KR102510953B1 - A composition for preventing or treating allergic disease - Google Patents
A composition for preventing or treating allergic disease Download PDFInfo
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- KR102510953B1 KR102510953B1 KR1020200158569A KR20200158569A KR102510953B1 KR 102510953 B1 KR102510953 B1 KR 102510953B1 KR 1020200158569 A KR1020200158569 A KR 1020200158569A KR 20200158569 A KR20200158569 A KR 20200158569A KR 102510953 B1 KR102510953 B1 KR 102510953B1
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Abstract
본 발명은 아토피 피부염의 예방, 치료 또는 개선용 조성물에 관한 것으로서, 유산균의 일종인 리모시락토바실러스 루테리 (Limosilactobacillus reuteri) 균주가 분비한 물질을 이용함으로써 아토피 피부염의 병증을 경감시킬 수 있다.The present invention relates to a composition for preventing, treating, or improving atopic dermatitis, and the symptoms of atopic dermatitis can be alleviated by using a substance secreted by a strain of Limosilactobacillus reuteri, a type of lactic acid bacteria.
Description
본 발명은 리모시락토바실루스 루테리 (Limosilactobacillus reuteri) 균주의 배양액을 유효성분으로 포함하는 알러지성 질환의 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating allergic diseases comprising a culture solution of a Limosilactobacillus reuteri strain as an active ingredient.
아토피 피부염 (atopic dermatitis)은 소아에서 흔히 나타나고 성인이 되어서도 증상이 지속될 수 있는 만성 알러지 염증성 피부 반응을 일으키는 피부염 질환에 해당한다. 가려움증이 심한 습진 병변이 피부에 생기며, 증상이 나타나면 그 부위를 긁거나 문지르게 되고 그 결과 피부 증상이 더욱 악화되는 것이 아토피 피부염의 특징으로 볼 수 있다. 아토피 피부염 환자는 전 세계적으로 증가 추세에 있으며, 1970 년대까지는 6 세 이하 어린이의 약 3 %가 아토피를 앓고 있다고 보고되었으나 최근에는 어린이의 20 %, 성인에서도 1 내지 3 % 정도 발생하는 것으로 추정되고 있다. 우리 나라의 경우 2008 년 서울시에서 조사한 유병률은 설문지에서 19.1 %, 의사의 실제 진찰에서 9.2 %로 보고되었으며, 지역, 연령, 성별, 사회문화적 특성에 따라 다양한 유병률을 보이고 있다.Atopic dermatitis (atopic dermatitis) corresponds to a dermatitis disease that causes a chronic allergic inflammatory skin reaction that often appears in children and may persist even into adults. It is characteristic of atopic dermatitis that severely itchy eczema lesions are formed on the skin, and when symptoms appear, the area is scratched or rubbed, and as a result, the skin symptoms are further aggravated. Patients with atopic dermatitis are on the rise worldwide, and until the 1970s, it was reported that about 3% of children under the age of 6 suffered from atopy, but recently it is estimated that 20% of children and 1 to 3% of adults also develop atopic dermatitis. . In Korea, the prevalence rate surveyed by Seoul Metropolitan Government in 2008 was reported to be 19.1% in the questionnaire and 9.2% in the actual examination by doctors, showing various prevalence rates according to region, age, gender, and sociocultural characteristics.
아토피 피부염은 환자의 유전적인 소인과 환경적인 요인, 환자의 면역학적 이상과 피부 보호막 역할을 하는 피부장벽기능의 이상 등 여러 원인이 복합적으로 작용하는 것으로 알려져 있다. 아토피 피부염은 견디기 힘든 가려움증을 유발하며 이로 인해 불면증, 정서장애, 학습장애, 환경 적응 능력의 감소, 사회적 활동력의 감소 등이 유발될 수 있다. 또한, 심한 가려움과 습진이 동반될 수 있는데 마치 피부를 청결히 관리하지 못하고 있거나 전염성 피부질환을 앓고 있는 것으로 오인되어 대인관계에도 지장을 초래할 수 있으며, 특히 사춘기 환자의 경우 자아 형성에도 나쁜 영향을 미칠 수 있는 만큼 아토피 피부염의 예방 및 치료가 필수적으로 요구된다. It is known that atopic dermatitis is caused by a combination of various causes, such as the patient's genetic predisposition and environmental factors, the patient's immunological abnormality, and the abnormality of the skin barrier function that serves as a skin barrier. Atopic dermatitis causes unbearable itching, which can lead to insomnia, emotional disorders, learning disabilities, reduced ability to adapt to the environment, and reduced social activity. In addition, it can be accompanied by severe itching and eczema, which can be mistaken for not keeping the skin clean or suffering from a contagious skin disease, which can interfere with interpersonal relationships. As much as there is, prevention and treatment of atopic dermatitis are essential.
이에 따라 최근 아토피 피부염을 효과적으로 예방, 개선 또는 치료하기 위한 맞춤형 예방제 또는 치료제에 대한 연구가 활발히 이루어지고 있다. Accordingly, studies on customized preventive or therapeutic agents for effectively preventing, improving or treating atopic dermatitis have recently been actively conducted.
본 발명의 일 목적은 알러지성 질환의 예방, 개선 또는 치료용 조성물을 제공하는 것이다.One object of the present invention is to provide a composition for preventing, improving or treating allergic diseases.
본 발명의 다른 목적은 상기한 조성물을 제조하는 방법을 제공하는 것이다.Another object of the present invention is to provide a method for preparing the above composition.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당 업계에서 통상의 지식을 가진 자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problems, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.
이하, 본원에 기재된 다양한 구체예가 도면을 참조로 기재된다. 하기 설명에서, 본 발명의 완전한 이해를 위해서, 다양한 특이적 상세 사항, 예컨대, 특이적 형태, 조성물 및 공정 등이 기재되어 있다. 그러나, 특정의 구체예는 이들 특이적 상세 사항 중 하나 이상 없이, 또는 다른 공지된 방법 및 형태와 함께 실행될 수 있다. 다른 예에서, 공지된 공정 및 제조 기술은 본 발명을 불필요하게 모호하게 하지 않게 하기 위해서, 특정의 상세사항으로 기재되지 않는다. "한 가지 구체예" 또는 "구체예"에 대한 본 명세서 전체를 통한 참조는 구체예와 결부되어 기재된 특별한 특징, 형태, 조성 또는 특성이 본 발명의 하나 이상의 구체예에 포함됨을 의미한다. 따라서, 본 명세서 전체에 걸친 다양한 위치에서 표현된 "한 가지 구체예에서" 또는 "구체예"의 상황은 반드시 본 발명의 동일한 구체예를 나타내지는 않는다. 추가로, 특별한 특징, 형태, 조성, 또는 특성은 하나 이상의 구체예에서 어떠한 적합한 방법으로 조합될 수 있다.Hereinafter, various embodiments described herein are described with reference to the drawings. In the following description, numerous specific details are set forth, such as specific forms, compositions and processes, etc., in order to provide a thorough understanding of the present invention. However, certain embodiments may be practiced without one or more of these specific details, or with other known methods and forms. In other instances, well known processes and manufacturing techniques have not been described in specific detail in order not to unnecessarily obscure the present invention. Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, form, composition or characteristic described in connection with the embodiment is included in one or more embodiments of the invention. Thus, the appearances of "in one embodiment" or "an embodiment" in various places throughout this specification do not necessarily refer to the same embodiment of the invention. Additionally, particular features, forms, compositions, or properties may be combined in one or more embodiments in any suitable way.
명세서 내에 특별한 정의가 없으면 본 명세서에 사용된 모든 과학적 및 기술적인 용어는 본 발명이 속하는 기술분야에서 당업자에 의하여 통상적으로 이해되는 것과 동일한 의미를 가진다. Unless there is a specific definition within the specification, all scientific and technical terms used herein have the same meaning as commonly understood by a person skilled in the art to which the present invention belongs.
