KR101685333B1 - Composition and method for the protection of articular cartilage - Google Patents

Composition and method for the protection of articular cartilage Download PDF

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KR101685333B1
KR101685333B1 KR1020167014135A KR20167014135A KR101685333B1 KR 101685333 B1 KR101685333 B1 KR 101685333B1 KR 1020167014135 A KR1020167014135 A KR 1020167014135A KR 20167014135 A KR20167014135 A KR 20167014135A KR 101685333 B1 KR101685333 B1 KR 101685333B1
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무하메드 마제에드
사랑 바니
안자리 판데이
칼야남 나가브허즈하남
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Abstract

포유동물의 관절 연골에 대한 병리학적 손상을 예방하기 위한 칼레빈 A(Calebin A)의 신규한 치료학적 잠재력 및 이의 조성물이 개시되어 있다.Disclosed are novel therapeutic potentials of Calebin A and compositions thereof for preventing pathological damage to articular cartilage in mammals.

Description

관절 연골의 보호를 위한 조성물 및 방법{COMPOSITION AND METHOD FOR THE PROTECTION OF ARTICULAR CARTILAGE}Technical Field [0001] The present invention relates to a composition and a method for protecting articular cartilage,

본 발명은 일반적으로, 관절 연골(articular cartilage)에 대한 보호 조성물 및 방법과 관계가 있다. 명확하게, 본 발명은, 관절 연골에 대한 병리학적 손상을 예방하기 위한 칼레빈 A(Calebin A)의 잠재력(potential)과 관계가 있다. The present invention relates generally to a protective composition and method for articular cartilage. Clearly, the present invention relates to the potential of Calebin A to prevent pathological damage to articular cartilage.

선행 기술의 기재Description of prior art

관절 연골은, 활막 관절(synovial joint)을 형성하는 뼈의 상기 관절 표면을 뒤덮는, 특수 결합 조직(specialized connective tissue)이다. 관절 연골은, 활막 관절이 낮은 마찰(low friction) 및 상대적으로 통증없는 동작(pain free motion)을 제공하는 능력을 부여한다. 관절 연골 구조 및 기능은, 근본적인 병리학적 질병 증상 및 닳음 및 찢어짐, 트라우마(추락 또는 사고) 후에 손상되기 쉽다(Articular cartilage structures and functions are prone to damage following trauma, wear and tear and underlying pathological disease conditions). 관절 연골 조직은 일반적으로, 결함(defect)의 형성 및 조직의 손실을 유도하는 질병 또는 부상 후에, [자가 회복(self repair)의 과정] 재생되지 않는다. 이러한 비-재생에 기인하는 이유는, (ⅰ) 보다 적은 세포의 구성요소; (ⅱ) 좋지 못한 신진대사; 및 (ⅲ) 조밀한 매트릭스 섬유(dense matrix fibers) 때문에, 상기 조직에서 갈라지고 이동하기 위한 선천적인 연골 세포(innate chondrocytes)의 제한된 능력을 포함한다. 따라서, 트라우마 및 질병으로 인한 손상으로부터 관절 연골을 보호할 수 있는 유효 성분은, 이러한 트라우마에 걸리기 쉬운 개인의 삶의 질을 개선하기 위해 상당한 능력을 제공하는 중요한 기술적인 영역을 구성한다. Articular cartilage is a specialized connective tissue that covers the joint surface of the bone forming the synovial joint. Articular cartilage gives the synovial membrane the ability to provide low friction and relatively pain free motion. Articular cartilage structures and functions are prone to damage after trauma (tears, trauma, and accidents) and underlying pathological disease symptoms (wear and tear and underlying pathological disease conditions). Articular cartilage tissue is generally not regenerated [the process of self repair] after a disease or injury that leads to the formation of defects and loss of tissue. The reason for this non-regeneration is (i) less cellular components; (Ii) bad metabolism; And (iii) the limited ability of innate chondrocytes to cleave and migrate from the tissue due to dense matrix fibers. Thus, the active ingredients that can protect the articular cartilage from trauma and disease-induced injury constitute an important technical area that provides significant capability to improve the quality of life of individuals susceptible to such trauma.

본 발명의 원리는, 포유동물의 관절 연골에 대한 병리학적 손상을 예방하기 위한 칼레빈 A의 잠재력 및 이의 조성물을 나타낸다. The principles of the present invention represent the potential of callavin A and compositions thereof to prevent pathological damage to articular cartilage in mammals.

본 발명은 상기 언급된 목적을 이행하고, 추가로 관련된 장점을 제공한다. The present invention fulfills the above-mentioned objects and provides further related advantages.

본 발명의 요약SUMMARY OF THE INVENTION

본 발명은, 포유동물의 관절 연골에 대한 병리학적 손상을 예방하기 위한, 칼레빈 A 의 잠재력 및 이의 조성물에 관한 것이다. The present invention relates to the potential of calbena A and compositions thereof for preventing pathological damage to articular cartilage in mammals.

