KR102313557B1 - A pharmaceutical composition for treating arthritis comprising natural extracts which regulate an activity of immune cells of mesenteric lymph node in mesentery - Google Patents
A pharmaceutical composition for treating arthritis comprising natural extracts which regulate an activity of immune cells of mesenteric lymph node in mesentery Download PDFInfo
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- KR102313557B1 KR102313557B1 KR1020190134664A KR20190134664A KR102313557B1 KR 102313557 B1 KR102313557 B1 KR 102313557B1 KR 1020190134664 A KR1020190134664 A KR 1020190134664A KR 20190134664 A KR20190134664 A KR 20190134664A KR 102313557 B1 KR102313557 B1 KR 102313557B1
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- mushroom extract
- pharmaceutical composition
- arthritis
- extract
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Abstract
본 발명은 장간막 림프절 면역세포 활성을 조절하는 천연물 추출물을 유효성분으로 하는 관절염 치료용 약학 조성물에 관한 것으로, 본 발명의 조성물을 사용하여, 자가면역질환 또는 관절염을 효과적으로 치료할 수 있다.The present invention relates to a pharmaceutical composition for the treatment of arthritis comprising, as an active ingredient, a natural extract that modulates mesenteric lymph node immune cell activity, and by using the composition of the present invention, autoimmune disease or arthritis can be effectively treated.
Description
본 발명은 장간막 림프절 면역세포의 활성을 조절하는 천연물 추출물을 유효성분으로 하는 관절염 치료용 약학 조성물에 관한 것이다. The present invention relates to a pharmaceutical composition for the treatment of arthritis comprising, as an active ingredient, a natural extract that modulates the activity of mesenteric lymph node immune cells.
관절염은 연골 관련 질환의 대표적인 것으로, 류머티스 관절염 (rheumatoid arthritis)과 퇴행성 관절염 (degenerative arthritis, osteoarthritis)으로 대별되며, 교통사고나 과도한 운동으로 무릎관절 연골이 손상된 경우도 흔히 발견된다. 현재, 우리나라에서 100만 명 정도의 관절염 환자가 있으며, 여성이 남성보다 배 이상 많고 그 중에서도 특히 갱년기 여성에게서 많이 볼 수 있는 질환이다 (Belmonte-S. MA et al; Arthritis Rheum, 30, pp 1214-1225, 1987). 연골조직은 관절을 구성하고 있으며, 관절 운동의 전달력을 흡수한다. 이와 같은 연골조직이 손상되면, 붓기, 열감, 통증을 동반한 관절염(arthritis)이 유발되는데, 관절염은 인종에 무관하게 발병하며 그 원인에 따라 100 여종 이상으로 나누어진다. 그 중 가장 흔한 형태가 주로 노화에 의해 발병하는 퇴행성 관절 질환(degenerative joint disease)인 골관절염(osteoarthritis)이며, 그 외 자가 면역질환인 류마티스성 관절염(rheumatoid arthritis)과 건선성 관절염(psoriatic arthritis), 감염에 의한 패혈성 관절염(septic arthritis) 등이 있다. Arthritis is a representative cartilage-related disease, and is roughly divided into rheumatoid arthritis and degenerative arthritis (osteoarthritis), and cartilage of the knee joint is often damaged due to a traffic accident or excessive exercise. Currently, there are about 1 million arthritis patients in Korea, and the number of women is more than twice that of men, and among them, it is a disease that is particularly common in menopausal women (Belmonte-S. MA et al; Arthritis Rheum, 30, pp 1214- 1225, 1987). Cartilage tissue constitutes the joint and absorbs the transmission force of joint motion. When the cartilage tissue is damaged, arthritis (arthritis) accompanied by swelling, heat, and pain is induced. Arthritis occurs regardless of race and is divided into more than 100 types according to the cause. Among them, the most common form is osteoarthritis, a degenerative joint disease mainly caused by aging, and other autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis, and infection. septic arthritis caused by
류마티스 관절염(rheumatoid arthritis)은 성인에서 가장 흔하게 발병하는 염증성 관절염으로, 그 원인이 아직 완전히 알려지지 않았으나, 자가면역 기전으로 인한 관절 내 활막의 염증 반응으로 이해되고 있다. 류마티스 관절염을 치료하는 데 사용되는 항류마티스 약제들과 생물학적 제재들이 염증 조절을 통해 관절염을 개선하는 효과를 보이지만, 궁극적인 치료 목표인 관해를 유도하기에는 아직 부족하다. 여러 환자들에서 치료 효과가 불완전하고, 치료 약제 관련 부작용이 치료에 걸림돌이 되고 있으며, 생물학적 제제를 장기간 사용할 때 그 약제에 대한 항체가 생성되어 치료 효과가 떨어지기도 한다. Rheumatoid arthritis (rheumatoid arthritis) is the most common inflammatory arthritis in adults, the cause is not yet fully known, but is understood as an inflammatory response of the synovial membrane in the joint due to an autoimmune mechanism. Although antirheumatic drugs and biological agents used to treat rheumatoid arthritis have shown to improve arthritis through inflammation control, they are still insufficient to induce remission, the ultimate treatment goal. In many patients, the therapeutic effect is incomplete, side effects related to therapeutic drugs are an obstacle to treatment, and when a biological agent is used for a long time, antibodies to the drug are generated and the therapeutic effect is reduced.
이와 같은 관절염을 치료하기 위하여, 전통적으로 자가골 이식 (autografting)과 동종골 이식 (allografting) 그리고 인조골 이식(artificial bone grafting) 등의 연구가 수행되었으나, 골 채취 부위의 감염, 혈종 등과 같은 합병증 유발(자가골 이식), 공여자로부터의 질병 전염 가능성(동종골 이식), 근본적인 골 생성이 되지 않는(인조골 이식) 문제점을 가지고 있는 것으로 알려졌다.In order to treat such arthritis, studies such as autografting, allografting, and artificial bone grafting have been traditionally performed, but complications such as infection and hematoma at the bone extraction site have been induced (autografting). It is known to have problems such as transplantation), the possibility of disease transmission from the donor (allogeneic bone transplantation), and the inability to fundamentally generate bone (artificial bone transplantation).
따라서 현재 기존의 치료법이 갖는 단점을 극복한 새로운 신규 치료법 내지는 치료제가 절실히 요구되고 있는 실정이다.Therefore, there is an urgent need for a new treatment or therapeutic agent that overcomes the disadvantages of the current treatment.
본 발명은 선별된 추출물을 유효성분으로 자가면역질환 또는 관절염을 치료하거나 증상을 완화 또는 개선하는 조성물을 제공하는 것으로 목적으로 한다.An object of the present invention is to provide a composition for treating autoimmune diseases or arthritis or alleviating or improving symptoms using the selected extract as an active ingredient.
이하, 본원에 기재된 다양한 구체예가 도면을 참조로 기재된다. 하기 설명에서, 본 발명의 완전한 이해를 위해서, 다양한 특이적 상세사항, 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. 본 발명 내 특별한 정의가 없으면 본 명세서에 사용된 모든 과학적 및 기술적인 용어는 본 발명이 속하는 기술분야에서 당업자에 의하여 통상적으로 이해되는 것과 동일한 의미를 가진다.Hereinafter, various embodiments described herein are described with reference to the drawings. In the following description, various specific details are set forth, such as specific forms, compositions and processes, and the like, for a thorough understanding of the present invention. However, certain embodiments may be practiced without one or more of these specific details, or in conjunction 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, references to "in one embodiment" or "an embodiment" in various places throughout this specification do not necessarily refer to the same embodiment of the invention. Additionally, the particular features, forms, compositions, or properties may be combined in any suitable manner in one or more embodiments. Unless otherwise defined in the present invention, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
본 발명의 일 구현 예에 따르면, 능이버섯(Sarcodon imbricatus) 추출물, 석이버섯(Umbilicaria esculenta) 추출물, 및 찔레버섯(Phellinus ribis) 추출물로 구성된 군으로부터 선택된 어느 하나 이상을 유효성분으로 포함하는 자가면역질환의 예방 또는 치료용 약학 조성물을 제공한다.According to one embodiment of the present invention, autoimmune disease comprising any one or more selected from the group consisting of Sarcodon imbricatus extract, Umbilicaria esculenta extract, and Phellinus ribis extract as an active ingredient. It provides a pharmaceutical composition for the prevention or treatment of.