본 발명의 일 구현 예에 따르면, 리모시락토바실러스 루테리 (Limosilactobacillus reuteri) 균주의 배양액을 유효성분으로 포함하는 알러지성 질환의 예방, 개선 또는 치료용 조성물에 관한 것이다. According to one embodiment of the present invention, it relates to a composition for preventing, improving or treating allergic diseases comprising a culture solution of a Limosilactobacillus reuteri strain as an active ingredient.
본 발명에서 상기 "리모시락토바실러스 루테리 (Limosilactobacillus reuteri) 균주"는 최근 락토바실러스 루테리로부터 리모시락토바실러스 루테리로 명칭이 바뀌었으며, 상기 균주는 초기에 락토바실러스 퍼멘툼 (L. fermentum)으로 잘못 분류되었다가 1960 년대에 미생물 학자 Gerhard Reuter의 추가 연구를 통하여 락토바실러스 루테리 (L. reuteri)와 락토바실러스 퍼멘툼 (L. fermentum)을 구별하기 시작했으며, Reuter는 이 종을 종국적으로 유산균 발효 생물형 II로 재분류하였다. 리모시락토바실러스는 자연계에 널리 분포하는 당류를 발효하여 에너지를 획득하여 다량의 유산을 생성하는 세균으로 형태적으로는 그람 양성 무포자 간균으로 다형성을 나타낸다. 리모시락토바실러스 속에 포함된 루테리 균주는 인체의 위, 소장, 대장, 모유 등 인체의 여러 곳에서 발견되는 유산균 종으로 유산균을 섭취하지 않아도 원래부터 인간의 몸에서 발견되는 내생균종에 해당한다. 주로 리모시락토바실러스 루테리 균주는 아동 설사를 감소시키거나 영유아들에게 흔히 발생하는 영아 산통에 효과가 있는 것으로 알려져 있으며, 항진균 효능이 있어 조산아에게 쉽게 발생하는 칸디다증을 예방하고 치유하는 역할을 하는 것으로도 알려져 있으며, 염증성 장질환, 과민성 대장증후군, 기능성 위장장애, 변비 등 각종 장질환의 증상을 줄이는 데 효과가 있는 것으로도 보고된 바 있다. In the present invention, the "Limosilactobacillus reuteri strain" was recently renamed from Lactobacillus reuteri to Limosilactobacillus reuteri, and the strain was initially misclassified as L. fermentum. In the 1960s, further research by microbiologist Gerhard Reuter began to distinguish between L. reuteri and L. fermentum, which Reuter eventually classified as Lactobacillus fermenting biotype II. reclassified as Rimocylactobacillus is a bacterium that obtains energy by fermenting sugars widely distributed in nature and produces a large amount of lactic acid. Reuteri strains included in the genus Limosylactobacillus are lactic acid bacteria species found in various places in the human body, such as the stomach, small intestine, large intestine, and breast milk. Primarily, the Limosylactobacillus reuteri strain is known to reduce diarrhea in children or to be effective in infant colic, which is common in infants, and is also known to play a role in preventing and curing candidiasis, which easily occurs in premature infants, due to its antifungal effect. It has also been reported to be effective in reducing symptoms of various intestinal diseases such as inflammatory bowel disease, irritable bowel syndrome, functional gastrointestinal disorder, and constipation.
본 발명에서 상기 리모시락토바실러스 루테리 균주는 바람직하게는 락토바실러스 루테리 MBF4112 (Lactobacillus reuteri MBF4112)일 수 있다. 본 발명에 따른 락토바실러스 루테리 MBF4112 균주의 배양액은 특히 아토피 피부염 질환의 증상을 경감시키는 활성이 매우 뛰어나며, 상기 균주는 국내 기탁기관인 한국생명공학연구원 생물자원센터 (Korean Collection for Type Cultures; KCTC)에 기탁되어 있다(균주명: Lactobacillus reuteri MBF4112, 기탁 번호: KCTC 13232BP, 기탁 일자: 2017 년 3 월 23 일). In the present invention, the R. reuteri strain may preferably be Lactobacillus reuteri MBF4112 ( Lactobacillus reuteri MBF4112). The culture solution of the Lactobacillus reuteri MBF4112 strain according to the present invention is particularly excellent in alleviating the symptoms of atopic dermatitis, and the strain was deposited at the Korea Research Institute of Bioscience and Biotechnology (Korean Collection for Type Cultures; KCTC), a domestic depository institution. (strain name: Lactobacillus reuteri MBF4112, accession number: KCTC 13232BP, accession date: March 23, 2017).
본 발명에서 상기 배양액은 리모시락토바실러스 루테리 균주를 배지로부터 배양하여 수득될 수 있으며, 바람직하게는 락토바실러스 루테리 MBF4112 (Lactobacillus reuteri MBF4112) 균주를 배양하여 수득될 수 있다. In the present invention, the culture solution may be obtained by culturing the Remocylactobacillus reuteri strain in a medium, preferably obtained by culturing the Lactobacillus reuteri MBF4112 strain.
본 발명에서 상기 배지는 MRS 배지(Lactobacilli MRS brothMRS medium), BCP 배지 (bromocresol purple medium), M-17 Broth 배지, Rogosa 한천 배지, BSM 한천 배지, Rogosa SL 한천 배지 및 BL 한천 배지로 이루어진 군에서 선택된 1 종 이상일 수 있으며, 바람직하게는 MRS 배지일 수 있으나, 이에 제한되는 것은 아니다.In the present invention, the medium is selected from the group consisting of MRS medium (Lactobacilli MRS brothMRS medium), BCP medium (bromocresol purple medium), M-17 Broth medium, Rogosa agar medium, BSM agar medium, Rogosa SL agar medium and BL agar medium It may be one or more, preferably MRS medium, but is not limited thereto.
본 발명의 MRS 배지는 5 내지 15 g/L 프로테오스 펩톤 No.3 (proteose peptone No.3), 5 내지 15 g/L 육류 추출물 (beef extract), 3 내지 7 g/L 효모 추출물 (yeast extract), 15 내지 25 g/L 덱스트로오스 (dextrose; C6H12O6), 0.2 내지 1.8 g/L 폴리소르베이트 80 (polysorbate 80; C64H124O26), 1 내지 3 g/L 암모늄 시트레이트 (ammonium citrate; C6H17N3O7), 3 내지 7 g/L 소듐 아세테이트 (sodium acetate; CH3COONa), 0.05 내지 0.15 g/L 마그네슘 설페이트 (magnesium sulfate; MgSO4), 0.03 내지 0.07 g/L 망가니즈 설페이트 (Manganese sulfate; MnSO4), 1.5 내지 2.5 g/L 디포타슘 포스페이트 (dipotassium hydrogen phosphate; K2HPO4)의 조성을 가질 수 있고, 바람직하게는 10 g/L 프로테오스 펩톤 No.3 (proteose peptone No.3), 10 g/L 육류 추출물 (beef extract), 5 g/L 효모 추출물 (yeast extract), 20 g/L 덱스트로오스 (dextrose; C6H12O6), 1 g/L 폴리소르베이트 80 (polysorbate 80; C64H124O26), 2 g/L 암모늄 시트레이트 (ammonium citrate; C6H17N3O7), 5 g/L 소듐 아세테이트 (sodium acetate; CH3COONa), 0.1 g/L 마그네슘 설페이트 (magnesium sulfate; MgSO4), 0.05 g/L 망가니즈 설페이트 (Manganese sulfate; MnSO4), 2 g/L 디포타슘 포스페이트 (dipotassium hydrogen phosphate; K2HPO4)의 조성을 가질 수 있으나, 이에 제한되는 것은 아니다. The MRS medium of the present invention contains 5 to 15 g/L proteose peptone No.3, 5 to 15 g/L beef extract, and 3 to 7 g/L yeast extract. extract), 15 to 25 g/L dextrose (C 6 H 12 O 6 ), 0.2 to 1.8 g/L polysorbate 80 (C 64 H 124 O 26 ), 1 to 3 g/ L ammonium citrate (C 6 H 17 N 3 O 7 ), 3 to 7 g/L sodium acetate (CH 3 COONa), 0.05 to 0.15 g/L magnesium sulfate (MgSO 4) , 0.03 to 0.07 g/L manganese sulfate (MnSO 4 ), 1.5 to 2.5 g/L dipotassium hydrogen phosphate (K 2 HPO 4 ), preferably 10 g/L Proteose peptone No.3 (proteose peptone No.3), 10 g/L beef extract, 5 g/L yeast extract, 20 g/L dextrose (C 6 H 12 O 6 ), 1 g/L polysorbate 80 (C 64 H 124 O 26 ), 2 g/L ammonium citrate (C 6 H 17 N 3 O 7 ), 5 g/L Sodium acetate (CH 3 COONa), 0.1 g/L magnesium sulfate (MgSO 4 ) , 0.05 g/L Manganese sulfate (MnSO 4 ), 2 g/L dipotassium hydrogen phosphate (dipotassium hydrogen phos phate; K 2 HPO 4 ), but is not limited thereto.
