KR20230024502A - Extracellular vesicles comprising miRNA and uses thereof - Google Patents
Extracellular vesicles comprising miRNA and uses thereof Download PDFInfo
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- KR20230024502A KR20230024502A KR1020210106379A KR20210106379A KR20230024502A KR 20230024502 A KR20230024502 A KR 20230024502A KR 1020210106379 A KR1020210106379 A KR 1020210106379A KR 20210106379 A KR20210106379 A KR 20210106379A KR 20230024502 A KR20230024502 A KR 20230024502A
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- streptococcus
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Abstract
Description
본 발명은 miRNA를 포함하는 세포외 소포 및 이의 용도에 관한 것으로, 구체적으로는 miRNA를 포함하는 세포외 소포 및 이의 다양한 약학적 용도에 관한 것이다.The present invention relates to extracellular vesicles containing miRNAs and uses thereof, and more particularly, to extracellular vesicles containing miRNAs and various pharmaceutical uses thereof.
염증은 상처나 질병에 반응하는 인체의 면역 반응으로, 자외선이나 활성산소, 자유라디칼 등의 산화적 스트레스 등이 염증성 인자를 활성화시켜 각종 질병 및 피부의 노화를 일으킨다. 혈관 활성 폴리펩타이드인 키닌(Kinin), 플라스민(Plasmin) 또는 보체(Complement) 등이 혈관 확장과 수축 및 주화성(Chemotaxis) 작용을 하고, 그 외에 인터루킨-6(IL-6) 등과 같은 림포카인과 아라키돈산(Arachidonic acid) 등이 염증 반응을 담당한다. 아라키돈산은 싸이클로옥시게나아제(Cyclooxygenase) 혹은 리포옥시게나아제(Lipooxygenase)의 2가지 경로를 거쳐 염증 매개체인 프로스타글란딘(Prostaglandin) 또는 류코트리엔(Lukotriene)들로 대사되어 다양한 염증 반응을 매개한다.Inflammation is an immune response of the human body in response to wounds or diseases, and oxidative stress such as ultraviolet rays, active oxygen, and free radicals activate inflammatory factors to cause various diseases and aging of the skin. Vasoactive polypeptides, such as Kinin, Plasmin, or Complement, act on vasodilation, contraction, and chemotaxis, and other lymphocytes such as interleukin-6 (IL-6) Phosphorus and arachidonic acid are responsible for the inflammatory response. Arachidonic acid is metabolized into prostaglandin or leukotrienes, which are inflammatory mediators, through two pathways, cyclooxygenase and lipooxygenase, to mediate various inflammatory reactions.
이 중 염증성 장질환(inflammatory bowel disease)은 장에 만성적인 원인 불명의 염증을 일으키는 질환으로 궤양성 대장염과 크론병으로 나눌 수 있고, 베체트병도 여기에 포함된다. 염증성 장 질환의 발생 원인이나 병태생리에 대해서는 아직까지 명확히 알려져 있지 않지만, 유전적 요인, 장내 세균이나 음식물 등의 환경적 요인, 면역학적 요인 등이 복합적으로 발생 기전에 관여할 것으로 추정되고 있다. 종래의 궤양성 대장염 및 크론병의 발생율은 서양인에게 높다고 알려져 있었으나, 최근 식습관 등 생활 습관의 변화로 인해 국내를 비롯한 동양에서도 환자수가 급증하고 있다. 그럼에도 불구하고 원인이 불분명한 이유 등으로 근본적 치료법은 아직 확립되어 있지 않아 완전한 치료를 목표로 하는 것이 아니라 증상의 진행을 지연 및 완화시키고, 이러한 상태를 가능한 한 장기간 유지하는 약제가 사용되고 있는 실정이다. 이러한 대중요법을 위한 약제로서는 주로 아미노살리실산 제제, 부신피질 스테로이드제, 면역억제제, TNF-α단일클론항체 등이 사용되고 있지만, 다양한 부작용이 보고되고 있다. 예를 들어, 아미노살리실산 제제로서 자주 사용하는 설파살라진은 구역질, 구토, 식욕부진, 발진, 두통, 백혈구 감소, 이상 적혈구, 단백뇨, 설사 등의 부작용이 보고되고 있다. 부신피질 스테로이드제인 프레드니솔론은 경구투여, 관장, 좌약, 정맥 주사 등으로 사용되지만 위궤양이나 장기 사용에 의한 부작용이 강한 문제점이 있다.Among them, inflammatory bowel disease (IBD) is a disease that causes chronic inflammation of unknown cause in the intestine and can be divided into ulcerative colitis and Crohn's disease, and Behçet's disease is also included here. Although the cause or pathophysiology of inflammatory bowel disease is not yet clearly known, it is estimated that genetic factors, environmental factors such as intestinal bacteria or food, and immunological factors are complexly involved in the development mechanism. Conventionally, it was known that the incidence of ulcerative colitis and Crohn's disease was high in Westerners, but recently, due to changes in lifestyle such as eating habits, the number of patients is rapidly increasing in Korea as well as in the Orient. Nevertheless, because the cause is unclear, the fundamental treatment has not yet been established, so drugs that do not aim at complete treatment but delay and alleviate the progression of symptoms and maintain these conditions for as long as possible are being used. Aminosalicylic acid preparations, adrenocortical steroids, immunosuppressants, TNF-α monoclonal antibodies, etc. are mainly used as drugs for such public therapy, but various side effects have been reported. For example, sulfasalazine, which is frequently used as an aminosalicylic acid preparation, has been reported to have side effects such as nausea, vomiting, anorexia, rash, headache, leukopenia, abnormal red blood cells, proteinuria, and diarrhea. Prednisolone, an adrenal cortical steroid, is used for oral administration, enema, suppository, intravenous injection, etc., but has serious side effects due to gastric ulcer or long-term use.
한편, 염증 반응에 관여하는 많은 장애에는 자가면역 장애가 연루되어 있다. 자가면역 장애는, 면역계가 실수로 건강한 신체 조직을 공격하여 파괴하는 경우 발생하는 병태이다. 자가면역 장애를 앓고 있는 환자에서, 면역계는 건강한 신체 조직과 항원의 차이를 구별할 수 없다. 그 결과, 면역 반응이 정상 신체 조직을 파괴한다. 면역계로 하여금 건강한 신체 조직과 항원 간의 차이를 구별하지 못하게 유발하는 것이 무엇인지는 알려져 있지 않다. On the other hand, autoimmune disorders are implicated in many disorders involved in the inflammatory response. Autoimmune disorders are conditions that occur when the immune system mistakenly attacks and destroys healthy body tissue. In patients suffering from autoimmune disorders, the immune system cannot differentiate between healthy body tissue and antigens. As a result, the immune response destroys normal body tissue. It is not known what causes the immune system to be unable to differentiate between healthy body tissues and antigens.
최근에는 합성의약품보다 부작용이 적은 생물의약품에 대한 연구, 개발이 활발하게 이루어지고 있으며, 특히 세포외 소포를 이용한 다양한 치료제에 대한 연구가 다수 진행되고 있다. 그러나 이들은 대부분 줄기세포 유래의 세포외 소포에 관한 것이며, 염증성 질환의 치료용으로 사용할 수 있는 세포외 소포의 지표 성분에 대한 연구가 활발하게 이루어지고 있지 않고 있다. Recently, research and development on biological drugs with fewer side effects than synthetic drugs have been actively conducted, and in particular, a number of studies on various therapeutic agents using extracellular vesicles are being conducted. However, these mostly relate to stem cell-derived extracellular vesicles, and studies on marker components of extracellular vesicles that can be used for the treatment of inflammatory diseases have not been actively conducted.
상기와 같은 문제점을 해결하기 위해 염증 질환의 예방 또는 치료에 사용될 수 있는 특정 지표 성분을 포함하는 세포외 소포를 제공하고, 상기 세포외 소포를 유효성분으로 포함함으로써 부작용이 낮으면서도 염증 질환의 예방, 개선 또는 치료 효과가 우수한 약학적 조성물, 염증 질환의 예방 또는 개선 효과가 우수한 화장료 조성물 또는 식품 조성물을 제공하고자 한다.In order to solve the above problems, providing an extracellular vesicle containing a specific indicator component that can be used for the prevention or treatment of inflammatory diseases, and including the extracellular vesicles as an active ingredient to prevent inflammatory diseases with low side effects, It is intended to provide a pharmaceutical composition with excellent improvement or treatment effect, a cosmetic composition or food composition with excellent prevention or improvement effect of inflammatory diseases.
또한, 상기 약학적 조성물을 이용한 염증 질환의 치료방법을 제공하고자 한다.In addition, it is intended to provide a method of treating inflammatory diseases using the pharmaceutical composition.
상기와 같은 목적을 달성하기 위해 본 발명은 지표 성분으로 miRNA를 포함하는 세포외 소포를 제공한다. In order to achieve the above object, the present invention provides an extracellular vesicle containing miRNA as a marker component.
또한, 상기 세포외 소포를 유효성분으로 포함하는 염증 질환의 예방, 개선 또는 치료용 약학적 조성물을 제공한다.In addition, it provides a pharmaceutical composition for preventing, improving or treating inflammatory diseases comprising the extracellular vesicles as an active ingredient.
또한, 상기 세포외 소포를 유효성분으로 포함하는 염증 질환의 예방 또는 개선용 화장료 조성물을 제공한다.In addition, it provides a cosmetic composition for preventing or improving inflammatory diseases comprising the extracellular vesicles as an active ingredient.
또한, 상기 세포외 소포를 유효성분으로 포함하는 염증 질환의 예방 또는 개선용 식품 조성물을 제공한다.In addition, it provides a food composition for preventing or improving inflammatory diseases comprising the extracellular vesicles as an active ingredient.