본 발명의 조성물에서 이용되는 능이버섯 추출물, 석이버섯 추출물 및 찔레버섯 추출물은 능이버섯, 석이버섯 및 찔레버섯에 추출용매를 처리하여 수득하는 경우에는, 다양한 추출용매가 이용될 수 있다. When the neungi mushroom extract, shiitake mushroom extract, and iris mushroom extract used in the composition of the present invention are obtained by treating neungi mushroom, shiitake mushroom and briar mushroom with an extraction solvent, various extraction solvents may be used.
본 발명에서 상기 추출용매로는 극성 용매 또는 비극성 용매를 이용할 수 있다. 본 발명에서 상기 극성 용매로는 (i) 물, (ii) 알코올(비제한적 예시로, 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올, 노말-부탄올, 1-펜탄올, 2-부톡시에탄올 또는 에틸렌글리콜), (iii) 아세트산, (iv) DMFO(dimethyl-formamide) 및 (v) DMSO(dimethyl sulfoxide)로부터 선택될 수 있으나, 이에 제한되는 것은 아니다. 또한, 본 발명에서 상기 비극성 용매로는 메틸렌 클로라이드, 아세톤, 아세토나이트릴, 에틸 아세테이트, 메틸 아세테이트, 플루오로알칸, 펜탄, 헥산, 2,2,4-트리메틸펜탄, 데칸, 사이클로헥산, 사이클로펜탄, 디이소부틸렌, 1-펜텐, 1-클로로부탄, 1-클로로펜탄, o-자일렌, 디이소프로필 에테르, 2-클로로프로판, 톨루엔, 1-클로로프로판, 클로로벤젠, 벤젠, 디에틸 에테르, 디에틸 설파이드, 클로로포름, 1,2-디클로로에탄, 어닐린, 디에틸아민, 에테르, 사염화탄소 및 THF로부터 선택될 수 있으나, 이에 제한되지 않는다. In the present invention, a polar solvent or a non-polar solvent may be used as the extraction solvent. In the present invention, as the polar solvent, (i) water, (ii) alcohol (as non-limiting examples, methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1-pentanol, 2- butoxyethanol or ethylene glycol), (iii) acetic acid, (iv) DMFO (dimethyl-formamide), and (v) DMSO (dimethyl sulfoxide), but is not limited thereto. In the present invention, the non-polar solvent includes methylene chloride, acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, Diisobutylene, 1-pentene, 1-chlorobutane, 1-chloropentane, o-xylene, diisopropyl ether, 2-chloropropane, toluene, 1-chloropropane, chlorobenzene, benzene, diethyl ether, diethyl sulfide, chloroform, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride and THF, but is not limited thereto.
바람직하게는, 본 발명에서 상기 능이버섯 추출물, 상기 석이버섯 추출물 및 상기 찔레버섯 추출물은 상기 능이버섯, 상기 석이버섯 및 상기 찔레버섯에 (a) 탄소수 1-4의 무수 또는 함수 저급 알코올(메탄올, 에탄올, 프로판올, 부탄올 등), (b) 물, (c) 상기 저급 알코올과 물과의 혼합용매, (d) 메틸렌 클로라이드, (e) 에틸 아세테이트, (f) 클로로포름, (g) 부틸아세테이트, (h) 1,3-부틸렌글리콜, (i) 헥산 및 (j) 디에틸에테르로부터 선택된 1종 이상의 추출용매를 처리하여 수득된 것일 수 있으며, 보다 바람직하게는 상기 능이버섯, 상기 석이버섯 및 상기 찔레버섯에 물, 메탄올 또는 이의 혼합물을 처리하여 수득된 것일 수 있다.Preferably, in the present invention, the neungi mushroom extract, the shiitake mushroom extract and the iris mushroom extract include (a) anhydrous or hydrous lower alcohol (methanol, ethanol, propanol, butanol, etc.), (b) water, (c) a mixed solvent of the lower alcohol and water, (d) methylene chloride, (e) ethyl acetate, (f) chloroform, (g) butyl acetate, ( h) 1,3-butylene glycol, (i) hexane, and (j) may be obtained by treating at least one extraction solvent selected from diethyl ether, more preferably the oyster mushroom, the shiitake mushroom and the It may be obtained by treating brier mushrooms with water, methanol, or a mixture thereof.
본 발명에서 추출 방법으로는 냉침 추출, 열 추출, 초음파 추출, 환류 냉각 추출 등 당업계에서 당업자에 의해 통상적으로 사용하는 모든 추출 방법을 사용할 수 있다.As the extraction method in the present invention, all extraction methods commonly used by those skilled in the art, such as cold extraction, heat extraction, ultrasonic extraction, and reflux cooling extraction, may be used.
본 발명에서 상기 추출 방법의 일 예시로, 건조된 상기 능이버섯, 상기 석이버섯 및 상기 찔레버섯을 세절하여 건조중량의 1 내지 20 배, 바람직하게는 2 내지 6배의 추출 용매를 첨가한 뒤, 20 내지 150℃ 바람직하게는 70 내지 120℃의 추출온도에서 약 1시간 내지 10일, 바람직하게는 약 2시간 내지 5시간 동안 환류냉각 추출방법으로 추출할 수 있으나, 이에 제한되는 것은 아니다.As an example of the extraction method in the present invention, the dried neungi mushroom, the shiitake mushroom and the brier mushroom are chopped and an extraction solvent of 1 to 20 times the dry weight, preferably 2 to 6 times of the dry weight is added, Extraction may be performed by reflux cooling extraction at an extraction temperature of 20 to 150° C., preferably 70 to 120° C., for about 1 hour to 10 days, preferably for about 2 hours to 5 hours, but is not limited thereto.
본 발명에서 상기 추출물은 상술한 바와 같이 당업계에서 조추출물(crude extract)로 통용되는 의미를 갖지만, 광의적으로는 추출물을 추가적으로 분획(fractionation)한 분획물도 포함한다. 즉, 능이버섯 추출물, 석이버섯 추출물 및 찔레버섯 추출물은 상술한 추출용매를 이용하여 얻은 것뿐만 아니라, 여기에 정제과정을 추가적으로 적용하여 얻은 것도 포함한다. 예컨대, 상기 추출물을 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 얻은 분획, 다양한 크로마토그래피(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 분획도 본 발명의 능이버섯 추출물, 석이버섯 추출물 및 찔레버섯 추출물에 포함되는 것이다.In the present invention, the extract has the meaning commonly used as a crude extract in the art as described above, but in a broad sense also includes a fraction obtained by additionally fractionating the extract. That is, the neungyi mushroom extract, the shiitake mushroom extract and the briar mushroom extract include not only those obtained using the above-described extraction solvent, but also those obtained by additionally applying a purification process thereto. For example, a fraction obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (prepared for separation according to size, charge, hydrophobicity or affinity), etc. The fractions obtained through the purification method are also included in the neungyi mushroom extract, the shiitake mushroom extract, and the iris mushroom extract of the present invention.
