KR-102963038-B1 - Composition for Inhibiting Persister Cell Comprising Extract of Pine Leaves

Abstract

The present invention relates to a composition for inhibiting persistent cells comprising pine needle extract. In the present invention, persistent bacteria that are not killed even by antibiotic treatment can be effectively inhibited using pine needle extract. Therefore, the composition for inhibiting persistent bacteria according to the present invention can be used to prevent and treat infectious diseases caused by bacteria, particularly recurrent or chronic infections, and can exhibit excellent effects, and can also be usefully applied to cosmetic compositions for improving dermatitis.

Inventors

• 김태종
• 김민준
• 김대윤

Assignees

• 국민대학교산학협력단

Dates

Publication Date

20260512

Application Date

20220609

Claims (14)

1. A composition for inhibiting persistent cells comprising pine needle extract, The above composition is used after antibiotic treatment or treated together with antibiotics, The above-mentioned persistent bacteria is a persistent bacterium of Staphylococcus aureus , and The above-mentioned persistent bacteria are bacteria that survive even when treated with an antibiotic at a concentration of five times or more of the minimum inhibitory concentration (MIC), and A composition for inhibiting persistent bacteria, wherein the above antibiotic is tobramycin.
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4. In Article 1, A composition for inhibiting persistent bacteria, wherein the concentration of the above pine needle extract is 0.001 to 10 g/L.
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7. In Article 1, A composition for inhibiting persistent bacteria, wherein the weight ratio of pine needle extract to antibiotic is 0.1:1 to 1,000:1.
8. A composition for the prevention or treatment of bacterial infectious diseases comprising a composition for inhibiting persistent bacteria according to any one of claims 1, 4, and 7, A composition for the prevention or treatment of a bacterial infectious disease, wherein the above bacterial infectious disease is an infectious disease caused by Staphylococcus aureus .
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10. In Article 8, A composition for the prevention or treatment of a bacterial infectious disease, wherein the bacterial infectious disease is one or more inflammatory diseases selected from the group consisting of respiratory infection, sinusitis, pneumonia, endocarditis, osteomyelitis, arthritis, cellulitis, gastroenteritis, postoperative wound infection, and dermatitis.
11. In Article 8, A composition for the prevention or treatment of a bacterial infectious disease, wherein the bacterial infectious disease is a palindromic or chronic disease.
12. A cosmetic composition for improving dermatitis comprising a composition for inhibiting persistent bacteria according to any one of claims 1, 4, and 7, A cosmetic composition for improving dermatitis, wherein the above-mentioned dermatitis is caused by Staphylococcus aureus .
13. In Article 12, A cosmetic composition for improving dermatitis, wherein the above dermatitis is an abscess, folliculitis, boil, or acne.
14. In Article 12, A cosmetic composition for improving dermatitis, wherein the above-mentioned dermatitis is recurrent or chronic dermatitis.

Description

Composition for Inhibiting Persister Cells Comprising Extract of Pine Leaves The present invention relates to a composition for inhibiting persistent bacteria comprising pine needle extract, and more specifically, to a composition capable of inhibiting persistent bacteria that are not killed even by antibiotic treatment using pine needle extract, a pharmaceutical composition and a cosmetic composition utilizing the same. Antibiotics are substances that inhibit the growth and proliferation of bacteria. Since the discovery of penicillin, the first antibiotic, various antibiotics have been researched and developed and are widely used to inhibit pathogens. For example, Korean Patent Publication No. 10-2016-0086479 discloses a cyclic depsipeptide compound as a compound that exhibits antibacterial activity against Staphylococcus aureus or Salmonella. However, some bacterial populations exhibit the characteristic of not being killed even by treatment with high concentrations of antibiotics. These bacteria are called persistent cells. In the 1942 paper *Hobby et al. , Observations on the mechanism of action of penicillin, Exp Biol Med 1942;50:281-5*, experimental results were reported showing that infection recurred in Staphylococcus aureus despite treatment with high concentrations of penicillin. Subsequently, in the paper *Bigger et al. , The bactericidal action of penicillin on Staphylococcus pyogenes , Irish J Med Sci 1944;19:553-68*, results were revealed showing that bacteria were not completely killed when treated with penicillin, and the surviving bacteria were named persistent cells. Persistent bacteria survive with minimal cellular metabolism and do not respond to common antibiotics. Notably, unlike antibiotic-resistant bacteria that exhibit resistance through genetic mutation, persistent bacteria do not respond to antibiotics regardless of whether or not they have mutated. Specifically, while the mechanism of acquiring antibiotic resistance involves inhibiting the binding of antibiotics to targets through genetic mutation, the phenomenon of persistent bacteria not responding to antibiotics is due to physiological characteristics in which the effect on the target's function is offset even though the antibiotic binds to the target. Consequently, persistent bacteria are not killed even by antibiotic treatment, and there is a problem that the limitations of therapeutic efficacy for infectious diseases cannot be overcome unless the issue of residual persistence of such bacteria is resolved. In particular, surviving persistent bacteria can multiply again and cause reinfection, posing a serious risk to immunocompromised patients. In fact, it has been reported that persistent bacteria of pathogens have a fatal effect on patients with cystic fibrosis, such as those with HIV infection. However, in order to inhibit persistent bacteria, a strategy different from conventional antimicrobial activity against common or resistant bacteria is required, and thus it is difficult to discover substances that exhibit an inhibitory effect on persistent bacteria. Figure 1 is a graph showing the ratio of persistent bacteria to oxacillin, tobramycin, or ciprofloxacin when pine needle extract is treated at different concentrations in one embodiment of the present invention. Figure 2 is a graph showing the inhibition rate of persistent bacteria formation against oxacillin, tobramycin, or ciprofloxacin when pine needle extract is treated at different concentrations in one embodiment of the present invention. Specific embodiments of the present invention will be described in more detail below. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by a skilled expert in the art to which the present invention pertains. In general, the nomenclature used herein is well known and commonly used in the art. The present invention relates to a composition capable of effectively inhibiting persistent cells. Persistent bacteria are bacteria that are not affected by treatment with substances that kill bacteria or inhibit bacterial growth, namely antibiotics, and survive even when exposed to high concentrations or high-efficiency antibiotics. For example, the above-mentioned persistent bacteria can be interpreted as bacteria that survive even when treated with an antibiotic at a dose of five times or more, for example, ten times, the minimum inhibitory concentration (MIC). In this case, the above-mentioned minimum inhibitory concentration refers to the minimum concentration at which the antibiotic exhibits an antibacterial effect. Due to these persistent bacteria, there are limitations to the antimicrobial effects of antibiotics, and there is a problem in that it is difficult to prevent bacteria from reproducing after antibiotic treatment. In particular, since a certain proportion of the bacterial population acts as persistent bacteria regardless of genetic mutations, general antimicr