본 발명은 하기의 장점을 제공한다.The present invention provides the following advantages.

1. 포유동물의 관절 연골에 대한 병리학적 손상을 예방하기 위한, 칼레빈 A의 신규한 치료학적 잠재력 및 이의 조성물의 내용.1. The novel therapeutic potential of calbena A and the content of its composition for preventing pathological damage to articular cartilage in mammals.

본 발명의 그 밖의 특징 및 장점은, 하나의 예로서, 본 발명의 원리를 설명하는, 첨부된 이미지와 함께 취해진, 하기의 보다 상세한 설명으로부터 명백할 것이다. Other features and advantages of the present invention will become apparent from the following more detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the invention.

도 1 은, 관절염 대조 그룹의 랫 발 조직 절편(rat paw tissue section)의 조직병리학(histopathology)을 나타낸 것이다.
도 2 는, 칼레빈 A(10 mg/kg)로 처리된 그룹의 랫 발 조직 절편의 조직병리학을 나타낸 것이다.
도 3 은, 칼레빈 A(20 mg/kg)로 처리된 그룹의 랫 발 조직 절편의 조직병리학을 나타낸 것이다. Figure 1 shows the histopathology of the rat paw tissue section of the arthritis control group.
Figure 2 shows the histopathology of the rat tissue sections of the group treated with calbene A (10 mg / kg).
Figure 3 shows the histopathology of a rat tissue section of a group treated with calbene A (20 mg / kg).

가장 바람직한 실시형태의 상세한 설명DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

(도 1, 2 및 3)(Figures 1, 2 and 3)

가장 바람직한 실시형태에서, 본 발명은, 병리학적 손상으로부터 포유동물의 관절 연골을 보호하기 위한 유효용량으로(in effective amounts) 칼레빈 A를 사용하는 방법에 관한 것으로서, 상기 방법은 상기 보호를 필요로 하는 포유동물에게 칼레빈 A의 유효량(effective dose)을 투여하는 단계를 포함한다. In a most preferred embodiment, the present invention relates to a method of using caliche A in effective amounts to protect the articular cartilage of a mammal from pathological damage, said method comprising the steps of: Comprising administering an effective dose of calbene A to the mammal.

다른 바람직한 실시형태에서, 본 발명은, 병리학적 손상으로부터 포유동물의 관절 연골을 보호하는 방법에 관한 것으로서, 상기 방법은 상기 보호를 필요로 하는 포유동물에게 칼레빈 A의 유효량을 투여하는 단계를 포함한다. In another preferred embodiment, the present invention relates to a method of protecting articular cartilage of a mammal from pathological damage, said method comprising administering to said mammal in need of such protection an effective amount of calbene A do.

포유동물의 관절 연골에 대한 병리학적 손상을 보호하기 위한 칼레빈 A 의 신규한 치료학적 잠재력 및 이의 조성물은 하기에 기재된 설명적인 실시예에서 명확하게 밝혀져 있다. The novel therapeutic potential of callavin A for protecting pathological damage to articular cartilage in mammals and compositions thereof are well known in the illustrative examples set forth below.

설명적인 실시예 1Illustrative Embodiment 1

병리학적 손상 : 동물 모델에서 아쥬반트 유도된 관절염(Adjuvant induced arthritis)Pathological damage: Adjuvant induced arthritis in animal models.

사용된 동물 : 암컷 수컷의 알비노 위스타 랫(Albino Wistar rats of either sex)Animals used: Albino Wistar rats of either sex

동물의 몸무게 : 140-180 gramsAnimal weight: 140-180 grams

동물/그룹의 수 : 05Number of animals / groups: 05

방법론 : 만성 관절염은, 왼쪽 뒷다리에 유동파라핀(liquid paraffin)에서 균질화된, 사멸된 결핵균(Mycobacterium tuberculosis)의 (0.5 % w/v) 현탁액의 0.05 mL의 주사에 의해 랫에서 유도되었다. Methodology Chronic arthritis was induced in the rat by injection of 0.05 mL of a suspension of 0.5% w / v of killed Mycobacterium tuberculosis homogenized in liquid paraffin on the left hind leg.

[표 A][Table A]

Figure 112016051040843-pat00001
Figure 112016051040843-pat00001

조직병리학 : Histopathology:

대조 그룹 및 처리된 그룹에서 상기 동물의 오른쪽 발목 관절이, 뒷발(hind paw)로부터 분리되었고, 계량되고, 24 시간 동안 10 % 완충된 포르말린에 담근 다음에, 10 % EDTA에서 석회질 제거(decalcification) 되었다. 상기 관절은 탈수되었고, 처리된 다음에, 파라핀(56 내지 58 ℃) 블록(blocks)이 제조되었고, [헤마톡시린(hematoxylin) 및 에오신(eosin)] 착색되었고, 복합 현미경(compound microscope) 하에서 검사되었다[(Patel P, Patel D, Patel N. Experimental investigation of anti-rheumatoid activity of Pleurotus sajorcaju in adjuvant-induced arthritic rats. Chinese Journal of Natural Medicines, 2012; 10 (4): 0269-0274]. The right ankle joint of the animal was removed from hind paws in the control and treated groups, weighed, soaked in 10% buffered formalin for 24 hours, then decalcified in 10% EDTA . The joints were dehydrated and treated and paraffin (56-58 ° C) blocks were made and hematoxylin and eosin were stained and examined under a compound microscope Patel P, Patel D, Patel N. Experimental investigation of the anti-rheumatoid activity of Pleurotus sajorcaju in adjuvant-induced arthritic rats. Chinese Journal of Natural Medicines, 2012; 10 (4): 0269-0274].

