KR102659787B1 - Composition for Preventing Biofilm Formation Comprising Behenic Acid - Google Patents
Composition for Preventing Biofilm Formation Comprising Behenic Acid Download PDFInfo
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- KR102659787B1 KR102659787B1 KR1020220004061A KR20220004061A KR102659787B1 KR 102659787 B1 KR102659787 B1 KR 102659787B1 KR 1020220004061 A KR1020220004061 A KR 1020220004061A KR 20220004061 A KR20220004061 A KR 20220004061A KR 102659787 B1 KR102659787 B1 KR 102659787B1
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- composition
- present
- biofilm
- behenic acid
- microorganisms
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Classifications
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/02—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
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- Emergency Medicine (AREA)
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- Agronomy & Crop Science (AREA)
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- Communicable Diseases (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
본 발명은 베헨산을 유효성분으로 포함하여 바이오필름의 형성을 억제할 수 있는 조성물에 관한 것이다.
본 발명에 따른 조성물은 베헨산을 포함하여 미생물의 생장에는 영향을 미치지 않으면서, 바이오필름의 형성만을 특이적으로 억제할 수 있다. 이에 따라, 본 발명의 조성물은 내성균 출현의 우려 없이 바이오필름 억제 효과를 나타낼 수 있으므로, 피부 개선용 화장료 조성물, 바이오필름으로 인한 감염성 질환의 예방 또는 치료용 약학 조성물 및 기능성 식품에 효과적으로 사용될 수 있다.The present invention relates to a composition that contains behenic acid as an active ingredient and can inhibit the formation of biofilm.
The composition according to the present invention contains behenic acid and can specifically inhibit the formation of biofilm without affecting the growth of microorganisms. Accordingly, the composition of the present invention can exhibit a biofilm inhibition effect without fear of emergence of resistant bacteria, and therefore can be effectively used in cosmetic compositions for skin improvement, pharmaceutical compositions for preventing or treating infectious diseases caused by biofilms, and functional foods.
Description
본 발명은 베헨산을 포함함으로써 바이오필름의 형성을 억제할 수 있는 조성물에 관한 것으로, 보다 상세하게는, 베헨산을 포함하여 미생물의 생장에는 영향을 미치지 않으면서 바이오필름의 형성을 특이적으로 억제할 수 있는 조성물에 관한 것이다.The present invention relates to a composition capable of inhibiting the formation of biofilm by containing behenic acid, and more specifically, by containing behenic acid, to specifically inhibit the formation of biofilm without affecting the growth of microorganisms. It relates to a composition that can.
바이오필름(생물막, biofilm)은 미생물에 의해 형성된 막 형태의 군집체를 의미하는 것으로, 미생물은 고체 표면에 부착되어 군락을 형성하고 서서히 성장하면서 세포외 폴리머에 의해 덮인 바이오필름을 형성한다. 바이오필름은 미생물의 성장이 가능한 다양한 환경에서 흔하게 발견되며 인간에게 유해한 영향을 미치는데, 예를 들어 바이오필름으로 오염된 의료용 장치나 이식물을 인체에 사용하는 경우 심각한 감염증을 유발할 수 있다. Biofilm refers to a colony in the form of a film formed by microorganisms. Microorganisms attach to a solid surface, form a colony, and grow slowly to form a biofilm covered by an extracellular polymer. Biofilms are commonly found in various environments where microbial growth is possible and have harmful effects on humans. For example, using medical devices or implants contaminated with biofilms in the human body can cause serious infections.
바이오필름 형태의 미생물은 물리적인 세척으로 제거가 어렵고, 부유 상태의 미생물에 비하여 화학적 살균제 및 항생제에 대해 저항성이 매우 높다는 특징이 있다. 특히, 바이오필름을 형성하는 미생물 중 황색포도상구균(Staphylococcus aureus)은 그람 양성 병원균으로서 피부염, 장염, 농양 등 다양한 감염증을 유발하는 원인균이며, 메티실린과 같은 항생제에 대한 내성이 높다. 따라서 황색포도상구균에 의해 바이오필름이 형성되면 항생제를 사용하더라도 바이오필름의 억제 또는 제거가 매우 어렵다는 문제가 있다.Microorganisms in the form of biofilms are difficult to remove by physical washing and have a very high resistance to chemical disinfectants and antibiotics compared to floating microorganisms. In particular, among the microorganisms that form biofilms, Staphylococcus aureus is a Gram-positive pathogen that causes various infections such as dermatitis, enteritis, and abscesses, and has high resistance to antibiotics such as methicillin. Therefore, when a biofilm is formed by Staphylococcus aureus, there is a problem that it is very difficult to suppress or remove the biofilm even when antibiotics are used.
이에 따라, 살균제 또는 항생제로 바이오필름의 형성을 억제하기 위해서는 매우 많은 양의 제제를 사용해야 한다. 그런데, 미생물에 다량의 항생제를 지속적으로 사용하게 되면 항생제에 대한 저항성이 더욱 높아지고, 내성균 출현에 의해 바이오필름의 억제가 갈수록 어려워지는 문제가 발생한다.Accordingly, in order to suppress the formation of biofilm with a disinfectant or antibiotic, a very large amount of agent must be used. However, if large amounts of antibiotics are continuously used on microorganisms, resistance to antibiotics increases, and suppression of biofilms becomes increasingly difficult due to the emergence of resistant bacteria.
바이오필름의 형성을 억제하기 위한 기술로서, 대한민국 등록특허공보 제10-1691123호에서는 시트랄(Citral), 히노키티올(Hinokitiol) 및 리날로올(Linalool)을 이용하여 메티실린 내성 균주에 항균 활성을 나타냄으로써 바이오필름을 억제하는 기술을 기재하고 있다. 또한, 대한민국 공개특허공보 제10-2021-0108207호에서는 트리페닐포스포니움을 포함하는 지질친화성 양이온 화합물을 이용함으로써 내성균에 대해서도 항균 활성을 나타내어 그람 양성균의 바이오필름 형성을 억제할 수 있는 조성물을 기재하고 있다. 상기 기술들에 따르면 항생제 내성균에 대해서도 바이오필름 억제 활성을 나타낼 수 있다는 효과가 있으나, 미생물의 생장을 억제하는 활성이 동시에 나타나기 때문에 항균제의 반복 사용에 따른 저항성 증가 문제는 해결할 수 없다는 한계가 있었다. As a technology for suppressing the formation of biofilm, Republic of Korea Patent Publication No. 10-1691123 uses Citral, Hinokitiol, and Linalool to exhibit antibacterial activity against methicillin-resistant strains. The technology for suppressing biofilm is described. In addition, Republic of Korea Patent Publication No. 10-2021-0108207 discloses a composition that exhibits antibacterial activity against resistant bacteria by using a lipophilic cationic compound containing triphenylphosphonium and can inhibit biofilm formation of Gram-positive bacteria. It is listed. According to the above technologies, there is an effect of showing biofilm inhibition activity even against antibiotic-resistant bacteria, but there is a limitation in that the problem of increased resistance due to repeated use of antibacterial agents cannot be solved because the activity of inhibiting the growth of microorganisms is shown at the same time.