본 발명의 배지는 pH가 8.0 미만이며, 바람직하게는 5.50 내지 7.15의 pH를 갖는다.The medium of the present invention has a pH of less than 8.0, and preferably has a pH of 5.50 to 7.15.
본 발명에서, 상기 균주의 배양 조건은 특별히 제한하지 않으며, 통상적인 균주의 배양 조건 하에서 수행될 수 있으나, 예컨대, 35 내지 38 ℃의 온도 및 8 내지 12 부피% CO2 조건 하에서, 20 내지 30 시간, 22 내지 28 시간 또는 23 내지 25 시간 동안 수행될 수 있다.In the present invention, the culture conditions of the strain are not particularly limited, and may be performed under conventional strain culture conditions, for example, at a temperature of 35 to 38 °C and 8 to 12 vol% CO 2 conditions, 20 to 30 hours , 22 to 28 hours or 23 to 25 hours.
본 발명에서, 상기 배양액은 상기와 같이 균주의 배양 후 원심 분리하여 펠릿 (pellet)은 제외하고 분리하는 방식으로 수득될 수 있다. In the present invention, the culture medium may be obtained by centrifugation after culturing the strain as described above to separate the pellets.
본 발명에서, 상기 조성물은 상기 배양액의 농축물을 포함할 수 있다. 여기서, 상기 농축은 진공 농축에 의해 수행될 수 있고, 보다 상세하게는 상기 배양액을 10 내지 90 ℃, 바람직하게는 30 내지 50 ℃ 범위에서 가열하며, 1 내지 80 torr의 진공상태의 압력으로 5 내지 10 시간 동안 수분을 증발시키는 방식으로 수행될 수 있으나, 이에 제한되는 것은 아니다. In the present invention, the composition may include a concentrate of the culture medium. Here, the concentration may be performed by vacuum concentration, and more specifically, the culture medium is heated in the range of 10 to 90 ° C., preferably 30 to 50 ° C., and a vacuum pressure of 1 to 80 torr is applied to 5 to 90 torr. It may be performed by evaporating moisture for 10 hours, but is not limited thereto.
본 발명에서, 상기 조성물은 상기 배양액의 동결 건조물을 포함할 수 있다. 여기서, 상기 동결 건조는 상기 배양액 또는 상기 배양액의 농축물을 10 내지 -70 ℃, 바람직하게는 -30 내지 -60 ℃, 더욱 바람직하게는 -50 ℃로 동결시킨 후, 동결 건조기에서 1 내지 80 torr의 진공상태의 압력조건으로 2 내지 96 시간, 바람직하게는 24 시간 동안 수분을 증발시키는 방식으로 수행될 수 있으나, 이에 제한되는 것은 아니다.In the present invention, the composition may include a freeze-dried product of the culture medium. Here, the freeze-drying is performed by freezing the culture medium or the concentrate of the culture medium at 10 to -70 ° C, preferably -30 to -60 ° C, more preferably -50 ° C, and then using a freeze dryer at 1 to 80 torr. It may be carried out by evaporating moisture for 2 to 96 hours, preferably for 24 hours, under vacuum pressure conditions, but is not limited thereto.
본 발명의 상기 알러지성 질환은 부종, 과민증 (anaphylaxis), 알러지성 비염 (allergic rhinitis), 천식 (asthma), 알러지성 결막염 (allergic conjunctivitis), 알러지성 피부염 (allergic dermatitis), 접촉성 피부염, 아토피 피부염, 두드러기, 소양증, 곤충 알러지, 식품 알러지 및 약품 알러지로 이루어진 군에서 선택되는 적어도 하나를 포함할 수 있고, 바람직하게는 아토피 피부염일 수 있으나, 이에 제한되는 것은 아니다.The allergic disease of the present invention is edema, anaphylaxis, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, contact dermatitis, atopic dermatitis , hives, it may include at least one selected from the group consisting of pruritus, insect allergy, food allergy and drug allergy, preferably atopic dermatitis, but is not limited thereto.
본 발명의 상기 "아토피 피부염 (Atopic Dermatitis)"은 한국 질병관리청의 정의에 따르면 피부에 발생하는 만성 알러지 염증성 질환으로 소아에서 흔히 나타나고 성인이 되어서도 증상이 지속될 수 있는 만성 피부 반응을 말한다. 가족 중에 천식, 알러지성 비염 등 다른 알러지성 질환이 있는 경우 아토피 피부염이 발생할 가능성이 높으며, 식품이나 집먼지 진드기 같은 알레르겐에 의해 발생할 수 있다. 또한, 급격한 실내 온도와 습도 변화, 땀이나 침, 꽉 끼거나 거친 재질의 옷, 피부를 문지르거나 긁는 것, 스트레스, 세균 감염 등도 아토피 피부염을 악화시키는 요인으로 알려져 있다. 아토피 피부염은 만성적으로 재발하는 특성이 있고, 삶의 질까지 위협하는 질환이기에 이에 대한 치료제의 개발이 필수적으로 요구된다. According to the definition of the Korea Centers for Disease Control and Prevention, the "Atopic Dermatitis" of the present invention is a chronic allergic inflammatory disease that occurs in the skin, which often appears in children and refers to a chronic skin reaction in which symptoms may persist even into adults. If there are other allergic diseases such as asthma and allergic rhinitis in the family, atopic dermatitis is highly likely to occur, and it can be caused by allergens such as food or house dust mites. In addition, rapid changes in room temperature and humidity, sweat or saliva, tight or rough clothes, rubbing or scratching the skin, stress, bacterial infection, etc. are also known to aggravate atopic dermatitis. Since atopic dermatitis has chronic recurrent characteristics and is a disease that threatens the quality of life, it is essential to develop a therapeutic agent for it.
본 발명에서, 상기 "예방"은 본 발명의 조성물을 이용하여 알러지성 질환의 임상 증상이 확산되지 않도록 질환의 발병에 대해 보호하는 요법을 사용하는 모든 행위를 지칭하며, 보다 상세하게는 아토피 피부염 증상의 발현, 재발 또는 확산을 억제하는 것을 말한다. In the present invention, the "prevention" refers to any act of using a therapy to protect against the onset of an allergic disease so that the clinical symptoms of an allergic disease do not spread using the composition of the present invention, and more specifically, atopic dermatitis symptoms inhibition of the expression, recurrence or spread of
본 발명에서, 상기 "개선"은 본 발명의 조성물을 조사하여 알러지성 질환, 보다 구체적으로는 아토피 피부염이 호전되거나 이롭게 되는 모든 행위라면 제한없이 포함할 수 있다.In the present invention, the "improvement" may include without limitation any action that improves or benefits allergic diseases, more specifically, atopic dermatitis by examining the composition of the present invention.
