an antimicrobial composition for preventing food corruption and an antimicrobial composition for preventing and treating pathogens comprising an urushiol derivative synthesized as an allergic non-induced as an active ingredient.

Since lactose has been introduced through various herbal medicines and herbaceous trees, it has been widely used in folk remedies such as gastric ulcer, hookworm, abdominal pain, pain and constipation. Korean J. food sci.technol, 31, 855-863, 1999 ). In addition, it is known to be effective as a blood repellent, digestive agent and blue blood agent ( Cho Young-sik et al., Korean J. food sci. Technol, 32, 1389-95, 2000 ). It has been widely used as a paint for furniture, etc. ( Yang, Jang-soo, Applied Chem. 4, 284-7, 2000 ).

Urushiol is the main component of 60-65% of the sumac sap, anticancer ( Myong Jo Kim et al., Korean J. med. Crop sci, 10, 288-93, 2002 ) and antioxidant activity ( Lee Jeong-Chae et al. , J. Bioche.Mol. Biol. 36, 337-343, 2003 ), as well as antimicrobial activity ( Otto Vogl et al. Journal of Polymer Science: Part A: Polymer Chemistry. 38 , 4327, 2000 ). Known.

That is, urushiol refers to a group of compounds having saturated or unsaturated branched hydrocarbons composed of 15 to 17 carbon atoms at the 3rd position of the catechol (1,2-benzenediol, pyrocatechol) structure, as shown in FIG. The presence of urushiol derivatives has been reported ( Chang-Soon Choi et al., J. Fd Hyg. Safety. 20, 18-21, 2005 ).

On the other hand, the antimicrobial activity of Darren et al. ( Darren Yang et al., Biomaterials 30, 6035 ?? 6040, 2009 ) showed that the antimicrobial activity was different depending on the carbon chain length of fatty acids. have.

As described above, among the urushiol derivatives, 3-pentadecylcatechol, 3- (8 Z ) -8-pentadecenylcatehol, 3- (8 Z , 11 Z ) -8,11-pentedecadienylcatechol, and 3-[(8 Z , 11 Z , 14 Z ) -8,11,14-pentadecatri enyl)] catechol has been reported for antimicrobial experiments ( Myong-Jo Kim et al., Korean J. Plant.Res., 10, 231-234 , 1997 ). However, the results are for compounds derived from nature, and of course are for allergenic compounds.

As such, natural urushiol has not been put to practical use due to the fatal disadvantage of acting as an allergen causing compound.

However, the present inventors have recently succeeded in synthesizing allergic non- induced novel urushiol derivatives having different lengths of fat-soluble long chain side chains while maintaining the structural basic skeleton of urushiol ( Moon, Je Hak, Repub. Korean Kongkae Taeho Kongbo, KR 2009066135 A 20090623 , 2009 ) ( Kim Jin-young, Chonnam National University, Master's Thesis, 2008 ), opened up the possibility of practical use of Urushiol.

In addition, the present inventors have succeeded in synthesizing and securing urushiol derivatives having different lengths of branched hydrocarbons ( Jin-Young Kim, Chonnam National University, MS Thesis, 2008 ). Accordingly, based on the result that the length and length of fatty acid carbon chains affect antimicrobial activity, the side chain hydrocarbons are longer or shorter than urushiol, which is known to exert antimicrobial activity, thereby improving antimicrobial activity than natural urushiol. In order to identify the synthetic urushiol derivatives that can be synthesized, the antimicrobial activity of the urushiol derivatives having different lengths of side chain hydrocarbons was studied.

The present inventors have studied to solve the problems of natural urushiol, which has been recognized as an antiallergic activity, but it has been recognized that it is not practical to use because of allergens. Among the synthetic urushiol derivatives, the synthetic urushiol derivatives having non-induced allergy and strong antibacterial activity are specifically identified. By this, the present invention was completed.

Accordingly, it is an object of the present invention to provide an antimicrobial composition comprising the synthetic urushiol derivatives as an active ingredient, revealing the function of the synthetic urushiol derivatives having allergenic non-induced and strong antibacterial activity compared to natural urushiol.

 Another object of the present invention to provide an antimicrobial composition that can be used for the control and prevention of food rot bacteria as well as the prevention and prevention of food rot bacteria based on the antibacterial activity of allergic non-induced synthetic urushiol derivatives as an active ingredient. It is.

The objects of the present invention are not limited to the above-mentioned objects, and other objects that are not mentioned will be clearly understood by those skilled in the art from the following description.