이에 따라, 내성균 출현의 우려 없이 바이오필름을 효과적으로 억제하기 위하여, 미생물의 생장에는 영향을 미치지 않으면서 바이오필름 형성만을 특이적으로 억제할 수 있는 새로운 전략이 필요한 상황이다.Accordingly, in order to effectively suppress biofilms without fear of the emergence of resistant bacteria, a new strategy is needed that can specifically suppress biofilm formation without affecting the growth of microorganisms.
본 발명의 목적은 미생물의 생장을 저해하지 않으면서 바이오필름 형성을 특이적으로 억제할 수 있는 조성물을 제공하는 것이다.The purpose of the present invention is to provide a composition that can specifically inhibit biofilm formation without inhibiting the growth of microorganisms.
본 발명의 다른 목적은 상기 조성물을 포함하는 피부 개선용 화장료 조성물을 제공하는 것이다.Another object of the present invention is to provide a cosmetic composition for improving skin containing the composition.
본 발명의 또 다른 목적은 상기 조성물을 포함하는 감염성 질환의 예방 또는 치료용 약학 조성물을 제공하는 것이다.Another object of the present invention is to provide a pharmaceutical composition for preventing or treating infectious diseases, including the composition.
본 발명의 또 다른 목적은 상기 조성물을 포함하는 감염성 질환의 예방 또는 개선용 기능성 식품을 제공하는 것이다.Another object of the present invention is to provide a functional food for preventing or improving infectious diseases containing the composition.
상술한 바와 같은 목적을 달성하기 위하여, 본 발명은 베헨산을 유효성분으로 포함하는 바이오필름 형성 억제용 조성물을 제공한다.In order to achieve the above-described object, the present invention provides a composition for inhibiting biofilm formation containing behenic acid as an active ingredient.
본 발명에서, 상기 베헨산의 농도는 8 내지 40mg/L일 수 있다.In the present invention, the concentration of behenic acid may be 8 to 40 mg/L.
본 발명에서, 상기 조성물은 포도상구균 속(Staphylococcus sp.) 미생물에 의한 바이오필름 형성을 억제하는 것일 수 있다.In the present invention, the composition may inhibit biofilm formation by Staphylococcus sp. microorganisms.
본 발명에서, 상기 포도상구균 속 미생물은 황색포도상구균 및 항생제 내성 황색포도상구균으로 구성된 군에서 선택되는 1종 이상일 수 있다.In the present invention, the microorganism of the genus Staphylococcus may be one or more types selected from the group consisting of Staphylococcus aureus and antibiotic-resistant Staphylococcus aureus.
본 발명은 또한, 베헨산을 유효성분으로 포함하는 바이오필름 형성 억제용 조성물을 포함하는 피부 개선용 화장료 조성물을 제공한다.The present invention also provides a cosmetic composition for improving skin, including a composition for inhibiting biofilm formation containing behenic acid as an active ingredient.
본 발명에서, 상기 화장료 조성물은 아토피 피부 또는 여드름 피부 개선용일 수 있다.In the present invention, the cosmetic composition may be used to improve atopic skin or acne skin.
본 발명은 또한, 베헨산을 유효성분으로 포함하는 바이오필름 형성 억제용 조성물을 포함하는 감염성 질환의 예방 또는 치료용 약학 조성물을 제공한다.The present invention also provides a pharmaceutical composition for preventing or treating infectious diseases, including a composition for inhibiting biofilm formation containing behenic acid as an active ingredient.
본 발명에서, 상기 감염성 질환은 포도상구균 속(Staphylococcus sp.) 미생물의 바이오필름에 의해 유발되는 것일 수 있다.In the present invention, the infectious disease may be caused by a biofilm of Staphylococcus sp. microorganisms.
본 발명에서, 상기 감염성 질환은 식중독, 피부염, 농양, 심내막염, 골수염, 폐렴, 장염, 패혈증, 균혈증, 근막염, 방광염 및 복막염으로 구성된 군에서 선택되는 질환일 수 있다.In the present invention, the infectious disease may be a disease selected from the group consisting of food poisoning, dermatitis, abscess, endocarditis, osteomyelitis, pneumonia, enteritis, sepsis, bacteremia, fasciitis, cystitis, and peritonitis.
본 발명은 또한, 베헨산을 유효성분으로 포함하는 바이오필름 형성 억제용 조성물을 포함하는 감염성 질환의 예방 또는 개선용 기능성 식품을 제공한다. The present invention also provides a functional food for preventing or improving infectious diseases, including a composition for inhibiting biofilm formation containing behenic acid as an active ingredient.
본 발명에서, 상기 감염성 질환은 포도상구균 속(Staphylococcus sp.) 미생물의 바이오필름에 의해 유발되는 것일 수 있다.In the present invention, the infectious disease may be caused by a biofilm of Staphylococcus sp. microorganisms.
본 발명에 따른 조성물은 베헨산을 포함하여 미생물의 생장에는 영향을 미치지 않으면서, 바이오필름의 형성만을 특이적으로 억제할 수 있다. 이에 따라, 본 발명의 조성물은 내성균 출현의 우려 없이 바이오필름 억제 효과를 나타낼 수 있으므로, 피부 개선용 화장료 조성물, 바이오필름으로 인한 감염성 질환의 예방 또는 치료용 약학 조성물 및 기능성 식품에 효과적으로 사용될 수 있다.The composition according to the present invention contains behenic acid and can specifically inhibit the formation of biofilm without affecting the growth of microorganisms. Accordingly, the composition of the present invention can exhibit a biofilm inhibition effect without fear of emergence of resistant bacteria, and therefore can be effectively used in cosmetic compositions for skin improvement, pharmaceutical compositions for preventing or treating infectious diseases caused by biofilms, and functional foods.
도 1은 본 발명의 일 실시예에서 베헨산의 농도에 따른 황색포도상구균의 세포 밀도 및 바이오필름 형성 비율 변화를 측정한 결과 그래프이다.Figure 1 is a graph showing the results of measuring changes in cell density and biofilm formation rate of Staphylococcus aureus according to the concentration of behenic acid in one embodiment of the present invention.
이하, 본 발명의 구체적인 구현 형태에 대해서 보다 상세히 설명한다. 다른 식으로 정의되지 않는 한, 본 명세서에서 사용된 모든 기술적 및 과학적 용어들은 본 발명이 속하는 기술 분야에서 숙련된 전문가에 의해서 통상적으로 이해되는 것과 동일한 의미를 갖는다. 일반적으로, 본 명세서에서 사용된 명명법은 본 기술 분야에서 잘 알려져 있고 통상적으로 사용되는 것이다.Hereinafter, specific implementation forms of the present invention will be described in more detail. Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by a person skilled in the art to which the present invention pertains. In general, the nomenclature used herein is well known and commonly used in the art.
본 발명은 베헨산을 포함하는 바이오필름 형성 억제용 조성물에 관한 것이다.The present invention relates to a composition for inhibiting biofilm formation containing behenic acid.