상기 miRNA는 다음의 miRNA 중 선택되는 어느 하나 이상일 수 있다:The miRNA may be any one or more selected from the following miRNAs:
let-7a-1; let-7a-2; let-7a-3; let-7a-5p; let-7b; let-7b-5p; let-7c; let-7c-5p; let-7d; let-7d-5p; let-7e; let-7e-5p; let-7f-1; let-7f-1-3p; let-7f-2; let-7f-5p; let-7g; let-7g-5p; let-7i; let-7i-3p; mir-1-1; mir-1-2; mir-1-3p; mir-7-1; mir-7-2; mir-7-3; mir-9-1; mir-9-2; mir-9-3; mir-10a; mir-10a-3p; mir-10a-5p; mir-10b; mir-15a; mir-15b; mir-16-1; mir-16-2; mir-17; mir-17-3p; mir-17-5p; mir-18a; mir-18b; mir-19a; mir-19b-1; mir-19b-2; mir-20a; mir-20b; mir-21; mir-21-5p; mir-22; mir-22-3p; mir-23a; mir-23b; mir-23b-3p; mir-23c; mir-24-1; mir-24-2; mir-24-3; mir-24-3p; mir-25; mir-26a-1; mir-26a-2; mir-26a-5p; mir-26b; mir-26b-5p; mir-27a; mir-27b; mir-27b-3p; mir-28; mir-29a; mir-29b-1; mir-29b-2; mir-29c; mir-30a; mir-30a-5p; mir-30b; mir-30c-1; mir-30c-2; mir-30c-5p; mir-30d; mir-30e; mir-30e-5p; mir-31; mir-32; mir-33a; mir-33b; mir-34a; mir-34b; mir-34c; mir-92a-1; mir-92a-2; mir-92a-3p; mir-92b; mir-93; mir-93-5p; mir-95; mir-96; mir-98; mir-99a; mir-99b; mir-99b-5p; mir-100; mir-101-1; mir-101-2; mir-103a; mir-103a-1; mir-103a-2; mir-103a-3p; mir-103-1; mir-103-1-as; mir-103-2; mir-103-2-as; mir-105-1; mir-105-2; mir-106a; mir-106b; mir-106b-3p; mir-107; mir-122; mir-124-1; mir-124-2; mir-124-3; mir-125a; mir-125b-1; mir-125b-2; mir-125b-2-3p; mir-126; mir-126-3p; mir-127; mir-128-1; mir-128-2; mir-129-1; mir-129-2; mir-130a; mir-130b; mir-132; mir-132; mir-133a-1; mir-133a-2; mir-133a-3p; mir-133b; mir-134; mir-135a-1; mir-135a-2; mir-135b; mir-136; mir-137; mir-137-3p; mir-138-1; mir-138-2; mir-139; mir-140; mir-141; mir-142; mir-143; mir-143-3p; mir-144; mir-145; mir-146a; mir-146b; mir-147; mir-147b; mir-148a; mir-148b; mir-149; mir-150; mir-151; mir-152; mir-153-1; mir-153-2; mir-154; mir-155; mir-181a-1; mir-181a-2; mir-181a-5p; mir-181b-1; mir-181b-2; mir-181b-5p; mir-181c; mir-181d; mir-182; mir-183; mir-184; mir-185; mir-186; mir-187; mir-188; mir-190; mir-190b; mir-191; mir-192; mir-192-3p; mir-192-5p; mir-193a; mir-193b; mir-194-1; mir-194-2; mir-195; mir-196a-1; mir-196a-2; mir-196b; mir-197; mir-198; mir-199a-1; mir-199a-2; mir-199a-3p; mir-199b; mir-199b-3p; mir-200a; mir-200b; mir-200c; mir-200c-5p; mir-202; mir-203; mir-204; mir-205; mir-206; mir-208a; mir-208b; mir-208b-3p; mir-208b-5p; mir-210; mir-211; mir-212; mir-214; mir-215; mir-216a; mir-216b; mir-217; mir-217-5p; mir-218-1; mir-218-2; mir-218-5p; mir-219; mir-219b; mir-219-1; mir-219-2; mir-221; mir-222; mir-222-3p; mir-223; mir-224; mir-296; mir-297; mir-298; mir-299; mir-300; mir-301a; mir-301b; mir-302a; mir-302b; mir-302c; mir-302d; mir-302e; mir-302f; mir-320a; mir-320b-1; mir-320b-2; mir-320c-1; mir-320c-2; mir-320d-1; mir-320d-2; mir-320e; mir-323; mir-323b; mir-324; mir-325; mir-326; mir-328; mir-329-1; mir-329-2; mir-330; mir-331; mir-335; mir-337; mir-338; mir-339; mir-340; mir-342; mir-342-3p; mir-345; mir-346; mir-361; mir-362; mir-363; mir-365a; mir-365b; mir-365-1; mir-365-2; mir-367; mir-367-3p; mir-367-5p; mir-369; mir-370; mir-37; mir-372; mir-373; mir-374a; mir-374b; mir-374c; mir-375; mir-376a-1; mir-376a-2; mir-376b; mir-376c; mir-377; mir-378; mir-378a; mir-378a-3p; mir-378b; mir-378c; mir-379; mir-380; mir-381; mir-382; mir-383; mir-384; mir-409; mir-410; mir-411; mir-412; mir-412-5p; mir-421; mir-422a; mir-423; mir-424; mir-425; mir-429; mir-431; mir-432; mir-433; mir-448; mir-449a; mir-449b; mir-449c; mir-449c-5p; mir-450a-1; mir-450a-2; mir-450b; mir-451; mir-452; mir-454; mir-455; mir-466; mir-483; mir-484; mir-485; mir-486; mir-486-1; mir-486-2; mir-486-5p; mir-487a; mir-487b; mir-487b-3p; mir-488; mir-489; mir-489-3p; mir-490; mir-491; ,mir-492; mir-493; mir-494; mir-495; mir-496; mir-497; mir-498; mir-499; mir-499b; mir-499b-5p; mir-500a; mir-500b; mir-501; mir-502; mir-503; mir-504; mir-505; mir-506; mir-507; mir-508; mir-509-1; mir-509-2; mir-509-3; mir-509-5p; mir-510; mir-511-1; mir-511-2; mir-512-1; mir-512-2; mir-513a-1; mir-513a-2; mir-513b; mir-513c; mir-514-1; mir-514-2; mir-514-3; mir-514b; mir-515-1; mir-515-2; mir-516a-1; mir-516a-2; 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mir-218-2; mir-218-5p; mir-219; mir-219b; mir-219-1; mir-219-2; mir-221; mir-222; mir-222-3p; mir-223; mir-224; mir-296; mir-297; mir-298; mir-299; mir-300; mir-301a; mir-301b; mir-302a; mir-302b; mir-302c; mir-302d; mir-302e; mir-302f; mir-320a; mir-320b-1; mir-320b-2; mir-320c-1; mir-320c-2; mir-320d-1; mir-320d-2; mir-320e; mir-323; mir-323b; mir-324; mir-325; mir-326; mir-328; mir-329-1; mir-329-2; mir-330; mir-331; mir-335; mir-337; mir-338; mir-339; mir-340; mir-342; mir-342-3p; mir-345; mir-346; mir-361; mir-362; mir-363; mir-365a; mir-365b; mir-365-1; mir-365-2; mir-367; mir-367-3p; mir-367-5p; mir-369; mir-370; mir-37; mir-372; mir-373; mir-374a; mir-374b; mir-374c; mir-375; mir-376a-1; mir-376a-2; mir-376b; mir-376c; mir-377; mir-378; mir-378a; mir-378a-3p; mir-378b; mir-378c; mir-379; mir-380; mir-381; mir-382; mir-383; mir-384; mir-409; mir-410; mir-411; mir-412; mir-412-5p; mir-421; mir-422a; mir-423; mir-424; mir-425; mir-429; mir-431; mir-432; mir-433; mir-448; mir-449a; mir-449b; mir-449c; mir-449c-5p; mir-450a-1; mir-450a-2; mir-450b; mir-451; mir-452; mir-454; mir-455; mir-466; mir-483; mir-484; mir-485; mir-486; mir-486-1; mir-486-2; mir-486-5p; mir-487a; mir-487b; mir-487b-3p; mir-488; mir-489; mir-489-3p; mir-490; mir-491; ,mir-492; mir-493; mir-494; mir-495; mir-496; mir-497; mir-498; mir-499; mir-499b; mir-499b-5p; mir-500a; mir-500b; mir-501; mir-502; mir-503; mir-504; mir-505; mir-506; mir-507; mir-508; mir-509-1; mir-509-2; mir-509-3; mir-509-5p; mir-510; mir-511-1; mir-511-2; mir-512-1; mir-512-2; mir-513a-1; mir-513a-2; mir-513b; mir-513c; mir-514-1; mir-514-2; mir-514-3; mir-514b; mir-515-1; mir-515-2; mir-516a-1; mir-516a-2; mir-516b-1; mir-516b-2; mir-517a; mir-517b; mir-517c; mir-518a-1; mir-518a-2; mir-518b; mir-518c; mir-518d; mir-518e; mir-518f; mir-519a-1; mir-519a-2; mir-519b; mir-519c; mir-519d; mir-519e; mir-520a; mir-520b; mir-520c; mir-520d; mir-520e; mir-520f; mir-520g; mir-520h; mir-521-1; mir-521-2; mir-522; mir-523; mir-524; mir-525; mir-526a-1; mir-526a-2; mir-526b; mir-527; mir-532; mir-539; mir-541; mir-542; mir-543; mir-544; mir-544b; mir-545; mir-548a-1; mir-548a-2; mir-548a-3; mir-548aa-1; mir-548aa-2; mir-548aq; mir-548b; mir-548c; mir-548d-1; mir-548d-2; mir-548e; mir-548f-1; mir-548f-2; mir-548f-3; mir-548f-4; mir-548f-5; mir-548g; mir-548h-1; mir-548h-2; mir-548h-3; mir-548h-4; mir-548i-1; mir-548i-2; mir-548i-3; mir-548i-4; mir-548j; mir-548k; mir-548l; mir-548m; mir-548n; mir-548o; mir-548p; mir-548s; mir-548t; mir-548u; mir-548v; mir-548w; mir-548x; mir-548y; mir-548z; mir-549; mir-550a-1; mir-550a-2; mir-550a-3; mir-550b-1; mir-550b-2; mir-551a; mir-551b; mir-552; mir-553; mir-554; mir-555; mir-556; mir-557; mir-558; mir-559; mir-561; mir-562; mir-563; mir-564; mir-566; mir-567; mir-568; mir-569; mir-570; mir-571; mir-572; mir-573; mir-574; mir-575; mir-576; mir-577; mir-578; mir-579; mir-580; mir-581; mir-582; mir-583; mir-584; mir-584-3p; mir-584-5p; mir-585; mir-586; mir-587; mir-588; mir-589; mir-590; mir-591; mir-592; mir-593; mir-595; mir-596; mir-597; mir-598; mir-599; mir-600; mir-601; mir-602; mir-603; mir-604; mir-605; mir-606; mir-607; mir-608; mir-609; mir-610; mir-611; mir-612; mir-613; mir-614; mir-615; mir-616; mir-617; mir-618; mir-619; mir-620; mir-621; mir-622; mir-623; mir-624; mir-625; mir-626; mir-627; mir-628; mir-629; mir-630; mir-631; mir-632; mir-633; mir-634; mir-635; mir-636; mir-637; mir-638; mir-639; mir-640; mir-641; mir-642a; mir-642b; mir-643; mir-644; mir-645; mir-646; mir-647; mir-648; mir-649; mir-650; mir-651; mir-652; mir-653; mir-654; mir-655; mir-656; mir-657; mir-658; mir-659; mir-660; mir-661; mir-662; mir-663; mir-663a; mir-663b; mir-664; mir-665; mir-668; mir-670; mir-671; mir-675; mir-676; mir-708; mir-711; mir-718; mir-720; mir-744; mir-758; mir-759; mir-760; mir-761; mir-762; mir-764; mir-765; mir-766; mir-767; mir-769; mir-770; mir-802; mir-873; mir-874; mir-875; mir-876; mir-877; mir-885; mir-887; mir-888; mir-889; mir-890; mir-891a; mir-891b; mir-892a; mir-892b; mir-920; mir-921; mir-922; mir-924; mir-933; mir-934; mir-935; mir-936; mir-937; mir-938; mir-939; mir-940; mir-941-1; mir-941-2; mir-941-3; mir-941-4; mir-942; mir