본 발명에서, 상기 "치료"는 본 발명의 조성물을 이용하여 알러지성 질환, 보다 구체적으로는 아토피 피부염이 호전되거나 이롭게 되는 모든 행위라면 제한없이 포함할 수 있다.In the present invention, the "treatment" may include without limitation any action that improves or benefits allergic diseases, more specifically, atopic dermatitis using the composition of the present invention.
본 발명의 조성물은 약학적 조성물, 화장료 조성물 또는 식품 조성물의 용도로 사용될 수 있으나, 이에 제한되는 것은 아니다. The composition of the present invention may be used for purposes of pharmaceutical compositions, cosmetic compositions or food compositions, but is not limited thereto.
본 발명에 있어서, 상기 약학적 조성물은 캡슐, 정제, 과립, 주사제, 연고제, 분말 또는 음료 형태임을 특징으로 할 수 있으며, 상기 약학적 조성물은 인간을 대상으로 하는 것을 특징으로 할 수 있다. In the present invention, the pharmaceutical composition may be in the form of capsules, tablets, granules, injections, ointments, powders or beverages, and the pharmaceutical composition may be intended for humans.
본 발명의 약학적 조성물은 이들로 한정되는 것은 아니지만, 각각 통상의 방법에 따라 산제, 과립제, 캡슐, 정제, 수성 현탁액 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 본 발명의 약학적 조성물은 약제적으로 허용 가능한 담체를 포함할 수 있다. 약제학적으로 허용되는 담체는 경구 투여 시에는 결합제, 활탁제, 붕해제, 부형제, 가용화제, 분산제, 안정화제, 현탁화제, 색소, 향료 등을 사용할 수 있으며, 주사제의 경우에는 완충제, 보존제, 무통화제, 가용화제, 등장제, 안정화제 등을 혼합하여 사용할 수 있으며, 국소투여용의 경우에는 기제, 부형제, 윤활제, 보존제 등을 사용할 수 있다. 본 발명의 약학적 조성물의 제형은 상술한 바와 같은 약제학적으로 허용되는 담체와 혼합하여 다양하게 제조될 수 있다. 예를 들어, 경구 투여시에는 정제, 트로키, 캡슐, 엘릭서 (elixir), 서스펜션, 시럽, 웨이퍼 등의 형태로 제조할 수 있으며, 주사제의 경우에는 단위 투약 앰플 또는 다수회 투약 형태로 제조할 수 있다. 기타, 용액, 현탁액, 정제, 캡슐, 서방형 제제 등으로 제형할 수 있다.The pharmaceutical composition of the present invention is not limited to these, but is formulated according to conventional methods into oral formulations such as powders, granules, capsules, tablets, aqueous suspensions, external preparations, suppositories and sterile injection solutions. can The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers may include binders, lubricants, disintegrants, excipients, solubilizers, dispersants, stabilizers, suspending agents, pigments, flavors, etc. for oral administration, and buffers, preservatives, and painless agents for injections. A topical, solubilizing agent, isotonic agent, stabilizer, etc. may be mixed and used, and in the case of topical administration, a base, excipient, lubricant, preservative, etc. may be used. The formulation of the pharmaceutical composition of the present invention may be variously prepared by mixing with the above-described pharmaceutically acceptable carrier. For example, for oral administration, it can be prepared in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, etc., and in the case of injections, it can be prepared in unit dosage ampoules or multiple dosage forms. there is. In addition, it may be formulated into solutions, suspensions, tablets, capsules, sustained-release preparations, and the like.
한편, 제제화에 적합한 담체, 부형제 및 희석제의 예로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말디톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 또는 광물유 등이 사용될 수 있다. 또한, 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제 등을 추가로 포함할 수 있다.On the other hand, examples of carriers, excipients and diluents suitable for formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil and the like can be used. In addition, fillers, anti-coagulants, lubricants, wetting agents, flavoring agents, emulsifiers, preservatives, and the like may be further included.
본 발명에 따른 약학적 조성물의 투여 경로는 이들로 한정되는 것은 아니지만 구강, 정맥내, 근육내, 동맥내, 골수내, 경막내, 심장내, 경피, 피하, 복강내, 비강내, 장관, 국소, 설하 또는 직장이 포함된다. 경구 또는 비경구 투하가 바람직하다. The route of administration of the pharmaceutical composition according to the present invention is, but is not limited to, oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical , sublingual or rectal. Oral or parenteral administration is preferred.
본 발명에서, "비경구"는 피하, 피내, 정맥내, 근육내, 관절내, 활액낭내, 흉골내, 경막내, 병소내 및 두개골내 주사 또는 주입기술을 포함한다. 본 발명의 약학적 조성물은 또한 직장 투여를 위한 좌제의 형태로 투여될 수 있다.In the present invention, "parenteral" includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intracapsular, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques. The pharmaceutical composition of the present invention may also be administered in the form of a suppository for rectal administration.
본 발명의 약학적 조성물은 사용된 특정 화합물의 활성, 연령, 체중, 일반적인 건강, 성별, 정식, 투여시간, 투여경로, 배출율, 약물 배합 및 예방 또는 치료될 특정 질환의 중증을 포함한 여러 요인에 따라 다양하게 변할 수 있고, 상기 약학적 조성물의 투여량은 환자의 상태, 체중, 질병의 정도, 약무형태, 투여경로 및 기간에 따라 다르지만 당업자에 의해 적절하게 선택될 수 있고, 1 일 0.0001 내지 50 mg/kg 또는 0.001 내지 50 mg/kg으로 투여할 수 있다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. 본 발명에 따른 의약 조성물은 환제, 당의정, 캡슐, 액제, 겔, 시럽, 슬러리, 현탁제로 제형될 수 있다.The pharmaceutical composition of the present invention depends on various factors including the activity of the specific compound used, age, body weight, general health, sex, diet, administration time, route of administration, excretion rate, drug combination and severity of the specific disease to be prevented or treated. The dosage of the pharmaceutical composition may be variously varied, and the dosage of the pharmaceutical composition varies depending on the patient's condition, weight, disease severity, drug form, administration route and period, but may be appropriately selected by those skilled in the art, and is 0.0001 to 50 mg per day. /kg or 0.001 to 50 mg/kg. Administration may be administered once a day, or may be administered in several divided doses. The dosage is not intended to limit the scope of the present invention in any way. The pharmaceutical composition according to the present invention may be formulated into a pill, dragee, capsule, liquid, gel, syrup, slurry, or suspension.
본 발명에 있어서, 상기 화장료 조성물은 화장수, 영양 로션, 영양 에센스, 마사지 크림, 미용목욕물 첨가제, 바디 로션, 바디 밀크, 배스 오일, 베이비 오일, 베이비파우더, 샤워겔, 샤워크림, 선스크린 로션, 선스크린 크림, 선탠 크림, 스킨 로션, 스킨 크림, 자외선차단용 화장품, 클렌징밀크, 탈모제화장용, 페이스 및 바디로션, 페이스 및 바디크림, 피부미백크림, 핸드로션, 헤어로션, 화장용크림, 쟈스민 오일, 목욕비누, 물비누, 미용비누, 샴푸, 손세정제 (핸드클리너), 약용비누비의료용, 크림비누, 페이셜워시, 전신 세정제, 두피 세정제, 헤어린스, 화장비누, 치아미백용 겔, 치약 등의 형태로 제조될 수 있다. 이를 위해 본 발명의 조성물은 화장료 조성물의 제조에 통상적으로 사용하는 용매나, 적절한 담체, 부형제 또는 희석제를 더 포함할 수 있다.In the present invention, the cosmetic composition is cosmetic water, nutrient lotion, nutrient essence, massage cream, beauty bath water additive, body lotion, body milk, bath oil, baby oil, baby powder, shower gel, shower cream, sunscreen lotion, sunscreen Screen cream, suntan cream, skin lotion, skin cream, sunscreen cosmetics, cleansing milk, depilatory makeup, face and body lotion, face and body cream, skin whitening cream, hand lotion, hair lotion, cosmetic cream, jasmine oil , bath soap, water soap, beauty soap, shampoo, hand sanitizer (hand cleaner), medicated soap, medical soap, cream soap, facial wash, body cleanser, scalp cleanser, hair rinse, cosmetic soap, tooth whitening gel, toothpaste, etc. can be manufactured with To this end, the composition of the present invention may further include a solvent or an appropriate carrier, excipient or diluent commonly used in the preparation of cosmetic compositions.