본 발명에서 이용되는 능이버섯 추출물, 석이버섯 추출물 및 찔레버섯 추출물은 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다.The neungi mushroom extract, shiitake mushroom extract, and iris mushroom extract used in the present invention may be prepared in a powder state by additional processes such as distillation under reduced pressure and freeze-drying or spray-drying.
한편, 본 발명의 추출물은 상기한 추출 용매뿐만 아니라, 다른 추출 용매를 이용하여도 실질적으로 동일한 효과를 나타내는 본 발명의 추출물이 얻어질 수 다는 것은 당업자에게 자명한 것이다. On the other hand, it is apparent to those skilled in the art that the extract of the present invention can be obtained using not only the above-described extraction solvent, but also the extract of the present invention exhibiting substantially the same effect even when other extraction solvents are used.
본 발명에서 상기 능이버섯 추출물, 상기 석이버섯 추출물 및 상기 찔레버섯 추출물 제조에 사용되는 능이버섯, 석이버섯 및 찔레버섯의 부위는 특별히 제한하지 않는다. In the present invention, the neungi mushroom extract, the shiitake mushroom extract, and the part of the neungi mushroom, shiitake mushroom and briar mushroom used in the preparation of the iris mushroom extract are not particularly limited.
본 발명의 약학 조성물은 석이버섯 추출물 및 찔레버섯 추출물을 유효성분으로 포함할 수 있고, 능이버섯 추출물을 추가로 더 포함할 수 있다.The pharmaceutical composition of the present invention may include a shiitake mushroom extract and an iris mushroom extract as active ingredients, and may further include a neungyi mushroom extract.
본 발명에서 상기와 같이 석이버섯 추출물 및 찔레버섯 추출물을 병용 투여함으로써 자가면역질환 치료 효과가 현저한 약학 조성물을 제공할 수 있다.In the present invention, it is possible to provide a pharmaceutical composition with a remarkable therapeutic effect on autoimmune diseases by co-administering the shiitake mushroom extract and the iris mushroom extract as described above.
본 발명에서 상기 석이버섯 추출물과 찔레버섯 추출물은 1:0.01~100의 중량비, 보다 바람직하게는 1:0.1~10의 중량비로 사용될 수 있다.In the present invention, the shiitake mushroom extract and briar mushroom extract may be used in a weight ratio of 1:0.01 to 100, more preferably, in a weight ratio of 1:0.1 to 10.
본 발명에서 상기 자가면역질환은 개체 자신의 조직에 대해 일어나고 지정된 비-악성 질환 또는 장애이다. 모든 정상 개체에 있어서 가장 중요한 특성 중의 하나는 자기(self)를 구성하고 있는 항원물질에 대해서는 해롭게 반응하지 않는 반면, 비자기(non-self) 항원들에 대해서는 이를 인식하고 반응하여 제거할 수 있다. 자기항원에 대한 생체의 무반응을 면역학적 무반응성(immunologic unresponsiveness) 또는 관용(tolerance)이라고 한다. 그러나 자기관용을 유도 또는 유지함에 있어서 이상이 생기면 자기항원에 대하여 면역반응이 일어나게 되고, 그 결과 자신의 조직을 공격하는 현상이 발생하는데 상기 과정에 의해 발생되는 질환을 자가면역질환이라고 한다. 상기 자기 면역 질환은 자신의 장기조직이나 그 성분에 대해 항체가 생산되는 염증성 질환으로서, 다수의 조직과 장기에 만성적인 전신적 염증을 일으키는 질병을 총칭할 수 있다. 상기 자가면역질환은, 이에 한정하지는 않지만, 류마티스 관절염, 염증성 척추관절염, 성인형 스틸씨병, 대식세포 활성증후군, 전신경화증, 다발성근염, 피부근염, 혈관염, 혼합 결합조직질환, 쇼그렌 증후군, 궤양성 대장염, 크론병, 알러지성 천식, 알러지성 비염, 아토피성 피부염, 담마진, 누선염, 결막염, 건선, 심상성 천포창, 파킨슨병, 근위축성 측색경화증, 중증 근무력증, 다발성경화증, 알츠하이머 질환, 뇌졸중, 동맥경화증, 혈관 재협착, I형 당뇨병, II형 당뇨병, 당뇨성 망막증 및 만성 갑상선염으로 이루어진 군에서 하나 이상 선택될 수 있으나, 이에 제한되는 것은 아니다. In the present invention, the autoimmune disease is a non-malignant disease or disorder that occurs and is directed to an individual's own tissue. One of the most important characteristics of all normal individuals is that they do not react harmfully to antigenic substances constituting self, while they can recognize and react to non-self antigens and remove them. The non-response of the living body to the self-antigen is called immunologic unresponsiveness or tolerance. However, when there is an abnormality in inducing or maintaining self-tolerance, an immune response to the self-antigen occurs, and as a result, a phenomenon of attacking one's own tissue occurs. The disease caused by the above process is called an autoimmune disease. The autoimmune disease is an inflammatory disease in which antibodies are produced against one's own organ tissues or components thereof, and may collectively refer to diseases that cause chronic systemic inflammation in multiple tissues and organs. The autoimmune diseases include, but are not limited to, rheumatoid arthritis, inflammatory spondyloarthritis, adult Still's disease, macrophage activation syndrome, systemic sclerosis, polymyositis, dermatomyositis, vasculitis, mixed connective tissue disease, Sjogren's syndrome, ulcerative colitis , Crohn's disease, allergic asthma, allergic rhinitis, atopic dermatitis, urticaria, laryngitis, conjunctivitis, psoriasis, pemphigus vulgaris, Parkinson's disease, amyotrophic lateral sclerosis, myasthenia gravis, multiple sclerosis, Alzheimer's disease, stroke, arteriosclerosis, At least one may be selected from the group consisting of vascular restenosis, type I diabetes, type II diabetes, diabetic retinopathy, and chronic thyroiditis, but is not limited thereto.
본 발명에서 상기 약학 조성물은, 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 약학 조성물은 약제적으로 허용 가능한 담체를 포함할 수 있으나, 이에 제한되는 것은 아니다. 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 약학 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.In the present invention, the pharmaceutical composition may be formulated and used in the form of oral dosage forms such as powders, granules, capsules, tablets, and aqueous suspensions, external preparations, suppositories, and sterile injection solutions, respectively, according to conventional methods. The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier, but is not limited thereto. Pharmaceutically acceptable carriers may include binders, lubricants, disintegrants, excipients, solubilizers, dispersants, stabilizers, suspending agents, dyes, fragrances, etc., for oral administration, and in the case of injections, buffers, preservatives, pain-freezing agents A topical agent, solubilizer, 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 dosage form of the pharmaceutical composition of the present invention can be prepared in various ways by mixing with a pharmaceutically acceptable carrier as described above. For example, in the case of 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 the form of unit dose ampoules or multiple doses. have. In addition, it can be formulated as a solution, suspension, tablet, capsule, sustained release formulation, 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.Meanwhile, examples of suitable carriers, excipients and diluents 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 may be used. In addition, fillers, anti-agglomeration agents, lubricants, wetting agents, fragrances, emulsifiers, preservatives and the like may be further included.
본 발명에서 상기 약학 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 in the present invention is not limited thereto, but oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual or rectal. Oral or parenteral administration is preferred.