조직병리학 결과: Histopathology Results:

상기 대조 관절염 그룹의 상기 랫 발 조직(도 1)은, 활액 조직(synovial tissue)과 함께 병소의(focally) 손상된 관절 연골(화살표)을 나타낸다. 상기 관절 연골 및 활액 조직은 분산된 유상피 세포(scattered epitheloid cells)와 함께 풍부한 호산구성 건락 괴사(abundant eosinophilic caeseous necrosis)로 대체되고, 보다 적은 저조하게 형성된 불분명한 육아종(few poorly formed ill-defined granulomas)이 있었다. The rat foot tissue (FIG. 1) of the control arthritis group exhibits articular cartilage (arrows) focally damaged with synovial tissue. The articular cartilage and synovial fluid are replaced by abundant eosinophilic caeses necrosis with scattered epitheloid cells and fewer poorly formed ill-defined granulomas ).

칼레빈 A(10 mg/kg)로 처리된 그룹의 상기 랫 발 조직(도 2)은, 상기 관절에서 활액 조직과 함께 온전한 관절의 연골을 나타내었다. 상기 활액 조직은, 충혈된 혈관의 공간(congested vascular spaces)(긴-화살표), 분산된 림프구(scattered lymphocytes)(짧은-화살표) 및 온전한 활액 내벽(intact synovial lining)으로 이루어져있다. 어떠한 육아종도 관찰되지 않았다. The rat tissue (FIG. 2) of the group treated with calbene A (10 mg / kg) showed cartilage of the joints intact with synovial tissue in the joints. The synovial tissue consists of congested vascular spaces (long arrows), scattered lymphocytes (short arrows) and intact synovial lining. No granuloma was observed.

칼레빈 A(20 mg/kg)로 처리된 상기 그룹의 상기 랫 발 조직(도 3)은, 상기 관절에서 활액 조직과 함께 온전한 관절 연골을 나타내었다. 상기 활액 조직은, 가벼운 활액 상피 과증식(mild synovial epithelial hyperplasia)(짧은-화살표), 분산된 림프구(scattered lymphocytes)(긴-화살표) 및 온전한 혈관의 공간으로 이루어져 있다. 어떠한 육아종도 관찰되지 않았다. The rat foot tissue (FIG. 3) of the above group treated with calbene A (20 mg / kg) exhibited intact articular cartilage with synovial tissue in the joints. The synovial tissue consists of mild synovial epithelial hyperplasia (short-arrow), scattered lymphocytes (long-arrow), and a space of intact blood vessels. No granuloma was observed.

관절염 랫의 조직병리학 연구는, 칼레빈 A와 함께 관절 연골의 투여량 의존적인 보호(dose dependant protection)를 나타낸다. Histopathological studies of arthritis rats show dose dependent protection of articular cartilage with calla vin A.

본 발명은 바람직한 실시형태에 관련하여 기재되어 있는 반면에, 본 발명이 이에 한정되지 않음을 본 분야의 숙련자에 의해 명확하게 이해될 것이다. 또한, 본 발명의 범위는 오직 첨부된 특허청구범위와 함께 해석될 것이다. While the present invention has been described with reference to preferred embodiments, it will be understood by those skilled in the art that the present invention is not limited thereto. Further, the scope of the present invention will be construed only with reference to the appended claims.

Claims (2)

관절 연골에서의 면역 매개된 손상, 결핵균 감염 후의 관절염, 또는 퇴행성 관절염을 예방 또는 치료하기 위한, 칼레빈 A(Calebin A)를 포함하는 약제학적 조성물.
A pharmaceutical composition comprising Calebin A for preventing or treating immunomodulatory damage in articular cartilage, arthritis following Mycobacterium tuberculosis infection, or degenerative arthritis.
인간을 제외한 포유동물에서 관절 연골에서의 면역 매개된 손상, 결핵균 감염 후의 관절염, 또는 퇴행성 관절염을 예방 또는 치료하기 위한 방법으로서, 상기 방법은 상기 포유동물에게 칼레빈 A의 유효량을 투여하는 단계를 포함하는, 방법.A method for preventing or treating immune mediated damage in articular cartilage, arthritis, or degenerative arthritis following infection with M. tuberculosis in a mammal other than a human, the method comprising administering to said mammal an effective amount of calbene A How to.
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