바이오필름(생물막, biofilm)은 미생물에 의해 형성된 막 형태의 군집체를 의미한다. 미생물은 고체 표면에 부착되어 군락을 형성하고, 서서히 성장하면서 세포외 폴리머(extracellular polymeric substance, EPS)에 의해 덮인 바이오필름을 형성한다.Biofilm refers to a colony in the form of a film formed by microorganisms. Microorganisms attach to solid surfaces, form colonies, and grow slowly to form a biofilm covered by extracellular polymeric substance (EPS).
바이오필름 제거 활성은 일반적인 항균 활성과 구별되는 개념으로, 바이오필름 형태의 미생물은 물리적인 세척으로 제거가 어렵고, 부유 상태의 미생물에 비하여 화학적 살균제 및 항생제에 대해 저항성이 매우 높다. 따라서, 살균제 또는 항생제로 바이오필름을 제거하거나 바이오필름에 의한 감염을 치료하기 위해서는 매우 많은 양의 제제를 사용해야 한다. 그런데, 항생제의 과다 사용이 반복되면 저항성이 더욱 높아지고 내성균 출현에 의해 미생물에 의한 바이오필름 형성 제어가 더욱 어려워지는 문제가 발생한다.Biofilm removal activity is a concept that is distinct from general antibacterial activity. Microorganisms in the form of biofilms are difficult to remove by physical washing, and have very high resistance to chemical disinfectants and antibiotics compared to microorganisms in suspended state. Therefore, in order to remove biofilms or treat infections caused by biofilms with disinfectants or antibiotics, a very large amount of agents must be used. However, if excessive use of antibiotics is repeated, resistance increases and the emergence of resistant bacteria makes it more difficult to control biofilm formation by microorganisms.
본 발명에서는, 베헨산을 이용하여 내성균 출현의 우려 없이 바이오필름을 효과적으로 억제할 수 있는 새로운 전략을 제안한다.In the present invention, we propose a new strategy that can effectively suppress biofilms using behenic acid without fear of emergence of resistant bacteria.
본 발명에서 사용되는 베헨산(C21H43COOH)은 카르복실기를 가지며 22개의 탄소로 구성된 포화 지방산이다. 일반적으로, 불포화 지방산의 경우 항균 활성 및 바이오필름 억제 활성이 있는 것으로 보고된 바 있으나, 포화 지방산, 특히 장쇄 포화 지방산의 미생물 생장 조절 활성은 알려진 바 없다.Behenic acid (C 21 H 43 COOH) used in the present invention is a saturated fatty acid that has a carboxyl group and consists of 22 carbons. In general, unsaturated fatty acids have been reported to have antibacterial and biofilm inhibitory activities, but the microbial growth-regulating activity of saturated fatty acids, especially long-chain saturated fatty acids, is not known.
이와 같은 상황에서, 본 발명의 발명자들은 장쇄 포화 지방산 중에서 베헨산을 이용하는 경우 황색포도상구균의 바이오필름을 효과적으로 억제할 수 있을 뿐만 아니라, 미생물의 생장에는 영향을 미치지 않는다는 것을 발견함으로써 본 발명을 완성하였다.In this situation, the inventors of the present invention completed the present invention by discovering that the use of behenic acid among long-chain saturated fatty acids not only effectively inhibits the biofilm of Staphylococcus aureus, but also does not affect the growth of microorganisms. .
본 발명에 따르면, 베헨산을 유효성분으로 포함하는 조성물을 이용함으로써 미생물의 생장에는 영향을 적게 미치면서 바이오필름을 특이적으로 억제할 수 있다. 이에 따라, 기존의 항생제나 살균제와 달리 미생물의 내성 증가 문제를 유발하지 않으면서 우수한 바이오필름 형성 억제 효과를 나타낼 수 있다. 이 때, "유효성분으로 포함하는"이라는 표현은 베헨산의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. According to the present invention, biofilm can be specifically inhibited with little effect on the growth of microorganisms by using a composition containing behenic acid as an active ingredient. Accordingly, unlike existing antibiotics or disinfectants, it can exhibit an excellent biofilm formation inhibition effect without causing the problem of increased resistance of microorganisms. At this time, the expression “containing as an active ingredient” means containing a sufficient amount to achieve the efficacy or activity of behenic acid.
본 발명의 조성물에서, 베헨산의 농도는 8 내지 40mg/L일 수 있으며, 바람직하게는 20 내지 30mg/L일 수 있다. 상기 농도 범위에서, 미생물의 생장을 억제하지 않으면서 바이오필름의 형성만을 특이적으로 억제하는 효과가 나타날 수 있다. In the composition of the present invention, the concentration of behenic acid may be 8 to 40 mg/L, preferably 20 to 30 mg/L. In the above concentration range, the effect of specifically inhibiting the formation of biofilm without inhibiting the growth of microorganisms may be achieved.
본 발명의 조성물은 포도상구균 속(Staphylococcus sp.) 미생물에 의한 바이오필름 형성을 억제할 수 있다. 구체적으로, 본 발명의 조성물은 황색포도상구균(Staphylococcus aureus)에 의한 바이오필름 형성을 억제할 수 있다. 또한, 베헨산은 바이오필름의 형성은 억제하면서도 미생물 자체의 생장을 억제하지 않으므로 미생물에 항생제 저항성이 발생하지 않으며, 항생제 내성균에 의한 바이오필름 형성 또한 억제할 수 있다. 본 발명에서, 상기 항생제 내성균은 메티실린(methicillin), 반코마이신(vancomycin), 세팔로스포린(cephalosporin) 및 리팜피신(rifampicin)으로 구성된 군에서 선택되는 항생제에 대한 내성균일 수 있으며, 예를 들어 메티실린 내성 황색포도상구균(Methicillin Resistant Staphylococcus aureus, MRSA)일 수 있다.The composition of the present invention can inhibit biofilm formation by Staphylococcus sp. microorganisms. Specifically, the composition of the present invention can inhibit biofilm formation by Staphylococcus aureus . In addition, behenic acid inhibits the formation of biofilms but does not inhibit the growth of microorganisms themselves, so antibiotic resistance does not occur in microorganisms, and it can also inhibit biofilm formation by antibiotic-resistant bacteria. In the present invention, the antibiotic-resistant bacteria may be resistant to antibiotics selected from the group consisting of methicillin, vancomycin, cephalosporin, and rifampicin, for example, methicillin-resistant. It may be Staphylococcus aureus (Methicillin Resistant Staphylococcus aureus, MRSA).
본 발명의 조성물은 바이오필름의 형성을 억제하는 효과가 우수하므로, 미생물의 생장 또는 증식이 가능한 표면에 코팅제로 사용되어 바이오필름의 형성을 방지할 수 있다.Since the composition of the present invention has an excellent effect of inhibiting the formation of biofilm, it can be used as a coating agent on surfaces where microorganisms can grow or proliferate to prevent the formation of biofilm.