본 발명에서, 비경구는 피하, 피내, 정맥내, 근육내, 관절내, 활액낭내, 흉골내, 경막내, 병소내 및 두개골내 주사 또는 주입기술을 포함한다. 본 발명의 약학 조성물은 또한 직장 투여를 위한 좌제의 형태로 투여될 수 있다.In the present invention, parenteral includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intrasynovial, 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 상기 약학 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 약학 조성물의 투여량은 환자의 상태, 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만 당업자에 의해 적절하게 선택될 수 있고, 1일 0.0001 내지 50mg/kg 또는 0.001 내지 50mg/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 several factors including the activity of the specific compound used, age, weight, general health, sex, formula, administration time, administration route, excretion rate, drug formulation, and the severity of the specific disease to be prevented or treated. The dosage of the pharmaceutical composition may vary depending on the patient's condition, weight, degree of disease, drug form, administration route and period, but may be appropriately selected by those skilled in the art, and 0.0001 to 50 mg/kg per day Or 0.001 to 50 mg/kg may be administered. Administration may be administered once a day, or may be administered in several divided doses. The above dosage does not limit the scope of the present invention in any way. The pharmaceutical composition according to the present invention may be formulated as pills, dragees, capsules, solutions, gels, syrups, slurries, and suspensions.
본 발명의 상기 약학 조성물은 인간을 대상으로 하는 것을 특징으로 할 수 있다.The pharmaceutical composition of the present invention may be characterized in that it targets humans.
본 발명에서, 상기 예방은 본 발명의 조성물을 이용하여 자가면역질환 또는 관절염의 증상을 차단하거나, 자가면역질환 또는 관절염의 증상의 억제 또는 지연시키는 모든 행위라면 제한없이 포함할 수 있다. In the present invention, the prevention may include, without limitation, any action that blocks symptoms of autoimmune disease or arthritis using the composition of the present invention, or suppresses or delays symptoms of autoimmune disease or arthritis.
본 발명에서, 상기 치료는 본 발명의 조성물을 이용하여 자가면역질환 또는 관절염 증상이 호전되거나 이롭게 되는 모든 행위라면 제한없이 포함할 수 있다.In the present invention, the treatment may include, without limitation, any action in which autoimmune disease or arthritis symptoms are improved or beneficial using the composition of the present invention.
본 발명에서 상기 약학 조성물은 장간막 림프절 면역세포가 IL-10 분비를 촉진하거나 IL-12 또는 IL-6 분비를 억제함으로써 자가면역질환을 효과적으로 예방 또는 치료할 수 있다. In the present invention, the pharmaceutical composition can effectively prevent or treat autoimmune diseases by promoting IL-10 secretion by mesenteric lymph node immune cells or inhibiting IL-12 or IL-6 secretion.
본 발명에서, 상기 장간막 림프절 면역세포, 보다 자세하게는 장간막 림프절은 장점막에 존재하는 B 세포와 T 세포의 활성화 및 분화가 이루어지는 조직으로서 장점막 면역계에서 중추적 역할을 담당한다. 특히, 장간막 림프절에서 수지상세포 등에 의해 분비되는 사이토카인들은 염증 반응을 억제하는 조절 T 세포(regulatory T cell, Treg 세포)와 염증 반응을 매개하는 Th1 세포와 Th17 세포의 분화에 직접적으로 관여한다. 장점막 면역계에서 생성된 Treg 세포는 신체의 여러 기관으로 이동하여 염증 반응을 억제하는 작용을 나타낸다. 따라서, Treg 세포의 분화를 촉진하는 사이토카인인 IL-10을 증가시키고, Treg 세포의 분화를 억제하고 Th17 세포 분화를 촉진하는 사이토카인인 IL-6을 감소시키며, Th1 세포의 분화를 유도하는 IL-12를 감소시키는 물질은 자가면역질환 및 류마티스 관절염에 치료 효능을 나타낸다고 할 수 있다.In the present invention, the mesenteric lymph node immune cells, more specifically mesenteric lymph nodes, are tissues in which B cells and T cells present in the intestinal mucosa are activated and differentiated, and play a central role in the intestinal mucosa immune system. In particular, cytokines secreted by dendritic cells from mesenteric lymph nodes are directly involved in the differentiation of regulatory T cells (regulatory T cells, Treg cells) that suppress the inflammatory response and Th1 cells and Th17 cells that mediate the inflammatory response. Treg cells produced in the intestinal mucosa display the action of suppressing the inflammatory response by migrating to various organs of the body. Therefore, it increases IL-10, a cytokine that promotes Treg cell differentiation, decreases IL-6, a cytokine that inhibits Treg cell differentiation and promotes Th17 cell differentiation, and induces Th1 cell differentiation. Substances that reduce -12 can be said to have therapeutic efficacy in autoimmune diseases and rheumatoid arthritis.
본 발명에서, 상기 IL-10은 수용성 사이토카인 중 하나로 이합체를 이루며, IL-10Rα와 IL-10β로 이루어진 헤테로다이머 수용체와 상호작용한다. 류마티스 관절염과 같은 자가 면역 질환 및 크론병이나 건선과 같은 만성염증성질환에서 방어적인 역할을 한다. 특히 염증 억제 작용을 하는 Breg 세포, Treg 세포, M2 대식 세포 등에서 주로 분비되는 IL-10은 호중구의 활성화와 염증 부위로의 침투를 억제하고, 대식세포를 M2 표현형으로 전환시키는 역할을 하며, TNF-α와 같은 류마티즘 증상에 핵심적인 역할을 하는 염증성 사이토카인의 발현을 억제함으로써 류마티즘의 증상을 완화시킬 수 있다(Chen, Z., Bozec, A., Ramming, A. & Schett, G. J. N. R. R. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. 1 (2018) 참조).In the present invention, the IL-10 forms a dimer as one of the water-soluble cytokines, and interacts with a heterodimeric receptor composed of IL-10Rα and IL-10β. It plays a protective role in autoimmune diseases such as rheumatoid arthritis and chronic inflammatory diseases such as Crohn's disease and psoriasis. In particular, IL-10, which is mainly secreted from Breg cells, Treg cells, and M2 macrophages, which have an inhibitory effect on inflammation, inhibits the activation of neutrophils and penetration into the inflammatory site, and plays a role in converting macrophages into the M2 phenotype, and TNF- It is possible to alleviate the symptoms of rheumatism by suppressing the expression of inflammatory cytokines that play a key role in rheumatoid symptoms, such as α (Chen, Z., Bozec, A., Ramming, A. & Schett, GJNRR Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. 1 (2018)).
본 발명에서, 상기 IL-6은 염증성 사이토카인 중 하나로 급성기 단백질 합성을 자극하고 골수에서 호중구 생성을 담당한다. 또한 B세포의 성장을 지원하고 Treg 세포에 길항적이다(Erkelens MN, Mebius RE (March 2017). "Retinoic Acid and Immune Homeostasis: A Balancing Act". Trends in Immunology. 38 (3): 168-180.). IL-6은 또한 Th17 세포 분화를 촉진함으로써 IL-6의 과도한 발현은 류마티스 관절염과 다발성 경화증을 유도할 수 있다(Kimura A & Kishimoto T (2010)"IL-6: Regulator of Treg/Th17 balance". Journal of Immunology. 40: 1830-1835)In the present invention, the IL-6 is one of the inflammatory cytokines that stimulates protein synthesis in the acute phase and is responsible for the production of neutrophils in the bone marrow. It also supports the growth of B cells and is antagonistic to Treg cells (Erkelens MN, Mebius RE (March 2017). "Retinoic Acid and Immune Homeostasis: A Balancing Act". Trends in Immunology. 38 (3): 168-180. ). IL-6 also promotes Th17 cell differentiation, so that excessive expression of IL-6 can induce rheumatoid arthritis and multiple sclerosis (Kimura A & Kishimoto T (2010) "IL-6: Regulator of Treg/Th17 balance"). Journal of Immunology. 40: 1830-1835)
본 발명에서, 상기 IL-12는 IL-12A(P35) 및 IL-12B(P40) 두개의 유전자에서 각각 코딩되는 염증성 사이토카인으로, 자가면역질환을 악화시키며 Th1 세포의 분화를 유도한다(Hirohata, S. "Human Th1 responses driven by IL-12 are associated with enhanced expression of CD40 ligand." Clinical and experimental immunology vol. 115,1 (1999): 78-85.).In the present invention, the IL-12 is an inflammatory cytokine encoded by two genes, IL-12A (P35) and IL-12B (P40), respectively, exacerbating autoimmune diseases and inducing differentiation of Th1 cells (Hirohata, S. "Human Th1 responses driven by IL-12 are associated with enhanced expression of CD40 ligand." Clinical and experimental immunology vol. 115,1 (1999): 78-85.).