-942-3p; mir-943; mir-944; mir-1178; mir-1179; mir-1180; mir-1181; mir-1182; mir-1183; mir-1184-1; mir-1184-2; mir-1184-3; mir-1185-1; mir-1185-2; mir-1193; mir-1197; mir-1200; mir-1202; mir-1203; mir-1204; mir-1205; mir-1206; mir-1207; mir-1208; mir-1224; mir-1225; mir-1226; mir-1227; mir-1228; mir-1229; mir-1231; mir-1233-1; mir-1233-2; mir-1234; mir-1236; mir-1236-5p; mir-1237; mir-1238; mir-1243; mir-1244-1; mir-1244-2; mir-1244-3; mir-1245; mir-1246; mir-1247; mir-1248; mir-1249; mir-1250; mir-1251; mir-1251-3p; mir-1252; mir-1253; mir-1254; mir-1255a; mir-1255b-1; mir-1255b-2; mir-1256; mir-1257; mir-1258; mir-1260; mir-1260b; mir-1261; mir-1262; mir-1263; mir-1264; mir-1265; mir-1266; mir-1267; mir-1268a; mir-1269; mir-1270-1; mir-1270-2; mir-1271; mir-1272; mir-1273; mir-1273c; mir-1273d; mir-1273e; mir-1274a; mir-1274b; mir-1275; mir-1276; mir-1277; mir-1278; mir-1279; mir-1280; mir-1281; mir-1282; mir-1283-1; mir-1283-2; mir-1284; mir-1285-1; mir-1285-2; mir-1286; mir-1287; mir-1288; mir-1289-1; mir-1289-2; mir-1290; mir-1291; mir-1292; mir-1293; mir-1294; mir-1295; mir-1296; mir-1297; mir-1298; mir-1299; mir-1301; mir-1302-1; mir-1302-4; mir-1302-10; mir-1302-11; mir-1302-2; mir-1302-3; mir-1302-4; mir-1302-5; mir-1302-6; mir-1302-7; mir-1302-8; mir-1302-9; mir-1303; mir-1304; mir-1305; mir-1306; mir-1307; mir-1321; mir-1322; mir-1323; mir-1324; mir-1468; mir-1469; mir-1470; mir-1471; mir-1537; mir-1538; mir-1539; mir-1825; mir-1827; mir-1908; mir-1909; mir-1909-5p; mir-1910; mir-1911; mir-1912; mir-1913; mir-1914; mir-1915; mir-1972-1; mir-1972-2; mir-1973; mir-1976; mir-2052; mir-2053; mir-2054; mir-2110; mir-2113; mir-2114; mir-2115; mir-2116; mir-2117; mir-2276; mir-2277; mir-2278; mir-2355; mir-2355-3p; mir-2861; mir-2909; mir-3065; mir-3074; mir-3115; mir-3116-1; mir-3116-2; mir-3117; mir-3118-1; mir-3118-2; mir-3118-3; mir-3118-4; mir-3118-5; mir-3118-6; mir-3119-1; mir-3119-2; mir-3120; mir-3121; mir-3122; mir-3123; mir-3124; mir-3125; mir-3126; mir-3127; mir-3128; mir-3129; mir-3130-1; mir-3130-2; mir-3131; mir-3132; mir-3133; mir-3134; mir-3135; mir-3136; mir-3137; mir-3138; mir-3139; mir-3140; mir-3141; mir-3142; mir-3143; mir-3144; mir-3145; mir-3146; mir-3147; mir-3148; mir-3149; mir-3150; mir-3151; mir-3152; mir-3153; mir-3154; mir-3155-a; mir-3155-b; mir-3156-1; mir-3156-2; mir-3156-3; mir-3157; mir-3158-1; mir-3158-2; mir-3158-5p; mir-3159; mir-3160; mir-3160-1; mir-3160-2; mir-3160-5p; mir-3161; mir-3162; mir-3163; mir-3164; mir-3165; mir-3166; mir-3167; mir-3168; mir-3169; mir-3170; mir-3171; mir-3173; mir-3174; mir-3175; mir-3176; mir-3177; mir-3178; mir-3179-1; mir-3179-2; mir-3179-3; mir-3180-1; mir-3180-2; mir-3180-3; mir-3180-4; mir-3180-5; mir-3181; mir-3182; mir-3183; mir-3184; mir-3185; mir-3186; mir-3187; mir-3188; mir-3189; mir-3190; mir-3191; mir-3192; mir-3193; mir-3194; mir-3195; mir-3196; mir-3197; mir-3198; mir-3198-1; mir-3198-2; mir-3199-1; mir-3199-2; mir-3200; mir-3201; mir-3202-1; mir-3202-2; mir-3605; mir-3606; mir-3607; mir-3609; mir-3610; mir-3611; mir-3612; mir-3613; mir-3614; mir-3615; mir-3616; mir-3617; mir-3618; mir-3619; mir-3620; mir-3621; mir-3622a; mir-3622b; mir-3646; mir-3647; mir-3648; mir-3649; mir-3650; mir-3651; mir-3652; mir-3653; mir-3654; mir-3655; mir-3656mir-3657; mir-3658; mir-3659; mir-3660; mir-3661; mir-3662; mir-3663; mir-3664; mir-3665; mir-3666; mir-3667; mir-3668; mir-3669; mir-3670; mir-3670; mir-3671; mir-3671; mir-3673; mir-3673; mir-3675; mir-3675; mir-3676; mir-3663; mir-3677; mir-3678; mir-3679; mir-3680; mir-3681; mir-3682; mir-3683; mir-3684; mir-3685; mir-3686; mir-3687; mir-3688-1; mir-3688-2; mir-3689a; mir-3689b; mir-3689d-1; mir-3689d-2; mir-3689e; mir-3690; mir-3691; mir-3692; mir-3713; mir-3714; mir-3907; mir-3908; mir-3909; mir-3910-1; mir-3910-2; mir-3911; mir-3912; mir-3913-1; mir-3913-2; mir-3913-5p; mir-3914-1; mir-3914-2; mir-3915; mir-3916; mir-3917; mir-3918; mir-3919; mir-3920; mir-3921; mir-3922; mir-3923; mir-3924; mir-3925; mir-3926-1; mir-3926-2; mir-3927; mir-3928; mir-3929; mir-3934; mir-3935; mir-3936; mir-3937; mir-3938; mir-3939; mir-3940; mir-3941; mir-3942; mir-3943; mir-3944; mir-3945; mir-3975; mir-3976; mir-3978; mir-4251; mir-4252; mir-4253; mir-4254; mir-4255; mir-4256; mir-4257; mir-4258; mir-4259; mir-4260; mir-4261; mir-4262; mir-4263; mir-4264; mir-4265; mir-4266; mir-4267; mir-4268; mir-4269; mir-4270; mir-4271; mir-4272; mir-4273; mir-4274; mir-4275; mir-4276; mir-4277; mir-4278; mir-4279; mir-4280; mir-4281; mir-4282; mir-4283-1; mir-4283-2; mir-4284; mir-4285; mir-4286; mir-4287; mir-4288; mir-4289; mir-4290; mir-4291; mir-4292; mir-4293; mir-4294; mir-4295; mir-4296; mir-4297; mir-4298; mir-4299; mir-4300; mir-4301; mir-4302; mir-4303; mir-4304; mir-4305; mir-4306; mir-4307; mir-4308; mir-4309; mir-4310; mir-4311; mir-4312; mir-4313; mir-4314; mir-4315; mir-4315-1; mir-4315-2; mir-4316; mir-4317; mir-4318; mir-4319; mir-4320; mir-4321; mir-4322; mir-4323; mir-4324; mir-4325; mir-4326; mir-4327; mir-4328; mir-4329; mir-4329; mir-4330; mir-4332; mir-4432; mir-4438; mir-4449; mir-4451; mir-4458; mir-4460; mir-4463; mir-4469; mir-4472; mir-4472-1; mir-4479; mir-4482; mir-4482-3p; mir-4482-5p; mir-4490; mir-4493; mir-4507; mir-4509; mir-4509-1; mir-4509-2; mir-4509-3; mir-4511; mir-4526; mir-4536-1; mir-4536-2; mir-4538; mir-4638; mir-4638-3p; mir-4639; mir-4639-3p; mir-4639-5p; mir-4658; mir-4688; mir-4690; mir-4698; mir-4714; mir-4714-5p; mir-4716; mir-4716-3p; mir-4717; mir-4717-5p; mir-4764; mir-4772; mir-4776-1; mir-4787; mir-4787-5p; mir-4788; mir-4800; mir-4800-3p; mir-4803; mir-4804; mir-5187; mir-5187-5p; mir-5188; mir-5190; mir-5192; mir-5194; mir-5583-1; mir-5583-3p; mir-5583-5p; mir-5588; mir-5683; mir-5708; mir-6069; mir-6070; mir-6082; mir-6124; mir-6127; mir-6501; mir-6501-3p; mir-6722; mir-6737; mir-6748; mir-6748-3p; mir-6753; mir-6769a, mir-6769b; mir-6773; mir-6779; mir-6779-5p; mir-6801; mir-6805; mir-6854; mir-6854-5p; mir-6878; mir-6882; mir-6882-5p; mir-7107; mir-7110; mir-7151; mir-7151-5p; mir-7161; mir-7161-5p; mir-7977; mir-8485; mir-9903; mir-10392; mir-10395; mir-10395-3p; mir-10395-5p; mir-10523; mir-12132; mir-12136.
상기 miRNA는 제한되는 것은 아니지만 바람직하게는 mir-192 또는 mir-10523일 수 있다.The miRNA may be preferably, but not limited to, mir-192 or mir-10523.
상기 세포외 소포(extracellular vesicle)는 10 내지 1000nm의 크기를 갖는 것일 수 있으며, 바람직하게는 20 내지 300 nm의 크기이며, 바람직하게는 50 내지 200nm, 더욱 바람직하게는 70 내지 150nm의 크기일 수 있으나, 이에 제한되는 것은 아니다. The extracellular vesicle may have a size of 10 to 1000 nm, preferably a size of 20 to 300 nm, preferably a size of 50 to 200 nm, and more preferably a size of 70 to 150 nm. , but is not limited thereto.
상기 세포외 소포는 미세 소포(microvesicle), 나노 소포(nanovesicle) 또는 엑소좀(exosome) 등을 포함하는 개념이다.The extracellular vesicle is a concept including microvesicles, nanovesicles, or exosomes.
상기 세포외 소포는 락토바실러스(Lactobacillus) 속, 류코노스톡(Leuconostoc) 속, 페디오코커스(Pediococcus) 속, 락토코커스(Lactococcus) 속, 스트렙토코커스(Streptococcus) 속, 에어로코커스(Aerococcus) 속, 카르노박테리움(Carnobacterium) 속, 엔테로코커스(Enterococcus) 속, 오에노코커스(Oenococcus) 속, 비피도박테리움 (Bifidobacterium) 속, 스포로락토바실러스(Sporolactobacillus) 속, 테트라제노코커스(Tetragenococcus) 속, 바고코커스(Vagococcus) 속, 바이셀라(Weisella), 프로피오니박테리움(Propionibacterium) 속, 페디오코커스(Pediococcus) 속, 스타필로코커스(Staphylococcus) 속, 펩토스트레포코커스(Peptostrepococcus) 속, 바실러스(Bacillus) 속, 미크로코커스(Micrococcus) 속, 리스테리아(Listeria) 속, 에스케리치아(Escherichia) 속, 데바로마이세스(Debaromyces) 속, 칸디다(Candida) 속, 사카로마이세스(Saccharomyces) 속, 피치아(Pichia) 속, 토룰롭시스(Torulopsis) 속, 아스퍼질러스(Aspergillus) 속, 리조푸스(Rhizopus) 속, 뮤코(Mucor) 속, 페니실리움(Penicillium) 속, 박테로이데스(Bacteroides) 속, 클로스트리디움(Clostridium) 속, 푸소박테리움(Fusobacterium) 속 및 멜리소코커스(Melissococcus) 속으로 이루어진 군에서 선택되는 어느 하나 이상으로부터 유래된 것일 수 있다.The extracellular vesicles are Lactobacillus, Leuconostoc, Pediococcus, Lactococcus, Streptococcus, Aerococcus, Carno Genus Carnobacterium, Genus Enterococcus, Genus Oenococcus, Genus Bifidobacterium, Genus Sporolactobacillus, Genus Tetragenococcus, Genus Bagococcus (Vagococcus), Weisella, Propionibacterium, Pediococcus, Staphylococcus, Peptostrepococcus, Bacillus , Micrococcus, Listeria, Escherichia, Debaromyces, Candida, Saccharomyces, Pichia ), Torulopsis, Aspergillus, Rhizopus, Mucor, Penicillium, Bacteroides, Clostri It may be derived from any one or more selected from the group consisting of the genus Clostridium, the genus Fusobacterium, and the genus Melissococcus.