본 발명의 예시적인 실시 형태에서, 바이오필름 형성 억제용 조성물은 의료용 장치 또는 이식물(implant)에 적용될 수 있다. 의료용 장치 또는 이식물은 의료 목적으로 생체에 적용되는 것이지만, 이러한 장치 또는 이식물이 바이오필름에 의해 오염되는 경우 오히려 생체를 위협하고 감염을 일으키는 문제가 발생할 수 있다. 본 발명은 상기 문제를 해결할 수 있는 것으로, 의료용 장치 또는 이식물에 바이오필름이 형성되는 것을 막고 이에 의한 감염을 방지할 수 있다.In an exemplary embodiment of the present invention, the composition for inhibiting biofilm formation may be applied to a medical device or implant. Medical devices or implants are applied to the living body for medical purposes, but if these devices or implants are contaminated with biofilm, problems that threaten the living body and cause infection may occur. The present invention can solve the above problems, preventing biofilms from forming on medical devices or implants and preventing infections caused by them.
본 발명에서, 상기 의료용 장치는 진찰용 장치, 진단용 장치, 수술용 장치, 치료용 장치, 임상시험용 장치, 방사선 관련 장치, 재활의학용 장치, 물리치료용 장치, 응급처치용 장치, 제약 관련 장치, 한방 관련 장치 등일 수 있다. 이 때, 의료용 장치란 의료 목적으로 사용되는 재료, 도구, 기구, 용품, 기기, 설비 및 장비를 포함하는 개념으로 해석된다. 또한, 상기 의료용 이식물은 생체 내에 일시적으로 또는 영구적으로 삽입되는 삽입물, 예를 들어 카테터(catheter), 배액관(stent), 인공 장기(artificial organs), 인공 뼈, 인공 관절, 렌즈, 임플란터블 센서(implantable sensor) 등을 포함할 수 있다.In the present invention, the medical device includes examination devices, diagnostic devices, surgical devices, treatment devices, clinical trial devices, radiation-related devices, rehabilitation medicine devices, physical therapy devices, first aid devices, pharmaceutical-related devices, It may be a device related to oriental medicine, etc. At this time, medical devices are interpreted as a concept that includes materials, tools, instruments, supplies, devices, facilities, and equipment used for medical purposes. In addition, the medical implants include implants that are temporarily or permanently inserted into the living body, such as catheters, drainage tubes (stent), artificial organs, artificial bones, artificial joints, lenses, and implantable sensors. (implantable sensor), etc. may be included.
본 발명의 예시적인 실시 형태에서, 바이오필름 형성 억제용 조성물은 주방용 기구 또는 장치에 코팅될 수 있다. 주방용 기구 또는 장치는 바이오필름에 의해 오염되기 쉬우며, 바이오필름은 물리적인 세척이나 일반 소독제 처리 과정에서 쉽게 제거되지 않고, 살균소독제를 이용하는 경우 내성 및 유해성의 문제가 있다. 본 발명은 이러한 문제를 해결하여, 식물성 포화 지방산을 이용하여 주방용 기구 또는 장치에 바이오필름이 형성되는 것을 막고 이에 의한 세균성 식중독을 방지할 수 있다.In an exemplary embodiment of the present invention, the composition for inhibiting biofilm formation may be coated on kitchen utensils or devices. Kitchen utensils or devices are easily contaminated by biofilm, and biofilm is not easily removed during physical cleaning or general disinfectant treatment, and there are problems with resistance and toxicity when using disinfectants. The present invention solves this problem and can prevent biofilm from forming on kitchen utensils or devices and bacterial food poisoning by using vegetable saturated fatty acids.
상기 주방용 기구 또는 장치는 조리, 요리, 식품 가공, 식품 보관, 식품 처리에 사용되는 기구 또는 장치로서, 도마, 식칼, 주걱, 국자 등의 조리용 기구; 유리 용기, 플라스틱 용기, 실리콘 용기 등의 식품 보관 용기; 커피머신, 토스터, 오븐, 냉장고 등의 주방 가전 등을 포함할 수 있다. 또한, 바이오필름은 식품의 표면에도 형성될 수 있으므로, 이를 방지하기 위하여 본 발명의 조성물을 식품에 직접 적용하는 것도 가능하다.The kitchen utensils or devices are utensils or devices used for cooking, cooking, food processing, food storage, and food processing, and include cooking utensils such as cutting boards, kitchen knives, spatulas, and ladles; Food storage containers such as glass containers, plastic containers, and silicone containers; This may include kitchen appliances such as coffee machines, toasters, ovens, and refrigerators. Additionally, since biofilm can also form on the surface of food, it is also possible to apply the composition of the present invention directly to food to prevent this.
본 발명의 바이오필름 형성 억제용 조성물이 코팅되는 대상체는 이에 한정되지 않으며, 바이오필름 형성의 우려가 있는 다양한 생활 용품에 사용될 수 있다.The object coated with the composition for inhibiting biofilm formation of the present invention is not limited to this, and can be used in various household products that are at risk of biofilm formation.
본 발명은 또한, 베헨산을 포함하는 화장료 조성물을 제공한다. 베헨산을 화장료에 적용하는 경우, 피부에서 미생물에 의한 바이오필름의 형성을 억제할 수 있으므로 피부 개선 효과를 나타낼 수 있다.The present invention also provides a cosmetic composition containing behenic acid. When behenic acid is applied to cosmetics, it can suppress the formation of biofilms caused by microorganisms on the skin, thereby showing a skin improvement effect.
포도상구균 속의 미생물은 피부의 표면 및 모공에 상재할 수 있으며, 그 중 황색포도상구균은 다른 포도상구균과 달리 정상인에게도 질병을 일으키는 병원균으로, 피부의 황색포도상구균은 피부에서 바이오필름을 형성하여 농양 등 다양한 표피 감염을 일으킬 수 있다. 특히 아토피 환자의 피부와 같이 피부 장벽이 손상된 상태에서는 이와 같은 현상이 더 잘 일어나 증상을 악화시키게 된다.Microorganisms belonging to the genus Staphylococcus can reside on the surface and pores of the skin. Among them, Staphylococcus aureus is a pathogen that causes disease even in normal people, unlike other staphylococci. Staphylococcus aureus forms a biofilm on the skin, causing abscesses, etc. It can cause a variety of superficial infections. In particular, when the skin barrier is damaged, such as the skin of atopic dermatitis patients, this phenomenon occurs more easily and worsens symptoms.
지방산 성분을 이용하여 화장료를 제조하는 것은 알려진 기술이지만, 일반적으로 지방산은 화장료에 보습 효과 또는 주름 개선 효과를 부여하기 위해 첨가되는 성분으로서, 베헨산을 피부에 적용하는 경우 황색포도상구균과 같은 병원균에 의한 바이오필름 형성을 억제할 수 있음은 알려진 바 없다.Manufacturing cosmetics using fatty acid ingredients is a known technology, but fatty acids are generally added to cosmetics to provide a moisturizing or wrinkle-improving effect. When behenic acid is applied to the skin, it can be used to protect against pathogens such as Staphylococcus aureus. It is not known that biofilm formation can be inhibited.