In order to achieve the above object of the present invention, the present invention provides an antimicrobial composition for preventing food corruption comprising an allergic non-induced urushiol derivative as an active ingredient having an antimicrobial activity against food decay bacteria.

In a preferred embodiment, the allergic non-induced urushiol derivative is 3-pentylcatechol or 3-eicosylcatechol.

In a preferred embodiment, the food rot bacteria is any one or more of Staphylococcus aureus, Gram-positive bacteria including Staphylococcus epidermidis , Escherichia coli, Pseudomonas aeruginosa, Gram-negative bacteria and yeast including Bacillus subtilis .

The present invention also provides an antimicrobial composition for preventing and treating pathogens, which includes an allergic non-induced urushiol derivative as an active ingredient as an active ingredient having antimicrobial activity against pathogens.

In a preferred embodiment, the allergic non-induced urushiol derivative is 3-pentylcatechol or 3-eicosylcatechol.

In a preferred embodiment, the pathogen is at least one of Salmonella typhimurium, Streptococcus mutans, Vibrio vulnificus, Candida albicans, Helicobacter pylori .

The present invention has the following excellent effects.

The antimicrobial composition of the present invention is useful as an antimicrobial agent by including a synthetic urushiol derivative known to have allergic non-induced and strong antimicrobial activity compared to natural urushiol in the synthetic urushiol derivative.

 The antimicrobial composition of the present invention can be used not only for the control and prevention of food rot bacteria, but also for the treatment and prevention of pathogenic infectious diseases, based on the antimicrobial activity of allergen-induced synthetic urushiol derivatives as an active ingredient.

The terms used in the present invention were selected as general terms as widely used as possible, but in some cases, the terms arbitrarily selected by the applicant are included. In this case, the meanings described or used in the detailed description of the present invention are considered, rather than simply the names of the terms. The meaning should be grasped.

Hereinafter, with reference to the preferred embodiment and the drawings will be described in detail the technical configuration of the present invention. However, the present invention is not limited to the embodiments described herein but may be embodied in other forms.

The present invention is to provide an antimicrobial composition for preventing food decay including allergic non-induced urushiol derivatives as an active ingredient having antimicrobial activity against food decay bacteria and / or pathogens.

First, in the present invention, the antibacterial activity was tested using two commercially available synthetic urushiol derivatives and two commercially available products having the structural formula shown in FIG. 2. Two commercially available products are catechol (catechol, pyrocatechol, 1,2-benzenediol, 1,2-dihydroxybenzene, C) and 3-methylcatechol (3-methylcatechol, 3-methyl-1,2-benzenediol, MC). And a structure-activity correlation.

4 synthetic urushiol derivatives are 3-pentylcatechol (3-pentylcatechol, 3-pentyl-1,2-benzenediol, PC), 3-decylcatechol (3-decylcatechol, 3-decyl-1,2-benzenediol, DC ), 3-pentadedecylcatechol (3-pentadecylcatechol, 3-pentadecyl-1,2-benzenediol, PDC), 3-eicosylcatechol (3-eicosylcatechol, 3-eicosyl-1,2-benzenediol, EC) .

As used herein, the term "synthetic urushiol derivative" refers to four compounds of PC, DC, PDC, and EC. The four synthetic urushiol derivatives include Sprague-Dawley rat [SD rat, 6-week-old, 160-180 g, male, SAMTACO Co., Ltd., allergen-induced experiments were conducted on four synthetic urushiol derivatives, and the side chain hydrocarbons bound to the catechol 3 -C ₅ H ₁₁ It was confirmed that phosphorus PC and EC with -C ₂₀ H ₄₁ did not cause allergy.

Thus, in the present invention, "allergic non-induced synthetic urushiol derivative" means PC and EC.

Example 1

An antimicrobial composition 1 was prepared using 3-pentylcatechol (PC) as an active ingredient.

Example 2

 An antimicrobial composition 2 was prepared using 3-eicosylcatechol (EC) as an active ingredient.

Comparative Example 1

Comparative composition 1 was prepared using pyrocatechol (C) as an active ingredient.

Comparative Example 2

Comparative Composition 2 was prepared using 3-methylcatechol (MC) as an active ingredient.

Comparative Example 3

Comparative composition 3 was prepared using 3-decylcatechol (DC) as an active ingredient.

Comparative Example 4

Comparative composition 4 was prepared using 3-pentadecylcatechol (PDC) as an active ingredient.

Experimental Example 1

The antimicrobial activity against the antimicrobial composition 1, antimicrobial composition 2, comparative compositions 1 to 4 was tested by the paper disc method for the microorganisms shown in Table 1 below.