본 발명에 있어서, 상기 화장료 조성물 내에 더 추가될 수 있는 용매의 종류는 특별히 한정하지 않으나, 예를 들어, 물, 식염수, DMSO 또는 이들의 조합을 사용할 수 있다. 또한, 담체, 부형제 또는 희석제로는 정제수, 오일, 왁스, 지방산, 지방산 알콜, 지방산 에스테르, 계면활성제, 흡습제 (humectant), 증점제, 항산화제, 점도 안정화제, 킬레이팅제, 완충제, 저급 알콜 등이 포함되지만, 이에 제한되는 것은 아니다. 또한, 필요에 따라 미백제, 보습제, 비타민, 자외선차단제, 향수, 염료, 항생제, 항박테리아제, 항진균제를 포함할 수 있다. In the present invention, the type of solvent that can be further added to the cosmetic composition is not particularly limited, but, for example, water, saline, DMSO, or a combination thereof may be used. In addition, carriers, excipients or diluents include purified water, oil, wax, fatty acids, fatty alcohols, fatty acid esters, surfactants, humectants, thickeners, antioxidants, viscosity stabilizers, chelating agents, buffers, lower alcohols, and the like. Includes, but is not limited to. In addition, whitening agents, moisturizing agents, vitamins, sunscreens, perfumes, dyes, antibiotics, antibacterial agents, and antifungal agents may be included as necessary.
또한, 본 발명에 있어서 상기 오일로서는 수소화 식물성유, 피마자유, 면실유, 올리브유, 야자인유, 호호바유, 아보카도유가 이용될 수 있으며, 왁스로는 밀랍, 경랍, 카르나우바, 칸델릴라, 몬탄, 세레신, 액체 파라핀, 라놀린이 이용될 수 있다.In the present invention, as the oil, hydrogenated vegetable oil, castor oil, cottonseed oil, olive oil, coconut oil, jojoba oil, and avocado oil may be used, and as the wax, beeswax, spermaceti, carnauba, candelilla, montan, ceresin , liquid paraffin, lanolin may be used.
또한, 본 발명에 있어서 상기 지방산으로는 스테아르산, 리놀레산, 리놀렌산, 올레산이 이용될 수 있고, 지방산 알콜로는 세틸 알콜, 옥틸 도데칸올, 올레일 알콜, 판텐올, 라놀린 알콜, 스테아릴 알콜, 헥사데칸올이 이용될 수 있으며 지방산 에스테르로는 이소프로필 미리스테이트, 이소프로필 팔미테이트, 부틸스테아레이트가 이용될 수 있다. 계면 활성제로는 당업계에 알려진 양이온 계면활성제, 음이온 계면활성제 및 비이온성 계면활성제가 사용 가능하며 가능한 한 천연물 유래의 계면활성제가 바람직하다. 그 외에도 화장품 분야에서 널리 알려진 흡습제, 증점제, 항산화제 등을 포함할 수 있으며, 이들의 종류와 양은 당업계에 공지된 바에 따른다.In the present invention, stearic acid, linoleic acid, linolenic acid, and oleic acid may be used as the fatty acid, and cetyl alcohol, octyl dodecanol, oleyl alcohol, panthenol, lanolin alcohol, stearyl alcohol, hexa Decanol may be used, and isopropyl myristate, isopropyl palmitate, and butyl stearate may be used as the fatty acid ester. As the surfactant, cationic surfactants, anionic surfactants, and nonionic surfactants known in the art can be used, and surfactants derived from natural products are preferred as much as possible. In addition, it may include a moisture absorbent, thickener, antioxidant, etc. widely known in the field of cosmetics, and the type and amount thereof are known in the art.
본 발명에 있어서, 상기 식품 조성물은 본 발명에서 목적으로 하는 적응증의 예방 또는 개선을 위해 다양하게 이용되는 것으로서, 각종 식품류, 예를 들어, 음료, 껌, 차, 비타민 복합제, 분말, 과립, 정제, 캡슐, 과자, 떡, 빵 등의 형태로 제조될 수 있다. 본 발명의 식품 조성물은 독성 및 부작용이 거의 없는 기존의 식품용 섭취물로부터 개량되어 구성된 것이므로 예방 목적으로 장기간 복용 시에도 안심하고 사용할 수 있다. 본 발명의 조성물이 식품 조성물에 포함될 때 그 양은 전체 중량의 0.1 내지 100 %의 비율로 첨가할 수 있다. 여기서, 상기 식품조성물이 음료 형태로 제조되는 경우 지시된 비율로 상기 식품 조성물을 함유하는 것 외에 특별한 제한점은 없으며 통상의 음료와 같이 여러가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 즉, 천연 탄수화물로서 포도당 등의 모노사카라이드, 과당 등의 디사카라이드, 슈크로스 등의 및 폴리사카라이드, 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜 등을 포함할 수 있다. 상기 향미제로서는 천연 향미제 (타우마틴, 스테비아 추출물 (예를 들어, 레바우디오시드 A, 글리시르히진등) 및 합성 향미제 (사카린, 아스파르탐 등) 등을 들 수 있다. 그 외 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 광물 (전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 통상적으로 본 발명의 조성물 100 중량부 당 0.1 내지 100 중량부의 범위에서 선택되는 것이 일반적이나, 이에 제한되는 것은 아니다.In the present invention, the food composition is variously used for the prevention or improvement of the target indication of the present invention, and various foods, such as beverages, gum, tea, vitamin complexes, powders, granules, tablets, It can be manufactured in the form of capsules, confectionery, rice cakes, bread, and the like. The food composition of the present invention can be safely used even when taken for a long period of time for preventive purposes because it is improved and composed of existing food intakes with little toxicity and side effects. When the composition of the present invention is included in the food composition, the amount may be added in an amount of 0.1 to 100% of the total weight. Here, when the food composition is prepared in the form of a beverage, there is no particular limitation except that the food composition is included in the indicated ratio, and various flavoring agents or natural carbohydrates may be included as additional ingredients as in conventional beverages. In other words, natural carbohydrates include monosaccharides such as glucose, disaccharides such as fructose, polysaccharides such as sucrose, and common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. can do. Examples of the flavoring agent include natural flavoring agents (thaumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.). The food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH regulators , stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, etc. These components may be used independently or in combination The ratio of these additives is usually 100 parts by weight of the composition of the present invention It is generally selected from the range of 0.1 to 100 parts by weight per, but is not limited thereto.
본 발명의 또 다른 구현 예에 따르면, 본 발명의 상기 조성물을 제조하는 방법에 관한 것이다.According to another embodiment of the present invention, it relates to a method for preparing the composition of the present invention.
본 발명의 상기 방법은 리모시락토바실러스 루테리 (Limosilactobacillus reuteri) 균주를 준비하는 단계를 포함할 수 있다. The method of the present invention may include preparing a Limosilactobacillus reuteri strain.