본 발명에 따라 베헨산을 피부 외용제로 적용하면, 피부에서 포도상구균 속 미생물, 특히 황색포도상구균에 의한 바이오필름 형성을 억제할 수 있으므로 피부 보호 및 장벽 기능 개선에 효과가 있다. 더욱이, 본 발명을 이용하면 항생제에 내성을 갖는 황색포도상구균에 의한 바이오필름 형성도 억제할 수 있으므로, 항생제의 지속 사용에 의해 내성균이 다량 존재하는 피부에도 효과적으로 사용될 수 있다. When behenic acid is applied as an external skin agent according to the present invention, it is effective in protecting the skin and improving barrier function because it can inhibit biofilm formation by Staphylococcus genus microorganisms, especially Staphylococcus aureus, on the skin. Moreover, using the present invention, biofilm formation by antibiotic-resistant Staphylococcus aureus can be suppressed, so it can be effectively used on skin where large amounts of resistant bacteria exist due to continuous use of antibiotics.
따라서, 본 발명의 화장료 조성물은 피부 장벽 강화, pH 조절, 보습 등 피부 상태를 개선하기 위한 기능성 화장품으로 활용될 수 있으며, 특히 아토피 피부, 여드름 피부 등 문제성 피부의 개선에 이용될 수 있다.Therefore, the cosmetic composition of the present invention can be used as a functional cosmetic to improve skin conditions such as strengthening the skin barrier, adjusting pH, and moisturizing. In particular, it can be used to improve problematic skin such as atopic skin and acne skin.
본 발명에 있어서, 상기 화장료 조성물의 제형은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있고, 예를 들어 용액, 유탁액, 현탁액, 페이스트, 겔, 크림, 로션, 파우더, 비누, 클렌징, 오일, 분말 또는 스프레이로 이루어진 군에서 선택된 제형일 수 있다.In the present invention, the formulation of the cosmetic composition can be prepared in any formulation commonly prepared in the art, for example, solution, emulsion, suspension, paste, gel, cream, lotion, powder, soap, cleansing , may be a formulation selected from the group consisting of oil, powder, or spray.
본 발명에서, 화장료 조성물의 제형이 용액 또는 유탁액인 경우 담체 성분으로서 용매, 용매화제 또는 유탁화제를 이용할 수 있다. 예컨대 물, 에탄올, 이소프로판올, 에틸카보네이트, 에틸아세테이트, 벤질알코올, 벤질벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌글리콜 또는 소르비탄의 지방산 에스테르를 이용할 수 있다.In the present invention, when the formulation of the cosmetic composition is a solution or emulsion, a solvent, solvating agent, or emulsifying agent can be used as a carrier component. For example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan can be used.
본 발명에서, 화장료 조성물의 제형이 현탁액인 경우 담체 성분으로서 물, 에탄올 또는 프로필렌글리콜과 같은 액상 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.In the present invention, when the formulation of the cosmetic composition is a suspension, the carrier component includes water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracant may be used.
본 발명에서, 화장료 조성물의 제형이 페이스트, 겔, 크림 또는 로션인 경우 담체 성분으로서 동물섬유, 식물 섬유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.In the present invention, when the formulation of the cosmetic composition is a paste, gel, cream or lotion, animal fiber, plant fiber, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or Zinc oxide, etc. may be used.
본 발명에서, 화장료 조성물의 제형이 파우더 또는 스프레이인 경우 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.In the present invention, when the formulation of the cosmetic composition is powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder can be used as the carrier ingredient, and especially in the case of spray, chlorofluorohydride may be used as a carrier ingredient. May contain propellants such as carbon, propane/butane or dimethyl ether.
본 발명에서, 화장료 조성물의 제형이 클렌징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 오일, 리놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.In the present invention, when the formulation of the cosmetic composition is cleansing, the carrier ingredients include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, and fatty acid amide. Ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, linoline derivative, or ethoxylated glycerol fatty acid ester can be used.
본 발명의 화장료 제형은 또한, 본 발명이 목적으로 하는 주 효과를 손상시키지 않는 범위 내에서, 바람직하게는 주 효과에 상승 효과를 줄 수 있는 다른 성분 등을 화장료의 제형 또는 사용목적에 따라 어려움 없이 선정하여 배합할 수 있다.The cosmetic formulation of the present invention also includes other ingredients that can have a synergistic effect on the main effect within a range that does not impair the main effect aimed at by the present invention, without difficulty depending on the formulation or purpose of use of the cosmetic. You can select and mix them.
본 발명에 있어서, 상기 화장료 조성물의 용도 및 기능은 특별히 제한되지 않으며, 목적에 따라 적절하게 선택할 수 있다. 예를 들어, 본 발명의 화장료 조성물은 스킨로션, 스킨소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스쳐 로션, 영양 로션, 맛사지크림, 영양크림, 모이스처크림, 핸드크림, 파운데이션, 에센스, 영양에센스, 팩, 비누, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션 및 바디클렌저로 군에서 선택된 하나 이상의 용도 및 기능을 가질 수 있다.In the present invention, the use and function of the cosmetic composition are not particularly limited and can be appropriately selected depending on the purpose. For example, the cosmetic composition of the present invention includes skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutritional lotion, massage cream, nutritional cream, moisture cream, hand cream, foundation, essence, nutritional essence. , pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion, and body cleanser. It may have one or more uses and functions selected from the group.
본 발명의 화장료 조성물은 베헨산 외에 화장료 조성물에 통상적으로 이용되는 성분들을 더 포함할 수 있으며, 예컨대 항산화제, 안정화제, 보습제, 용해화제, 비타민, 자외선 흡수제, 안료 및 향료와 같은 통상적인 보조제를 포함할 수 있고, 이외에 방부제 등을 더 포함할 수 있다.The cosmetic composition of the present invention may further include ingredients commonly used in cosmetic compositions in addition to behenic acid, such as conventional auxiliaries such as antioxidants, stabilizers, moisturizers, solubilizers, vitamins, ultraviolet absorbers, pigments, and fragrances. It may contain, and in addition, it may further contain preservatives, etc.
본 발명은 또한, 베헨산을 유효성분으로 포함하는 감염성 질환의 예방 또는 치료용 약학 조성물을 제공할 수 있다.The present invention can also provide a pharmaceutical composition for preventing or treating infectious diseases containing behenic acid as an active ingredient.
본 발명의 약학 조성물은 베헨산을 유효성분으로 포함하여, 미생물의 바이오필름, 구체적으로 포도상구균 속(Staphylococcus sp.) 미생물이 형성하는 바이오필름에 의해 유발되는 감염성 질환을 예방하거나 치료하는 효과를 나타낼 수 있다. 특히, 본 발명에서 베헨산은 병원균인 황색포도상구균이 바이오필름을 형성하는 것을 억제할 수 있으므로, 황색포도상구균의 바이오필름에 의해 유발되는 감염성 질환을 예방 또는 치료할 수 있다.The pharmaceutical composition of the present invention contains behenic acid as an active ingredient, and has the effect of preventing or treating infectious diseases caused by microbial biofilms, specifically biofilms formed by Staphylococcus sp. You can. In particular, in the present invention, behenic acid can inhibit the formation of biofilm by Staphylococcus aureus, a pathogen, and thus can prevent or treat infectious diseases caused by biofilm of Staphylococcus aureus.