본 발명의 다른 구현 예에 따르면, 능이버섯 추출물, 석이버섯 추출물, 및 찔레버섯 추출물로 구성된 군으로부터 선택된 어느 하나 이상을 유효성분으로 포함하는 자가면역질환의 예방 또는 개선용 식품 조성물을 제공한다.According to another embodiment of the present invention, there is provided a food composition for the prevention or improvement of autoimmune diseases comprising, as an active ingredient, any one or more selected from the group consisting of neungi mushroom extract, shiitake mushroom extract, and chrysanthemum extract.
본 발명의 조성물에서 이용되는 능이버섯 추출물, 석이버섯 추출물 및 찔레버섯 추출물은 능이버섯, 석이버섯 및 찔레버섯에 추출용매를 처리하여 수득하는 경우에는, 다양한 추출용매가 이용될 수 있다. When the neungi mushroom extract, shiitake mushroom extract, and iris mushroom extract used in the composition of the present invention are obtained by treating neungi mushroom, shiitake mushroom and briar mushroom with an extraction solvent, various extraction solvents may be used.
본 발명에서 상기 다양한 추출용매에 관한 기재는 앞서 기재된 바와 중복되어 명세서의 과도한 복잡을 피하기 위하여 이하 그 자세한 기재를 생략한다. In the present invention, the description of the various extraction solvents overlaps with those described above, and detailed description thereof will be omitted below in order to avoid excessive complexity of the specification.
본 발명에서 추출 방법으로는 냉침 추출, 열 추출, 초음파 추출, 환류 냉각 추출 등 당업계에서 당업자에 의해 통상적으로 사용하는 모든 추출 방법을 사용할 수 있다.As the extraction method in the present invention, all extraction methods commonly used by those skilled in the art, such as cold extraction, heat extraction, ultrasonic extraction, and reflux cooling extraction, may be used.
본 방법에서 상기 통상적으로 사용하는 모든 추출 방법에 관한 기재는 앞서 기재된 바와 중복되어 명세서의 과도한 복잡을 피하기 위하여 이하 그 자세한 기재를 생략한다.In the present method, descriptions of all extraction methods commonly used are duplicated with those described above, and detailed descriptions thereof will be omitted below in order to avoid excessive complexity of the specification.
본 발명에서 상기와 같이 석이버섯 추출물 및 찔레버섯 추출물을 병용 투여함으로써 자가면역질환의 예방 또는 개선 효과가 현저한 식품 조성물을 제공할 수 있다.In the present invention, it is possible to provide a food composition with a remarkable preventive or ameliorating effect of autoimmune diseases by co-administering the shiitake mushroom extract and the iris mushroom extract as described above.
본 발명에서 상기 석이버섯 추출물과 찔레버섯 추출물은 1:0.01~100의 중량비, 보다 바람직하게는 1:0.1~10의 중량비로 사용될 수 있다.In the present invention, the shiitake mushroom extract and briar mushroom extract may be used in a weight ratio of 1:0.01 to 100, more preferably, in a weight ratio of 1:0.1 to 10.
본 발명에서, 상기 자가면역질환에 관한 기재는 앞서 기재된 바와 중복되어 명세서의 과도한 복잡을 피하기 위하여 이하 그 자세한 기재를 생략한다.In the present invention, the description of the autoimmune disease overlaps with that described above, and thus detailed description thereof will be omitted below in order to avoid excessive complexity of the specification.
본 발명에서 상기 개선은 본 발명의 식품 조성물의 투여로 자가면역질환및 관절염의 증상이 호전 또는 이롭게 변경되는 모든 행위를 의미한다.In the present invention, the improvement refers to any action in which the symptoms of autoimmune diseases and arthritis are improved or beneficially changed by administration of the food composition of the present invention.
본 발명의 식품 조성물은 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 식물추출물로 구성된 것이므로 예방 목적으로 장기간 복용 시에도 안심하고 사용할 수 있다.The food composition of the present invention may be prepared in the form of various foods, for example, beverages, gums, tea, vitamin complexes, powders, granules, tablets, capsules, confectionery, rice cakes, bread, and the like. Since the food composition of the present invention is composed of a plant extract having almost no toxicity and side effects, it can be safely used even when taken for a long period of time for prophylactic purposes.
여기서, 상기 식품 조성물이 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.Here, when the food composition is prepared in the form of a beverage, there is no particular limitation other than containing the food composition in the indicated ratio, and it may contain various flavoring agents or natural carbohydrates as additional ingredients like a conventional beverage. That is, as natural carbohydrates, monosaccharides such as glucose, disaccharides such as fructose, and polysaccharides such as sucrose, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol are included. can do. Examples of the flavoring agent include natural flavoring agents (taumatine, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.).
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, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다.In addition, the food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), synthetic flavoring agents and flavoring agents such as natural flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners , pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like.
본 발명의 다른 일 구현 예에 따르면, 능이버섯 추출물, 석이버섯 추출물 및 찔레버섯 추출물로 구성된 군으로부터 선택된 어느 하나 이상을 유효성분으로 포함하는 관절염의 예방 또는 치료용 약학 조성물을 제공한다. According to another embodiment of the present invention, there is provided a pharmaceutical composition for the prevention or treatment of arthritis comprising, as an active ingredient, any one or more selected from the group consisting of neungi mushroom extract, shiitake mushroom extract, and iris mushroom extract.
본 발명의 조성물에서 이용되는 능이버섯 추출물, 석이버섯 추출물 및 찔레버섯 추출물은 능이버섯, 석이버섯 및 찔레버섯에 추출용매를 처리하여 수득하는 경우에는, 다양한 추출용매가 이용될 수 있다. When the neungi mushroom extract, shiitake mushroom extract, and iris mushroom extract used in the composition of the present invention are obtained by treating neungi mushroom, shiitake mushroom and briar mushroom with an extraction solvent, various extraction solvents may be used.
본 발명에서 상기 다양한 추출용매에 관한 기재는 앞서 기재된 바와 중복되어 명세서의 과도한 복잡을 피하기 위하여 이하 그 자세한 기재를 생략한다. In the present invention, the description of the various extraction solvents overlaps with those described above, and detailed description thereof will be omitted below in order to avoid excessive complexity of the specification.
본 발명에서 추출 방법으로는 냉침 추출, 열 추출, 초음파 추출, 환류 냉각 추출 등 당업계에서 당업자에 의해 통상적으로 사용하는 모든 추출 방법을 사용할 수 있다.As the extraction method in the present invention, all extraction methods commonly used by those skilled in the art, such as cold extraction, heat extraction, ultrasonic extraction, and reflux cooling extraction, may be used.