상기 세포외 소포의 구체적인 예로서, 바실러스 세레우스(Bacillus cereus), 바실러스 리케니포르미스(Bacillus licheniformis), 바실러스 서브틸리스(Bacillus Subtilis), 비피도박테리움 비피덤(Bifidobacterium bifidum), 비피도박테리움 인팬티스(Bifidobacterium infantis), 비피도박테리움 롱검(Bifidobacterium longum), 비피도박테리움 락티스(Bifidobacterium lactis), 비피도박테리움 애니몰리스(Bifidobacterium animalis), 엔테로코쿠스 패시움(Enterococcus Faecium), 엔테로코쿠스 패칼리스(Enterococcus Faecalis), 락토바실러스 애시도필러스(Lactobacillus acidopilus), 락토바실러스 케피르그라넘(Lactobacillus kefirgranum), 락토바실러스 케피라노팍시엔스(Lactobacillus kefiranofaciens), 락토바실러스 케피리(Lactobacillus kefiri), 락토바실러스 알리멘타리우스(Lactobacillus alimentarius), 락토바실러스 불가리쿠스(Lactobacillus bulgaricus), 락토바실러스 카세이(Lactobacillus casei), 락토바실러스 쿠르바투스(Lactobacillus curvatus), 락토바실러스 델브루키이(Lactobacillus delbrukii), 락토바실러스 존소니(Lactobacillus johnsonii), 락토바실러스 파르시미누스(Lactobacillus farciminus), 락토바실러스 가세리(Lactobacillus gasseri), 락토바실러스 헬베티쿠스(Lactobacillus helveticus), 락토바실러스 람노서스(Lactobacillus rhamnosus), 락토바실러스 레우테리(Lactobacillus reuteri), 락토바실러스 사케이(Lactobacillus sakei), 락토바실러스 락티스(Lactococcus lactis), 락토바실러스 브레비스(Lactobacillus brevis), 락토바실러스 플란타룸(Lactobacillus plantarum), 락토바실러스 펜토서스(Lactobacillus pentosus), 락토바실러스 김치(Lactobacillus kimchi), 락토바실러스 컨푸수스(Lactobacillus confusus), 락토바실러스 쿠르바투스(Lactobacillus curvatus), 스트렙토코쿠스 패시움(Streptococcus faecium), 스트렙토코쿠스 패칼리스(Streptococcus faecalis), 스트렙토코쿠스 아가락티애(Streptococcus agalactiae), 스트렙토코쿠스 뮤탄스(Streptococcus mutans), 스트렙토코쿠스 써모필러스(Streptococcus thermophilus), 스트렙토코쿠스 락티스(Streptococcus lactis), 바이셀라 컨푸사(Weissella confusa), 바이셀라 코리엔시스(Weissella koreensis), 바이셀라 김치(Weissella kimchii), 바이셀라 시바리아(Weissella cibaria), 바이셀라 비리데스켄스(Weissella viridescens), 페디오코커스 아시딜락티시(Pediococcus acidilactici), 페디오코커스 펜토사세우스(Pediococcus pentosaceus), 페디오코커스 아시딜락티시(Pediococcus acidilactici), 페디오코커스 할로필러스(Pediococcus halophilus), 스타필로코커스 카르노서스(Staphylococcus carnosus), 스타필로코커스 자일로서스(Staphylococcus xylosus), 스타필로코커스 아우레우스(Staphylococcus aureus), 에스케리치아 콜라이(Escherichia coli), 테트라제노코커스 할로필러스(Tetragenococcus halophilus), 사카로마이세스 세레비지애(Sacharomyces cerevisiae), 사카로마이세스 세르바찌(Saccharomyces servazzii), 사카로마이세스 보울라디(Saccharomyces boulardii) 및 리스테리아 모노사이토젠스(Listeria monocytogens) 등일 수 있으나, 이에 제한되는 것은 아니다. Specific examples of the extracellular vesicles include Bacillus cereus, Bacillus licheniformis, Bacillus Subtilis, Bifidobacterium bifidum, and Bifidobacter Bifidobacterium infantis, Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium animalis, Enterococcus Faecium ), Enterococcus Faecalis, Lactobacillus acidopilus, Lactobacillus kefirgranum, Lactobacillus kefiranofaciens, Lactobacillus kefiri ( Lactobacillus kefiri), Lactobacillus alimentarius, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus curvatus, Lactobacillus delbrukii , Lactobacillus johnsonii, Lactobacillus farciminus, Lactobacillus gasseri, Lactobacillus helveticus, Lactobacillus rhamnosus, Lactobacillus Lactobacillus reuteri, Lactobacillus sakei, lac Lactococcus lactis, Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus pentosus, Lactobacillus kimchi, Lactobacillus confusus confusus), Lactobacillus curvatus, Streptococcus faecium, Streptococcus faecalis, Streptococcus agalactiae, Streptococcus mutans ( Streptococcus mutans), Streptococcus thermophilus, Streptococcus lactis, Weissella confusa, Weissella koreensis, Weissella kimchii , Weissella cibaria, Weissella viridescens, Pediococcus acidilactici, Pediococcus pentosaceus, Pediococcus acidilactici Pediococcus acidilactici, Pediococcus halophilus, Staphylococcus carnosus, Staphylococcus xylosus, Staphylococcus aureus, S Escherichia coli, Tetragenococcus halophilus, Saccharomyces cerevisiae (Sa charomyces cerevisiae), Saccharomyces servazzii, Saccharomyces boulardii, and Listeria monocytogens, but are not limited thereto.
본 발명에서의 염증성 질환은 아토피 피부염, 여드름, 건선, 부비동염, 비염, 결막염, 천식, 피부염, 염증성 콜라겐 혈관질환, 사구체신염, 뇌염, 염증성 장염, 과민성 대장 증후군, 만성 폐쇄성 폐질환, 패혈증, 패혈성 쇼크증, 폐섬유증, 관절염, 염증성 골용해, 바이러스 또는 박테리아 감염에 의한 만성 염증질환, 염증성 장 질환, 관절염, 류마티스 관절염, 반응성 관절염, 골관절염, 공피증, 골다공증, 아테롬성 동맥경화증, 심근염, 심내막염, 심낭염, 낭성 섬유증, 하시모토 갑상선염, 그레이브스병, 나병, 매독, 라임병(Lyme disease), 보렐리아증(Borreliosis), 신경성-보렐리아증, 결핵, 사르코이드증(Sarcoidosis), 루프스, 동창성 루프스, 결핵성 루프스, 루프스 신염, 전신성 홍반성 루프스, 황반변성, 포도막염, 과민대장 증후군, 섬유근통, 만성피로 증후군, 만성피로 면역부전 증후군, 근육통성 뇌척수염, 근위축성 측삭경화증, 파키슨병, 및 다발성경화증, 자가면역질환 등을 포함할 수 있고, 바람직하게는 염증성 장 질환 또는 자가면역질환일 수 있으나 이에 제한되는 것은 아니다.Inflammatory diseases in the present invention include atopic dermatitis, acne, psoriasis, sinusitis, rhinitis, conjunctivitis, asthma, dermatitis, inflammatory collagen vascular disease, glomerulonephritis, encephalitis, inflammatory enteritis, irritable bowel syndrome, chronic obstructive pulmonary disease, sepsis, septic Shock, pulmonary fibrosis, arthritis, inflammatory osteolysis, chronic inflammatory diseases caused by viral or bacterial infection, inflammatory bowel disease, arthritis, rheumatoid arthritis, reactive arthritis, osteoarthritis, scleroderma, osteoporosis, atherosclerosis, myocarditis, endocarditis, pericarditis , Cystic fibrosis, Hashimoto's thyroiditis, Graves' disease, leprosy, syphilis, Lyme disease, Borreliosis, neurogenic-borreliosis, tuberculosis, sarcoidosis, lupus, lupus lupus, lupus tuberculosis, Lupus nephritis, systemic lupus erythematosus, macular degeneration, uveitis, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, chronic fatigue immunodeficiency syndrome, myalgic encephalomyelitis, amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, autoimmune diseases, etc. It may include, preferably may be inflammatory bowel disease or autoimmune disease, but is not limited thereto.
상기 염증성 장 질환은 크론병, 베체트병, 궤양성 대장염, 출혈성 직장 궤양, 회장 낭염 또는 이에 수반되는 장 병변 등을 포함한다.The inflammatory bowel disease includes Crohn's disease, Behçet's disease, ulcerative colitis, hemorrhagic rectal ulcer, ileal pouchitis or accompanying intestinal lesions, and the like.
상기 자가면역질환은 쇼그렌 증후군, 피부 근염, 아토피 피부염, 건선, 백반증, 원형탈모증, 제1형당뇨병, 자가면역 췌장염, 갑상선 기능이상증, 애디슨 씨병, 부신피질 분비 부전증, 다발성 경화증, 중증 근무력증, 천식, 류마티스 관절염, 결절다발 동맥염, 특발성 혈소판 감소성 자반병, 용혈성 빈혈, 항인지질 항체 증후군, 악성 빈혈, 셀리악 병, 자가면역 간염, 원발성 담증성 간경변 등을 포함할 수 있으나, 이에 제한되는 것은 아니다. The autoimmune diseases include Sjogren's syndrome, dermatomyositis, atopic dermatitis, psoriasis, vitiligo, alopecia areata, type 1 diabetes, autoimmune pancreatitis, thyroid dysfunction, Addison's disease, adrenocortical insufficiency, multiple sclerosis, myasthenia gravis, asthma, Rheumatoid arthritis, polyarteritis nodosa, idiopathic thrombocytopenic purpura, hemolytic anemia, antiphospholipid antibody syndrome, pernicious anemia, celiac disease, autoimmune hepatitis, primary biliary cirrhosis, etc. may be included, but is not limited thereto.
본 발명에 따른 약학 조성물은 유효성분인 세포외 소포 외에 약학적으로 허용되는 담체, 결합제, 활탁제, 붕해제, 부형제, 가용화제, 분산제, 안정화제, 현탁화제 등을 추가적으로 더 포함할 수 있고, 예를 들면 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말디톨, 전분, 알지네이트, 칼슘 포스페이트, 칼슘 실리케이트, 말토덱스트린, 이산화규소, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐피롤리돈, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 등일 수 있으나 이에 제한되는 것은 아니다.The pharmaceutical composition according to the present invention may further include a pharmaceutically acceptable carrier, binder, lubricant, disintegrant, excipient, solubilizer, dispersant, stabilizer, suspending agent, etc. Examples include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, alginate, calcium phosphate, calcium silicate, maltodextrin, silicon dioxide, cellulose, methyl cellulose, microcrystalline cellulose, poly It may be vinylpyrrolidone, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, etc., but is not limited thereto.
또한, 상기 약학 조성물은 당 업계에서 제제화에 통상적으로 사용되는 방법으로 정제, 캡슐, 서방형 제제, 엘릭서, 서스펜션, 시럽, 웨이퍼, 단위 투약 주사제 앰플, 현탁액 등의 제형으로 제조될 수 있다.In addition, the pharmaceutical composition may be prepared in a formulation such as a tablet, capsule, sustained-release preparation, elixir, suspension, syrup, wafer, unit dose injection ampoule, suspension, etc. by a method commonly used for formulation in the art.
상기 약학 조성물의 투여 방식은 경구 투여, 정맥내 투여, 근육내 투여, 동맥내 투여, 골수내 투여, 경막내 투여, 심장내 투여, 경피 투여, 피하 투여, 복강내 투여, 비강내 투여, 장관 투여, 구강 및 설하는 포함하는 국소 투여, 직장 투여, 국소 투여, 진피 투여, 점막 투여, 척추내 투여 등의 방법으로 투여될 수 있고, 바람직하게는 경구 투여일 수 있으나, 이에 제한되는 것은 아니다. The administration method of the pharmaceutical composition is oral administration, intravenous administration, intramuscular administration, intraarterial administration, intramedullary administration, intrathecal administration, intracardiac administration, transdermal administration, subcutaneous administration, intraperitoneal administration, intranasal administration, enteral administration , It may be administered by methods such as topical administration, rectal administration, topical administration, dermal administration, mucosal administration, intravertebral administration, including oral and sublingual administration, preferably oral administration, but is not limited thereto.
또한, 상기 투여 시 각 투여 방식에 적절한 제형으로 제제화되어 투여될 수 있으며, 제제화는 당 업계에서 널리 알려져 있는 방법으로 제제화될 수 있다.In addition, at the time of administration, it may be formulated and administered in a formulation suitable for each administration method, and the formulation may be formulated by a method widely known in the art.
상기 약학 조성물은 투여 대상의 연령, 체중, 건강 상태, 성별, 투여시간, 투여 경로, 배출율, 약물 배합 및 예방 또는 치료될 특정 질환의 중증을 포함한 여러 요인에 따라 적절하게 선택될 수 있고, 투여 횟수는 1일 1회 또는 2회, 격일마다, 격주마다, 격월 등의 방식으로 투여할 수 있다.The pharmaceutical composition may be appropriately selected according to various factors including the age, weight, health condition, sex, administration time, route of administration, excretion rate, drug combination and severity of a specific disease to be prevented or treated, and the number of administrations. can be administered once or twice a day, every other day, every other week, every other month, etc.
상기 화장료 조성물은 토너, 미스트, 로션, 에센스, 앰플, 크림, 비누, 클렌징폼, 클렌징 오일, 클렌징 워터, 샴푸, 린스, 트리트먼트, 두피 세정제 등의 다양한 형태로 제조될 수 있다. The cosmetic composition may be prepared in various forms such as toner, mist, lotion, essence, ampoule, cream, soap, cleansing foam, cleansing oil, cleansing water, shampoo, rinse, treatment, and scalp cleanser.
또한, 상기 화장료 조성물은 유효성분인 세포외 소포 외에 당 업계에서 화장품을 제조하기 위해 통상적으로 사용하는 용매, 담체, 부형제, 희석제, 증점제, 항산화제, 점도 안정제 등과 같은 첨가제를 추가적으로 더 포함할 수 있다.In addition, the cosmetic composition may additionally include additives such as solvents, carriers, excipients, diluents, thickeners, antioxidants, viscosity stabilizers, etc. commonly used in the art to manufacture cosmetics in addition to the active ingredient, extracellular vesicles. .