본 발명에서, 상기 감염성 질환은 식중독, 피부염, 농양, 심내막염, 골수염, 폐렴, 장염, 패혈증 및 균혈증을 비롯하여, 혈류 감염에 의해 파생되는 다양한 체내 감염, 예를 들어 근막염, 방광염, 복막염 등을 포함할 수 있다.In the present invention, the infectious disease may include food poisoning, dermatitis, abscess, endocarditis, osteomyelitis, pneumonia, enteritis, sepsis and bacteremia, as well as various body infections derived from bloodstream infection, such as fasciitis, cystitis, peritonitis, etc. You can.
본 발명에서, 상기 감염성 질환은 의료용 장치 및 이식물의 바이오필름에 의해 유발되는 의료 관련 감염(healthcare-associated infection, HAI)일 수 있다. 예를 들어, 상기 질환은 카테터 혈류 감염(catheter-related blood stream infection, CRBSI), 카테터 요로 감염(catheter-associated urinary tract infections, CAUTI), 복막 투석 복막염(CAPD Peritonitis) 등일 수 있다.In the present invention, the infectious disease may be a healthcare-associated infection (HAI) caused by biofilms on medical devices and implants. For example, the disease may be catheter-related blood stream infection (CRBSI), catheter-associated urinary tract infections (CAUTI), CAPD Peritonitis, etc.
본 발명에서, 상기 감염성 질환은 항생제 내성균의 바이오필름에 의한 질환, 예를 들어 "감염병의 예방 및 관리에 관한 법률"에서 법정감염병으로 지정된 메티실린 내성 황색포도상구균(MRSA) 감염증, 반코마이신 내성 황색포도상구균(VRSA) 감염증 등일 수 있다.In the present invention, the infectious disease is a disease caused by a biofilm of antibiotic-resistant bacteria, for example, methicillin-resistant Staphylococcus aureus (MRSA) infection, vancomycin-resistant Staphylococcus aureus, which is designated as a statutory infectious disease in the "Act on the Prevention and Control of Infectious Diseases." It may be a vococcal (VRSA) infection.
상기 약학 조성물은 베헨산 외에, 통상의 방법에 따른 적절한 약제학적으로 허용되는 담체, 부형제 또는 희석제를 추가로 포함할 수 있다. 상기 약제학적으로 허용되는 담체는 제제시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. In addition to behenic acid, the pharmaceutical composition may further include an appropriate pharmaceutically acceptable carrier, excipient, or diluent according to a conventional method. The pharmaceutically acceptable carriers are those commonly used in preparation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Includes, but is not limited to, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
본 발명의 약학 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. 적합한 약제학적으로 허용되는 담체 및 제제화에 관해서는 레밍턴의 문헌[Remington's Pharmaceutical Sciences (19th ed., 1995)]에 개시되어 있는 방법을 이용하여 각 성분에 따라 바람직하게 제제화할 수 있다. In addition to the above ingredients, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. Regarding suitable pharmaceutically acceptable carriers and formulations, they can be preferably formulated according to each ingredient using the method disclosed in Remington's Pharmaceutical Sciences (19th ed., 1995).
본 발명의 약학 조성물은 경구 또는 비경구 투여 모두 가능하며, 비경구 투여는 경피 투여, 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 등을 포함한다. 바람직하게, 본 발명의 약학 조성물은 외용제로 이용되어 경피 투여될 수 있다.The pharmaceutical composition of the present invention can be administered either orally or parenterally, and parenteral administration includes transdermal administration, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, etc. Preferably, the pharmaceutical composition of the present invention can be used as an external agent and administered transdermally.
경구 투여용 제형으로는 예를 들면 정제, 환제, 경질, 연질 캅셀제, 액제, 현탁제, 유화제, 시럽제, 과립제 등이 있는데, 이들 제형은 유효성분 이외에 희석제(예: 락토즈, 덱스트로즈, 수크로즈, 만니톨, 솔비톨, 셀룰로즈 및/또는 글리신), 활택제(예: 실리카, 탈크, 스테아르산 및 그의 마그네슘 또는 칼슘염 및/또는 폴리에틸렌 글리콜)를 추가로 포함할 수 있다. 또한, 상기 정제는 마그네슘 알루미늄 실리케이트, 전분 페이스트, 젤라틴, 트라가칸스, 메틸셀룰로즈, 나트륨 카복시메틸셀룰로즈 및/또는 폴리비닐피롤리딘과 같은 결합제를 함유할 수 있으며, 경우에 따라 전분, 한천, 알긴산 또는 그의 나트륨 염과 같은 붕해제 또는 비등 혼합물 및/또는 흡수제, 착색제, 향미제 및 감미제를 함유할 수 있다. 상기 제형은 통상적인 혼합, 과립화 또는 코팅 방법에 의해 제조될 수 있다.Dosage forms for oral administration include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, granules, etc. These dosage forms contain diluents (e.g. lactose, dextrose, water) in addition to the active ingredient. crose, mannitol, sorbitol, cellulose and/or glycine), lubricants (e.g. silica, talc, stearic acid and magnesium or calcium salts thereof and/or polyethylene glycol). Additionally, the tablets may contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases starch, agar, alginic acid. or disintegrants such as sodium salts thereof or effervescent mixtures and/or absorbents, colorants, flavoring and sweetening agents. The formulation can be prepared by conventional mixing, granulating or coating methods.
또한, 비경구 투여용 제형의 대표적인 것은 주사용 제제이며, 주사용 제제의 용매로서 물, 링거액, 등장성 생리 식염수 또는 현탁액을 들 수 있다. 상기 주사용 제제의 멸균 고정 오일은 용매 또는 현탁 매질로서 사용할 수 있으며 모노-, 디-글리세라이드를 포함하여 어떠한 무자극성 고정오일도 이러한 목적으로 사용될 수 있다. 또한, 상기 주사용 제제는 올레산과 같은 지방산을 사용할 수 있다.Additionally, representative formulations for parenteral administration are injectable formulations, and solvents for the injectable formulation include water, Ringer's solution, isotonic saline solution, or suspension. The sterile fixed oil of the injectable preparation can be used as a solvent or suspending medium, and any non-irritating fixed oil, including mono- and di-glycerides, can be used for this purpose. Additionally, the injectable preparation may use fatty acids such as oleic acid.
본 발명에 따른 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명에 있어서, "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 환자의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명에 따른 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 통상의 지식을 가진 기술자에 의해 용이하게 결정될 수 있다.The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat the disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type, severity, and activity of the patient's disease. , can be determined based on factors including sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, drugs used simultaneously, and other factors well known in the field of medicine. The composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect with the minimum amount without side effects, and this can be easily determined by a technician with ordinary knowledge.