본 방법에서 상기 통상적으로 사용하는 모든 추출 방법에 관한 기재는 앞서 기재된 바와 중복되어 명세서의 과도한 복잡을 피하기 위하여 이하 그 자세한 기재를 생략한다.In the present method, descriptions of all extraction methods commonly used are duplicated with those described above, and detailed descriptions thereof will be omitted below in order to avoid excessive complexity of the specification.
본 발명의 약학 조성물은 석이버섯 추출물 및 찔레버섯 추출물을 유효성분으로 포함할 수 있고, 능이버섯 추출물을 추가로 더 포함할 수 있다.The pharmaceutical composition of the present invention may include a shiitake mushroom extract and an iris mushroom extract as active ingredients, and may further include a neungyi mushroom extract.
본 발명에서 상기와 같이 석이버섯 추출물 및 찔레버섯 추출물을 병용 투여함으로써 관절염 치료 효과가 현저한 약학 조성물을 제공할 수 있다.In the present invention, it is possible to provide a pharmaceutical composition with a remarkable therapeutic effect on arthritis by co-administering the shiitake mushroom extract and the iris mushroom extract as described above.
본 발명에서 상기 석이버섯 추출물과 찔레버섯 추출물은 1:0.01~100의 중량비, 보다 바람직하게는 1:0.1~10의 중량비로 사용될 수 있다.In the present invention, the shiitake mushroom extract and briar mushroom extract may be used in a weight ratio of 1:0.01 to 100, more preferably, in a weight ratio of 1:0.1 to 10.
뼈(bone)는 인체의 연조직과 체중을 지탱해주고 내부기관을 둘러싸서 내부 장기를 외부의 충격으로부터 보호한다. 또한, 근육이나 장기를 구조적으로 지탱할 뿐만 아니라 체내의 칼슘이나 다른 필수 무기질, 즉 인이나 마그네슘과 같은 물질을 저장하는 인체의 중요한 부분 중 하나이다. 인체를 구성하는 뼈 사이에는 관절이 존재한다. 관절은 두개골이나 이의 치근처럼 서로 접하는 두 개의 뼈나 연골 사이에 가동성이 거의 또는 전혀 없는 부동성 관절과, 동물의 팔다리의 뼈나 턱뼈처럼 양쪽 뼈 사이에 결합조직이 많고 가동성이 큰 가동관절, 연합관절 및 반관절로 나뉜다. 일반적으로 관절이라 하는 것은 가동관절을 말하며, 이 가동관절은 양쪽의 뼈가 인대만으로 결합되어 있는 인대결합과 활액막성 결합으로 나뉜다. 활액막성 결합은 관절이 결합조직성의 주머니(관절낭)로 쌓여 있는 것으로, 관절낭의 안쪽은 윤활유의 성격을 하는 활액을 분비하고 외부에는 많은 인대가 부착되어 있어 관절을 보강한다.Bone (bone) supports the soft tissue and body weight of the human body and surrounds the internal organs to protect the internal organs from external impact. In addition, it is one of the important parts of the human body that not only structurally supports muscles or organs, but also stores substances such as calcium and other essential minerals in the body, such as phosphorus and magnesium. Joints exist between the bones that make up the human body. Joints include immobile joints with little or no mobility between two bones or cartilage in contact with each other, such as the skull or tooth roots, and movable joints with large amounts of connective tissue and high mobility between both bones, such as bones of an animal's limbs or jawbone, joint and semi-articular joints. divided into joints. Generally, a joint refers to a movable joint, and this movable joint is divided into a ligamentous joint and a synovial joint, in which the bones of both sides are joined only by ligaments. The synovial joint is a joint in which the joint is piled up with a connective tissue sac (joint capsule), and the inside of the joint capsule secretes synovial fluid that acts as a lubricating oil, and many ligaments are attached to the outside to reinforce the joint.
본 발명에서 상기 관절염은 힘줄, 인대 및 근육 등과 같은 관절 주변의 조직뿐만 아니라 신체의 기타 기관 내에서의 관절의 만성 염증을 의미할 수 있고, 바람직하게는 골관절염, 퇴행성 관절염, 박리성 골연골염, 관절 인대 손상, 반월상 연골판 손상, 감염으로 인한 관절염, 건선성 관절염, 강직성 척추염, 류마티스 관절염 및 소아기 류마티스 관절염으로 이루어진 군에서 선택된 1종 이상일 수 있으나, 이에 제한되는 것은 아니다.In the present invention, the arthritis may mean chronic inflammation of the joint in tissues around the joint, such as tendons, ligaments and muscles, as well as in other organs of the body, preferably osteoarthritis, degenerative arthritis, dissociative osteochondritis, joint It may be one or more selected from the group consisting of ligament damage, meniscus damage, arthritis due to infection, psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis, and juvenile rheumatoid arthritis, but is not limited thereto.
본 발명의 약학 조성물의 제형화 형태, 투여 경로 및 투여량에 대한 기재는 앞서 기재된 바와 중복되어 명세서의 과도한 복잡을 피하기 위하여 이하 그 자세한 기재를 생략한다.Description of the dosage form, administration route and dosage of the pharmaceutical composition of the present invention overlaps with those described above, and detailed description thereof will be omitted below in order to avoid excessive complexity of the specification.
본 발명의 상기 약학 조성물은 인간을 대상으로 하는 것을 특징으로 할 수 있다.The pharmaceutical composition of the present invention may be characterized in that it targets humans.
본 발명에서 제공하는 약학 조성물은 장간막 면역세포에 있어서 IL-10 분비를 촉진하거나 IL-12 또는 IL-6 분비를 억제함으로써 관절염을 효과적으로 예방 또는 치료할 수 있다. The pharmaceutical composition provided in the present invention can effectively prevent or treat arthritis by promoting IL-10 secretion or inhibiting IL-12 or IL-6 secretion in mesenteric immune cells.
본 발명의 다른 구현 예에 따르면, 능이버섯 추출물, 석이버섯 추출물, 및 찔레버섯 추출물로 구성된 군으로부터 선택된 어느 하나 이상을 유효성분으로 포함하는 관절염의 예방 또는 개선용 식품 조성물을 제공한다. According to another embodiment of the present invention, there is provided a food composition for preventing or improving arthritis comprising, as an active ingredient, any one or more selected from the group consisting of neungi mushroom extract, shiitake mushroom extract, and chrysanthemum extract.
본 발명의 조성물에서 이용되는 능이버섯 추출물, 석이버섯 추출물 및 찔레버섯 추출물은 능이버섯, 석이버섯 및 찔레버섯에 추출용매를 처리하여 수득하는 경우에는, 다양한 추출용매가 이용될 수 있다. When the neungi mushroom extract, shiitake mushroom extract, and iris mushroom extract used in the composition of the present invention are obtained by treating neungi mushroom, shiitake mushroom and briar mushroom with an extraction solvent, various extraction solvents may be used.
본 발명에서 상기 다양한 추출용매에 관한 기재는 앞서 기재된 바와 중복되어 명세서의 과도한 복잡을 피하기 위하여 이하 그 자세한 기재를 생략한다. In the present invention, the description of the various extraction solvents overlaps with those described above, and detailed description thereof will be omitted below in order to avoid excessive complexity of the specification.
본 발명에서 추출 방법으로는 냉침 추출, 열 추출, 초음파 추출, 환류 냉각 추출 등 당업계에서 당업자에 의해 통상적으로 사용하는 모든 추출 방법을 사용할 수 있다.As the extraction method in the present invention, all extraction methods commonly used by those skilled in the art, such as cold extraction, heat extraction, ultrasonic extraction, and reflux cooling extraction, may be used.