상기 식품 조성물은 음료, 껌, 차, 비타민 복합제, 분말, 과립, 정제, 캡슐, 과자, 등의 형태로 제조될 수 있다. The food composition may be prepared in the form of beverages, gum, tea, vitamin complexes, powders, granules, tablets, capsules, confectionery, and the like.
또한, 상기 식품 조성물은 유효성분인 세포외 소포 외에 당 업계에서 식품을 제조하기 위해 통상적으로 사용하는 향미제, 풍미제, 안정화제, 증점제, 방부제 등을 추가적으로 더 포함할 수 있다.In addition, the food composition may further include flavoring agents, flavoring agents, stabilizers, thickeners, preservatives, etc. commonly used in the art for preparing food in addition to extracellular vesicles as active ingredients.
본 발명은 miRNA를 지표 성분으로 포함하는 세포외 소포를 제공할 수 있고, 상기 세포외 소포를 유효성분으로 포함하는 염증 질환의 예방, 개선 또는 치료용 약학적 조성물을 제공할 수 있다. 특히, 본 발명은 합성의약품보다 부작용은 낮으면서 염증성 질환의 예방, 개선 또는 치료 효과가 뛰어난 약학적 조성물, 염증 질환의 예방 또는 개선용 화장료 조성물 및 염증 질환의 예방 또는 개선용 식품 조성물을 제공할 수 있다.The present invention can provide extracellular vesicles containing miRNA as an indicator component, and a pharmaceutical composition for preventing, improving or treating inflammatory diseases containing the extracellular vesicles as an active ingredient. In particular, the present invention can provide a pharmaceutical composition with excellent preventive, ameliorative or therapeutic effects of inflammatory diseases with lower side effects than synthetic drugs, a cosmetic composition for preventing or improving inflammatory diseases, and a food composition for preventing or improving inflammatory diseases. there is.
이하, 본 발명을 실시예 및 실험예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail by examples and experimental examples.
단, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예 및 실험예에 한정되는 것은 아니다.However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the contents of the present invention are not limited to the following Examples and Experimental Examples.
<실시예 1 내지 6> 세포외 소포의 분리<Examples 1 to 6> Separation of extracellular vesicles
락토바실러스 케피르그라넘 및 락토바실러스 케피라노팍시엔스(Lactobacillus kefiranofaciens), 락토바실러스 케피리(Lactobacillus kefiri), 바이셀라 코리엔시스(Weissella koreensis), 테트라제노코커스 할로필러스(Tetragenococcus halophilus) 및 비피도박테리움 애니몰리스(Bifidobacterium animalis)의 균주로부터 하기의 방법으로 세포외 소포를 분리하였다. Lactobacillus kefirgranum and Lactobacillus kefiranofaciens, Lactobacillus kefiri, Weissella koreensis, Tetragenococcus halophilus and Bifidobacter Extracellular vesicles were isolated from Bifidobacterium animalis strains by the following method.
(단계 1) 배양된 락토바실러스 속 균주의 배양액을 4℃에서 3,000 ×g으로 20분 동안 원심분리하여 배양액으로부터 락토바실러스 속 균주를 분리 및 제거하였다. 즉, 저속의 원심분리 공정을 통해 세포와 상등배양액을 분리하였다.(Step 1) The cultured Lactobacillus genus strain was centrifuged at 4° C. at 3,000 × g for 20 minutes to isolate and remove the Lactobacillus genus strain from the culture solution. That is, the cells and the supernatant culture were separated through a low-speed centrifugation process.
(단계 2) 상기 단계 1에서 원심분리된 배양액을 고속원심분리기를 이용하여 4℃에서 10,000 ×g으로 20분 동안 원심분리하여 추가적으로 세포 또는 세포 관련 잔해 및 잔여물 등을 제거하였다.(Step 2) The culture solution centrifuged in step 1 was centrifuged for 20 minutes at 10,000 × g at 4° C. using a high-speed centrifuge to further remove cells or cell-related debris and debris.
(단계 3) 상기 단계 2에서 원심분리된 배양액을 0.45 ㎛ 바틀 탑 필터를 통해 여과함으로써 배양액의 순도를 증가시켰다.(Step 3) The culture solution centrifuged in step 2 was filtered through a 0.45 μm bottle top filter to increase the purity of the culture solution.
(단계 4) 상기 단계 3에서 여과한 배양액을 4℃에서 110,000 ×g으로 1 시간 10분 동안 초고속원심분리하여 세포 외 소포를 분리하였다.(Step 4) Extracellular vesicles were separated by ultra-high-speed centrifugation for 1 hour and 10 minutes at 110,000 ×g at 4°C for the culture medium filtered in step 3.
(단계 5) 상기 단계 4에서 초고속원심분리 후 상등액을 제거하고 남은 세포외 소포 펠릿(pellet)을 완충용액(HEPES 버퍼)에 재현탁시켜 세포외 소포를 수득하였다.(Step 5) After ultra-high-speed centrifugation in step 4, the supernatant was removed, and the remaining extracellular vesicle pellet was resuspended in a buffer solution (HEPES buffer) to obtain extracellular vesicles.
<실험예 1> 세포외 소포의 지표 성분 선정<Experimental Example 1> Selection of indicator component of extracellular vesicles
실시예 1 내지 6에서 분리한 세포 외 소포의 지표성분을 분석하기 위해 다음과 같이 실험을 진행하였다. In order to analyze the marker component of the extracellular vesicles isolated in Examples 1 to 6, the experiment was conducted as follows.
RNA는 RNA Bioanalyzer pico 6000 chip을 이용하여 RNA-seq 수행업체에 의뢰하여 QC 진행 후 Illumina smarter kit로 라이브러리를 제작했다. RNA-seq은 크기 분할(size fractionation)을 통하여 20nt 사이즈의 유전체(genome)에 어댑터 결합 (adaptor ligation), RT-PCR 방법으로 증폭 후 Hi-seq으로 시퀀싱(sequencing)하였다. 실험 결과를 바탕으로 하여 상기 세포 외 소포들의 지표성분은 mir-192, mir-10523으로 선정하였다. RNA was requested to an RNA-seq performer using an RNA Bioanalyzer pico 6000 chip, and after QC, a library was produced with an Illumina smarter kit. RNA-seq was amplified by adapter ligation and RT-PCR to a 20nt genome through size fractionation, followed by sequencing by Hi-seq. Based on the experimental results, mir-192 and mir-10523 were selected as marker components of the extracellular vesicles.
<실험예2> miRNA 포함 여부에 따른 세포외 소포의 항염증 효과 평가<Experimental Example 2> Evaluation of anti-inflammatory effects of extracellular vesicles according to miRNA inclusion
본 발명에 따른 세포외 소포의 항염증 효과를 평가하기 위해 실시예 1-6의 mir-192, mir-10523를 포함하는 세포외 소포를 이용하여 IL-6억제능을 실험하였다. 구체적인 방법은 다음과 같다.In order to evaluate the anti-inflammatory effect of the extracellular vesicles according to the present invention, the IL-6 inhibitory ability was tested using the extracellular vesicles containing mir-192 and mir-10523 of Examples 1-6. The specific method is as follows.
마우스의 대식 세포인 Raw246.7 세포를 10% FBS 및 1% 페니실린-스트렙토마이신이 포함된 DMEM 배지에서 24시간 동안 배양시킨 후 수득한 세포외 소포를 동결건조시킨 샘플을 제작하였다. 상기 샘플1 mg/ml을 LPS(100 ng/ml)와 동시 처리하여 24시간 동안 배양시키고, ELISA를 이용하여 IL-6의 발현 수준을 측정하였다. 단, 양성 대조군으로는 커큐민(Curcumin)을 10μM로 처리하였다.Raw246.7 cells, which are mouse macrophages, were cultured in DMEM medium containing 10% FBS and 1% penicillin-streptomycin for 24 hours, and then freeze-dried extracellular vesicles were prepared to prepare samples. 1 mg/ml of the sample was simultaneously treated with LPS (100 ng/ml) and cultured for 24 hours, and the expression level of IL-6 was measured using ELISA. However, as a positive control, curcumin was treated with 10 μM.
비교예 1 내지 6은 상기 실시예 1 내지 6과 동일하되, mir-192, mir-10523와 같은 miRNA를 전혀 포함하지 않는 세포외 소포로 선정하였다.Comparative Examples 1 to 6 were the same as Examples 1 to 6, but extracellular vesicles that did not contain miRNAs such as mir-192 and mir-10523 were selected.
실험결과, 본 발명에 따른 mir-192, mir-10523를 포함하는 실시예 1 내지 6의 세포외 소포는 비교예 1 대비 IL-6 억제능이 우수한 것으로 나타났다. 추가적으로 실시예 1 내지 6 중에서는 락토바실러스 케피르그라넘 균주 유래 세포외 소포의 IL-6 억제능이 다른 균주 유래 세포외 소포 대비 우수한 것으로 나타났다.As a result of the experiment, the extracellular vesicles of Examples 1 to 6 containing mir-192 and mir-10523 according to the present invention showed superior IL-6 inhibitory activity compared to Comparative Example 1. Additionally, in Examples 1 to 6, the IL-6 inhibitory ability of extracellular vesicles derived from Lactobacillus kefirgranum strains was superior to that of extracellular vesicles derived from other strains.