구체적으로, 본 발명에 따른 조성물의 유효량은 환자의 나이, 성별, 체중에 따라 달라질 수 있으며, 일반적으로는 체중 1kg 당 0.001 내지 500mg, 바람직하게는 0.01 내지 100mg을 매일 또는 격일 투여하거나 1일 1 내지 3회로 나누어 투여할 수 있다. 그러나 투여 경로, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.Specifically, the effective amount of the composition according to the present invention may vary depending on the patient's age, gender, and weight, and is generally administered at 0.001 to 500 mg per 1 kg of body weight, preferably 0.01 to 100 mg every day or every other day, or 1 to 1 mg per day. It can be administered in three divided doses. However, since it may increase or decrease depending on the route of administration, gender, weight, age, etc., the above dosage does not limit the scope of the present invention in any way.
본 발명은 또한, 베헨산을 유효성분으로 포함하는 기능성 식품을 제공할 수 있다.The present invention can also provide a functional food containing behenic acid as an active ingredient.
본 발명에 따라 베헨산을 식품에 적용하는 경우, 감염성 질환, 구체적으로 포도상구균 속(Staphylococcus sp.) 미생물이 형성하는 바이오필름에 의해 유발되는 감염성 질환의 예방 또는 개선에 도움을 주는 기능성 식품을 제공할 수 있다.When behenic acid is applied to food according to the present invention, it provides a functional food that helps prevent or improve infectious diseases, specifically infectious diseases caused by biofilms formed by Staphylococcus sp. microorganisms. can do.
본 발명에서, 기능성 식품이란 건강 기능 식품, 영양 보조제, 식품 첨가제 등을 포함하는 의미일 수 있다.In the present invention, functional food may include health functional food, nutritional supplements, food additives, etc.
상기 기능성 식품은 음료, 껌, 차, 비타민 복합제, 건강보조 식품류일 수 있으며, 더욱 자세히는, 유제품, 제과물, 조미료, 음료 및 드링크제, 스낵, 캔디류, 젤리류, 아이스크림 및 냉동용 디저트, 아침 곡물류, 영양바, 스낵 바 초콜렛 제품, 가공 식품, 곡물 제품 및 파스타, 스프, 소스 및 드레싱, 과자 제품, 오일 및 지방 제품, 유제품 음료(dairy drink) 및 우유 음료, 차, 두유 및 콩 유제품(soy dairy-like product), 냉동식품, 조리 음식 및 대체 음식, 육류 제품, 치즈, 요구르트, 빵 및 롤빵, 케이크, 쿠키 및 크래커로 이루어진 군에서 선택된 어느 하나일 수 있다. The functional foods may include beverages, gum, tea, vitamin complexes, and health supplements, and more specifically, dairy products, confectionery products, seasonings, beverages and drink preparations, snacks, candies, jellies, ice cream and frozen desserts, and breakfast cereals. , nutritional bars, snack bars, chocolate products, processed foods, grain products and pasta, soups, sauces and dressings, confectionery products, oil and fat products, dairy drinks and milk drinks, tea, soy milk and soy dairy. -like product), frozen food, prepared food and alternative food, meat products, cheese, yogurt, bread and rolls, cakes, cookies and crackers.
또한, 상기 기능성 식품은 베헨산을 포함하는 캡슐, 정제, 분말, 액상 현탁액, 환제 및 과립제 등의 제형으로 제조될 수 있다.Additionally, the functional food may be manufactured in dosage forms such as capsules, tablets, powders, liquid suspensions, pills, and granules containing behenic acid.
본 발명에서, 상기 기능성 식품은 베헨산 외에도 유효성분으로서 식품 제조 시에 통상적으로 첨가되는 성분을 추가로 포함할 수 있다.In the present invention, the functional food may further include ingredients commonly added during food production as active ingredients in addition to behenic acid.
본 발명의 기능성 식품은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있으며, 과일주스나 야채 음료 제조를 위한 과육을 함유할 수 있다.The functional food of the present invention contains various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts. , organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated drinks, etc., and may contain pulp for producing fruit juice or vegetable drinks.
본 발명의 기능성 식품은 베헨산을 유효성분으로 포함함으로써 미생물의 생장에는 영향을 미치지 않으면서 바이오필름 형성을 특이적으로 억제할 수 있으므로, 내성균 출현의 우려 없이 감염성 질환의 예방 및 개선에 도움을 주는 등 건강 증진 효과를 나타낼 수 있다.The functional food of the present invention can specifically inhibit biofilm formation without affecting the growth of microorganisms by containing behenic acid as an active ingredient, thereby helping to prevent and improve infectious diseases without fear of the emergence of resistant bacteria. It can have health-promoting effects.
실시예Example
이하 실시예를 통하여 본 발명을 보다 상세하게 설명한다. 단, 이들 실시예는 본 발명을 예시적으로 설명하기 위하여 일부 실험방법과 구성을 나타낸 것으로, 본 발명의 범위가 이러한 실시예에 제한되는 것은 아니다.The present invention will be described in more detail through examples below. However, these examples show some experimental methods and configurations to illustratively illustrate the present invention, and the scope of the present invention is not limited to these examples.
실험 준비: 균주 전배양Experimental preparation: strain preculture
황색포도상구균으로서 Staphylococcus aureus ATCC 6538을 고체배지(Tryptic soy agar)에 3단 도말하여 37℃에서 24시간 동안 배양하였다. 그 후 단일 콜로니를 취하여 5mL 액체배지(Tryptic soy broth)에 넣고 37℃, 250rpm, 24시간 조건으로 배양하여 생장시킨 후, 실험에 사용하였다. Staphylococcus aureus ATCC 6538, a Staphylococcus aureus, was spread in three layers on solid medium (Tryptic soy agar) and cultured at 37°C for 24 hours. After that, a single colony was taken, placed in 5mL tryptic soy broth, grown by culturing at 37°C, 250rpm, 24 hours, and used in the experiment.
실험예 1: 베헨산 농도에 따른 황색포도상구균의 생장 및 바이오필름 변화 측정Experimental Example 1: Measurement of growth and biofilm changes of Staphylococcus aureus according to behenic acid concentration
황색포도상구균의 생장 및 바이오필름 형성에 있어서, 베헨산의 농도에 따른 영향을 확인하기 위하여 실험을 수행하였다. An experiment was performed to determine the effect of the concentration of behenic acid on the growth and biofilm formation of Staphylococcus aureus.
먼저, 균의 생장에 미치는 영향을 확인하기 위하여, 5mL 액체배지(Tryptic soy broth)에 화합물 stock을 50μL 처리하고, 전배양한 균을 0.1(Abs600nm)의 농도가 되도록 접종하였다. 이 용액을 96-well plate에 100μL씩 넣고 37℃, 250rpm, 24시간 조건으로 배양한 후, microplate reader로 600nm 파장에서 흡광도를 측정하여 균의 생장을 확인하였다. 측정한 값과 대조군 값에 대해 t-검정(t-test)을 실시하여 p값이 0.05 이상이 되면 화합물이 균의 생장에 영향을 미치지 않는 것으로 확인하였다. First, to determine the effect on bacterial growth, 50 μL of compound stock was treated in 5 mL tryptic soy broth, and the pre-cultured bacteria were inoculated to a concentration of 0.1 (Abs 600 nm ). 100 μL of this solution was added to each 96-well plate and cultured at 37°C, 250 rpm, 24 hours, and then the absorbance was measured at 600 nm using a microplate reader to confirm bacterial growth. A t-test was performed on the measured and control values, and it was confirmed that the compound did not affect the growth of bacteria when the p value was 0.05 or higher.