As shown in Table 1, five microorganisms ( Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis ) and five pathogens ( Salmonella typhimurium, Streptococcus mutans, Vibrio vulactnificus, Candilic al albicans ) The characteristics of the bacteria, the medium used and the culture conditions are as shown in Table 1 (Use strain and culture conditions and characteristics used for antimicrobial activity evaluation).

In the paper disk method described above, all the target compounds used 5 μmol per disc. As the benzoic acid, 2.5 μmol, 5 μmol and 10 μmol were used, respectively.

S. aureus , S. epidermidis , S. mutans , E. coli, P. aeruginosa and S. enterica were at 37 ℃, B. subtilis and V. vulnificus C. albicans was cultured at 25 ° C for 12-16 hours to measure the diameter size (mm) of growth support. At this time, the control was used for the nine strains benzoic acid (benzoic acid). The results are shown in Table 2 (size of growth support for food rot and pathogenic bacteria of urushiol derivatives) and FIGS. 3 to 11.

In addition, as a control compound of Helicobacter pylori, nalidixic acid (nalidixic acid), erythromycin (erythromycin), tetracycline (tetracycline) and ampicillin (ampicillin) were used, respectively. In addition, Helicobacter pylori measured the diameter size (mm) of growth support shown by incubating in a CO ₂ incubator (37 ° C., 10% CO ₂ , 95% humidity). The results are shown in Table 3 (size of growth support for Helicobacter pylori of urushiol derivatives) and FIG. 12.

3 to 11 in which the results of Table 2 are shown: 1: benzoic acid 2.5 μmol, 2: benzoic acid 5 μmol, 3: benzoic acid 10 μmol, C: comparative composition 1, MC: comparative composition 2, DC: comparative composition 3, PDC: comparative composition 4, PC: antimicrobial composition 1, EC: antimicrobial composition 2. 3 to 11 show that the low support of antimicrobial composition 1 (5 μmol) was greater than that of other comparative compositions as well as the low support of benzoic acid (5 μmol) in both test strains.

In addition, as apparent from Table 2, as an interesting phenomenon, although all the compounds of interest had a catechol structure, it was observed that there was a significant difference in activity with each other depending on the presence and length of branched hydrocarbons bonded to the third position. As a result, the antimicrobial activity is interpreted to be cooperatively involved in both the free catechol structure and the side chain hydrocarbon of suitable length. In other words, catechol (pyrocatechol, C), which has a free catechol structure but does not have branched hydrocarbons, showed very weak antimicrobial activity, and EC having -C ₂₀ H ₄₁ in the side chain with catechol structure Showed no antimicrobial activity at all.

 In addition, considering that the compounds having a catechol structure and having 1 to 10 branched carbon atoms showed activity, it was determined that the carbon number of the branched chain hydrocarbon was necessary before and after 5 carbon atoms to strongly express the activity.

In Table 12, the results of Table 3 are shown as 1: nalidixic acid 5μmol, 2: erythromycin 5μmol, 3: tetracycline 5μmol, 4: ampicillin 5μmol, C: Comparative composition 1, MC: Comparative composition 2, DC: comparative composition 3, PDC: comparative composition 4, PC: antimicrobial composition 1, EC: antimicrobial composition 2.

Table 3 and FIG. 12 show the difference between C (0 mm), MC (7.7 W 0.6 mm), DC (6.7 W 0.6 mm), PDC (8.0 ± 0 mm) and EC (0 mm) among the urushiol derivatives. However, low growth was not observed or very weakly observed.

However, the growth support (31.5 ± 0.5 mm) of PC, an allergic noninduced compound with catechol 3rd side chain of -C ₅ H ₁₁ , was used as a therapeutic agent for patients with Helicobacter pylori infection. mm), erythromycin (7.0 ± 0 mm), tetracycline (9.0 ± 0 mm) and ampicillin (7.0 ± 0 mm).

From these results, the antimicrobial activity of urushiol derivatives showed a similar tendency to that of five food rot bacteria and five pathogenic bacteria, and the side chain hydrocarbons of -C ₅ H _{11 in} the third catechol skeleton and non-allergic PC were used. The antimicrobial composition 1 containing the active ingredient showed the strongest antimicrobial activity. In particular, it can be seen that the results overwhelmingly exceed the antimicrobial activity of the compounds used as a Helicobacter pylori treatment.

Experimental Example 2

The antimicrobial activity of the antimicrobial composition 1, antimicrobial composition 2, comparative compositions 1 to 4 was tested for the antimicrobial activity by the method of minimal inhibition concentration for the microorganisms shown in Table 1.