본 방법에서 상기 통상적으로 사용하는 모든 추출 방법에 관한 기재는 앞서 기재된 바와 중복되어 명세서의 과도한 복잡을 피하기 위하여 이하 그 자세한 기재를 생략한다.In the present method, descriptions of all extraction methods commonly used are duplicated with those described above, and detailed descriptions thereof will be omitted below in order to avoid excessive complexity of the specification.
본 발명에서 상기와 같이 석이버섯 추출물 및 찔레버섯 추출물을 병용 투여함으로써 관절염의 예방 또는 개선 효과가 현저한 식품 조성물을 제공할 수 있다.In the present invention, it is possible to provide a food composition with a remarkable preventive or ameliorating effect of arthritis by co-administering the shiitake mushroom extract and the chrysanthemum extract as described above.
본 발명에서 상기 석이버섯 추출물과 찔레버섯 추출물은 1:0.01~100의 중량비, 보다 바람직하게는 1:0.1~10의 중량비로 사용될 수 있다.In the present invention, the shiitake mushroom extract and briar mushroom extract may be used in a weight ratio of 1:0.01 to 100, more preferably, in a weight ratio of 1:0.1 to 10.
본 발명에서, 상기 관절염에 관한 기재는 앞서 기재된 바와 중복되어 명세서의 과도한 복잡을 피하기 위하여 이하 그 자세한 기재를 생략한다.In the present invention, the description of the arthritis overlaps with those described above, and thus detailed description thereof will be omitted below in order to avoid excessive complexity of the specification.
본 발명에서 상기 개선은 본 발명의 식품 조성물의 투여로 자가면역질환및 관절염의 증상이 호전 또는 이롭게 변경되는 모든 행위를 의미한다.In the present invention, the improvement refers to any action in which the symptoms of autoimmune diseases and arthritis are improved or beneficially changed by administration of the food composition of the present invention.
본 발명의 식품 조성물의 종류 및 추가성분들에 대한 기재는 앞서 기재된 바와 중복되어 명세서의 과도한 복잡을 피하기 위하여 이하 그 자세한 기재를 생략한다.The description of the kind and additional components of the food composition of the present invention overlaps with those described above, and thus detailed description thereof will be omitted below in order to avoid excessive complexity of the specification.
본 발명은 능이버섯 추출물, 석이버섯 추출물 및 찔레버섯 추출물로 구성된 군으로부터 선택된 어느 하나 이상, 바람직하게는 석이버섯 추출물 및 찔레버섯 추출물을 병용 사용함으로써, IL-10 분비를 촉진하거나, IL-12 또는 IL-6 분비를 현저히 억제함으로써 자가면역질환 또는 관절염 등의 질환을 효과적으로 예방 또는 치료할 수 있다.The present invention promotes IL-10 secretion, or IL-12 or By significantly inhibiting IL-6 secretion, autoimmune diseases or diseases such as arthritis can be effectively prevented or treated.
도 1은 선별된 추출물로 인한 장간막 림프절 면역세포의 IL-10의 분비량을 보여준다.
도 2는 선별된 추출물로 인한 장간막 림프절 면역세포의 IL-12p40의 분비량을 보여준다.
도 3은 선별된 추출물로 인한 장간막 림프절 면역세포의 IL-10/IL-12p40의 분비량을 보여준다.
도 4는 선별된 추출물 및 그 혼합물로 인한 장간막 림프절 면역세포의 IL-10/IL-12p40의 분비량을 보여준다.
도 5는 선별된 추출물 및 그 혼합물로 인한 장간막 림프절 면역세포의 IL-10/IL-6의 분비량을 보여준다.1 shows the secretion amount of IL-10 from mesenteric lymph node immune cells due to the selected extract.
Figure 2 shows the secretion amount of IL-12p40 of mesenteric lymph node immune cells due to the selected extract.
3 shows the secretion amount of IL-10/IL-12p40 of mesenteric lymph node immune cells by the selected extract.
4 shows the secretion amount of IL-10/IL-12p40 of mesenteric lymph node immune cells by the selected extract and mixture thereof.
FIG. 5 shows the secretion amount of IL-10/IL-6 of mesenteric lymph node immune cells by the selected extracts and mixtures thereof.
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 illustrating the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
실시예 1Example 1
천연물로 인한 장간막 면역세포의 IL-10과 IL-12p40 유도량 측정Measurement of IL-10 and IL-12p40 induced amounts of mesenteric immune cells caused by natural products
생쥐(C57BL/6)의 장간막 림프절에서 분리한 백혈구 3x105개를 100㎕의 배양액(RPMI1640, 10% FBS, 5mM HEPES, 1mM sodium pyruvate, 1mM non-essential amino acid, 2mM L-glutamine, 55μM 2-mercaptoethanol, 100U/ml penicillin, 100μg/ml streptomycin)에 첨가하여 96 웰 플레이트에 분주하였다. 세포 활성화를 위하여 TLR7 작용제인 R848을 50㎕의 배양액에 녹여 최종 농도가 0.1μM이 되도록 첨가하였다. 천연물 추출물 시료는 50㎕의 배양액에 녹여 최종 농도가 100 μg/ml이 되도록 첨가하였다. 대조군의 경우 R848만 첨가하고, 천연물 시료는 첨가하지 않았다. 그 다음, 세포를 37℃에서 3일간 배양한 후 배양액 상층을 원심분리를 이용하여 분리하고, IL-10과 IL-12p40의 양을 ELISA kit (eBiosciences)를 이용하여 측정하였고, 그 결과를 도 1 내지 3에 나타내었다.Mice (C57BL / 6) in the
도 1 내지 3에서 보는 바와 같이, 다종의 천연물 추출물을 대상으로 실험한 결과, 장간막 면역세포부터 IL-10 분비를 유도하는 능력이 탁월하고 IL-12p40의 분비는 억제하거나 영향을 미치지 않는 4종의 천연물 추출물, 능이버섯 에탄올 추출물, 석이버섯 에탄올 추출물, 찔레버섯 에탄올 추출물, 찔레버섯 물 추출물을 선별하였다(도 1 및 2 참조). IL-10과 IL-12p40의 비율을 측정하였을 때도 이들 4종의 천연물이 대조군에 비해 IL-10/IL-12p40 비율을 200~300% 정도 증가시키는 효능을 보였다(도 3 참조).As shown in FIGS. 1 to 3 , as a result of testing with extracts of various kinds of natural products, the ability to induce IL-10 secretion from mesenteric immune cells is excellent and the secretion of IL-12p40 is not inhibited or affected by four types of Natural extracts, ethanol extracts from Neungyi mushroom, ethanol extracts from shiitake mushrooms, ethanol extracts from chrysanthemum mushrooms, and water extracts from chrysanthemums were selected (see FIGS. 1 and 2). When the ratio of IL-10 and IL-12p40 was measured, these four natural products showed an effect of increasing the IL-10/IL-12p40 ratio by 200 to 300% compared to the control group (see FIG. 3).