Claims (9)
let-7a-1; let-7a-2; let-7a-3; let-7a-5p; let-7b; let-7b-5p; let-7c; let-7c-5p; let-7d; let-7d-5p; let-7e; let-7e-5p; let-7f-1; let-7f-1-3p; let-7f-2; let-7f-5p; let-7g; let-7g-5p; let-7i; let-7i-3p; mir-1-1; mir-1-2; mir-1-3p; mir-7-1; mir-7-2; mir-7-3; mir-9-1; mir-9-2; mir-9-3; mir-10a; mir-10a-3p; mir-10a-5p; mir-10b; mir-15a; mir-15b; mir-16-1; mir-16-2; mir-17; mir-17-3p; mir-17-5p; mir-18a; mir-18b; mir-19a; mir-19b-1; mir-19b-2; mir-20a; mir-20b; mir-21; mir-21-5p; mir-22; mir-22-3p; mir-23a; mir-23b; mir-23b-3p; mir-23c; mir-24-1; mir-24-2; mir-24-3; mir-24-3p; mir-25; mir-26a-1; mir-26a-2; mir-26a-5p; mir-26b; mir-26b-5p; mir-27a; mir-27b; mir-27b-3p; mir-28; mir-29a; mir-29b-1; mir-29b-2; mir-29c; mir-30a; mir-30a-5p; mir-30b; mir-30c-1; mir-30c-2; mir-30c-5p; mir-30d; mir-30e; mir-30e-5p; mir-31; mir-32; mir-33a; mir-33b; mir-34a; mir-34b; mir-34c; mir-92a-1; mir-92a-2; mir-92a-3p; mir-92b; mir-93; mir-93-5p; mir-95; mir-96; mir-98; mir-99a; mir-99b; mir-99b-5p; mir-100; mir-101-1; mir-101-2; mir-103a; mir-103a-1; mir-103a-2; mir-103a-3p; mir-103-1; mir-103-1-as; mir-103-2; mir-103-2-as; mir-105-1; mir-105-2; mir-106a; mir-106b; mir-106b-3p; mir-107; mir-122; mir-124-1; mir-124-2; mir-124-3; mir-125a; mir-125b-1; mir-125b-2; mir-125b-2-3p; mir-126; mir-126-3p; mir-127; mir-128-1; mir-128-2; mir-129-1; mir-129-2; mir-130a; mir-130b; mir-132; mir-132; mir-133a-1; mir-133a-2; mir-133a-3p; mir-133b; mir-134; mir-135a-1; mir-135a-2; mir-135b; mir-136; mir-137; mir-137-3p; mir-138-1; mir-138-2; mir-139; mir-140; mir-141; mir-142; mir-143; mir-143-3p; mir-144; mir-145; mir-146a; mir-146b; mir-147; mir-147b; mir-148a; mir-148b; mir-149; mir-150; mir-151; mir-152; mir-153-1; mir-153-2; mir-154; mir-155; mir-181a-1; mir-181a-2; mir-181a-5p; mir-181b-1; mir-181b-2; mir-181b-5p; mir-181c; mir-181d; mir-182; mir-183; mir-184; mir-185; mir-186; mir-187; mir-188; mir-190; mir-190b; mir-191; mir-192; mir-192-3p; mir-192-5p; mir-193a; mir-193b; mir-194-1; mir-194-2; mir-195; mir-196a-1; mir-196a-2; mir-196b; mir-197; mir-198; mir-199a-1; mir-199a-2; mir-199a-3p; mir-199b; mir-199b-3p; mir-200a; mir-200b; mir-200c; mir-200c-5p; mir-202; mir-203; mir-204; mir-205; mir-206; mir-208a; mir-208b; mir-208b-3p; mir-208b-5p; mir-210; mir-211; mir-212; mir-214; mir-215; mir-216a; mir-216b; mir-217; mir-217-5p; mir-218-1; mir-218-2; mir-218-5p; mir-219; mir-219b; mir-219-1; mir-219-2; mir-221; mir-222; mir-222-3p; mir-223; mir-224; mir-296; mir-297; mir-298; mir-299; mir-300; mir-301a; mir-301b; mir-302a; mir-302b; mir-302c; mir-302d; mir-302e; mir-302f; mir-320a; mir-320b-1; mir-320b-2; mir-320c-1; mir-320c-2; mir-320d-1; mir-320d-2; mir-320e; mir-323; mir-323b; mir-324; mir-325; mir-326; mir-328; mir-329-1; mir-329-2; mir-330; mir-331; mir-335; mir-337; mir-338; mir-339; mir-340; mir-342; mir-342-3p; mir-345; mir-346; mir-361; mir-362; mir-363; mir-365a; mir-365b; mir-365-1; mir-365-2; mir-367; mir-367-3p; mir-367-5p; mir-369; mir-370; mir-37; mir-372; mir-373; mir-374a; mir-374b; mir-374c; mir-375; mir-376a-1; mir-376a-2; mir-376b; mir-376c; mir-377; mir-378; mir-378a; mir-378a-3p; mir-378b; mir-378c; mir-379; mir-380; mir-381; mir-382; mir-383; mir-384; mir-409; mir-410; mir-411; mir-412; mir-412-5p; mir-421; mir-422a; mir-423; mir-424; mir-425; mir-429; mir-431; mir-432; mir-433; mir-448; mir-449a; mir-449b; mir-449c; mir-449c-5p; mir-450a-1; mir-450a-2; mir-450b; mir-451; mir-452; mir-454; mir-455; mir-466; mir-483; mir-484; mir-485; mir-486; mir-486-1; mir-486-2; mir-486-5p; mir-487a; mir-487b; mir-487b-3p; mir-488; mir-489; mir-489-3p; mir-490; mir-491; ,mir-492; mir-493; mir-494; mir-495; mir-496; mir-497; mir-498; mir-499; mir-499b; mir-499b-5p; mir-500a; mir-500b; mir-501; mir-502; mir-503; mir-504; mir-505; mir-506; mir-507; mir-508; mir-509-1; mir-509-2; mir-509-3; mir-509-5p; mir-510; mir-511-1; mir-511-2; mir-512-1; mir-512-2; mir-513a-1; mir-513a-2; mir-513b; mir-513c; mir-514-1; mir-514-2; mir-514-3; mir-514b; mir-515-1; mir-515-2; mir-516a-1; mir-516a-2; mir-516b-1; mir-516b-2; mir-517a; mir-517b; mir-517c; mir-518a-1; mir-518a-2; mir-518b; mir-518c; mir-518d; mir-518e; mir-518f; mir-519a-1; mir-519a-2; mir-519b; mir-519c; mir-519d; mir-519e; mir-520a; mir-520b; mir-520c; mir-520d; mir-520e; mir-520f; mir-520g; mir-520h; mir-521-1; mir-521-2; mir-522; mir-523; mir-524; mir-525; mir-526a-1; mir-526a-2; mir-526b; mir-527; mir-532; mir-539; mir-541; mir-542; mir-543; mir-544; mir-544b; mir-545; mir-548a-1; mir-548a-2; mir-548a-3; mir-548aa-1; mir-548aa-2; mir-548aq; mir-548b; mir-548c; mir-548d-1; mir-548d-2; mir-548e; mir-548f-1; mir-548f-2; mir-548f-3; mir-548f-4; mir-548f-5; mir-548g; mir-548h-1; mir-548h-2; mir-548h-3; mir-548h-4; mir-548i-1; mir-548i-2; mir-548i-3; mir-548i-4; mir-548j; mir-548k; mir-548l; mir-548m; mir-548n; mir-548o; mir-548p; mir-548s; mir-548t; mir-548u; mir-548v; mir-548w; mir-548x; mir-548y; mir-548z; mir-549; mir-550a-1; mir-550a-2; mir-550a-3; mir-550b-1; mir-550b-2; mir-551a; mir-551b; mir-552; mir-553; mir-554; mir-555; mir-556; mir-557; mir-558; mir-559; mir-561; mir-562; mir-563; mir-564; mir-566; mir-567; mir-568; mir-569; mir-570; mir-571; mir-572; mir-573; mir-574; mir-575; mir-576; mir-577; mir-578; mir-579; mir-580; mir-581; mir-582; mir-583; mir-584; mir-584-3p; mir-584-5p; mir-585; mir-586; mir-587; mir-588; mir-589; mir-590; mir-591; mir-592; mir-593; mir-595; mir-596; mir-597; mir-598; mir-599; mir-600; mir-601; mir-602; mir-603; mir-604; mir-605; mir-606; mir-607; mir-608; mir-609; mir-610; mir-611; mir-612; mir-613; mir-614; mir-615; mir-616; mir-617; mir-618; mir-619; mir-620; mir-621; mir-622; mir-623; mir-624; mir-625; mir-626; mir-627; mir-628; mir-629; mir-630; mir-631; mir-632; mir-633; mir-634; mir-635; mir-636; mir-637; mir-638; mir-639; mir-640; mir-641; mir-642a; mir-642b; mir-643; mir-644; mir-645; mir-646; mir-647; mir-648; mir-649; mir-650; mir-651; mir-652; mir-653; mir-654; mir-655; mir-656; mir-657; mir-658; mir-659; mir-660; mir-661; mir-662; mir-663; mir-663a; mir-663b; mir-664; mir-665; mir-668; mir-670; mir-671; mir-675; mir-676; mir-708; mir-711; mir-718; mir-720; mir-744; mir-758; mir-759; mir-760; mir-761; mir-762; mir-764; mir-765; mir-766; mir-767; mir-769; mir-770; mir-802; mir-873; mir-874; mir-875; mir-876; mir-877; mir-885; mir-887; mir-888; mir-889; mir-890; mir-891a; mir-891b; mir-892a; mir-892b; mir-920; mir-921; mir-922; mir-924; mir-933; mir-934; mir-935; mir-936; mir-937; mir-938; mir-939; mir-940; mir-941-1; mir-941-2; mir-941-3; mir-941-4; mir-942; mir-942-3p; mir-943; mir-944; mir-1178; mir-1179; mir-1180; mir-1181; mir-1182; mir-1183; mir-1184-1; mir-1184-2; mir-1184-3; mir-1185-1; mir-1185-2; mir-1193; mir-1197; mir-1200; mir-1202; mir-1203; mir-1204; mir-1205; mir-1206; mir-1207; mir-1208; mir-1224; mir-1225; mir-1226; mir-1227; mir-1228; mir-1229; mir-1231; mir-1233-1; mir-1233-2; mir-1234; mir-1236; mir-1236-5p; mir-1237; mir-1238; mir-1243; mir-1244-1; mir-1244-2; mir-1244-3; mir-1245; mir-1246; mir-1247; mir-1248; mir-1249; mir-1250; mir-1251; mir-1251-3p; mir-1252; mir-1253; mir-1254; mir-1255a; mir-1255b-1; mir-1255b-2; mir-1256; mir-1257; mir-1258; mir-1260; mir-1260b; mir-1261; mir-1262; mir-1263; mir-1264; mir-1265; mir-1266; mir-1267; mir-1268a; mir-1269; mir-1270-1; mir-1270-2; mir-1271; mir-1272; mir-1273; mir-1273c; mir-1273d; mir-1273e; mir-1274a; mir-1274b; mir-1275; mir-1276; mir-1277; mir-1278; mir-1279; mir-1280; mir-1281; mir-1282; mir-1283-1; mir-1283-2; mir-1284; mir-1285-1; mir-1285-2; mir-1286; mir-1287; mir-1288; mir-1289-1; mir-1289-2; mir-1290; mir-1291; mir-1292; mir-1293; mir-1294; mir-1295; mir-1296; mir-1297; mir-1298; mir-1299; mir-1301; mir-1302-1; mir-1302-4; mir-1302-10; mir-1302-11; mir-1302-2; mir-1302-3; mir-1302-4; mir-1302-5; mir-1302-6; mir-1302-7; mir-1302-8; mir-1302-9; mir-1303; mir-1304; mir-1305; mir-1306; mir-1307; mir-1321; mir-1322; mir-1323; mir-1324; mir-1468; mir-1469; mir-1470; mir-1471; mir-1537; mir-1538; mir-1539; mir-1825; mir-1827; mir-1908; mir-1909; mir-1909-5p; mir-1910; mir-1911; mir-1912; mir-1913; mir-1914; mir-1915; mir-1972-1; mir-1972-2; mir-1973; mir-1976; mir-2052; mir-2053; mir-2054; mir-2110; mir-2113; mir-2114; mir-2115; mir-2116; mir-2117; mir-2276; mir-2277; mir-2278; mir-2355; mir-2355-3p; mir-2861; mir-2909; mir-3065; mir-3074; mir-3115; mir-3116-1; mir-3116-2; mir-3117; mir-3118-1; mir-3118-2; mir-3118-3; mir-3118-4; mir-3118-5; mir-3118-6; mir-3119-1;mir-3119-2; mir-3120; mir-3121; mir-3122; mir-3123; mir-3124; mir-3125; mir-3126; mir-3127; mir-3128; mir-3129; mir-3130-1; mir-3130-2; mir-3131; mir-3132; mir-3133; mir-3134; mir-3135; mir-3136; mir-3137; mir-3138; mir-3139; mir-3140; mir-3141; mir-3142; mir-3143; mir-3144; mir-3145; mir-3146; mir-3147; mir-3148; mir-3149; mir-3150; mir-3151; mir-3152; mir-3153; mir-3154; mir-3155-a; mir-3155-b; mir-3156-1; mir-3156-2; mir-3156-3; mir-3157; mir-3158-1; mir-3158-2; mir-3158-5p; mir-3159; mir-3160; mir-3160-1; mir-3160-2; mir-3160-5p; mir-3161; mir-3162; mir-3163; mir-3164; mir-3165; mir-3166; mir-3167; mir-3168; mir-3169; mir-3170; mir-3171; mir-3173; mir-3174; mir-3175; mir-3176; mir-3177; mir-3178; mir-3179-1; mir-3179-2; mir-3179-3; mir-3180-1; mir-3180-2; mir-3180-3; mir-3180-4; mir-3180-5; mir-3181; mir-3182; mir-3183; mir-3184; mir-3185; mir-3186; mir-3187; mir-3188; mir-3189; mir-3190; mir-3191; mir-3192; mir-3193; mir-3194; mir-3195; mir-3196; mir-3197; mir-3198; mir-3198-1; mir-3198-2; mir-3199-1; mir-3199-2; mir-3200; mir-3201; mir-3202-1; mir-3202-2; mir-3605; mir-3606; mir-3607; mir-3609; mir-3610; mir-3611; mir-3612; mir-3613; mir-3614; mir-3615; mir-3616; mir-3617; mir-3618; mir-3619; mir-3620; mir-3621; mir-3622a; mir-3622b; mir-3646; mir-3647; mir-3648; mir-3649; mir-3650; mir-3651; mir-3652; mir-3653; mir-3654; mir-3655; mir-3656mir-3657; mir-3658; mir-3659; mir-3660; mir-3661; mir-3662; mir-3663; mir-3664; mir-3665; mir-3666; mir-3667; mir-3668; mir-3669; mir-3670; mir-3670; mir-3671; mir-3671; mir-3673; mir-3673; mir-3675; mir-3675; mir-3676; mir-3663; mir-3677; mir-3678; mir-3679; mir-3680; mir-3681; mir-3682; mir-3683; mir-3684; mir-3685; mir-3686; mir-3687; mir-3688-1; mir-3688-2; mir-3689a; mir-3689b; mir-3689d-1; mir-3689d-2; mir-3689e; mir-3690; mir-3691; mir-3692; mir-3713; mir-3714; mir-3907; mir-3908; mir-3909; mir-3910-1; mir-3910-2; mir-3911; mir-3912; mir-3913-1; mir-3913-2; mir-3913-5p; mir-3914-1; mir-3914-2; mir-3915; mir-3916; mir-3917; mir-3918; mir-3919; mir-3920; mir-3921; mir-3922; mir-3923; mir-3924; mir-3925; mir-3926-1; mir-3926-2; mir-3927; mir-3928; mir-3929; mir-3934; mir-3935; mir-3936; mir-3937; mir-3938; mir-3939; mir-3940; mir-3941; mir-3942; mir-3943; mir-3944; mir-3945; mir-3975; mir-3976; mir-3978; mir-4251; mir-4252; mir-4253; mir-4254; mir-4255; mir-4256; mir-4257; mir-4258; mir-4259; mir-4260; mir-4261; mir-4262; mir-4263; mir-4264; mir-4265; mir-4266; mir-4267; mir-4268; mir-4269; mir-4270; mir-4271; mir-4272; mir-4273; mir-4274; mir-4275; mir-4276; mir-4277; mir-4278; mir-4279; mir-4280; mir-4281; mir-4282; mir-4283-1; mir-4283-2; mir-4284; mir-4285; mir-4286; mir-4287; mir-4288; mir-4289; mir-4290; mir-4291; mir-4292; mir-4293; mir-4294; mir-4295; mir-4296; mir-4297; mir-4298; mir-4299; mir-4300; mir-4301; mir-4302; mir-4303; mir-4304; mir-4305; mir-4306; mir-4307; mir-4308; mir-4309; mir-4310; mir-4311; mir-4312; mir-4313; mir-4314; mir-4315; mir-4315-1; mir-4315-2; mir-4316; mir-4317; mir-4318; mir-4319; mir-4320; mir-4321; mir-4322; mir-4323; mir-4324; mir-4325; mir-4326; mir-4327; mir-4328;mir-4329; mir-4329; mir-4330; mir-4332; mir-4432; mir-4438; mir-4449; mir-4451; mir-4458; mir-4460; mir-4463; mir-4469; mir-4472; mir-4472-1; mir-4479; mir-4482; mir-4482-3p; mir-4482-5p; mir-4490; mir-4493; mir-4507; mir-4509; mir-4509-1; mir-4509-2; mir-4509-3; mir-4511; mir-4526; mir-4536-1; mir-4536-2; mir-4538; mir-4638; mir-4638-3p; mir-4639; mir-4639-3p; mir-4639-5p; mir-4658; mir-4688; mir-4690; mir-4698; mir-4714; mir-4714-5p; mir-4716; mir-4716-3p; mir-4717; mir-4717-5p; mir-4764; mir-4772; mir-4776-1; mir-4787; mir-4787-5p; mir-4788; mir-4800; mir-4800-3p; mir-4803; mir-4804; mir-5187; mir-5187-5p; mir-5188; mir-5190; mir-5192; mir-5194; mir-5583-1; mir-5583-3p; mir-5583-5p; mir-5588; mir-5683; mir-5708; mir-6069; mir-6070; mir-6082; mir-6124; mir-6127; mir-6501; mir-6501-3p; mir-6722; mir-6737; mir-6748; mir-6748-3p; mir-6753; mir-6769a, mir-6769b; mir-6773; mir-6779; mir-6779-5p; mir-6801; mir-6805; mir-6854; mir-6854-5p; mir-6878; mir-6882; mir-6882-5p; mir-7107; mir-7110; mir-7151; mir-7151-5p; mir-7161; mir-7161-5p; mir-7977; mir-8485; mir-9903; mir-10392; mir-10395; mir-10395-3p; mir-10395-5p; mir-10523; mir-12132; mir-12136.The extracellular vesicle according to claim 1, wherein the miRNA is one or more selected from the following:
let-7a-1; let-7a-2; let-7a-3; let-7a-5p; let-7b; let-7b-5p; let-7c; let-7c-5p; let-7d; let-7d-5p; let-7e; let-7e-5p; let-7f-1; let-7f-1-3p; let-7f-2; let-7f-5p; let-7g; let-7g-5p; let-7i; let-7i-3p; mir-1-1; mir-1-2; mir-1-3p; mir-7-1; mir-7-2; mir-7-3; mir-9-1; mir-9-2; mir-9-3; mir-10a; mir-10a-3p; mir-10a-5p; mir-10b; mir-15a; mir-15b; mir-16-1; mir-16-2; mir-17; mir-17-3p; mir-17-5p; mir-18a; mir-18b; mir-19a; mir-19b-1; mir-19b-2; mir-20a; mir-20b; mir-21; mir-21-5p; mir-22; mir-22-3p; mir-23a; mir-23b; mir-23b-3p; mir-23c; mir-24-1; mir-24-2; mir-24-3; mir-24-3p; mir-25; mir-26a-1; mir-26a-2; mir-26a-5p; mir-26b; mir-26b-5p; mir-27a; mir-27b; mir-27b-3p; mir-28; mir-29a; mir-29b-1; mir-29b-2; mir-29c; mir-30a; mir-30a-5p; mir-30b; mir-30c-1; mir-30c-2; mir-30c-5p; mir-30d; mir-30e; mir-30e-5p; mir-31; mir-32; mir-33a; mir-33b; mir-34a; mir-34b; mir-34c; mir-92a-1; mir-92a-2; mir-92a-3p; mir-92b; mir-93; mir-93-5p; mir-95; mir-96; mir-98; mir-99a; mir-99b; mir-99b-5p; mir-100; mir-101-1; mir-101-2; mir-103a; mir-103a-1; mir-103a-2; mir-103a-3p; mir-103-1; mir-103-1-as; mir-103-2; mir-103-2-as; mir-105-1; mir-105-2; mir-106a; mir-106b; mir-106b-3p; mir-107; mir-122; mir-124-1; mir-124-2; mir-124-3; mir-125a; mir-125b-1; mir-125b-2; mir-125b-2-3p; mir-126; mir-126-3p; mir-127; mir-128-1; mir-128-2; mir-129-1; mir-129-2; mir-130a; mir-130b; mir-132; mir-132; mir-133a-1; mir-133a-2; mir-133a-3p; mir-133b; mir-134; mir-135a-1; mir-135a-2; mir-135b; mir-136; mir-137; mir-137-3p; mir-138-1; mir-138-2; mir-139; mir-140; mir-141; mir-142; mir-143; mir-143-3p; mir-144; mir-145; mir-146a; mir-146b; mir-147; mir-147b; mir-148a; mir-148b; mir-149; mir-150; mir-151; mir-152; mir-153-1; mir-153-2; mir-154; mir-155; mir-181a-1; mir-181a-2; mir-181a-5p; mir-181b-1; mir-181b-2; mir-181b-5p; mir-181c; mir-181d; mir-182; mir-183; mir-184; mir-185; mir-186; mir-187; mir-188; mir-190; mir-190b; mir-191; mir-192; mir-192-3p; mir-192-5p; mir-193a; mir-193b; mir-194-1; mir-194-2; mir-195; mir-196a-1; mir-196a-2; mir-196b; mir-197; mir-198; mir-199a-1; mir-199a-2; mir-199a-3p; mir-199b; mir-199b-3p; mir-200a; mir-200b; mir-200c; mir-200c-5p; mir-202; mir-203; mir-204; mir-205; mir-206; mir-208a; mir-208b; mir-208b-3p; mir-208b-5p; mir-210; mir-211; mir-212; mir-214; mir-215; mir-216a; mir-216b; mir-217; mir-217-5p; mir-218-1; mir-218-2; mir-218-5p; mir-219; mir-219b; mir-219-1; mir-219-2; mir-221; mir-222; mir-222-3p; mir-223; mir-224; mir-296; mir-297; mir-298; mir-299; mir-300; mir-301a; mir-301b; mir-302a; mir-302b; mir-302c; mir-302d; mir-302e; mir-302f; mir-320a; mir-320b-1; mir-320b-2; mir-320c-1; mir-320c-2; mir-320d-1; mir-320d-2; mir-320e; mir-323; mir-323b; mir-324; mir-325; mir-326; mir-328; mir-329-1; mir-329-2; mir-330; mir-331; mir-335; mir-337; mir-338; mir-339; mir-340; mir-342; mir-342-3p; mir-345; mir-346; mir-361; mir-362; mir-363; mir-365a; mir-365b; mir-365-1; mir-365-2; mir-367; mir-367-3p; mir-367-5p; mir-369; mir-370; mir-37; mir-372; mir-373; mir-374a; mir-374b; mir-374c; mir-375; mir-376a-1; mir-376a-2; mir-376b; mir-376c; mir-377; mir-378; mir-378a; mir-378a-3p; mir-378b; mir-378c; mir-379; mir-380; mir-381; mir-382; mir-383; mir-384; mir-409; mir-410; mir-411; mir-412; mir-412-5p; mir-421; mir-422a; mir-423; mir-424; mir-425; mir-429; mir-431; mir-432; mir-433; mir-448; mir-449a; mir-449b; mir-449c; mir-449c-5p; mir-450a-1; mir-450a-2; mir-450b; mir-451; mir-452; mir-454; mir-455; mir-466; mir-483; mir-484; mir-485; mir-486; mir-486-1; mir-486-2; mir-486-5p; mir-487a; mir-487b; mir-487b-3p; mir-488; mir-489; mir-489-3p; mir-490; mir-491; ,mir-492; mir-493; mir-494; mir-495; mir-496; mir-497; mir-498; mir-499; mir-499b; mir-499b-5p; mir-500a; mir-500b; mir-501; mir-502; mir-503; mir-504; mir-505; mir-506; mir-507; mir-508; mir-509-1; mir-509-2; mir-509-3; mir-509-5p; mir-510; mir-511-1; mir-511-2; mir-512-1; mir-512-2; mir-513a-1; mir-513a-2; mir-513b; mir-513c; mir-514-1; mir-514-2; mir-514-3; mir-514b; mir-515-1; mir-515-2; mir-516a-1; mir-516a-2; mir-516b-1; mir-516b-2; mir-517a; mir-517b; mir-517c; mir-518a-1; mir-518a-2; mir-518b; mir-518c; mir-518d; mir-518e; mir-518f; mir-519a-1; mir-519a-2; mir-519b; mir-519c; mir-519d; mir-519e; mir-520a; mir-520b; mir-520c; mir-520d; mir-520e; mir-520f; mir-520g; mir-520h; mir-521-1; mir-521-2; mir-522; mir-523; mir-524; mir-525; mir-526a-1; mir-526a-2; mir-526b; mir-527; mir-532; mir-539; mir-541; mir-542; mir-543; mir-544; mir-544b; mir-545; mir-548a-1; mir-548a-2; mir-548a-3; mir-548aa-1; mir-548aa-2; mir-548aq; mir-548b; mir-548c; mir-548d-1; mir-548d-2; mir-548e; mir-548f-1; mir-548f-2; mir-548f-3; mir-548f-4; mir-548f-5; mir-548g; mir-548h-1; mir-548h-2; mir-548h-3; mir-548h-4; mir-548i-1; mir-548i-2; mir-548i-3; mir-548i-4; mir-548j; mir-548k; mir-548l; mir-548m; mir-548n; mir-548o; mir-548p; mir-548s; mir-548t; mir-548u; mir-548v; mir-548w; mir-548x; mir-548y; mir-548z; mir-549; mir