First, several stopper sterile test tubes were arranged in sequence, and 5 mL of sterile medium corresponding to each strain was aseptically dispensed into the test tube. As shown in Table 4, the antimicrobial composition 1, the antimicrobial composition 2, the comparative compositions 1 to 4 and the control benzoic acid containing synthetic urushiol derivatives were dissolved in ethanol, respectively, and added to the test tube by 1000 μg / mL, and then sequentially into the test tube. Dilution (500, 250, 125-4 μg / mL). Aseptically inoculated so as to give a final concentration of 10 ^{5-10 7} cfu / mL from each of the pre-cultured cultures in each test tube, and then S. aureus , S. epidermidis , S. mutans , E. coli, P. aeruginosa and S. enterica at 37 ° C, B. subtilis and V. vulnificus C. albicans was incubated at 25 ° C. for 12-16 hours. H. pylori was incubated for 18 hours in a CO ₂ incubator (37 ℃, 10% CO ₂ , 95% humidity). Take 1 mL from each test tube, place it in a Petri dish, disintegrate about 10-15 mL of agar previously sterilized and maintained at 50 ° C, mix well, coagulate, and incubate for 12-18 hours under each culture temperature condition. Afterwards, the colony-free minimum concentration was determined as the minimum inhibition concentration (MIC), which is shown in Tables 4 and 5 below.

Referring to Table 4 (Minimum Inhibitory Concentration Values for Food Strains and Pathogenic Bacteria of Urushiol Derivatives), the results of the minimum inhibitory concentration of S. aureus showed that the side chain hydrocarbons of the urushiol derivatives were -C ₁₀ H _{31 and} -C _{15 ,} respectively. DC (0.08 ± 0 μmol / mL) and PDC (0.09 ± 0 μmol / mL) composed of H ₃₁ showed antimicrobial activity at lower concentrations than the control benzoic acid (0.20 ± 0 μmol / mL). DC and PDC showed similar trends in all 9 strains as well as S. aureus . However, previous studies have shown that DC and PDC are allergens with severe dermatitis. Therefore, these two compounds were judged to be difficult to actually use as antibacterial agents.

However, EC with -C ₂₀ H ₄₁ , a side chain hydrocarbon identified as an allergic non-induced compound, exhibited antimicrobial activity at 0.08 ± 0 μmol / mL, which is lower in S. aureus than the control benzoic acid (0.20 ± 0 μmol / mL). Showed. Most of the 9 strains, as well as S. aureus , did not reach DC or PDC but showed superior antimicrobial activity than benzoic acid. However, PC, which showed the highest antimicrobial activity on solid media using paper disc method, was identified as -C ₅ H ₁₁ as non-allergic compound by -C ₅ H _11. No activity was shown. However, PC showed less activity than C without side chain and MC with -CH ₃ at side chain, and PC (0.08 ± 0 μmol / mL) was specific for E. coli except DC. It showed superior antimicrobial activity.

Referring to Table 5 showing the minimum inhibitory concentration values for Helicobacter pylori of urushiol derivatives, the PDC (0.03 ± 0.02 μmol) and EC (0.03) of the side chain hydrocarbons of the urushiol derivatives consisted of -C ₁₅ H ₃₁ and -C ₂₀ H ₄₁ ± 0.02 μmol) showed antimicrobial activity at low concentrations. And DC (0.04 ± 0.04 μmol)> PC (0.07 ± 0 μmol)> MC (0.27 ± 0.12 μmol)> C (0.30 ± 0.13 μmol) showed the antimicrobial activity. Antimicrobial composition 2 (0.03 ± 0.02 μmol) containing EC as an active ingredient, which is an allergic non-induced compound with -C ₂₀ H ₄₁ as the catechol backbone 3rd side chain, was antibacterial at a lower concentration than ampicillin (0.14 ± 0 μmol) in the control. It showed activity, and showed similar antimicrobial activity to nalidic acid (0.02 ± 0.01 mol) and erythromycin (0.03 ± 0 µmol), but less than tetracycline (0.002 ± 0 µmol).

However, the antimicrobial composition containing PC as an active ingredient, which was identified as the allergic non-induced compound in the previous study as -C ₅ H ₁₁ , showed the highest antibacterial activity on the solid medium using the paper disk method. The minimum inhibitory concentration of 1 showed better antimicrobial activity than ampicillin (0.14 ± 0 μmol).