본 발명에서, 상기 리모시락토바실러스 루테리 균주는 바람직하게는 락토바실러스 루테리 MBF4112 (Lactobacillus reuteri MBF4112)일 수 있으며, 상기 균주에 관한 기재는 조성물에서 기재한 바와 동일하여, 본 명세서의 과도한 복잡성을 피하기 위하여 생략한다. In the present invention, the R. reuteri strain may preferably be Lactobacillus reuteri MBF4112, and the description of the strain is the same as that described in the composition, in order to avoid excessive complexity in the present specification. omit
본 발명의 상기 방법은 준비된 리모시락토바실러스 루테리 (Limosilactobacillus reuteri) 균주를 배양하는 단계를 포함한다. The method of the present invention includes culturing the prepared Limosilactobacillus reuteri strain.
본 발명에서, 상기 배지는 MRS 배지(Lactobacilli MRS brothMRS medium), BCP 배지 (bromocresol purple medium), M-17 Broth 배지, Rogosa 한천 배지, BSM 한천 배지, Rogosa SL 한천 배지 및 BL 한천 배지로 이루어진 군에서 선택된 1 종 이상일 수 있으며, 바람직하게는 MRS 배지일 수 있으나, 이에 제한되는 것은 아니다.In the present invention, the medium is in the group consisting of MRS medium (Lactobacilli MRS brothMRS medium), BCP medium (bromocresol purple medium), M-17 Broth medium, Rogosa agar medium, BSM agar medium, Rogosa SL agar medium and BL agar medium It may be one or more selected species, preferably MRS medium, but is not limited thereto.
본 발명의 MRS 배지는 5 내지 15 g/L 프로테오스 펩톤 No.3 (proteose peptone No.3), 5 내지 15 g/L 육류 추출물 (beef extract), 3 내지 7 g/L 효모 추출물 (yeast extract), 15 내지 25 g/L 덱스트로오스 (dextrose; C6H12O6), 0.2 내지 1.8 g/L 폴리소르베이트 80 (polysorbate 80; C64H124O26), 1 내지 3 g/L 암모늄 시트레이트 (ammonium citrate; C6H17N3O7), 3 내지 7 g/L 소듐 아세테이트 (sodium acetate; CH3COONa), 0.05 내지 0.15 g/L 마그네슘 설페이트 (magnesium sulfate; MgSO4), 0.03 내지 0.07 g/L 망가니즈 설페이트 (Manganese sulfate; MnSO4), 1.5 내지 2.5 g/L 디포타슘 포스페이트 (dipotassium hydrogen phosphate; K2HPO4)의 조성을 가질 수 있고, 바람직하게는 10 g/L 프로테오스 펩톤 No.3 (proteose peptone No.3), 10 g/L 육류 추출물 (beef extract), 5 g/L 효모 추출물 (yeast extract), 20 g/L 덱스트로오스 (dextrose; C6H12O6), 1 g/L 폴리소르베이트 80 (polysorbate 80; C64H124O26), 2 g/L 암모늄 시트레이트 (ammonium citrate; C6H17N3O7), 5 g/L 소듐 아세테이트 (sodium acetate; CH3COONa), 0.1 g/L 마그네슘 설페이트 (magnesium sulfate; MgSO4), 0.05 g/L 망가니즈 설페이트 (Manganese sulfate; MnSO4), 2 g/L 디포타슘 포스페이트 (dipotassium hydrogen phosphate; K2HPO4)의 조성을 가질 수 있으나, 이에 제한되는 것은 아니다. The MRS medium of the present invention contains 5 to 15 g/L proteose peptone No.3, 5 to 15 g/L beef extract, and 3 to 7 g/L yeast extract. extract), 15 to 25 g/L dextrose (C 6 H 12 O 6 ), 0.2 to 1.8 g/L polysorbate 80 (C 64 H 124 O 26 ), 1 to 3 g/ L ammonium citrate (C 6 H 17 N 3 O 7 ), 3 to 7 g/L sodium acetate (CH 3 COONa), 0.05 to 0.15 g/L magnesium sulfate (MgSO 4) , 0.03 to 0.07 g/L manganese sulfate (MnSO 4 ), 1.5 to 2.5 g/L dipotassium hydrogen phosphate (K 2 HPO 4 ), preferably 10 g/L Proteose peptone No.3 (proteose peptone No.3), 10 g/L beef extract, 5 g/L yeast extract, 20 g/L dextrose (C 6 H 12 O 6 ), 1 g/L polysorbate 80 (C 64 H 124 O 26 ), 2 g/L ammonium citrate (C 6 H 17 N 3 O 7 ), 5 g/L Sodium acetate (CH 3 COONa), 0.1 g/L magnesium sulfate (MgSO 4 ) , 0.05 g/L Manganese sulfate (MnSO 4 ), 2 g/L dipotassium hydrogen phosphate (dipotassium hydrogen phos phate; K 2 HPO 4 ), but is not limited thereto.
본 발명의 배지는 pH가 8.0 미만이며, 바람직하게는 5.50 내지 7.15의 pH를 갖는다.The medium of the present invention has a pH of less than 8.0, and preferably has a pH of 5.50 to 7.15.
본 발명에서, 상기 균주의 배양 조건은 특별히 제한하지 않으며, 통상적인 균주의 배양 조건 하에서 수행될 수 있으나, 예컨대, 35 내지 38 ℃의 온도 및 8 내지 12 부피% CO2 조건 하에서, 20 내지 30 시간, 22 내지 28 시간 또는 23 내지 25 시간 동안 수행될 수 있다.In the present invention, the culture conditions of the strain are not particularly limited, and may be performed under conventional strain culture conditions, for example, at a temperature of 35 to 38 °C and 8 to 12 vol% CO 2 conditions, 20 to 30 hours , 22 to 28 hours or 23 to 25 hours.
본 발명의 상기 방법은 배양액을 분리하여 얻어진 농축물을 동결 건조하는 단계를 추가로 포함할 수 있다.The method of the present invention may further include the step of freeze-drying the concentrate obtained by separating the culture medium.
본 발명에서, 상기 배양액의 분리는 상기 균주를 배양 배지로부터 일정 조건 하에 배양한 후 원심 분리하여 펠릿 (pellet)은 제외하고 분리하는 방식으로 수행될 수 있다. 이러한 방식으로 분리된 배양액을 진공 농축하여 농축물을 수득할 수 있으며, 상기 배양액을 10 내지 90 ℃, 바람직하게는 30 내지 50 ℃ 범위에서 가열하며, 1 내지 80 torr의 진공상태의 압력으로 5 내지 10 시간 동안 수분을 증발시키는 방식으로 농축물을 수득할 수 있으나, 이에 제한되는 것은 아니다.In the present invention, the separation of the culture solution may be performed by culturing the strain from a culture medium under certain conditions and then centrifuging to separate the pellet except for the pellet. A concentrate can be obtained by vacuum concentrating the culture solution separated in this way, and the culture solution is heated in the range of 10 to 90 ° C., preferably 30 to 50 ° C., and at a vacuum pressure of 1 to 80 torr. A concentrate may be obtained by evaporating moisture for 10 hours, but is not limited thereto.
본 발명에서, 상기 분리 후 동결 건조하는 단계는 상기 배양액의 농축물을 10 내지 -70 ℃, 바람직하게는 -30 내지 -60 ℃, 더욱 바람직하게는 -50 ℃로 동결시킨 후, 동결 건조기에서 1 내지 80 torr의 진공상태의 압력조건으로 2 내지 96 시간, 바람직하게는 24 시간 동안 수분을 증발시킴으로써 동결건조물을 수득할 수 있으나, 이에 제한되는 것은 아니다.In the present invention, the freeze-drying step after the separation is performed by freezing the concentrate of the culture medium at 10 to -70 ° C, preferably -30 to -60 ° C, more preferably -50 ° C, and then in a freeze dryer for 1 A lyophilized product can be obtained by evaporating moisture for 2 to 96 hours, preferably 24 hours under a vacuum pressure condition of 80 torr, but is not limited thereto.