-550a-1; mir-550a-2; mir-550a-3; mir-550b-1; mir-550b-2; mir-551a; mir-551b; mir-552; mir-553; mir-554; mir-555; mir-556; mir-557; mir-558; mir-559; mir-561; mir-562; mir-563; mir-564; mir-566; mir-567; mir-568; mir-569; mir-570; mir-571; mir-572; mir-573; mir-574; mir-575; mir-576; mir-577; mir-578; mir-579; mir-580; mir-581; mir-582; mir-583; mir-584; mir-584-3p; mir-584-5p; mir-585; mir-586; mir-587; mir-588; mir-589; mir-590; mir-591; mir-592; mir-593; mir-595; mir-596; mir-597; mir-598; mir-599; mir-600; mir-601; mir-602; mir-603; mir-604; mir-605; mir-606; mir-607; mir-608; mir-609; mir-610; mir-611; mir-612; mir-613; mir-614; mir-615; mir-616; mir-617; mir-618; mir-619; mir-620; mir-621; mir-622; mir-623; mir-624; mir-625; mir-626; mir-627; mir-628; mir-629; mir-630; mir-631; mir-632; mir-633; mir-634; mir-635; mir-636; mir-637; mir-638; mir-639; mir-640; mir-641; mir-642a; mir-642b; mir-643; mir-644; mir-645; mir-646; mir-647; mir-648; mir-649; mir-650; mir-651; mir-652; mir-653; mir-654; mir-655; mir-656; mir-657; mir-658; mir-659; mir-660; mir-661; mir-662; mir-663; mir-663a; mir-663b; mir-664; mir-665; mir-668; mir-670; mir-671; mir-675; mir-676; mir-708; mir-711; mir-718; mir-720; mir-744; mir-758; mir-759; mir-760; mir-761; mir-762; mir-764; mir-765; mir-766; mir-767; mir-769; mir-770; mir-802; mir-873; mir-874; mir-875; mir-876; mir-877; mir-885; mir-887; mir-888; mir-889; mir-890; mir-891a; mir-891b; mir-892a; mir-892b; mir-920; mir-921; mir-922; mir-924; mir-933; mir-934; mir-935; mir-936; mir-937; mir-938; mir-939; mir-940; mir-941-1; mir-941-2; mir-941-3; mir-941-4; mir-942; mir-942-3p; mir-943; mir-944; mir-1178; mir-1179; mir-1180; mir-1181; mir-1182; mir-1183; mir-1184-1; mir-1184-2; mir-1184-3; mir-1185-1; mir-1185-2; mir-1193; mir-1197; mir-1200; mir-1202; mir-1203; mir-1204; mir-1205; mir-1206; mir-1207; mir-1208; mir-1224; mir-1225; mir-1226; mir-1227; mir-1228; mir-1229; mir-1231; mir-1233-1; mir-1233-2; mir-1234; mir-1236; mir-1236-5p; mir-1237; mir-1238; mir-1243; mir-1244-1; mir-1244-2; mir-1244-3; mir-1245; mir-1246; mir-1247; mir-1248; mir-1249; mir-1250; mir-1251; mir-1251-3p; mir-1252; mir-1253; mir-1254; mir-1255a; mir-1255b-1; mir-1255b-2; mir-1256; mir-1257; mir-1258; mir-1260; mir-1260b; mir-1261; mir-1262; mir-1263; mir-1264; mir-1265; mir-1266; mir-1267; mir-1268a; mir-1269; mir-1270-1; mir-1270-2; mir-1271; mir-1272; mir-1273; mir-1273c; mir-1273d; mir-1273e; mir-1274a; mir-1274b; mir-1275; mir-1276; mir-1277; mir-1278; mir-1279; mir-1280; mir-1281; mir-1282; mir-1283-1; mir-1283-2; mir-1284; mir-1285-1; mir-1285-2; mir-1286; mir-1287; mir-1288; mir-1289-1; mir-1289-2; mir-1290; mir-1291; mir-1292; mir-1293; mir-1294; mir-1295; mir-1296; mir-1297; mir-1298; mir-1299; mir-1301; mir-1302-1; mir-1302-4; mir-1302-10; mir-1302-11; mir-1302-2; mir-1302-3; mir-1302-4; mir-1302-5; mir-1302-6; mir-1302-7; mir-1302-8; mir-1302-9; mir-1303; mir-1304; mir-1305; mir-1306; mir-1307; mir-1321; mir-1322; mir-1323; mir-1324; mir-1468; mir-1469; mir-1470; mir-1471; mir-1537; mir-1538; mir-1539; mir-1825; mir-1827; mir-1908; mir-1909; mir-1909-5p; mir-1910; mir-1911; mir-1912; mir-1913; mir-1914; mir-1915; mir-1972-1; mir-1972-2; mir-1973; mir-1976; mir-2052; mir-2053; mir-2054; mir-2110; mir-2113; mir-2114; mir-2115; mir-2116; mir-2117; mir-2276; mir-2277; mir-2278; mir-2355; mir-2355-3p; mir-2861; mir-2909; mir-3065; mir-3074; mir-3115; mir-3116-1; mir-3116-2; mir-3117; mir-3118-1; mir-3118-2; mir-3118-3; mir-3118-4; mir-3118-5; mir-3118-6; mir-3119-1; mir-3119-2; mir-3120; mir-3121; mir-3122; mir-3123; mir-3124; mir-3125; mir-3126; mir-3127; mir-3128; mir-3129; mir-3130-1; mir-3130-2; mir-3131; mir-3132; mir-3133; mir-3134; mir-3135; mir-3136; mir-3137; mir-3138; mir-3139; mir-3140; mir-3141; mir-3142; mir-3143; mir-3144; mir-3145; mir-3146; mir-3147; mir-3148; mir-3149; mir-3150; mir-3151; mir-3152; mir-3153; mir-3154; mir-3155-a; mir-3155-b; mir-3156-1; mir-3156-2; mir-3156-3; mir-3157; mir-3158-1; mir-3158-2; mir-3158-5p; mir-3159; mir-3160; mir-3160-1; mir-3160-2; mir-3160-5p; mir-3161; mir-3162; mir-3163; mir-3164; mir-3165; mir-3166; mir-3167; mir-3168; mir-3169; mir-3170; mir-3171; mir-3173; mir-3174; mir-3175; mir-3176; mir-3177; mir-3178; mir-3179-1; mir-3179-2; mir-3179-3; mir-3180-1; mir-3180-2; mir-3180-3; mir-3180-4; mir-3180-5; mir-3181; mir-3182; mir-3183; mir-3184; mir-3185; mir-3186; mir-3187; mir-3188; mir-3189; mir-3190; mir-3191; mir-3192; mir-3193; mir-3194; mir-3195; mir-3196; mir-3197; mir-3198; mir-3198-1; mir-3198-2; mir-3199-1; mir-3199-2; mir-3200; mir-3201; mir-3202-1; mir-3202-2; mir-3605; mir-3606; mir-3607; mir-3609; mir-3610; mir-3611; mir-3612; mir-3613; mir-3614; mir-3615; mir-3616; mir-3617; mir-3618; mir-3619; mir-3620; mir-3621; mir-3622a; mir-3622b; mir-3646; mir-3647; mir-3648; mir-3649; mir-3650; mir-3651; mir-3652; mir-3653; mir-3654; mir-3655; mir-3656mir-3657; mir-3658; mir-3659; mir-3660; mir-3661; mir-3662; mir-3663; mir-3664; mir-3665; mir-3666; mir-3667; mir-3668; mir-3669; mir-3670; mir-3670; mir-3671; mir-3671; mir-3673; mir-3673; mir-3675; mir-3675; mir-3676; mir-3663; mir-3677; mir-3678; mir-3679; mir-3680; mir-3681; mir-3682; mir-3683; mir-3684; mir-3685; mir-3686; mir-3687; mir-3688-1; mir-3688-2; mir-3689a; mir-3689b; mir-3689d-1; mir-3689d-2; mir-3689e; mir-3690; mir-3691; mir-3692; mir-3713; mir-3714; mir-3907; mir-3908; mir-3909; mir-3910-1; mir-3910-2; mir-3911; mir-3912; mir-3913-1; mir-3913-2; mir-3913-5p; mir-3914-1; mir-3914-2; mir-3915; mir-3916; mir-3917; mir-3918; mir-3919; mir-3920; mir-3921; mir-3922; mir-3923; mir-3924; mir-3925; mir-3926-1; mir-3926-2; mir-3927; mir-3928; mir-3929; mir-3934; mir-3935; mir-3936; mir-3937; mir-3938; mir-3939; mir-3940; mir-3941; mir-3942; mir-3943; mir-3944; mir-3945; mir-3975; mir-3976; mir-3978; mir-4251; mir-4252; mir-4253; mir-4254; mir-4255; mir-4256; mir-4257; mir-4258; mir-4259; mir-4260; mir-4261; mir-4262; mir-4263; mir-4264; mir-4265; mir-4266; mir-4267; mir-4268; mir-4269; mir-4270; mir-4271; mir-4272; mir-4273; mir-4274; mir-4275; mir-4276; mir-4277; mir-4278; mir-4279; mir-4280; mir-4281; mir-4282; mir-4283-1; mir-4283-2; mir-4284; mir-4285; mir-4286; mir-4287; mir-4288; mir-4289; mir-4290; mir-4291; mir-4292; mir-4293; mir-4294; mir-4295; mir-4296; mir-4297; mir-4298; mir-4299; mir-4300; mir-4301; mir-4302; mir-4303; mir-4304; mir-4305; mir-4306; mir-4307; mir-4308; mir-4309; mir-4310; mir-4311; mir-4312; mir-4313; mir-4314; mir-4315; mir-4315-1; mir-4315-2; mir-4316; mir-4317; mir-4318; mir-4319; mir-4320; mir-4321; mir-4322; mir-4323; mir-4324; mir-4325; mir-4326; mir-4327; mir-4328; mir-4329; mir-4329; mir-4330; mir-4332; mir-4432; mir-4438; mir-4449; mir-4451; mir-4458; mir-4460; mir-4463; mir-4469; mir-4472; mir-4472-1; mir-4479; mir-4482; mir-4482-3p; mir-4482-5p; mir-4490; mir-4493; mir-4507; mir-4509; mir-4509-1; mir-4509-2; mir-4509-3; mir-4511; mir-4526; mir-4536-1; mir-4536-2; mir-4538; mir-4638; mir-4638-3p; mir-4639; mir-4639-3p; mir-4639-5p; mir-4658; mir-4688; mir-4690; mir-4698; mir-4714; mir-4714-5p; mir-4716; mir-4716-3p; mir-4717; mir-4717-5p; mir-4764; mir-4772; mir-4776-1; mir-4787; mir-4787-5p; mir-4788; mir-4800; mir-4800-3p; mir-4803; mir-4804; mir-5187; mir-5187-5p; mir-5188; mir-5190; mir-5192; mir-5194; mir-5583-1; mir-5583-3p; mir-5583-5p; mir-5588; mir-5683; mir-5708; mir-6069; mir-6070; mir-6082; mir-6124; mir-6127; mir-6501; mir-6501-3p; mir-6722; mir-6737; mir-6748; mir-6748-3p; mir-6753; mir-6769a, mir-6769b; mir-6773; mir-6779; mir-6779-5p; mir-6801; mir-6805; mir-6854; mir-6854-5p; mir-6878; mir-6882; mir-6882-5p; mir-7107; mir-7110; mir-7151; mir-7151-5p; mir-7161; mir-7161-5p; mir-7977; mir-8485; mir-9903; mir-10392; mir-10395; mir-10395-3p; mir-10395-5p; mir-10523; mir-12132; mir-12136.
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CN116159071A (en) * | 2023-04-26 | 2023-05-26 | 中山大学中山眼科中心 | Application of miR-543 in preparation of medicine for treating nerve injury |
CN117660286A (en) * | 2023-12-12 | 2024-03-08 | 广州医科大学附属第一医院(广州呼吸中心) | Recombinant lactococcus lactis, preparation, construction method and application thereof |
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KR20200053532A (en) | 2017-09-08 | 2020-05-18 | 에벨로 바이오사이언시즈, 인크. | Extracellular vesicle from Prevotella |
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CN116159071A (en) * | 2023-04-26 | 2023-05-26 | 中山大学中山眼科中心 | Application of miR-543 in preparation of medicine for treating nerve injury |
CN117660286A (en) * | 2023-12-12 | 2024-03-08 | 广州医科大学附属第一医院(广州呼吸中心) | Recombinant lactococcus lactis, preparation, construction method and application thereof |
CN117660286B (en) * | 2023-12-12 | 2024-05-10 | 广州医科大学附属第一医院(广州呼吸中心) | Recombinant lactococcus lactis, preparation, construction method and application thereof |
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