한편, 바이오필름 형성에 미치는 영향을 확인하기 위하여, 균의 생장 흡광도를 측정한 후 96-well plate내에 있는 부유균(planktonic cell)은 버리고 2차 증류수로 3회 세척하였다. 그 후, 1% crystal violet 용액을 100μL씩 넣어 실온에서 15분 동안 염색하고, 다시 2차 증류수로 3번 세척하여 염색된 바이오필름만 남도록 하였다. 95% 에탄올을 100μL씩 넣고 실온에서 15분 동안 놔둔 후, microplate reader로 600nm 파장에서 흡광도를 측정하여 바이오필름 형성을 확인하였다. Meanwhile, in order to confirm the effect on biofilm formation, the absorbance of bacterial growth was measured, and then the planktonic cells in the 96-well plate were discarded and washed three times with double distilled water. Afterwards, 100 μL of 1% crystal violet solution was added at a time to stain for 15 minutes at room temperature, and then washed three times with double distilled water to ensure that only the stained biofilm remained. After adding 100 μL of 95% ethanol and leaving it at room temperature for 15 minutes, biofilm formation was confirmed by measuring absorbance at a wavelength of 600 nm using a microplate reader.
상기 방법을 이용하여, 베헨산의 처리 농도를 각각 2.5, 5, 8, 10, 20, 30 및 40mg/L가 되도록 조절하여 실험을 수행하고, 농도에 따른 황색포도상구균의 생장(a) 및 바이오필름 형성(b)에 대한 결과 그래프를 도 1에 나타내었다.Using the above method, an experiment was performed by adjusting the treatment concentration of behenic acid to 2.5, 5, 8, 10, 20, 30, and 40 mg/L, respectively, and the growth (a) and bioactivity of Staphylococcus aureus according to concentration A graph of the results for film formation (b) is shown in Figure 1.
도 1의 실험 결과를 참조하면, 베헨산을 처리한 결과 황색포도상구균의 생장에는 거의 영향을 미치지 않으면서 바이오필름 형성은 억제되는 효과가 나타나는 것을 확인하였으며, 특히 8 내지 40mg/L, 바람직하게 20 내지 30mg/L의 농도에서 바이오필름 억제 효과가 매우 우수한 것을 확인하였다.Referring to the experimental results in Figure 1, it was confirmed that treatment with behenic acid had the effect of suppressing biofilm formation while having little effect on the growth of Staphylococcus aureus, especially at 8 to 40 mg/L, preferably 20 mg/L. It was confirmed that the biofilm inhibition effect was very excellent at a concentration of 30 mg/L.
따라서, 베헨산에 의한 바이오필름 형성 억제 현상은 항균 활성에 의한 것이 아니라, 바이오필름만을 특이적으로 억제하는 활성에 의한 것임을 확인할 수 있었다. 또한, 베헨산은 미생물의 생장에 영향을 미치지 않으면서 바이오필름 형성 억제 효과를 나타낼 수 있으므로, 종래 살균제나 항생제 사용에 의한 내성균 출현의 우려 없이 바이오필름만을 억제할 수 있음을 확인할 수 있었다.Therefore, it was confirmed that the inhibition of biofilm formation by behenic acid was not due to antibacterial activity, but was due to activity that specifically inhibits biofilm. In addition, since behenic acid can exhibit an effect of inhibiting biofilm formation without affecting the growth of microorganisms, it was confirmed that only biofilms can be inhibited without concern about the emergence of resistant bacteria due to the use of conventional disinfectants or antibiotics.
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로서 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, those skilled in the art to which the present invention pertains will understand that the present invention can be implemented in other specific forms without changing its technical idea or essential features. In this regard, the embodiments described above should be understood in all respects as illustrative and not restrictive. The scope of the present invention should be construed as including the meaning and scope of the patent claims described below rather than the detailed description above, and all changes or modified forms derived from the equivalent concept thereof are included in the scope of the present invention.
Claims (11)
상기 베헨산의 농도가 8 내지 40mg/L인, 바이오필름 형성 억제용 조성물.
A composition for inhibiting biofilm formation containing behenic acid as an active ingredient,
A composition for inhibiting biofilm formation, wherein the concentration of behenic acid is 8 to 40 mg/L.
상기 조성물이 포도상구균 속(Staphylococcus sp.) 미생물에 의한 바이오필름 형성을 억제하는, 바이오필름 형성 억제용 조성물.
According to claim 1,
A composition for inhibiting biofilm formation, wherein the composition inhibits biofilm formation by Staphylococcus sp. microorganisms.
상기 포도상구균 속 미생물이 황색포도상구균 및 항생제 내성 황색포도상구균으로 구성된 군에서 선택되는 1종 이상인, 바이오필름 형성 억제용 조성물.
According to claim 3,
The Staphylococcus genus microorganism is at least one selected from the group consisting of Staphylococcus aureus and antibiotic-resistant Staphylococcus aureus, Composition for inhibiting biofilm formation.
A cosmetic composition for skin improvement comprising the composition of any one of claims 1, 3, and 4.
상기 화장료 조성물이 아토피 피부 또는 여드름 피부 개선용인, 화장료 조성물.
According to claim 5,
A cosmetic composition for improving atopic skin or acne skin.
A pharmaceutical composition for preventing or treating infectious diseases, comprising the composition of any one of claims 1, 3, and 4.
상기 감염성 질환이 포도상구균 속(Staphylococcus sp.) 미생물의 바이오필름에 의해 유발되는, 감염성 질환의 예방 또는 치료용 약학 조성물.
According to claim 7,
A pharmaceutical composition for preventing or treating an infectious disease, wherein the infectious disease is caused by a biofilm of Staphylococcus sp. microorganisms.
상기 감염성 질환이 식중독, 피부염, 농양, 심내막염, 골수염, 폐렴, 장염, 패혈증, 균혈증, 근막염, 방광염 및 복막염으로 구성된 군에서 선택되는, 감염성 질환의 예방 또는 치료용 약학 조성물.
According to claim 7,
A pharmaceutical composition for preventing or treating an infectious disease, wherein the infectious disease is selected from the group consisting of food poisoning, dermatitis, abscess, endocarditis, osteomyelitis, pneumonia, enteritis, sepsis, bacteremia, fasciitis, cystitis and peritonitis.
A functional food for preventing or improving infectious diseases, comprising the composition of any one of claims 1, 3, and 4.
상기 감염성 질환이 포도상구균 속(Staphylococcus sp.) 미생물의 바이오필름에 의해 유발되는, 감염성 질환의 예방 또는 개선용 기능성 식품.According to claim 10,
A functional food for preventing or improving infectious diseases, where the infectious diseases are caused by biofilms of Staphylococcus sp. microorganisms.
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