As a result of evaluating the antimicrobial activity against the antimicrobial compositions 1 and 2 of the present invention by the paper disk method, the antimicrobial compositions 1 and 2 of the present invention were antimicrobial activity against five kinds of food rot and five pathogens. It confirmed that it was shown.

In addition, as a result of evaluating the antimicrobial activity by the minimum inhibitory concentration method, the antibacterial composition 2 containing EC, an allergic non-induced urushiol derivative, as an active ingredient against five food rot bacteria and five pathogens was used as a control. At lower concentrations, it showed strong antibacterial activity.

Therefore, the antimicrobial composition (or antimicrobial agent) of the present invention contains an allergic non-induced urushiol derivative compound as an active ingredient and is useful for controlling and preventing food decay bacteria and / or pathogens.

In addition, the antimicrobial composition of the present invention may contain an additive appropriately selected depending on the purpose of use, either alone or 0.001 to 99% by weight of the allergic non-induced urushiol derivative compound. The present invention is not particularly limited to the selective use and content of these additives, and can be appropriately adjusted according to the method of use and dosage form at a professional level in the art. That is, the additive added to the antimicrobial composition of the present invention may be, for example, an excipient or a diluent of a material included in a conventional antimicrobial agent, and examples thereof include saline solution, buffer solution, dextrose, isoparaffin, water, glycerol, and ethanol. May be used, but is not limited thereto.

In addition, the formulation of the antimicrobial composition of the present invention can be appropriately adjusted according to the method of use and use, for example, liquids, suspensions, granules, fragrances, powders, syrups, aerosols, extracts, ointments, induction extracts, emulsions, Premises, eye drops, injections, spirits, capsules, creams, pills.

In addition, the antimicrobial composition of the present invention can be used as a cleaning agent, pharmaceuticals, food additives, fragrances, cosmetics, paints for the purpose of inhibiting the production and growth of fungi that produce pathogenic bacteria or toxins. When used as a medicament, it can be used as a disinfectant, therapeutic agent, or preventive agent. When used as a food additive, the antimicrobial composition is preferably adjusted according to the type of food and the method of use. When used as a fragrance, it may further comprise a volatile substance.

The present invention has been shown and described with reference to the preferred embodiments as described above, but is not limited to the above embodiments, those skilled in the art without departing from the spirit of the present invention. Various changes and modifications will be possible.

Figure 1 shows the structural formula of urushiol isolated from lacquer.

Figure 2 shows the structural formula and the compound name of the related compounds of the commercial urushiol derivatives used for the antimicrobial activity and the control compound used as a control compound.

Figure 3 shows low support for Staphylococcus aureus of urushiol derivatives.

4 shows low support for Staphylococcus epidermidis of urushiol derivatives.

5 shows low support for Pseudomonas aeruginosa of urushiol derivatives.

Figure 6 shows low support for Escherichia coli of urushiol derivatives.

Figure 7 shows low support for Bacillus subtilis of urushiol derivatives.

Figure 8 shows low support for Salmonella enterica of urushiol derivatives.

Figure 9 shows low support for Streptococcus mutans of urushiol derivatives.

Figure 10 shows low support for Vibrio vulnificus of urushiol derivatives.

Figure 11 shows low support for Candida albicans of urushiol derivatives.

12 shows low support for Helicobacter pylori of urushiol derivatives.

Claims (6)

An antimicrobial composition for preventing food decay, comprising an allergic non-induced urushiol derivative as an active ingredient having antimicrobial activity against food decay bacteria. The method of claim 1, The allergic non-induced urushiol derivative is 3-pentylcatechol (3-pentylcatechol) or 3-eicosylcatechol (3-eicosylcatechol) characterized in that anti-corruption antimicrobial composition. The method of claim 1, The food decay bacteria Staphylococcus aureus, Staphylococcus epidermidis , Gram-positive bacteria , Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis , Antimicrobial composition for preventing food corruption, characterized in that any one or more of. An antimicrobial composition for preventing and treating pathogens comprising an allergic non-induced urushiol derivative as an active ingredient as an active ingredient having antimicrobial activity against pathogens. The method of claim 4, wherein The allergic non-induced urushiol derivative is 3-pentylcatechol (3-pentylcatechol) or 3-eicosylcatechol (3-eicosylcatechol) antimicrobial composition for the prevention and treatment of pathogens, characterized in that. The method of claim 4, wherein The pathogen is Salmonella typhimurium, Streptococcus mutans, Vibrio vulnificus, Candida albicans, Helicobacter pylori antimicrobial composition for the prevention and treatment of pathogens, characterized in that any one or more.

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