본 발명의 리모시락토바실러스 루테리 (Limosilactobacillus reuteri) 균주의 배양액은 아토피 피부염의 병증 완화 및 개선 효과가 뛰어나며, 궁극적으로 아토피 피부염의 예방, 치료 또는 개선을 위한 의약품, 의약외품 등으로 다양하게 활용할 수 있다. The culture solution of the Limosilactobacillus reuteri strain of the present invention is excellent in alleviating and improving the symptoms of atopic dermatitis, and ultimately can be used in various ways as pharmaceuticals, quasi-drugs, etc. for preventing, treating or improving atopic dermatitis.
도 1은 본 발명의 일 실시예에 따른 음성 대조군, 양성 대조군 (betamethasone) 및 균주의 배양액 처리군 (MBF4112)의 귀 두께를 측정한 결과를 나타낸 도이다.
도 2는 본 발명의 일 실시예에 따른 음성 대조군, 양성 대조군 (betamethasone) 및 균주의 배양액 처리군 (MBF4112)으로부터 아토피 피부염 관련 유전자 TSLP의 발현 정도를 실시간 중합효소 연쇄반응 (Real-time polymerase chain reaction)을 이용하여 측정한 결과를 나타낸 도이다.
도 3은 본 발명의 일 실시예에 따른 같은 음성 대조군, 리모시락토바실러스 루테리 (Limosilactobacillus reuteri)에 속하는 균주 (MBF4112 및 MBF01)의 배양액을 처리한 각 군의 귀 두께를 측정한 결과를 나타낸 도이다.1 is a diagram showing the results of measuring the ear thickness of a negative control group, a positive control group (betamethasone) and a strain culture solution treatment group (MBF4112) according to an embodiment of the present invention.
Figure 2 shows the expression level of the atopic dermatitis-related gene TSLP from the negative control group, the positive control group (betamethasone) and the strain culture solution treatment group (MBF4112) according to an embodiment of the present invention by Real-time polymerase chain reaction ) is a diagram showing the results measured using.
Figure 3 is a diagram showing the results of measuring the ear thickness of each group treated with culture solutions of strains (MBF4112 and MBF01) belonging to the same negative control group, Limosilactobacillus reuteri, according to an embodiment of the present invention. .
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for explaining the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
준비예: 리모시락토바실러스 루테리(Limosilactobacillus reuteri) 균주 배양액의 준비Preparation Example: Preparation of Limosilactobacillus reuteri strain culture solution
본 발명의 발명자들은 한국 생명공학연구원으로부터 리모시락토바실러스 루테리에 속하는 "락토바실러스 루테리 MBF4112 (Lactobacillus reuteri MBF4112)" 균주를 수득하였다. 상기에서 수득한 MBF4112 균주를 유산균 배지인 150 ml의 MRS (de Man, Rogosa and Sharpe) 액체 배지에서 24 시간 동안 37 ℃의 인큐베이터에서 혐기 조건으로 정치 배양하였다. 그 후 원심 분리하여 펠릿 (pellet)은 제외하고 배양액만을 따로 분리하였으며, 분리된 배양액을 동결 건조하여 분말로 제조하였다. The inventors of the present invention obtained a "Lactobacillus reuteri MBF4112" strain belonging to Rimobacteria reuteri from the Korea Research Institute of Bioscience and Biotechnology. The MBF4112 strain obtained above was statically cultured in 150 ml of MRS (de Man, Rogosa and Sharpe) liquid medium, which is a lactic acid bacteria medium, for 24 hours in a 37° C. incubator under anaerobic conditions. Thereafter, only the culture solution was separated by centrifugation except for the pellet, and the separated culture solution was freeze-dried to prepare a powder.
실시예 1: 마우스 귀 두께의 측정Example 1: Measurement of mouse ear thickness
본 발명의 발명자들은 리모시락토바실러스 루테리 (Lactobacillus reuteri MBF4112) 균주 배양액의 효과를 확인하기 위해서, 실험군은 상기 제조예에서 제조된 동결 건조된 분말을 70 % 에탄올에 용해하여 마우스 귀에 8 배 희석하여 아토피 피부염을 유발하기 하루 전날부터 도포하기 시작하여 6 일간 매일 도포하였다. 음성 대조군은 마우스 귀에 70 % 에탄올을 도포하였으며, 양성 대조군은 마우스 귀에 아토피 피부염의 병증을 완화시키는 것으로 잘 알려진 스테로이드제인 베타메타손 (betamethasone)을 70 % 에탄올에 0.05 %로 용해하여 도포하였다.In order to confirm the effect of the culture solution of the strain Lactobacillus reuteri MBF4112, the inventors of the present invention dissolved the freeze-dried powder prepared in the above Preparation Example in 70% ethanol and diluted 8-fold in mouse ears to atopic dermatitis. It was applied daily for 6 days starting from the day before the induction of dermatitis. As a negative control, 70% ethanol was applied to the mouse ears, and as a positive control, betamethasone, a steroid known to alleviate the symptoms of atopic dermatitis, was dissolved in 70% ethanol at 0.05% and applied to the mouse ears.
상기와 같은 첫 도포 이후, 아토피 피부염을 유발하기 위해 마우스를 마취한 후 왼쪽 귀에는 대조군으로 100 % 에탄올을 도포하고 오른쪽 귀에 MC903 (Calcipotriol)을 매일 2 mM 씩 100 % 에탄올에 용해하여 도포하였으며, 15 분 동안 말린 뒤에 실험군은 동결건조한 리모시락토바실러스 루테리 (Lactobacillus reuteri MBF4112) 균주의 배양액을 70 % 에탄올에 용해한 후 8 배 희석한 용액을 양쪽 귀 모두에 도포하였고, 음성 대조군은 70 % 에탄올을, 양성 대조군은 70 % 에탄올에 0.05 %로 용해된 베타메타손 (betamethasone)을 마우스 양쪽 귀에 5 일간 매일 도포하였다. 아토피 피부염의 병증 정도를 확인하기 위하여 마우스 귀의 두께를 매일 같은 시각에 측정하였다. 이 때, 귀 두께는 MC903 (Calcipotriol)을 도포한 오른쪽 귀의 두께에서 100 % 에탄올을 도포한 왼쪽 귀의 두께를 뺀 값을 사용하였다.After the first application as above, after anesthetizing the mouse to induce atopic dermatitis, 100% ethanol was applied to the left ear as a control, and MC903 (Calcipotriol) was dissolved in 100% ethanol at 2 mM daily and applied to the right ear. After drying for 15 minutes, the experimental group dissolved the lyophilized culture medium of the Lactobacillus reuteri MBF4112 strain in 70% ethanol and applied the 8-fold diluted solution to both ears. As a control group, betamethasone dissolved in 0.05% in 70% ethanol was applied to both ears of mice daily for 5 days. In order to confirm the severity of atopic dermatitis, the thickness of the ears of mice was measured at the same time every day. At this time, the ear thickness was obtained by subtracting the thickness of the left ear coated with 100% ethanol from the thickness of the right ear coated with MC903 (Calcipotriol).
그 결과, 마우스 급성 아토피 피부염 모델에 리모시락토바실러스 루테리 (Lactobacillus reuteri MBF4112) 균주의 배양액을 동결 건조한 뒤 70 % 에탄올에 용해하고 8 배 희석하여 발라준 결과 음성 대조군에 비하여 귀 두께가 덜 두꺼워진 것을 확인할 수 있었다(도 1 참조). 귀 두께는 아토피 피부염의 병증의 정도를 보여주기 때문에 리모시락토바실러스 루테리 (Lactobacillus reuteri MBF4112) 균주가 분비한 물질에 의하여 아토피 피부염의 병증이 경감된 것으로 볼 수 있다.As a result, when the culture solution of the Lactobacillus reuteri MBF4112 strain was lyophilized and dissolved in 70% ethanol and diluted 8 times to the mouse acute atopic dermatitis model, the ear thickness was less thick than that of the negative control group. It was confirmed (see FIG. 1). Since ear thickness shows the severity of atopic dermatitis, it can be seen that the symptoms of atopic dermatitis are alleviated by substances secreted by the strain Lactobacillus reuteri MBF4112.
실시예 2: TSLP 발현 정도의 측정Example 2: Measurement of TSLP expression level
상기 실시예 1에서의 음성 대조군, 양성 대조군 및 실험군으로부터 리모시락토바실러스 루테리 (Lactobacillus reuteri MBF4112) 균주가 분비한 물질의 아토피 피부염 병증 완화의 효과를 확인하고자 MC903 (Calcipotriol)을 마우스 귀에 5 번 발라주고 다음 날인 6 일째에 마우스를 희생하여 귀에서 아토피 피부염 관련 사이토카인의 유전자인 TSLP (Thymic stromal lymphopoietin)의 양을 실시간 중합효소 연쇄반응 (Real-time polymerase chain reaction)을 이용하여 측정하였다. In order to confirm the effect of mitigating atopic dermatitis symptoms of substances secreted by the Lactobacillus reuteri MBF4112 strain from the negative control, positive control and experimental groups in Example 1, MC903 (Calcipotriol) was applied to the
그 결과, 아토피 피부염을 유발하는 것으로 잘 알려져 있는 TSLP 유전자의 발현 정도 또한 음성 대조군에 비하여 감소하는 것을 확인할 수 있다(도 2 참조).As a result, it can be confirmed that the expression level of the TSLP gene, which is well known to induce atopic dermatitis, is also decreased compared to the negative control group (see FIG. 2).
상기 결과에 비추어, 리모시락토바실러스 루테리 (Lactobacillus reuteri MBF4112) 균주가 분비한 물질이 아토피 피부염 예방 또는 치료제로서 활용될 수 있는 가능성을 확인하였다. In light of the above results, it was confirmed that the substance secreted by the Lactobacillus reuteri MBF4112 strain could be used as a preventive or therapeutic agent for atopic dermatitis.
실시예 3: 리모시락토바실러스 루테리Example 3: Remocylactobacillus reuteri (( Limosilactobacillus reuteri) 균주 간의 비교 실험Limosilactobacillus reuteri) strain comparison experiment
본 발명에서의 리모시락토바실러스 루테리 (Lactobacillus reuteri MBF4112) 균주의 배양액의 치료 효과를 확인하고자 리모시락토바실러스 루테리의 다른 스트레인 (strain)인 MBF01의 배양액에서도 동일한 효능이 나타나는지 확인하고자 하였다. 상기한 실시예 1 에서와 같은 방식으로 마우스의 귀 두께를 측정한 결과를 도 3에 나타내었다. In order to confirm the therapeutic effect of the culture medium of the strain Lactobacillus reuteri MBF4112 in the present invention, it was attempted to determine whether the same efficacy was also exhibited in the culture medium of MBF01, another strain of Rimocilactobacillus reuteri. The results of measuring the ear thickness of mice in the same manner as in Example 1 are shown in FIG. 3 .
그 결과, MBF4112 균주 배양액을 도포할 시 음성 대조군 및 MBF01의 배양액을 도포한 군에 비하여 귀 두께가 덜 두꺼워진 것을 확인하였다. 이를 통해, 같은 유산균인 리모시락토바실러스 루테리 배양액일지라도 스트레인에 따라 아토피 피부염의 치료 효과가 달리 나타나는 것을 확인할 수 있으며, MBF4112 균주 배양액의 아토피 피부염의 치료 효과가 MBF01의 배양액의 효과보다 현저히 뛰어난 것을 확인할 수 있었다(도 3 참조). As a result, when the MBF4112 strain culture solution was applied, it was confirmed that the ear thickness was less thick compared to the negative control group and the group applied with the MBF01 culture solution. Through this, it can be confirmed that the treatment effect of atopic dermatitis is different depending on the strain even in the culture medium of the same lactic acid bacterium, Limosylactobacillus reuteri, and the treatment effect of atopic dermatitis of the culture medium of MBF4112 strain is significantly superior to that of the culture medium of MBF01. There was (see Figure 3).
이상으로 본 발명의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현 예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.Having described specific parts of the present invention in detail above, it is clear that these specific techniques are only preferred embodiments for those skilled in the art, and the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.
Claims (20)
상기 리모시락토바실러스 루테리 균주는 Lactobacillus reuteri MBF4112(기탁 번호: KCTC 13232BP)이고,
상기 알러지성 질환은 아토피 피부염인, 조성물.A pharmaceutical composition for preventing or treating allergic diseases, comprising a culture solution of Limosilactobacillus reuteri strain as an active ingredient,
The Remocylactobacillus reuteri strain is Lactobacillus reuteri MBF4112 (accession number: KCTC 13232BP),
The allergic disease is atopic dermatitis, the composition.
상기 배양액은 상기 균주를 MRS 배지(Lactobacilli MRS brothMRS medium), BCP 배지 (bromocresol purple medium), M-17 Broth 배지, Rogosa 한천 배지, BSM 한천 배지, Rogosa SL 한천 배지 및 BL 한천 배지로 이루어진 군에서 선택된 1 종 이상의 배지에서 배양하여 얻어진 것인, 약학적 조성물. According to claim 1,
The culture medium is selected from the group consisting of MRS medium (Lactobacilli MRS brothMRS medium), BCP medium (bromocresol purple medium), M-17 Broth medium, Rogosa agar medium, BSM agar medium, Rogosa SL agar medium and BL agar medium It is obtained by culturing in one or more types of media, a pharmaceutical composition.
상기 배양액은 배양액의 농축액 또는 동결 건조물인, 약학적 조성물.According to claim 1,
The culture medium is a concentrate or freeze-dried product of the culture medium, a pharmaceutical composition.
상기 리모시락토바실러스 루테리 균주는 Lactobacillus reuteri MBF4112(기탁 번호: KCTC 13232BP)이고,
상기 알러지성 질환은 아토피 피부염인, 조성물.A cosmetic composition for preventing or improving allergic diseases, comprising a culture solution of Limosilactobacillus reuteri strain as an active ingredient,
The Remocylactobacillus reuteri strain is Lactobacillus reuteri MBF4112 (accession number: KCTC 13232BP),
The allergic disease is atopic dermatitis, the composition.
상기 리모시락토바실러스 루테리 균주는 Lactobacillus reuteri MBF4112(기탁 번호: KCTC 13232BP)이고,
상기 알러지성 질환은 아토피 피부염인, 조성물.A food composition for preventing or improving allergic diseases, comprising a culture solution of Limosilactobacillus reuteri strain as an active ingredient,
The Remocylactobacillus reuteri strain is Lactobacillus reuteri MBF4112 (accession number: KCTC 13232BP),
The allergic disease is atopic dermatitis, the composition.
상기 균주를 배양하는 단계를 포함하는, 알러지성 질환의 예방, 치료 또는 개선용 조성물의 제조 방법으로,
상기 리모시락토바실러스 루테리 균주는 Lactobacillus reuteri MBF4112(기탁 번호: KCTC 13232BP)이고,
상기 알러지성 질환은 아토피 피부염인, 방법.Preparing a Limosilactobacillus reuteri strain; and
A method for producing a composition for preventing, treating or improving allergic diseases, comprising culturing the strain,
The Remocylactobacillus reuteri strain is Lactobacillus reuteri MBF4112 (accession number: KCTC 13232BP),
The allergic disease is atopic dermatitis, the method.
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