실시예 2Example 2
천연물로 인한 장간막 면역세포의 IL-10과 IL-12, IL-6 유도량 측정Measurement of IL-10, IL-12, and IL-6 induced amounts of mesenteric immune cells caused by natural products
생쥐(C57BL/6)의 장간막 림프절에서 분리한 백혈구 3x105개를 50㎕의 배양액(RPMI1640, 10% FBS, 5mM HEPES, 1mM sodium pyruvate, 1mM non-essential amino acid, 2mM L-glutamine, 55μM 2-mercaptoethanol, 100U/ml penicillin, 100μg/ml streptomycin)에 첨가하여 96 웰 플레이트에 분주하였다. 세포 활성화를 위하여 TLR7 작용제인 R848을 50㎕의 배양액에 녹여 최종 농도가 0.1μM이 되도록 첨가하였다. 천연물 추출물 시료인 능이버섯 추출물(A), 석이버섯 추출물(B) 및 찔레버섯 추출물(C)는 25㎕의 배양액에 녹여 최종 농도가 100 μg/ml이 되도록 준비하였다. 천연물 추출물 시료를 단독 또는 혼합물(A+B, A+C, B+C)을 세포에 첨가하였다. 대조군의 경우 R848만 첨가하고, 천연물 시료는 첨가하지 않았다. 각 웰당 200 μl 가 되게 배양액을 첨가하였다. 그 다음, 세포를 37℃에서 3일간 배양한 후 배양액 상층을 원심분리를 이용하여 분리하고, IL-10, IL-12 그리고 IL-6의 양을 ELISA kit (eBiosciences)를 이용하여 측정하였다. 측정 결과를 이용하여 IL-12에 대한 IL-10의 양 및 IL-6에 대한 IL-10의 양을 비교하여 염증성 사이토카인 대비 항염증성 사이토카인 분비 비율을 확인하였고, 그 결과를 도 4 및 5에 나타내었다.3x105 leukocytes isolated from mesenteric lymph nodes of mice (C57BL/6) were cultured in 50 μl of culture medium (RPMI1640, 10% FBS, 5mM HEPES, 1mM sodium pyruvate, 1mM non-essential amino acid, 2mM L-glutamine, 55μM 2-mercaptoethanol , 100U/ml penicillin, 100μg/ml streptomycin) and aliquoted in 96-well plates. For cell activation, R848, a TLR7 agonist, was dissolved in 50 μl of a culture solution and added to a final concentration of 0.1 μM. The natural extract samples, Neungyi mushroom extract (A), shiitake mushroom extract (B), and iris mushroom extract (C) were dissolved in 25 μl of culture solution to prepare a final concentration of 100 μg/ml. The natural extract sample alone or a mixture (A+B, A+C, B+C) was added to the cells. For the control, only R848 was added, and no natural product sample was added. The culture solution was added to make 200 μl per well. Then, after culturing the cells at 37° C. for 3 days, the supernatant of the culture medium was separated using centrifugation, and the amounts of IL-10, IL-12 and IL-6 were measured using an ELISA kit (eBiosciences). Using the measurement result, the amount of IL-10 for IL-12 and the amount of IL-10 for IL-6 were compared to determine the ratio of secretion of anti-inflammatory cytokines to inflammatory cytokines, and the results are shown in FIGS. 4 and 5 shown in
도 4 및 5에서 보는 바와 같이, 능이버섯 추출물(A), 석이버섯 추출물(B) 및 찔레버섯 추출물(C)을 단독으로 투여한 경우보다 석이버섯 추출물(B)과 찔레버섯 추출물(C)을 병용 투여한 경우 염증성 사이토카인 대비 항염증성 사이토카인 분비 비율이 현저히 높은 것을 확인할 수 있었다.As shown in FIGS. 4 and 5 , the Shiitake mushroom extract (B) and the Shiitake mushroom extract (C) than when the Neungyi mushroom extract (A), the shiitake mushroom extract (B) and the iris mushroom extract (C) were administered alone. In the case of co-administration, it was confirmed that the secretion ratio of anti-inflammatory cytokines compared to inflammatory cytokines was significantly higher.
이로부터 본 발명에 따른 능이버섯 추출물, 석이버섯 추출물 및 찔레버섯 추출물은 장간막 면역세포에 있어서 IL-10 분비를 촉진하거나, IL-12 또는 IL-6 분비를 현저히 억제함으로써 자가면역질환 또는 관절염을 효과적으로 치료할 수 있음을 알 수 있고, 특히 석이버섯 추출물 및 찔레버섯 추출물을 병용 투여하는 경우 시너지 효과를 얻을 수 있음을 알 수 있다. From this, the neungi mushroom extract, the shiitake mushroom extract and the iris mushroom extract according to the present invention promote IL-10 secretion in mesenteric immune cells or significantly inhibit IL-12 or IL-6 secretion, thereby effectively preventing autoimmune diseases or arthritis. It can be seen that it can be treated, and in particular, it can be seen that a synergistic effect can be obtained when the shiitake mushroom extract and the iris mushroom extract are co-administered.
이상으로 본 발명의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.As described above in detail a specific part of the present invention, for those of ordinary skill in the art, this specific description is only a preferred embodiment, and it is clear that 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 their equivalents.
Claims (10)
상기 약학 조성물은 석이버섯 추출물 및 찔레버섯 추출물을 유효성분으로 포함하는 자가면역질환 치료용 약학 조성물.The method of claim 1,
The pharmaceutical composition is a pharmaceutical composition for the treatment of autoimmune diseases comprising a shiitake mushroom extract and an iris mushroom extract as active ingredients.
상기 자가면역질환은 류마티스 관절염, 염증성 척추관절염, 성인형 스틸씨병, 대식세포 활성증후군, 전신경화증, 다발성근염, 피부근염, 혈관염, 혼합 결합조직질환, 쇼그렌 증후군, 궤양성 대장염, 크론병, 알러지성 천식, 알러지성 비염, 아토피성 피부염, 담마진, 누선염, 결막염, 건선, 심상성 천포창, 근위축성 측색경화증, 중증 근무력증, 다발성경화증, 혈관 재협착 및 만성 갑상선염으로 이루어진 군에서 하나 이상인 약학 조성물.The method of claim 1,
The autoimmune disease is rheumatoid arthritis, inflammatory spondyloarthritis, adult Still's disease, macrophage activation syndrome, systemic sclerosis, polymyositis, dermatomyositis, vasculitis, mixed connective tissue disease, Sjogren's syndrome, ulcerative colitis, Crohn's disease, allergic At least one pharmaceutical composition from the group consisting of asthma, allergic rhinitis, atopic dermatitis, urticaria, lacrimal glanditis, conjunctivitis, psoriasis, pemphigus vulgaris, amyotrophic lateral sclerosis, myasthenia gravis, multiple sclerosis, vascular restenosis and chronic thyroiditis.
장간막 면역세포가 IL-10 분비를 촉진하거나 IL-12 분비를 억제하거나 IL-6 분비를 억제하는 약학 조성물.The method of claim 1,
A pharmaceutical composition in which mesenteric immune cells promote IL-10 secretion, inhibit IL-12 secretion, or inhibit IL-6 secretion.
상기 약학 조성물은 석이버섯 추출물 및 찔레버섯 추출물을 유효성분으로 포함하는 관절염 치료용 약학 조성물.7. The method of claim 6,
The pharmaceutical composition is a pharmaceutical composition for the treatment of arthritis comprising a shiitake mushroom extract and an iris mushroom extract as active ingredients.
상기 관절염은 골관절염, 퇴행성 관절염, 박리성 골연골염, 관절 인대 손상, 반월상 연골판 손상, 감염으로 인한 관절염, 건선성 관절염, 강직성 척추염, 류마티스 관절염 및 소아기 류마티스 관절염으로 이루어진 군에서 선택된 1종 이상인, 약학 조성물.7. The method of claim 6,
The arthritis is at least one selected from the group consisting of osteoarthritis, degenerative arthritis, dissociative osteochondritis, joint ligament damage, meniscus damage, arthritis due to infection, psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis and juvenile rheumatoid arthritis, pharmaceutical composition.
상기 약학 조성물은 장간막 면역세포에 있어서 IL-10 분비를 촉진하거나, IL-12 또는 IL-6 분비를 억제하는 것인, 약학 조성물.7. The method of claim 6,
The pharmaceutical composition promotes IL-10 secretion in mesenteric immune cells, or inhibits IL-12 or IL-6 secretion, a pharmaceutical composition.
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